APRETUDE is indicated for pre‑exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating APRETUDE (with or without an oral lead-in with oral cabotegravir) for HIV-1 PrEP [see Dosage and Administration (2.2, 2.4), Contraindications (4), Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "APRETUDE is indicated for pre‑exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating APRETUDE (with or without an oral lead-in with oral cabotegravir) for HIV-1 PrEP [see Dosage and Administration (2.2, 2.4), Contraindications (4), Warnings and Precautions (5.1)]." }

Individuals must be tested for HIV-1 infection prior to initiating APRETUDE or oral cabotegravir, and with each subsequent injection of APRETUDE, using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection. If an antigen/antibody-specific test is used and provides negative results, then such negative results should be confirmed using an RNA-specific assay, even if the results of the RNA-assay are available after APRETUDE or oral cabotegravir administration [see Contraindications (4), Warnings and Precautions (5.1)].

Prior to starting APRETUDE, healthcare providers should carefully select individuals who agree to the required injection dosing and testing schedule and counsel individuals about the importance of adherence to scheduled dosing visits to help reduce the risk of acquiring HIV-1 infection and development of resistance [see Dosage and Administration (2.1), Warnings and Precautions (5.1, 5.3), Microbiology (12.4)].

The healthcare provider and individual may decide to use an oral lead-in with oral cabotegravir prior to the initiation of APRETUDE to assess the tolerability of cabotegravir or the healthcare provider and individual may proceed directly to injection of APRETUDE without the use of an oral lead-in [see Dosage and Administration (2.5)].

No safety and efficacy data are available for use of APRETUDE without an oral lead-in [see Warnings and Precautions (5.3), Adverse Reactions (6.1)]. However, in HIV-1 treatment clinical trials, data show that an oral lead-in is not needed to ensure adequate plasma cabotegravir exposure upon initiation of injections and that the safety and efficacy results of CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) were similar when administered with and without an oral lead-in.

Initiation Injections

If an oral lead-in is used, initiation injections should be administered on the last day of oral lead‑in or within 3 days thereafter. The recommended initiation injection doses of APRETUDE in individuals is a single 600‑mg (3-mL) intramuscular injection of APRETUDE given 1 month apart for 2 consecutive months (Table 1 and Table 2). Individuals may be given the second APRETUDE initiation injection up to 7 days before or after the date the individual is scheduled to receive the injections.

Continuation Injections

After the 2 initiation injection doses given consecutively 1 month apart, the recommended continuation injection dose of APRETUDE is a single 600-mg (3-mL) intramuscular injection of APRETUDE every 2 months (Table 2). Individuals may be given APRETUDE up to 7 days before or after the date the individual is scheduled to receive the injections.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1. Recommended Dosing Schedule (with Oral Lead-In) for Pre-Exposure Prophylaxis in Adults and Adolescents Weighing at Least 35 kg</span> </caption> <col width="36%"/> <col width="32%"/> <col width="32%"/> <tfoot> <tr class="First"> <td align="left" colspan="3" valign="top"><span class="Sup">a</span> Should be administered on the last day of oral lead-in or within 3 days thereafter.</td> </tr> <tr class="Last"> <td align="left" colspan="3" valign="top"><span class="Sup">b</span> Individuals may be given APRETUDE up to 7 days before or after the date the individual is scheduled to receive the injections.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Oral Lead-In </span> <br/> <span class="Bold">(at Least 28 Days)</span> </p> <p> <span class="Bold">(Month Prior </span> <br/> <span class="Bold">to Starting Injections)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Intramuscular (Gluteal)</span> <br/> <span class="Bold">Initiation Injection </span> <br/> <span class="Bold">(Month 1 and Month 2)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Intramuscular (Gluteal) Continuation Injection </span> <br/> <span class="Bold">(Month 4 and </span> <br/> <span class="Bold">Every 2 Months Onwards)</span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Oral cabotegravir 30 mg by mouth once daily for 28 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">APRETUDE<span class="Sup">a</span> </p> <p>600-mg (3 mL)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">APRETUDE<span class="Sup">b</span> </p> <p>600-mg (3 mL)</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table cellpadding="0pt" width="100%"> <caption> <span>Table 2. Recommended Dosing Schedule (Direct to Injection) for Pre-Exposure Prophylaxis in Adults and Adolescents Weighing at Least 35 kg</span> </caption> <col width="50%"/> <col width="50%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="2" valign="top"><span class="Sup">a</span> Individuals may be given APRETUDE up to 7 days before or after the date the individual is scheduled to receive the injections.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Intramuscular (Gluteal) </span> <br/> <span class="Bold">Initiation Injection </span> <br/> <span class="Bold">(Month 1 and Month 2)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Intramuscular (Gluteal) </span> <br/> <span class="Bold">Continuation Injection </span> <br/> <span class="Bold">(Month 4 and Every 2 Months Onwards)</span> </p> </td> </tr> <tr> <td align="center" class="Lrule Rrule" valign="top"> <p class="First">APRETUDE<span class="Sup">a</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">APRETUDE<span class="Sup">a</span> </p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">600-mg (3 mL)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">600-mg (3 mL)</p> </td> </tr> </tbody> </table></div>

Adherence to the injection dosing schedule is strongly recommended [see Dosage and Administration (2.3)]. Individuals who miss a scheduled injection visit should be clinically reassessed to ensure resumption of APRETUDE remains appropriate [see Dosage and Administration (2.2), Warnings and Precautions (5.1, 5.2)]. Refer to Table 3 for dosing recommendations after missed injections.

Planned Missed Injections

If an individual plans to miss a scheduled every-2-month continuation injection visit by more than 7 days, take daily oral cabotegravir for up to 2 months to replace 1 missed scheduled every-2-month injection. The recommended oral daily dose is one 30-mg tablet of oral cabotegravir. The first dose of oral cabotegravir (or alternative oral PrEP regimen) should be taken approximately 2 months after the last injection dose of APRETUDE. Restart injection with APRETUDE on the day oral cabotegravir dosing completes or within 3 days, thereafter, as recommended in Table 3. For oral PrEP durations greater than 2 months, an alternative regimen to oral cabotegravir is recommended.

Unplanned Missed Injections

If a scheduled injection visit is missed or delayed by more than 7 days and oral dosing has not been taken in the interim, clinically reassess the individual to determine if resumption of injection dosing remains appropriate [see Warnings and Precautions (5.1)]. If the injection dosing schedule will be continued, see Table 3 for dosing recommendations.

<div class="scrollingtable"><table cellpadding="5.75pt" width="100%"> <caption> <span>Table 3. Injection Dosing Recommendations after Missed Injections</span> </caption> <col width="38%"/> <col width="62%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Time since Last Injection</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Recommendation</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">If second injection is missed and time since first injection is:</span> </p> </td><td class="Botrule Lrule Rrule" valign="bottom"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Less than or equal to 2 months</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">Administer 600-mg (3-mL) gluteal intramuscular injection of APRETUDE as soon as possible, then continue to follow the every-2-month injection dosing schedule.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Greater than 2 months</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">Restart with 600-mg (3-mL) gluteal intramuscular injection of APRETUDE, followed by a second 600-mg (3-mL) initiation injection dose 1 month later. Then continue to follow the every-2-month injection dosing schedule thereafter.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">If third or subsequent injection is missed and time since prior injection is:</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Less than or equal to 3 months</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">Administer 600-mg (3-mL) intramuscular injection of APRETUDE as soon as possible, then continue with the every-2-month injection dosing schedule.</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Greater than 3 months</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">Restart with 600-mg (3-mL) gluteal intramuscular injection of APRETUDE, followed by the second 600-mg (3-mL) initiation injection dose 1 month later. Then continue with the every-2-month injection dosing schedule thereafter.</p> </td> </tr> </tbody> </table></div>

Refer to the Instructions for Use for complete administration instructions with illustrations. Carefully follow these instructions and ensure that the vial adaptor is used correctly when preparing the suspension for injection to avoid leakage.

APRETUDE is a suspension for gluteal intramuscular injection that does not need further dilution or reconstitution.

The ventrogluteal site is recommended for injection. A dorsogluteal approach (upper outer quadrant) is acceptable, if preferred by the healthcare professional. Do not administer by any other route or anatomical site. Consider the body mass index (BMI) of the individual to ensure that the needle length is sufficient to reach the gluteus muscle. Longer needle lengths (not included in the dosing kit) may be required for individuals with higher BMI (e.g., >30 kg/m2) to ensure that the injection is administered intramuscularly as opposed to subcutaneously.

If the pack has been stored in the refrigerator, the vial should be brought to room temperature prior to administration (not to exceed 30°C [86°F]).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The APRETUDE vial has a brown tint to the glass that may limit visual inspection. Discard the vial if the medicine exhibits particulate matter or discoloration.

Shake the vial vigorously so that the suspension looks uniform before injecting. Small air bubbles are expected and acceptable.

Once the suspension has been drawn into the syringe, the injection should be administered as soon as possible, but may remain in the syringe for up to 2 hours. The filled syringe should not be placed in the refrigerator. If the medicine remains in the syringe for more than 2 hours, the filled syringe and needle must be discarded [see How Supplied/Storage and Handling (16)].

Injection: Single-dose vial containing 600 mg/3 mL (200 mg/mL) of cabotegravir extended‑release injectable suspension.

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APRETUDE is contraindicated in individuals:

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Use APRETUDE for HIV-1 PrEP to reduce the risk of HIV-1 infection as part of a comprehensive prevention strategy including adherence to the administration schedule and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs). APRETUDE is not always effective in preventing HIV-1 acquisition [see Clinical Studies (14.1)]. The time from initiation of APRETUDE for HIV-1 PrEP to maximal protection against HIV-1 infection is unknown.

Risk for HIV-1 acquisition includes behavioral, biological, or epidemiologic factors including, but not limited to, condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high prevalence area or network.

Counsel individuals on the use of other prevention measures (e.g., consistent and correct condom use; knowledge of partner(s)’ HIV-1 status, including viral suppression status; regular testing for STIs that can facilitate HIV-1 transmission). Inform individuals about and support their efforts in reducing sexual risk behavior.

Use APRETUDE to reduce the risk of acquiring HIV-1 only in individuals confirmed to be HIV‑1 negative [see Contraindications (4)]. HIV-1 resistance substitutions may emerge in individuals with undiagnosed HIV‑1 infection who are taking only APRETUDE, because APRETUDE alone does not constitute a complete regimen for HIV-1 treatment [see Microbiology (12.4)]; therefore, care should be taken to minimize the risk of initiating or continuing APRETUDE before confirming the individual is HIV-1 negative.

When using APRETUDE for HIV-1 PrEP, HIV-1 testing should be repeated prior to each injection and upon diagnosis of any other STIs [see Dosage and Administration (2.2, 2.5)].

Counsel individuals without HIV-1 to strictly adhere to the recommended dosing and testing schedule for APRETUDE in order to reduce the risk of HIV-1 acquisition and the potential development of resistance [see Dosage and Administration (2.3, 2.5), Microbiology (12.4)]. Some individuals, such as adolescents, may benefit from frequent visits and counseling to support adherence to the dosing and testing schedule [see Use in Specific Populations (8.4), Microbiology (12.4), Clinical Studies (14)].

There is a potential risk of developing resistance to APRETUDE if an individual acquires HIV-1 either before or while taking APRETUDE or following discontinuation of APRETUDE [see Warnings and Precautions (5.1, 5.3)].

To minimize this risk, it is essential to clinically reassess individuals for risk of HIV-1 acquisition and to test before each injection to confirm HIV-1 negative status. Individuals who are confirmed to have HIV-1 infection must transition to a complete HIV-1 treatment regimen.

Alternative forms of PrEP should be considered following discontinuation of APRETUDE for those individuals at continuing risk of HIV-1 acquisition and initiated within 2 months of the final injection of APRETUDE.

Residual concentrations of cabotegravir may remain in the systemic circulation of individuals for prolonged periods (up to 12 months or longer). It is important to carefully select individuals who agree to the required every-2-month injection dosing schedule because non-adherence to every‑2-monthly injections or missed doses could lead to HIV-1 acquisition and development of resistance.

Healthcare providers should take the prolonged-release characteristics of cabotegravir into consideration when APRETUDE is prescribed [see Dosage and Administration (2.3), Warnings and Precautions (5.1, 5.2), Drug Interactions (7.1), Use in Specific Populations (8.1, 8.2), Overdosage (10)].

Serious or severe hypersensitivity reactions have been reported with cabotegravir and include Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) [see Adverse Reactions (6.2)]. Administration of cabotegravir oral lead-in dosing was used in clinical studies to help identify participants who may be at risk of a hypersensitivity reaction. Remain vigilant and discontinue APRETUDE if a hypersensitivity reaction is suspected [see Dosage and Administration (2.4), Contraindications (4), Adverse Reactions (6)].

Discontinue APRETUDE immediately if signs or symptoms of hypersensitivity reactions develop (including, but not limited to, severe rash, or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, mucosal involvement [oral blisters or lesions], conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing). Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated. For information regarding the long-acting properties of APRETUDE [see Warnings and Precautions (5.3)].

Hepatotoxicity has been reported in a limited number of individuals receiving cabotegravir with or without known pre-existing hepatic disease or identifiable risk factors [see Adverse Reactions (6.1)].

Clinical and laboratory monitoring should be considered and APRETUDE should be discontinued if hepatotoxicity is suspected and individuals managed as clinically indicated. For information regarding the long-acting properties of APRETUDE [see Warnings and Precautions (5.3)].

Depressive disorders (including depression, depressed mood, major depression, persistent depressive disorder, suicidal ideation, suicide attempt) have been reported with APRETUDE [see Adverse Reactions (6.1)]. Promptly evaluate individuals with depressive symptoms to assess whether the symptoms are related to APRETUDE and to determine whether the risks of continued therapy outweigh the benefits.

The concomitant use of APRETUDE and other drugs may result in reduced drug concentration of APRETUDE [see Contraindications (4), Drug Interactions (7.2, 7.3)].

See Table 8 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during use of, and after discontinuation of APRETUDE; review concomitant medications during use of APRETUDE [see Drug Interactions (7.3, 7.4)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect rates observed in practice.

Clinical Trials Experience in Adults

The safety assessment of APRETUDE is based on the analysis of data from 2 international, multicenter, double-blind trials, HPTN 083 and HPTN 084 [see Clinical Studies (14.1)].

Adverse reactions were reported while on blinded study product following exposure to APRETUDE extended-release injectable suspension and oral cabotegravir tablets as oral lead-in. The median time on blinded study product in HPTN 083 was 65 weeks and 2 days (range: 1 day to 156 weeks and 1 day), with a total exposure on cabotegravir of 3,231 person‑years. The median time on blinded study product in HPTN 084 was 64 weeks and 1 day (range: 1 day to 153 weeks and 1 day), with a total exposure on cabotegravir of 2,009 person‑years.

The most common adverse reactions regardless of severity reported in at least 1% of participants in HPTN 083 or HPTN 084 are presented in Table 4.

In HPTN 083, 6% of participants in the group receiving APRETUDE intramuscular injection every 2 months and 4% of participants receiving oral TRUVADA [emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF)] once daily discontinued due to adverse events (all causality). Non-injection-site–associated adverse events leading to discontinuation and occurring in ≥1% of participants were increased alanine aminotransferase with APRETUDE and TRUVADA.

In HPTN 084, 1% of participants receiving APRETUDE and 1% of participants receiving TRUVADA discontinued due to adverse events. The most commonly reported adverse event (all causality) leading to discontinuation was increased alanine aminotransferase (<1%) with APRETUDE and TRUVADA. The side-by-side tabulation is to simplify presentation; direct comparison across trials should not be made due to differing trials.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 4. Adverse Drug Reactions<span class="Sup">a</span> (All Grades) Reported in at Least 1% of Participants Receiving APRETUDE in Either HPTN 083 or HPTN 084</span> </caption> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <tfoot> <tr class="First"> <td align="left" colspan="5" valign="top"><span class="Sup">a</span> Adverse reactions defined as “treatment-related” as assessed by the investigator, with exception of injection site reactions, where all injection site reactions were reported regardless of causality.</td> </tr> <tr> <td align="left" colspan="5" valign="top"><span class="Sup">b</span> Participants who received injection: HPTN 083, APRETUDE (n = 2,117) and TRUVADA (n = 2,081); HPTN 084, APRETUDE (n = 1,519) and TRUVADA (n = 1,516).</td> </tr> <tr> <td align="left" colspan="5" valign="top"><span class="Sup">c</span> Pyrexia includes pyrexia, feeling hot, chills, influenza-like illness.</td> </tr> <tr> <td align="left" colspan="5" valign="top"><span class="Sup">d</span> Fatigue includes fatigue, malaise.</td> </tr> <tr> <td align="left" colspan="5" valign="top"><span class="Sup">e</span> Sleep disorders includes insomnia, abnormal dreams.</td> </tr> <tr> <td align="left" colspan="5" valign="top"><span class="Sup">f</span> Abdominal pain includes abdominal pain, upper abdominal pain.</td> </tr> <tr class="Last"> <td align="left" colspan="5" valign="top"><span class="Sup">g</span> Rash includes rash, erythema, pruritis, macular, papular, maculopapular.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Adverse Reactions</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">HPTN 083</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">HPTN 084</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">APRETUDE</span> </p> <p> <span class="Bold">Every 2 Months</span> </p> <p> <span class="Bold">(n = 2,281)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">TRUVADA</span> </p> <p> <span class="Bold">Once Daily</span> </p> <p> <span class="Bold">(n = 2,285)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">APRETUDE</span> </p> <p> <span class="Bold">Every 2 Months</span> </p> <p> <span class="Bold">(n = 1,614)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">TRUVADA</span> </p> <p> <span class="Bold">Once Daily</span> </p> <p> <span class="Bold">(n = 1,610)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Injection site reactions<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">82%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">35%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">38%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">11%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Diarrhea</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Headache</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">12%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">13%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pyrexia<span class="Sup">c</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Fatigue<span class="Sup">d</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Sleep disorders<span class="Sup">e</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Nausea</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">8%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Dizziness</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">6%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Flatulence</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Abdominal pain<span class="Sup">f</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Vomiting</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Myalgia</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Rash<span class="Sup">g</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Decreased appetite</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Somnolence</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Back pain</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Upper respiratory tract infection</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4%</p> </td> </tr> </tbody> </table></div>

Injection-Associated Adverse Reactions: Local Injection Site Reactions (ISRs) with APRETUDE: The most frequent adverse reactions associated with the intramuscular administration of APRETUDE in HPTN 083 were ISRs. After 20,286 injections, 8,900 ISRs were reported. Of the 2,117 participants who received at least one injection of APRETUDE, 1,740 (82%) participants experienced at least one ISR, of which a total of 3% of participants discontinued APRETUDE because of ISRs. Among the participants who received APRETUDE and experienced at least one ISR, the maximum severity of reactions was mild (Grade 1) in 41% of participants, moderate (Grade 2) in 56% of participants, and severe (Grade 3) in 3% of participants. The median duration of overall ISR events was 4 days. The proportion of participants reporting ISRs at each visit and the severity of the ISRs decreased over time. The most commonly reported ISRs (all causality and grades) in at least 1% of participants who received APRETUDE and experienced at least one ISR from HPTN 083 are presented in Table 5.

The most frequent adverse reactions associated with the intramuscular administration of APRETUDE in HPTN 084 were ISRs. After 13,068 injections, 1,171 ISRs were reported. Of the 1,519 participants who received at least one injection of APRETUDE, 578 (38%) participants experienced at least one ISR. No participants discontinued APRETUDE because of ISRs. Among the participants who received APRETUDE and experienced at least one ISR, the maximum severity of reactions was mild (Grade 1) in 66% of participants, moderate (Grade 2) in 34% of participants, and severe (Grade 3) in less than 1% of participants. The median duration of overall ISR events was 8 days. The proportion of participants reporting ISRs at each visit and the severity of the ISRs generally decreased over time. The most commonly reported ISRs (all causality and grades) in at least 1% of participants who received APRETUDE and experienced at least one ISR from HPTN 084 are presented in Table 5.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 5. Injection Site Reactions (All Grades) Reported in at Least 1% of Participants Who Experienced at Least One Injection Site Reaction (All Causality) with APRETUDE in Either HPTN 083 or HPTN 084</span> </caption> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="5" valign="top"><span class="Sup">a</span> Placebo injectable suspension: intralipid 20% fat emulsion.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Injection Site Reactions</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">HPTN 083</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">HPTN 084</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">APRETUDE</span> </p> <p> <span class="Bold">(n = 1,740)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">TRUVADA<span class="Sup">a</span></span> </p> <p> <span class="Bold">(n = 724)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">APRETUDE</span> </p> <p> <span class="Bold">(n = 578)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">TRUVADA<span class="Sup">a</span></span> </p> <p> <span class="Bold">(n = 166)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pain/tenderness</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">98%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">95%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">90%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">87%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Nodules</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">15%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">14%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Induration</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">15%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">12%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Swelling</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">12%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">18%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Bruising </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Erythema</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pruritus</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">6%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">11%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Warmth</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Anesthesia</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Abscess</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Discoloration</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> </tbody> </table></div>

          Other Injection-Associated Adverse Reactions: In the HPTN 083 clinical trial, an increased incidence of pyrexia (including pyrexia, feeling hot, chills, influenza-like illness) (4%) was reported by participants receiving APRETUDE compared with participants receiving TRUVADA (<1%). There were no differences reported in the incidence of pyrexia between groups in HPTN 084.

Vasovagal or pre-syncopal reactions considered treatment related were reported in <1% of participants after injection with APRETUDE in HPTN 083. None were reported as treatment related by the investigators in HPTN 084.

Less Common Adverse Reactions: The following select adverse reactions (regardless of severity) occurred in <1% of participants receiving APRETUDE in HPTN 083 or HPTN 084.

          Hepatobiliary Disorders: Hepatotoxicity.

          Investigations: Weight increase (see below).

          Psychiatric Disorders: Depression; suicidal ideation, and suicide attempt (these events were observed primarily in participants with a pre‑existing history of depression or other psychiatric illness).

Weight Increase: At the Week 41 and Week 97 timepoints in HPTN 083, participants who received APRETUDE gained a median of 1.2 kg (Interquartile Range [IQR]; -1.0, 3.5; n = 1,623) and 2.1 kg (IQR; -0.9, 5.9; n = 601) in weight from baseline. Those who received TRUVADA gained a median of 0 kg (IQR; -2.1, 2.4; n = 1,611) and 1 kg (IQR; -1.9, 4.0; n = 598) in weight from baseline, respectively.

At the Week 41 and 97 timepoints in HPTN 084, participants who received APRETUDE gained a median of 2 kg (IQR; 0.0, 5.0; n = 1,151) and 4 kg (IQR; 0.0, 8.0; n = 216) in weight from baseline, respectively. Those who received TRUVADA gained a median of 1 kg (IQR; -1.0, 4.0; n = 1,131) and 3 kg (IQR; -1.0, 6.0; n = 218) in weight from baseline, respectively.

Laboratory Abnormalities: Grade 3 or 4 post-baseline maximum toxicity laboratory abnormalities for HPTN 083 or HPTN 084 are summarized in Table 6.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 6. Laboratory Abnormalities (Grades 3 to 4) in ≥1% of Participants in Either HPTN 083 or HPTN 084</span> </caption> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="5" valign="top">ALT = Alanine transaminase, ULN = upper limit of normal, AST = Aspartate aminotransferase.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Laboratory Parameter</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">HPTN 083</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">HPTN 084</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">APRETUDE</span> </p> <p> <span class="Bold">Every 2 Months</span> </p> <p> <span class="Bold">(n = 2,281)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">TRUVADA</span> </p> <p> <span class="Bold">Once Daily</span> </p> <p> <span class="Bold">(n = 2,285)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">APRETUDE</span> </p> <p> <span class="Bold">Every 2 Months</span> </p> <p> <span class="Bold">(n = 1,614)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">TRUVADA</span> </p> <p> <span class="Bold">Once Daily</span> </p> <p> <span class="Bold">(n = 1,610)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">ALT (≥5.0 x ULN)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">AST (≥5.0 x ULN)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Creatine phosphokinase (≥10.0 x ULN)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">15%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">14%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Lipase (≥3.0 x ULN)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Creatinine (&gt;1.8 x ULN) or increase to ≥1.5 x baseline)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4%</p> </td> </tr> </tbody> </table></div>

          Serum Lipids: Changes from baseline to Month 15 in total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and total cholesterol to HDL ratio in HPTN 083 and HPTN 084 are presented in Table 7.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 7. Fasting Lipid Values, Median Change from Baseline<span class="Sup">a</span> at Week 57, Reported in HPTN 083 and HPTN 084</span> </caption> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="5" valign="top"><span class="Sup">a</span> Nearly 60% of participants with baseline data available had Week 57 data available in both arms of both trials. Within each trial, baseline values were comparable among participants receiving APRETUDE and TRUVADA.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">HPTN 083</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">HPTN 084</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">APRETUDE</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">TRUVADA</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">APRETUDE</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">TRUVADA</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Total cholesterol (mg/dL)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">+1.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-10.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">+0.2</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-3.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">LDL cholesterol (mg/dL)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">+1.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-6.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-1.1</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-5.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">HDL cholesterol (mg/dL)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-0.2</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-3.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-0.8</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-2.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Triglycerides (mg/dL)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">+2.7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">+3.1</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">+0.7</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Total cholesterol:<br/>HDL cholesterol ratio</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">+0.1</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">+0.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">+0.1</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">+0.1</p> </td> </tr> </tbody> </table></div>

Clinical Trials Experience in Adolescents

In adolescents receiving APRETUDE for HIV-1 PrEP, the safety data were comparable to the safety data reported in adults receiving APRETUDE for HIV-1 PrEP [see Use in Specific Populations (8.4)].

The following adverse reactions have been identified during postmarketing use of APRETUDE or cabotegravir-containing regimens. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders

Hypersensitivity reactions (including angioedema and urticaria) [see Warnings and Precautions (5.4)].

Skin and Subcutaneous Tissue Disorders

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) [see Warnings and Precautions (5.4)].

Residual concentrations of cabotegravir may remain in the systemic circulation of individuals for prolonged periods (up to 12 months or longer). These residual concentrations are not expected to affect the exposures of antiretroviral drugs that are initiated after discontinuation of APRETUDE [see Warnings and Precautions (5.3), Drug Interactions (7.4), Clinical Pharmacology (12.3)].

Cabotegravir is primarily metabolized by UGT1A1 with some contribution from UGT1A9. Drugs that are strong inducers of UGT1A1 or 1A9 are expected to decrease cabotegravir plasma concentrations; therefore, coadministration of APRETUDE with these drugs is contraindicated [see Contraindications (4)].

Information regarding potential drug interactions with cabotegravir is provided in Table 8. These recommendations are based on either drug interaction trials following oral administration of cabotegravir or predicted interactions due to the expected magnitude of the interaction [see Contraindications (4), Warnings and Precautions (5.7), Clinical Pharmacology (12.3)]. Table 8 includes potentially significant interactions but is not all inclusive.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 8. Drug Interactions with APRETUDE</span> </caption> <col width="30%"/> <col width="22%"/> <col width="48%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="3" valign="top">↑ = Increase, ↓ = Decrease, ↔ = No change.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Concomitant Drug Class: </span> </p> <p> <span class="Bold">Drug Name</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Effect on Concentration</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Clinical Comment</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Anticonvulsants:</p> <p>Carbamazepine</p> <p>Oxcarbazepine</p> <p>Phenobarbital</p> <p>Phenytoin</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">↓Cabotegravir</p> </td><td align="center" class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Coadministration is contraindicated with APRETUDE due to potential for significant decreases in plasma concentration of APRETUDE.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Antimycobacterials:</p> <p>Rifampin</p> <p>Rifapentine</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">↓Cabotegravir</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Antimycobacterial:</p> <p>Rifabutin</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">↓Cabotegravir</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">When rifabutin is started before or concomitantly with the first initiation injection of APRETUDE, the recommended dosing of APRETUDE is one 600-mg (3-mL) injection, followed 2 weeks later by a second 600‑mg (3-mL) initiation injection and monthly thereafter while on rifabutin. When rifabutin is started at the time of the second initiation injection or later, the recommended dosing schedule of APRETUDE is 600‑mg (3 mL) monthly while on rifabutin.</p> <p>After stopping rifabutin, the recommended dosing schedule of APRETUDE is 600-mg (3 mL) every 2 months.</p> </td> </tr> </tbody> </table></div>

Based on drug interaction study results, the following drugs can be coadministered with cabotegravir (non-antiretrovirals) or given after discontinuation of cabotegravir (antiretrovirals and non-antiretrovirals) without a dose adjustment: etravirine, midazolam, oral contraceptives containing levonorgestrel and ethinyl estradiol, and rilpivirine [see Clinical Pharmacology (12.3)].

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to APRETUDE during pregnancy. Healthcare providers are encouraged to register individuals by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.

Risk Summary

There are insufficient human data on the use of APRETUDE during pregnancy to adequately assess a drug-associated risk of birth defects and miscarriage. Discuss the benefit-risk of using APRETUDE with individuals of childbearing potential or during pregnancy.

Cabotegravir use in pregnant individuals has not been evaluated. APRETUDE should be used during pregnancy only if the expected benefit justifies the potential risk to the fetus.

The APR has been established to monitor for birth defects following prenatal exposure to antiretrovirals. The rate of miscarriage is not reported in the APR. The background rate for major birth defects in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) is 2.7%. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15% to 20%. The APR uses the MACDP as the U.S. reference population for birth defects in the general population. The MACDP evaluates mothers and infants from a limited geographic area and does not include outcomes for births that occurred at <20 weeks’ gestation.

In animal reproduction studies with oral cabotegravir, a delay in the onset of parturition and increased stillbirths and neonatal deaths were observed in a rat pre- and postnatal development study at >28 times the exposure at the recommended human dose (RHD). No evidence of adverse developmental outcomes was observed with oral cabotegravir in rats or rabbits (>28 times or similar to the exposure at the RHD, respectively) given during organogenesis (see Data).

Clinical Considerations

Cabotegravir is detected in systemic circulation for up to 12 months or longer after discontinuing injections of APRETUDE; therefore, consideration should be given to the potential for fetal exposure during pregnancy [see Warnings and Precautions (5.3)].

Data

Animal Data: Cabotegravir was administered orally to pregnant rats at 0, 0.5, 5, or 1,000 mg/kg/day from 15 days before cohabitation, during cohabitation, and from Gestation Days 0 to 17. There were no effects on fetal viability when fetuses were delivered by caesarean, although a minor decrease in fetal body weight was observed at 1,000 mg/kg/day (>28 times the exposure in humans at the RHD). No drug-related fetal toxicities were observed at 5 mg/kg/day (approximately 13 times the exposure in humans at the RHD), and no drug-related fetal malformations were observed at any dose.

Cabotegravir was administered orally to pregnant rabbits at 0, 30, 500, or 2,000 mg/kg/day from Gestation Days 7 to 19. No drug-related fetal toxicities were observed at 2,000 mg/kg/day (approximately 0.7 times the exposure in humans at the RHD).

In a rat pre- and postnatal development study, cabotegravir was administered orally to pregnant rats at 0, 0.5, 5, or 1,000 mg/kg/day from Gestation Day 6 to Lactation Day 21. A delay in the onset of parturition and increases in the number of stillbirths and neonatal deaths by Lactation Day 4 were observed at 1,000 mg/kg/day (>28 times the exposure in humans at the RHD); there were no alterations to growth and development of surviving offspring. In a cross-fostering study, similar incidences of stillbirths and early postnatal deaths were observed when rat pups born to cabotegravir-treated mothers were nursed from birth by control mothers. There was no effect on neonatal survival of control pups nursed from birth by cabotegravir-treated mothers. A lower dose of 5 mg/kg/day (13 times the exposure at the RHD) was not associated with delayed parturition or neonatal mortality in rats. Studies in pregnant rats showed that cabotegravir crosses the placenta and can be detected in fetal tissue.

Risk Summary

There are no data on the presence of cabotegravir in human milk. Cabotegravir is present in animal milk (see Data). When a drug is present in animal milk, it is likely that the drug will be present in human milk. It is not known if cabotegravir affects human milk production, or has effects on the breastfed infant. If cabotegravir is present in human milk, residual exposures may remain for 12 months or longer after the last injections have been administered [see Warnings and Precautions (5.3)].

Cabotegravir concentrations may be detectable in systemic circulation for up to 12 months or longer after discontinuing injections of APRETUDE. Breastfeeding should only be considered if the expected benefit justifies the potential risk to the infant, including the potential risk for adverse reaction in the breastfed child, along with the risk of HIV-1 acquisition due to nonadherence and subsequent vertical transmission to the child. Breastfeeding is not recommended if acute HIV-1 infection is suspected to avoid the risk of postnatal transmission of HIV-1 infection.

Data

Animal lactation studies with cabotegravir have not been conducted. However, cabotegravir was detected in the plasma of nursing pups on Lactation Day 10 in the rat pre- and postnatal development study.

The safety and effectiveness of APRETUDE for HIV-1 PrEP in adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition is supported by data from 2 adequate and well-controlled trials of APRETUDE for HIV-1 PrEP in adults with additional safety and pharmacokinetic data from studies in adults with HIV-1 who were administered CABENUVA, and in adolescent participants with HIV-1 who were administered separate components of CABENUVA in addition to their current antiretroviral therapy [see Dosage and Administration (2.5), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.1)].

APRETUDE for HIV-1 PrEP was evaluated in 2 open-label multicenter clinical trials, HPTN 083-01 and HPTN 084-01, in adolescent individuals 12 to less than 18 years of age weighing at least 35 kg who are at risk for HIV-1 acquisition. Sixty-four adolescents were enrolled. Of these, 62 adolescent participants received one or more injections. In adolescents receiving APRETUDE for HIV-1 PrEP, the safety data were comparable to the safety data reported in adults receiving APRETUDE for HIV-1 PrEP.

While using APRETUDE, HIV-1 testing should be conducted prior to initiating APRETUDE (with or without an oral lead-in with oral cabotegravir) and prior to each injection of APRETUDE. Adolescents may benefit from more frequent visits and counseling to support adherence to the dosing and testing schedule [see Dosage and Administration (2.2), Warnings and Precautions (5.1)].

The safety, efficacy, and pharmacokinetics of APRETUDE in pediatric participants younger than 12 years of age or weighing <35 kg have not been established.

No dose adjustment is required in elderly individuals. There are limited data available on the use of APRETUDE in individuals aged 65 years and older. In general, caution should be exercised in administration of APRETUDE in elderly individuals, reflecting greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy [see Clinical Pharmacology (12.3)].

Based on studies with oral cabotegravir, no dosage adjustment of APRETUDE is necessary for individuals with mild (creatinine clearance ≥60 to <90 mL/min), moderate (creatinine clearance ≥30 to <60 mL/min) or severe renal impairment (creatinine clearance ≥15 to <30 mL/min) [see Clinical Pharmacology (12.3)]. In individuals with end-stage renal disease not on dialysis, effects on the pharmacokinetics of cabotegravir are unknown. As cabotegravir is >99% protein bound, dialysis is not expected to alter exposures of cabotegravir.

Based on studies with oral cabotegravir, no dosage adjustment of APRETUDE is necessary for individuals with mild or moderate hepatic impairment (Child-Pugh A or B). The effect of severe hepatic impairment (Child-Pugh C) on the pharmacokinetics of cabotegravir is unknown [see Clinical Pharmacology (12.3)].

There is no known specific treatment for overdose with APRETUDE. If overdose occurs, monitor the individual and apply standard supportive treatment as required as well as observation of the clinical status of the individual. As APRETUDE is highly bound to plasma proteins, it is unlikely that it will be significantly removed by dialysis. Consider the prolonged exposure to APRETUDE following an injection when assessing treatment needs and recovery [see Warnings and Precautions (5.5)].

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APRETUDE contains cabotegravir extended-release injectable suspension, an HIV INSTI.

{ "type": "p", "children": [], "text": "APRETUDE contains cabotegravir extended-release injectable suspension, an HIV INSTI." }

The chemical name of cabotegravir is (3S,11aR)-N-[(2,4-difluorophenyl)methyl]-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamide. The empirical formula is C19H17F2N3O5 and the molecular weight is 405.35 g/mol. It has the following structural formula:

{ "type": "p", "children": [], "text": "The chemical name of cabotegravir is (3S,11aR)-N-[(2,4-difluorophenyl)methyl]-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamide. The empirical formula is C19H17F2N3O5 and the molecular weight is 405.35 g/mol. It has the following structural formula:" }

Cabotegravir extended-release injectable suspension is a white to light pink free-flowing suspension for intramuscular injection in a sterile single-dose vial. Each vial contains 3 mL of the following: cabotegravir 200 mg/mL and the inactive ingredients mannitol (35 mg/mL), polyethylene glycol (PEG) 3350 (20 mg/mL), polysorbate 20 (20 mg/mL), and Water for Injection.

{ "type": "p", "children": [], "text": "Cabotegravir extended-release injectable suspension is a white to light pink free-flowing suspension for intramuscular injection in a sterile single-dose vial. Each vial contains 3 mL of the following: cabotegravir 200 mg/mL and the inactive ingredients mannitol (35 mg/mL), polyethylene glycol (PEG) 3350 (20 mg/mL), polysorbate 20 (20 mg/mL), and Water for Injection." }

The vial stoppers are not made with natural rubber latex.

{ "type": "p", "children": [], "text": "The vial stoppers are not made with natural rubber latex." }

Cabotegravir is an HIV-1 antiretroviral drug [see Microbiology (12.4)] in a long-acting formulation.

Cardiac Electrophysiology

At a dose of cabotegravir 150 mg orally every 12 hours (10 times the recommended total daily oral lead‑in dosage of APRETUDE), the QT interval is not prolonged to any clinically relevant extent. Administration of 3 doses of cabotegravir 150 mg orally every 12 hours resulted in a geometric mean Cmax approximately 2.8- and 5.6-fold above the geometric mean steady-state Cmax associated with the recommended 30-mg dose of oral cabotegravir and the recommended 600-mg dose given every 2 months of cabotegravir extended-release injectable suspension, respectively.

Absorption, Distribution, and Elimination

The pharmacokinetic properties of cabotegravir are provided in Table 9. The multiple-dose pharmacokinetic parameters are provided in Table 10. For the pharmacokinetic properties of oral cabotegravir, refer to the full prescribing information for VOCABRIA (cabotegravir).

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 9. Pharmacokinetic Properties of Cabotegravir</span> </caption> <col width="65%"/> <col width="35%"/> <tfoot> <tr class="First"> <td align="left" colspan="2" valign="top">CSF = Cerebrospinal fluid.<br/> <span class="Sup">a</span> When taken orally with a high-fat meal versus fasted, the AUC<span class="Sub">(0-inf)</span> (geometric mean ratio [90% CI] of cabotegravir are 1.14 [1.02, 1.28]).<br/> <span class="Sup">b</span> The clinical relevance of CSF-to-plasma concentration ratios is unknown. Concentrations were measured at steady-state 1 week after intramuscular administration of cabotegravir extended-release injectable suspensions given monthly or every 2 months.</td> </tr> <tr> <td align="left" colspan="2" valign="top"><span class="Sup">c</span> Elimination half-life driven by slow absorption rate from the intramuscular injection site.</td> </tr> <tr class="Last"> <td align="left" colspan="2" valign="top"><span class="Sup">d</span> Dosing in mass balance studies: single-dose oral administration of [<span class="Sup">14</span>C] cabotegravir.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Toprule" valign="top"> <p class="First"> <span class="Bold">Absorption<span class="Sup">a</span></span> </p> </td><td class="Botrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">T<span class="Sub">max</span> (days), median</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">7</p> </td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First"> <span class="Bold">Distribution</span> </p> </td><td class="Botrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">% Bound to human plasma proteins</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&gt;99.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Blood-to-plasma ratio</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.52</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">CSF-to-plasma concentration ratio (median [range])<span class="Sup">b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.003</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.002 to 0.004)</p> </td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First"> <span class="Bold">Elimination</span> </p> </td><td class="Botrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">t<span class="Sub">1/2</span> (weeks), mean<span class="Sup">c</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5.6 to 11.5</p> </td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First"> <span class="Italics">Metabolism</span> </p> </td><td class="Botrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">    Metabolic pathways</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">UGT1A1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">UGT1A9 (minor)</p> </td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First"> <span class="Italics">Excretion</span> </p> </td><td class="Botrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">    Major route of elimination</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">Metabolism</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">    % of dose excreted as total <span class="Sup">14</span>C (unchanged drug) in urine<span class="Sup">d</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">27 (0)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">    % of dose excreted as total <span class="Sup">14</span>C (unchanged drug) in feces<span class="Sup">d</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">59 (47)</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 10. Pharmacokinetic Parameters following Once-Daily Oral Cabotegravir and following Initiation and Every-2-Month Continuation Intramuscular Injections of APRETUDE</span> </caption> <col width="29%"/> <col width="20%"/> <col width="17%"/> <col width="17%"/> <col width="17%"/> <tfoot> <tr class="First"> <td align="left" colspan="5" valign="top">IM = Intramuscular.</td> </tr> <tr> <td align="left" colspan="5" valign="top"><span class="Sup">a</span> Pharmacokinetic parameter values were based on individual post-hoc estimates from cabotegravir population pharmacokinetic models for patients in Phase 3 treatment studies of HIV treatment.</td> </tr> <tr> <td align="left" colspan="5" valign="top"><span class="Sup">b</span> tau is dosing interval: 24 hours for oral administration, 1 month for the initial injection, and 2 months for every 2 months for intramuscular injections of extended-release injectable suspension.</td> </tr> <tr> <td align="left" colspan="5" valign="top"><span class="Sup">c</span> Oral lead-in pharmacokinetic parameter values represent steady state.</td> </tr> <tr> <td align="left" colspan="5" valign="top"><span class="Sup">d</span> Initial injection C<span class="Sub">max</span> values primarily reflect oral dosing because the initial injection was administered on the same day as the last oral dose; however, AUC<span class="Sub">(0-tau)</span> and the C<span class="Sub">tau</span> values reflect the initial injection. When administered without oral lead-in to recipients with HIV-1 (n = 110), the observed cabotegravir geometric mean (5th, 95th percentile) C<span class="Sub">max</span> (1-week post‑initial injection) was 1.89 mcg/mL (0.438, 5.69) and C<span class="Sub">tau</span> was 1.43 mcg/mL (0.403, 3.90).</td> </tr> <tr class="Last"> <td align="left" colspan="5" valign="top"><span class="Sup">e</span> Pharmacokinetic parameter values represent steady state.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Dosing Phase</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Dosage Regimen</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Geometric Mean (5<span class="Sup">th</span>, 95<span class="Sup">th</span> Percentile)<span class="Sup">a</span></span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">AUC<span class="Sub">(0-tau)</span><span class="Sup">b</span></span> <br/> <span class="Bold">(mcg•h/mL)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">C<span class="Sub">max</span></span> <br/> <span class="Bold">(mcg/mL)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">C<span class="Sub">tau</span><span class="Sup">b</span></span> <br/> <span class="Bold">(mcg/mL)</span> </p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Oral lead-in<span class="Sup">c</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30 mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">145</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">8.0</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">4.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">once daily</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(93.5, 224)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(5.3, 11.9)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(2.8, 7.5)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Initial injection<span class="Sup">d</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">600 mg IM</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1,591</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">8.0</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">initial dose</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(714; 3,245)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(5.3, 11.9)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.65, 2.9)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Every-2-month injection<span class="Sup">e</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">600 mg IM</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">3,764</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">4.0</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.6</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">every 2 months</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(2,431; 5,857)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(2.3, 6.8)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.8, 3.0)</p> </td> </tr> </tbody> </table></div>

Specific Populations

No clinically significant differences in the pharmacokinetics of cabotegravir were observed based on age, sex, race/ethnicity, BMI, or UGT1A1 polymorphisms. There are no data available for the use of cabotegravir in participants with hepatitis B virus and hepatitis C virus co-infection in PrEP studies.

Renal Impairment: With oral cabotegravir, no clinically significant differences in the pharmacokinetics of cabotegravir are expected in individuals with mild, moderate, or severe renal impairment. Cabotegravir has not been studied in participants with end-stage renal disease not on dialysis. As cabotegravir is >99% protein bound, dialysis is not expected to alter exposures of cabotegravir [see Use in Specific Populations (8.6)].

Hepatic Impairment: No clinically significant differences in the pharmacokinetics of cabotegravir are expected in mild to moderate (Child-Pugh A or B) hepatic impairment. The effect of severe hepatic impairment (Child-Pugh C) on the pharmacokinetics of cabotegravir has not been studied [see Use in Specific Populations (8.7)].

Gender: Population pharmacokinetic analyses revealed no clinically relevant effect of gender on the exposure of cabotegravir. In addition, no clinically relevant differences in plasma cabotegravir concentrations were observed in PrEP studies by gender, including in cisgender men and transgender women (+/- hormone use). Therefore, no dose adjustment is necessary based on gender.

Geriatrics: No dose adjustment is required in elderly individuals. There are limited data available on the use of cabotegravir in individuals aged 65 years and older. In general, caution should be exercised in administration of cabotegravir in elderly individuals, reflecting greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy [see Use in Specific Populations (8.5)].

Pediatrics: Population pharmacokinetic analyses revealed no clinically relevant differences in exposure between adolescent participants and adult participants with and without HIV-1 from the cabotegravir development program; therefore, no dosage adjustment is needed for adolescents weighing ≥35 kg (Table 11).

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 11. Pharmacokinetic Parameters following Once-Daily Oral Cabotegravir and following Initiation and Every-2-Month Continuation Intramuscular Injections of APRETUDE in Adolescent Participants Aged 12 to Younger than 18 Years (≥35 kg)</span> </caption> <col width="22%"/> <col width="17%"/> <col width="22%"/> <col width="17%"/> <col width="22%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="5" valign="top">IM = intramuscular.<br/> <span class="Sup">a</span> Pharmacokinetic parameter values were based on individual post-hoc estimates from population pharmacokinetic models in both adolescents with HIV-1 (n = 147) weighing 35.2 to 98.5 kg and adolescents without HIV-1 (n = 62) weighing 39.9 to 167 kg. <br/> <span class="Sup">b</span> tau is dosing interval: 24 hours for oral administration, 1 month for the initial injection, and 2 months for every 2 months for intramuscular injections of extended-release injectable suspension.<br/> <span class="Sup">c</span> Oral lead-in pharmacokinetic parameter values represent steady state.<br/> <span class="Sup">d</span> Initial injection C<span class="Sub">max</span> values primarily reflect oral dosing because the initial injection was administered on the same day as the last oral dose; however, the AUC<span class="Sub">(0-tau)</span> and C<span class="Sub">tau</span> values reflect the initial injection.<br/> <span class="Sup">e</span> Pharmacokinetic parameter values represent steady state.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Dosing Phase</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Dosage Regimen</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="bottom"> <p class="First"> <span class="Bold">Geometric Mean (5<span class="Sup">th</span>, 95<span class="Sup">th</span> Percentile)<span class="Sup">a</span></span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">AUC<span class="Sub">(0-tau)</span><span class="Sup">b</span></span> </p> <p> <span class="Bold">(mcg•h/mL)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">C<span class="Sub">max</span></span> </p> <p> <span class="Bold">(mcg/mL)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">C<span class="Sub">tau</span><span class="Sup">b</span></span> </p> <p> <span class="Bold">(mcg/mL)</span> </p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Oral lead-in<span class="Sup">c</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30 mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">203</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">10.7</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">6.43</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">once daily</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(136, 320)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(7.36, 16.6)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(4.15, 10.5)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Initial injection<span class="Sup">d</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">600 mg IM</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">2,085</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">10.8</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.88</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">initial dose</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(1,056; 4,259)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(7.42, 16.6)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.801, 3.71)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Every-2-month injection<span class="Sup">e</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">600 mg IM</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">5,184</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">5.10</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">2.54</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">every 2 months</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(3,511; 7,677)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(3.06, 8.24)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(1.25, 4.19)</p> </td> </tr> </tbody> </table></div>

Drug Interaction Studies

Cabotegravir is not a clinically relevant inhibitor of the following enzymes and transporters: cytochrome P450 (CYP)1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4; UGT1A1, 1A3, 1A4, 1A6, 1A9, 2B4, 2B7, 2B15, and 2B17; P-glycoprotein (P‑gp); breast cancer resistance protein (BCRP); bile salt export pump (BSEP); organic cation transporter (OCT)1, OCT2; organic anion transporter polypeptide (OATP)1B1, OATP1B3; multidrug and toxin extrusion transporter (MATE) 1, MATE 2-K; and multidrug resistance protein (MRP)2 or MRP4.

In vitro, cabotegravir inhibited renal OAT1 (IC50 = 0.81 microM) and OAT3 (IC50 = 0.41 microM). Based on physiologically based pharmacokinetic (PBPK) modeling, cabotegravir may increase the AUC of OAT1/3 substrates up to approximately 80%.

In vitro, cabotegravir did not induce CYP1A2, CYP2B6, or CYP3A4.

‎Simulations using PBPK modeling show that no clinically significant interaction is expected during coadministration of cabotegravir with drugs that inhibit UGT1A1.

In vitro, cabotegravir was not a substrate of OATP1B1, OATP1B3, OATP2B1, or OCT1.

Cabotegravir is a substrate of P-gp and BCRP in vitro; however, because of its high permeability, no alteration in cabotegravir absorption is expected with coadministration of P-gp or BCRP inhibitors.

Drug interaction studies were not conducted with injectable cabotegravir. Drug interaction studies with oral cabotegravir are summarized in Tables 12 and 13.

<div class="scrollingtable"><table cellpadding="5.75pt" width="100%"> <caption> <span>Table 12. Effect of Coadministered Drugs on the Pharmacokinetics of Cabotegravir</span> </caption> <col width="20%"/> <col width="15%"/> <col width="5%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="6" valign="top">n = Maximum number of participants with data, CI = Confidence Interval.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Coadministered Drug(s)</span> </p> <p> <span class="Bold">and Dose(s)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Dose of Cabotegravir</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">n</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="bottom"> <p class="First"> <span class="Bold">Geometric Mean Ratio (90% CI) of Cabotegravir Pharmacokinetic Parameters with/without Coadministered Drugs</span> </p> <p> <span class="Bold">No Effect = 1.00</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">C<span class="Sub">max</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">AUC</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">C<span class="Sub">tau</span> or C<span class="Sub">24</span></span> </p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Etravirine</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30 mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">12</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.04</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.01</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.00</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">    200 mg twice daily</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">once daily</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.99, 1.09)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.96, 1.06)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.94, 1.06)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Rifabutin</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30 mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">12</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.83</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.77</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.74</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">    300 mg once daily</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">once daily</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.76, 0.90)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.74, 0.83)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.70, 0.78)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Rifampin</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30-mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">15</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.94</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.41</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.50</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">    600 mg once daily</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">single dose</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.87, 1.02)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.36, 0.46)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.44, 0.57)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Rilpivirine</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30 mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">11</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.05</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.12</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.14</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">    25 mg once daily</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">once daily</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.96, 1.15)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(1.05, 1.19)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(1.04, 1.24)</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table cellpadding="5.75pt" width="100%"> <caption> <span>Table 13. Effect of Cabotegravir on the Pharmacokinetics of Coadministered Drugs</span> </caption> <col width="25%"/> <col width="16%"/> <col width="5%"/> <col width="25%"/> <col width="16%"/> <col width="14%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="6" valign="top">n = Maximum number of participants with data, CI = Confidence Interval; NA = Not available.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Coadministered Drug(s)</span> </p> <p> <span class="Bold">and Dose(s)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Dose of Cabotegravir</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">n</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="bottom"> <p class="First"> <span class="Bold">Geometric Mean Ratio (90% CI) of Pharmacokinetic Parameters of Coadministered Drug with/without Cabotegravir</span> </p> <p> <span class="Bold">No Effect = 1.00</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">C<span class="Sub">max</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">AUC</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">C<span class="Sub">tau</span> or C<span class="Sub">24</span></span> </p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Ethinyl estradiol</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30 mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">19</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.92</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.02</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.00</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">    0.03 mg once daily</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">once daily</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.83, 1.03)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.97, 1.08)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.92, 1.10)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Levonorgestrel</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30 mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">19</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.05</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.12</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.07</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">    0.15 mg once daily</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">once daily</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.96, 1.15)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(1.07, 1.18)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(1.01, 1.15)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Midazolam</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30 mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">12</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.09</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.10</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">NA</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">    3 mg</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">once daily</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.94, 1.26)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.95, 1.26)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Rilpivirine</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30 mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">11</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.96</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.99</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.92</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">    25 mg once daily</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">once daily</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.85, 1.09)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.89, 1.09)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.79, 1.07)</p> </td> </tr> </tbody> </table></div>

Mechanism of Action

Cabotegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration that is essential for the HIV replication cycle. The mean 50% inhibitory concentration (IC50) value of cabotegravir in a strand transfer assay using purified recombinant HIV-1 integrase was 3.0 nM.

Antiviral Activity in Cell Culture

Cabotegravir exhibited antiviral activity against laboratory strains of HIV-1 (subtype B, n = 4) with mean 50 percent effective concentration (EC50) values of 0.22 to 1.7 nM in peripheral blood mononuclear cells (PBMCs) and 293 cells. Cabotegravir demonstrated antiviral activity in PBMCs against a panel of 24 HIV-1 clinical isolates (3 in each of group M subtypes A, B, C, D, E, F, and G and 3 in group O) with a median EC50 value of 0.19 nM (range: 0.02 to 1.06 nM, n = 24). The median EC50 value against subtype B clinical isolates was 0.05 nM (range: 0.02 to 0.50 nM, n = 3). Against clinical HIV-2 isolates, the median EC50 value was 0.12 nM (range: 0.10 to 0.14 nM, n = 3).

In cell culture, cabotegravir was not antagonistic in combination with the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine, or the nucleoside reverse transcriptase inhibitors (NRTIs) FTC, lamivudine (3TC), or TDF.

Resistance

Cell Culture: Cabotegravir-resistant viruses were selected during passage of HIV-1 strain IIIB in MT-2 cells in the presence of cabotegravir. Amino acid substitutions in integrase that emerged and conferred decreased susceptibility to cabotegravir included Q146L (fold change: 1.3 to 4.6), S153Y (fold change: 2.8 to 8.4), and I162M (fold change: 2.8). The integrase substitution T124A also emerged alone (fold change: 1.1 to 7.4 in cabotegravir susceptibility), in combination with S153Y (fold change: 3.6 to 6.6 in cabotegravir susceptibility) or I162M (2.8-fold change in cabotegravir susceptibility). Cell culture passage of virus harboring integrase substitutions Q148H, Q148K, or Q148R selected for additional substitutions (C56S, V72I, L74M, V75A, T122N, E138K, G140S, G149A, and M154I), with substituted viruses having reduced susceptibility to cabotegravir of 2.0- to 410-fold change. The combinations of E138K+Q148K and V72I+E138K+Q148K conferred the greatest reductions of 53- to 260‑fold change and 410‑fold change, respectively.

Clinical Trials: There were 12 incident infections and 4 prevalent infections among participants in the APRETUDE arm of HPTN 083. Genotypic data were generated for viruses from 13 of these 16 participants (4 participants with prevalent infections and 9 participants with incident infections) and phenotypic data were generated for 3 of these viruses. INSTI resistance-associated substitutions were detected in 5 viruses from participants who achieved target plasma concentrations of cabotegravir (≥0.65 mcg/mL [1.6 μM]) and included R263K (2-fold less susceptible to cabotegravir), E138A+Q148R (6-fold less susceptible to cabotegravir), E138K+Q148K, G140A+Q148R (13-fold less susceptible to cabotegravir), and L74I+E138E/K+G140G/S+Q148R+E157Q.

There were 3 incident infections and 1 prevalent infection among participants in the APRETUDE arm of HPTN 084. All 3 incident infections occurred during periods with cabotegravir exposures below the target concentration. No variants expressing INSTI resistance-associated substitutions were detected.

Cross-Resistance

Cross-resistance has been observed among INSTIs. Cabotegravir had reduced susceptibility (>5-fold change) to recombinant HIV-1 strain NL432 viruses harboring the following integrase amino acid substitutions: G118R, Q148K, Q148R, T66K+L74M, E92Q+N155H, E138A+Q148R, E138K+Q148K/R, G140C+Q148R, G140S+Q148H/K/R, Y143H+N155H, and Q148R+N155H (range: 5.1- to 81-fold). The substitutions E138K+Q148K and Q148R+N155H conferred the greatest reductions in susceptibility of 81- and 61-fold, respectively.

Virologic failure isolates from cabotegravir plus rilpivirine treatment in FLAIR, ATLAS, and ATLAS-2M exhibited cross-resistance to INSTIs and NNRTIs. All confirmed virologic isolates with genotypic evidence of cabotegravir resistance had cross-resistance to elvitegravir and raltegravir but retained phenotypic susceptibility to dolutegravir and when tested bictegravir.

Viruses harboring E138A+Q148R or G140A+Q148R with reduced susceptibility to cabotegravir were isolated from participants using APRETUDE in HPTN 083. These viruses remained susceptible to bictegravir and dolutegravir but had cross-resistance to elvitegravir and raltegravir.

Carcinogenesis

Two-year carcinogenicity studies in mice and rats were conducted with cabotegravir. In mice, no drug-related increases in tumor incidence were observed at cabotegravir exposures (AUC) up to approximately 8 times (males) and 7 times (females) higher than those in humans at the RHD. In rats, no drug-related increases in tumor incidence were observed at cabotegravir exposures up to approximately 26 times higher than those in humans at the RHD.

Mutagenesis

Cabotegravir was not genotoxic in the bacterial reverse mutation assay, mouse lymphoma assay, or in the in vivo rodent micronucleus assay.

Impairment of Fertility

In rats, no effects on fertility were observed at cabotegravir exposures (AUC) >20 times (male) and 28 times (female) the exposure in humans at the RHD.

The safety and efficacy of APRETUDE to reduce the risk of acquiring HIV-1 infection were evaluated in 2 randomized, double-blind, controlled, multinational trials, HPTN 083 in men and transgender women without HIV-1 who have sex with men and have evidence of high-risk behavior for HIV-1 infection and HPTN 084 in cisgender women without HIV-1 at risk of acquiring HIV-1.

Participants randomized to receive APRETUDE initiated oral lead-in dosing with 1 oral cabotegravir 30-mg tablet and a placebo daily for up to 5 weeks, followed by APRETUDE 600‑mg (3-mL) intramuscular injection at months 1 and 2 and every 2 months thereafter and a daily placebo tablet. Participants randomized to receive TRUVADA initiated oral TRUVADA (TDF 300 mg/FTC 200 mg) and placebo daily for up to 5 weeks, followed by oral TRUVADA daily and placebo intramuscular injection at months 1 and 2 and every 2 months thereafter.

Trial 201738 (HPTN 083 [NCT02720094])

In HPTN 083, a non-inferiority study, 4,566 cisgender men and transgender women who have sex with men were randomized 1:1 and received either APRETUDE (n = 2,281) or TRUVADA (n = 2,285) as blinded study medication up to Week 153.

At baseline, the median age of participants was 26 years, 12% were transgender women, 72% were non-White, and 67% were younger than 30 years.

The primary endpoint was the rate of incident HIV-1 infections among participants randomized to daily oral cabotegravir and intramuscular injections of APRETUDE every 2 months compared with daily oral TRUVADA (corrected for early stopping). The primary analysis demonstrated the superiority of APRETUDE compared with TRUVADA with a 66% reduction in the risk of acquiring HIV-1 infection, hazard ratio (95% CI) 0.34 (0.18, 0.62); further testing revealed 1 of the infections on APRETUDE to be prevalent then yielding a 69% reduction in the risk of HIV-1 incident infection relative to TRUVADA (Table 14).

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 14. HIV-1 Infection Results During Randomized Phase in HPTN 083: Extended Retrospective Virologic Testing with Readjudicated Endpoints<span class="Sup">a</span></span> </caption> <col width="30%"/> <col width="23%"/> <col width="23%"/> <col width="25%"/> <tfoot> <tr class="First"> <td align="left" colspan="4" valign="top"><span class="Sup">a</span> mITT from Supplemental Virology Report.</td> </tr> <tr class="Last"> <td align="left" colspan="4" valign="top"><span class="Sup">b</span> Following the primary analysis, extended retrospective virologic testing was performed to better characterize the timing of HIV-1 infections. As a result, 1 of the 13 HIV-1 incident infections in participants receiving APRETUDE was determined to be a prevalent infection. The original hazard ratio (95% CI) from the primary analysis is 0.34 (0.18, 0.62).</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="bottom"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">APRETUDE</span> </p> <p> <span class="Bold">(N = 2,278)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">TRUVADA</span> </p> <p> <span class="Bold">(N = 2,281)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Superiority <span class="Italics">P</span> Value</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Person-years</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3,211</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3,193</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">HIV-1 infections (incidence rate per 100 person-years)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">12<span class="Sup">b</span> (0.37)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">39 (1.22)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Hazard ratio (95% CI)</p> </td><td align="center" class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First">0.31 (0.16, 0.58)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.0003</p> </td> </tr> </tbody> </table></div>

Figure 1. Cumulative Incidence of HIV-1 Infections in HPTN 083

Results from all subgroup analyses were consistent with the overall protective effect. A lower rate of incident HIV‑1 infections was observed for participants randomized to APRETUDE compared with participants randomized to TRUVADA (Table 15).

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 15. Incident of HIV-1 Infections by Subgroup in HPTN 083: Extended Retrospective Virologic Testing with Readjudicated Endpoints<span class="Sup">a</span></span> </caption> <col width="15%"/> <col width="19%"/> <col width="19%"/> <col width="17%"/> <col width="17%"/> <col width="15%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="6" valign="top"><span class="Sup">a</span> mITT from Supplemental Virology Report. <br/> <span class="Sup">b</span> Cisgender men who have sex with men.<br/> <span class="Sup">c</span> Transgender women who have sex with men.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Subgroup</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">APRETUDE Incidence per 100 Person-Years</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">APRETUDE</span> </p> <p> <span class="Bold">Person-Years</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">TRUVADA</span> </p> <p> <span class="Bold">Incidence per 100 Person-Years</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">TRUVADA</span> </p> <p> <span class="Bold">Person-Years</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Hazard Ratio</span> </p> <p> <span class="Bold">(95% CI)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Age</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">&lt;30 years</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.47</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">2,110</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.66</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1,987</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.29</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.15, 0.59)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">≥30 years</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.18</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1,101</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.50</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1,206</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.39</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.08, 1.84)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Gender</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">MSM<span class="Sup">b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.35</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">2,836</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.14</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">2,803</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.32</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.16, 0.64)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">TGW<span class="Sup">c</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.54</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">371</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.80</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">389</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.34</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.08, 1.56)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Race (US)</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Black</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.58</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">691</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">2.28</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">703</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.26</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.09, 0.76)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Non-Black</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.00</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">836</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.50</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">801</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.11</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.00, 2.80)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Region</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">US</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.26</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1,528</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.33</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1,504</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.21</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.07, 0.60)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Latin America</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.49</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1,020</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.09</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1,011</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.47</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.17, 1.35)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Asia</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.35</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">570</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.03</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">581</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.39</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.08, 1.82)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Africa</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.08</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">93</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">2.07</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">97</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.63</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.06, 6.50)</p> </td> </tr> </tbody> </table></div>

Trial 201739 (HPTN 084 [NCT03164564])

In HPTN 084, a superiority study, 3,224 cisgender women were randomized 1:1 and received either APRETUDE (n = 1,614) or TRUVADA (n = 1,610) as blinded study medication up to Week 153.

At baseline, the median age of participants was 25 years, >99% were non-White, >99% were cisgender women, and 49% were <25 years of age.

The primary endpoint was the rate of incident HIV-1 infections among participants randomized to oral cabotegravir and injections of APRETUDE compared with oral TRUVADA (corrected for early stopping). The primary analysis demonstrated the superiority of APRETUDE compared with TRUVADA with an 88% reduction in the risk of acquiring incident HIV-1 infection, hazard ratio (95% CI) 0.12 (0.05, 0.31); further testing revealed 1 of the infections on APRETUDE to be prevalent then yielding a 90% reduction in the risk of HIV-1 incident infection relative to TRUVADA (Table 16).

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 16. HIV-1 Infection Results during Randomized Phase in HPTN 084: Extended Retrospective Virologic Testing with Readjudicated Endpoints<span class="Sup">a</span></span> </caption> <col width="31%"/> <col width="23%"/> <col width="23%"/> <col width="23%"/> <tfoot> <tr class="First"> <td align="left" colspan="4" valign="top"><span class="Sup">a</span> mITT from Supplemental Virology Report.</td> </tr> <tr class="Last"> <td align="left" colspan="4" valign="top"><span class="Sup">b </span>Following the primary analysis, extended retrospective virologic testing was performed to better characterize the timing of HIV-1 infections. As a result, 1 of the 4 HIV-1 incident infections in participants receiving APRETUDE was determined to be a prevalent infection. The original hazard ratio (95% CI) from the primary analysis is 0.12 (0.05, 0.31).</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">APRETUDE</span> </p> <p> <span class="Bold">(N = 1,613)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">TRUVADA</span> </p> <p> <span class="Bold">(N = 1,610)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Superiority</span> </p> <p> <span class="Bold"><span class="Italics">P</span> Value</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Person-years</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1,960</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1,946</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">HIV-1 incident infections (incidence rate per 100 person-years)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3<span class="Sup">b</span> (0.15)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">36 (1.85)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Hazard ratio (95% CI)</p> </td><td align="center" class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First">0.10 (0.04, 0.27)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;0.0001</p> </td> </tr> </tbody> </table></div>

Figure 2. Cumulative Incidence of HIV-1 Infections in HPTN 084

Results from pre-planned subgroup analyses were consistent with the overall protective effect. A lower rate of incident HIV-1 infections was observed for participants randomized to APRETUDE compared with participants randomized to TRUVADA (Table 17).

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 17. Incident of HIV-1 Infections by Subgroup in HPTN 084: Extended Retrospective Virologic Testing with Readjudicated Endpoints<span class="Sup">a</span></span> </caption> <col width="17%"/> <col width="17%"/> <col width="17%"/> <col width="17%"/> <col width="17%"/> <col width="17%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="6" valign="top"><span class="Sup">a</span> mITT from Supplemental Virology Report.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Subgroup</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">APRETUDE Incidence</span> </p> <p> <span class="Bold">per 100 Person-Years</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">APRETUDE Person-Years</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">TRUVADA Incidence</span> </p> <p> <span class="Bold">per 100 Person-Years</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">TRUVADA Person-Years</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Hazard Ratio</span> </p> <p> <span class="Bold">(95% CI)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="6" valign="top"> <p class="First"> <span class="Bold">Age</span> </p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">&lt;25 years</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.23</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">868</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">2.34</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">853</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.12</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.03, 0.46)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">≥25 years</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.09</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1,093</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.46</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1,093</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.09</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.02, 0.49)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="6" valign="top"> <p class="First"> <span class="Bold">Body Mass Index</span> </p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">&lt;30</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.22</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1,385</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.88</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1,435</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.12</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.04, 0.38)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">≥30</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.00</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">575</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.76</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">511</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.04</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.00, 0.93)</p> </td> </tr> </tbody> </table></div>

How Supplied

{ "type": "p", "children": [], "text": "\nHow Supplied\n" }

APRETUDE is supplied in a kit containing one 600-mg/3-mL single-dose (200-mg/mL) vial of cabotegravir extended-release injectable suspension, 1 syringe, 1 vial adapter, and 1 needle for intramuscular injection (23 gauge, 1½ inch) (NDC 49702-264-23). The vial stopper is not made with natural rubber latex.

{ "type": "p", "children": [], "text": "APRETUDE is supplied in a kit containing one 600-mg/3-mL single-dose (200-mg/mL) vial of cabotegravir extended-release injectable suspension, 1 syringe, 1 vial adapter, and 1 needle for intramuscular injection (23 gauge, 1½ inch) (NDC 49702-264-23). The vial stopper is not made with natural rubber latex." }

Storage and Handling

{ "type": "p", "children": [], "text": "\nStorage and Handling\n" }

Store APRETUDE at 2°C to 25°C (36°F to 77°F) in the original carton until ready to use. Exposure up to 30°C permitted. Do not freeze. Do not mix with any other product or diluent.

{ "type": "p", "children": [], "text": "Store APRETUDE at 2°C to 25°C (36°F to 77°F) in the original carton until ready to use. Exposure up to 30°C permitted. Do not freeze. Do not mix with any other product or diluent." }

If the pack has been stored in the refrigerator, the vial should be brought to room temperature prior to administration (not to exceed 30°C [86°F]).

{ "type": "p", "children": [], "text": "If the pack has been stored in the refrigerator, the vial should be brought to room temperature prior to administration (not to exceed 30°C [86°F]). " }

Once the suspension has been drawn into the syringe, the injection should be administered as soon as possible, but may remain in the syringe for up to 2 hours. The filled syringes should not be placed in the refrigerator. If the medicine remains in the syringe for more than 2 hours, the filled syringe and needle must be discarded [see Dosage and Administration (2.7)].

{ "type": "p", "children": [], "text": "Once the suspension has been drawn into the syringe, the injection should be administered as soon as possible, but may remain in the syringe for up to 2 hours. The filled syringes should not be placed in the refrigerator. If the medicine remains in the syringe for more than 2 hours, the filled syringe and needle must be discarded [see Dosage and Administration (2.7)]." }

Advise the individual to read the FDA-approved patient labeling (Patient Information).

{ "type": "p", "children": [], "text": "Advise the individual to read the FDA-approved patient labeling (Patient Information)." }

Important Information for Individuals without HIV-1 Taking APRETUDE for HIV-1 Pre‑Exposure Prophylaxis

{ "type": "p", "children": [], "text": "\nImportant Information for Individuals without HIV-1 Taking APRETUDE for HIV-1 Pre‑Exposure Prophylaxis\n" }

Advise individuals without HIV-1 about the following [see Warnings and Precautions (5.1)]:

{ "type": "p", "children": [], "text": "Advise individuals without HIV-1 about the following [see Warnings and Precautions (5.1)]:" }

{ "type": "", "children": [], "text": "" }

Potential Risk of Resistance with APRETUDE

{ "type": "p", "children": [], "text": "\nPotential Risk of Resistance with APRETUDE\n" }

Advise individuals there is a potential risk of developing resistance to APRETUDE if HIV-1 is acquired either before or while taking APRETUDE or following discontinuation of APRETUDE [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Advise individuals there is a potential risk of developing resistance to APRETUDE if HIV-1 is acquired either before or while taking APRETUDE or following discontinuation of APRETUDE [see Warnings and Precautions (5.2)]." }

To minimize this, it is essential that individuals are clinically reassessed for risk of HIV-1 acquisition and tested frequently to confirm HIV-1 negative status. Advise individuals who are confirmed to have with HIV-1 infection to consult with their healthcare professional, as HIV-1 treatment must be initiated [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "To minimize this, it is essential that individuals are clinically reassessed for risk of HIV-1 acquisition and tested frequently to confirm HIV-1 negative status. Advise individuals who are confirmed to have with HIV-1 infection to consult with their healthcare professional, as HIV-1 treatment must be initiated [see Warnings and Precautions (5.2)]." }

Inform individuals that alternative forms of PrEP should be considered following discontinuation of APRETUDE for those at continuing risk of HIV-1 acquisition and initiated within 2 months of the final injection of APRETUDE [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Inform individuals that alternative forms of PrEP should be considered following discontinuation of APRETUDE for those at continuing risk of HIV-1 acquisition and initiated within 2 months of the final injection of APRETUDE [see Warnings and Precautions (5.2)]. " }

Long-Acting Properties of APRETUDE

{ "type": "p", "children": [], "text": "\nLong-Acting Properties of APRETUDE\n" }

Advise individuals that APRETUDE is an extended-release injectable that may be systemically present for 12 months or longer and consideration should be taken regarding the prolonged release characteristics when APRETUDE is discontinued [see Warnings and Precautions (5.3), Drug Interactions (7)].

{ "type": "p", "children": [], "text": "Advise individuals that APRETUDE is an extended-release injectable that may be systemically present for 12 months or longer and consideration should be taken regarding the prolonged release characteristics when APRETUDE is discontinued [see Warnings and Precautions (5.3), Drug Interactions (7)]." }

Adherence to APRETUDE

{ "type": "p", "children": [], "text": "\nAdherence to APRETUDE\n" }

Counsel individuals about the importance of continued medication adherence and scheduled visits to help reduce the risk of acquiring HIV-1 infection and development of resistance [see Dosage and Administration (2.3), Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Counsel individuals about the importance of continued medication adherence and scheduled visits to help reduce the risk of acquiring HIV-1 infection and development of resistance [see Dosage and Administration (2.3), Warnings and Precautions (5.1)]." }

Hypersensitivity Reactions

{ "type": "p", "children": [], "text": "\nHypersensitivity Reactions \n" }

Advise individuals to immediately contact their healthcare provider if they develop a rash. Instruct individuals to immediately stop taking APRETUDE and seek medical attention if they develop a rash associated with any of the following symptoms as it may be a sign of a more serious reaction such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN): fever; generally ill feeling; extreme tiredness; muscle or joint aches; blisters; oral blisters or lesions; eye inflammation; facial swelling; swelling of the eyes, lips, tongue, or mouth; difficulty breathing; and/or signs and symptoms of liver problems (e.g., yellowing of the skin or whites of the eyes; dark or tea‑colored urine; pale-colored stools or bowel movements; nausea; vomiting; loss of appetite; or pain, aching, or sensitivity on the right side below the ribs). Advise individuals that if hypersensitivity occurs, they will be closely monitored, laboratory tests will be ordered, and appropriate therapy will be initiated [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "Advise individuals to immediately contact their healthcare provider if they develop a rash. Instruct individuals to immediately stop taking APRETUDE and seek medical attention if they develop a rash associated with any of the following symptoms as it may be a sign of a more serious reaction such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN): fever; generally ill feeling; extreme tiredness; muscle or joint aches; blisters; oral blisters or lesions; eye inflammation; facial swelling; swelling of the eyes, lips, tongue, or mouth; difficulty breathing; and/or signs and symptoms of liver problems (e.g., yellowing of the skin or whites of the eyes; dark or tea‑colored urine; pale-colored stools or bowel movements; nausea; vomiting; loss of appetite; or pain, aching, or sensitivity on the right side below the ribs). Advise individuals that if hypersensitivity occurs, they will be closely monitored, laboratory tests will be ordered, and appropriate therapy will be initiated [see Warnings and Precautions (5.4)]." }

Hepatotoxicity

{ "type": "p", "children": [], "text": "\nHepatotoxicity\n" }

Inform individuals that hepatotoxicity has been reported with cabotegravir [see Warnings and Precautions (5.5), Adverse Reactions (6.1)]. Inform individuals that clinical and laboratory monitoring should be considered and APRETUDE should be discontinued if hepatoxicity is confirmed [see Warnings and Precautions (5.5)].

{ "type": "p", "children": [], "text": "Inform individuals that hepatotoxicity has been reported with cabotegravir [see Warnings and Precautions (5.5), Adverse Reactions (6.1)]. Inform individuals that clinical and laboratory monitoring should be considered and APRETUDE should be discontinued if hepatoxicity is confirmed [see Warnings and Precautions (5.5)]." }

Depressive Disorders

{ "type": "p", "children": [], "text": "\nDepressive Disorders\n" }

Inform individuals that depressive disorders (including depression, depressed mood, major depression, persistent depressive disorder, suicidal ideation, suicide attempt) have been reported with APRETUDE [see Adverse Reactions (6.1)]. Advise individuals to seek prompt medical evaluation if they experience depressive symptoms [see Warnings and Precautions (5.6)].

{ "type": "p", "children": [], "text": "Inform individuals that depressive disorders (including depression, depressed mood, major depression, persistent depressive disorder, suicidal ideation, suicide attempt) have been reported with APRETUDE [see Adverse Reactions (6.1)]. Advise individuals to seek prompt medical evaluation if they experience depressive symptoms [see Warnings and Precautions (5.6)]. " }

Drug Interactions

{ "type": "p", "children": [], "text": "\nDrug Interactions\n" }

Inform individuals that APRETUDE may interact with other drugs and may reduce exposure of APRETUDE; therefore, advise individuals to report to their healthcare provider the use of any other prescription or nonprescription medication [see Contraindications (4), Warnings and Precautions (5.7), Drug Interactions (7.2, 7.3)].

{ "type": "p", "children": [], "text": "Inform individuals that APRETUDE may interact with other drugs and may reduce exposure of APRETUDE; therefore, advise individuals to report to their healthcare provider the use of any other prescription or nonprescription medication [see Contraindications (4), Warnings and Precautions (5.7), Drug Interactions (7.2, 7.3)]." }

Missed Dose

{ "type": "p", "children": [], "text": "\nMissed Dose\n" }

Inform individuals that APRETUDE can remain in the body for up to 12 months or longer after receiving their last injection. Advise individuals that they should contact their healthcare provider if they miss or plan to miss a scheduled monthly injection visit and that oral dosing may be used to replace up to 2 consecutive monthly injections. Advise individuals that if they discontinue use of APRETUDE, they will need to take other medicines for HIV-1 PrEP [see Dosage and Administration (2.3, 2.6), Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Inform individuals that APRETUDE can remain in the body for up to 12 months or longer after receiving their last injection. Advise individuals that they should contact their healthcare provider if they miss or plan to miss a scheduled monthly injection visit and that oral dosing may be used to replace up to 2 consecutive monthly injections. Advise individuals that if they discontinue use of APRETUDE, they will need to take other medicines for HIV-1 PrEP [see Dosage and Administration (2.3, 2.6), Warnings and Precautions (5.3)]." }

Pregnancy Registry

{ "type": "p", "children": [], "text": "\nPregnancy Registry\n" }

Inform individuals that there is an antiretroviral pregnancy registry to monitor fetal outcomes in those exposed to APRETUDE during pregnancy. Individuals who are of reproductive potential should be informed of the long duration of exposure of APRETUDE and that there is very limited clinical experience in human pregnancy [see Warnings and Precautions (5.3), Use in Specific Populations (8.1)].

{ "type": "p", "children": [], "text": "Inform individuals that there is an antiretroviral pregnancy registry to monitor fetal outcomes in those exposed to APRETUDE during pregnancy. Individuals who are of reproductive potential should be informed of the long duration of exposure of APRETUDE and that there is very limited clinical experience in human pregnancy [see Warnings and Precautions (5.3), Use in Specific Populations (8.1)]." }

Lactation

{ "type": "p", "children": [], "text": "\nLactation\n" }

Inform individuals that due to the potential for adverse reactions and residual concentrations in the systemic circulation for up to 12 months or longer after discontinuing injections of APRETUDE, it is recommended that mothers breastfeed only if the expected benefit justifies the potential risk to the infant. The benefits and risks of APRETUDE while breastfeeding should be evaluated, including the risk of HIV-1 acquisition due to medication nonadherence and subsequent mother to child transmission. Instruct mothers not to breastfeed if acute HIV-1 infection is suspected because of the risk of passing the HIV-1 virus to the baby [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "Inform individuals that due to the potential for adverse reactions and residual concentrations in the systemic circulation for up to 12 months or longer after discontinuing injections of APRETUDE, it is recommended that mothers breastfeed only if the expected benefit justifies the potential risk to the infant. The benefits and risks of APRETUDE while breastfeeding should be evaluated, including the risk of HIV-1 acquisition due to medication nonadherence and subsequent mother to child transmission. Instruct mothers not to breastfeed if acute HIV-1 infection is suspected because of the risk of passing the HIV-1 virus to the baby [see Use in Specific Populations (8.2)]." }

APRETUDE, CABENUVA, and VOCABRIA are trademarks owned by or licensed to the ViiV Healthcare group of companies.

{ "type": "p", "children": [], "text": "APRETUDE, CABENUVA, and VOCABRIA are trademarks owned by or licensed to the ViiV Healthcare group of companies." }

The other brand listed is a trademark owned by or licensed to its respective owner and is not a trademark owned by or licensed to the ViiV Healthcare group of companies. The maker of this brand is not affiliated with and does not endorse the ViiV Healthcare group of companies or its products.

{ "type": "p", "children": [], "text": "The other brand listed is a trademark owned by or licensed to its respective owner and is not a trademark owned by or licensed to the ViiV Healthcare group of companies. The maker of this brand is not affiliated with and does not endorse the ViiV Healthcare group of companies or its products. " }

Manufactured for:

{ "type": "p", "children": [], "text": "Manufactured for:" }

ViiV HealthcareDurham, NC 27701

{ "type": "p", "children": [], "text": "ViiV HealthcareDurham, NC 27701" }

©2025 ViiV Healthcare group of companies or its licensor.

{ "type": "p", "children": [], "text": "©2025 ViiV Healthcare group of companies or its licensor." }

APR:5PI

{ "type": "p", "children": [], "text": "APR:5PI" }

<div class="scrollingtable"><table width="100%"> <col width="3%"/> <col width="47%"/> <col width="50%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="middle"> <p class="First"> <span class="Bold">PATIENT INFORMATION</span> </p> <p> <span class="Bold">APRETUDE [AP-reh-tood]</span> </p> <p> <span class="Bold">(cabotegravir extended-release injectable suspension)</span> </p> <p> <span class="Bold">for intramuscular use</span> </p> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What is the most important information I should know about APRETUDE?</span> </p> <p> <span class="Bold">Important information for people who receive APRETUDE to help reduce their risk of getting human immunodeficiency virus-1 (HIV-1) infection, also called pre-exposure prophylaxis or “PrEP”:</span> </p> <p> <span class="Bold">Before receiving APRETUDE to reduce your risk of getting HIV-1:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">You must be HIV-1 negative to start APRETUDE. You must get tested to make sure that you do not already have HIV-1 infection.</span> </dd> <dt>•</dt> <dd> <span class="Bold">Do not receive APRETUDE for HIV-1 PrEP unless you are confirmed to be HIV-1 negative.</span> </dd> <dt>•</dt> <dd>Some HIV-1 tests can miss HIV-1 infection in a person who has recently become infected. If you have flu-like symptoms, you could have recently become infected with HIV-1. Tell your healthcare provider if you had a flu-like illness within the last month before starting APRETUDE or at any time while receiving APRETUDE. Symptoms of new HIV-1 infection include:</dd> </dl> </td> </tr> <tr> <td class="Lrule" valign="top"></td><td valign="top"> <dl> <dt> </dt> <dd>○   tiredness</dd> <dt> </dt> <dd>○   joint or muscle aches</dd> <dt> </dt> <dd>○   sore throat</dd> <dt> </dt> <dd>○   rash</dd> <dt> </dt> <dd>○   enlarged lymph nodes in the neck or groin</dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt> </dt> <dd>○   fever</dd> <dt> </dt> <dd>○   headache</dd> <dt> </dt> <dd>○   vomiting or diarrhea</dd> <dt> </dt> <dd>○   night sweats</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">While you are receiving APRETUDE for HIV-1 PrEP:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">APRETUDE does not prevent other sexually transmitted infections. Practice safer sex by using a latex or polyurethane condom to reduce the risk of getting sexually transmitted infections.</span> </dd> <dt>•</dt> <dd> <span class="Bold">You must stay HIV-1 negative to keep receiving APRETUDE for HIV-1 PrEP.</span> <dl> <dt>o</dt> <dd>Know your HIV-1 status and the HIV-1 status of your partners.</dd> <dt>o</dt> <dd>Ask your partners with HIV-1 if they are taking anti-HIV-1 medicines and have an undetectable viral load. An undetectable viral load is when the amount of virus in the blood is too low to be measured in a lab test. To maintain an undetectable viral load, your partners must keep taking HIV-1 medicine as prescribed. Your risk of getting HIV-1 is lower if your partners with HIV-1 are taking effective treatment.</dd> <dt>o</dt> <dd>Get tested for HIV-1 with each APRETUDE injection or when your healthcare provider tells you. You should not miss any HIV-1 tests. If you become HIV-1–infected and continue receiving APRETUDE because you do not know you are HIV-1–infected, the HIV-1 infection may become harder to treat.</dd> <dt>o</dt> <dd>Get tested for other sexually transmitted infections such as syphilis, chlamydia, and gonorrhea. These infections make it easier for HIV-1 to infect you.</dd> <dt>o</dt> <dd>If you think you were exposed to HIV-1, tell your healthcare provider right away. They may want to do more tests to be sure you are still HIV-1 negative.</dd> <dt>o</dt> <dd>Get information and support to help reduce sexual risk behaviors.</dd> <dt>o</dt> <dd>Do not miss any injections of APRETUDE. Missing injections increases your risk of getting HIV-1 infection.</dd> <dt>o</dt> <dd>If you do become HIV-1 positive, you will need to take other medicines to treat HIV-1. APRETUDE is not approved for treatment of HIV-1.</dd> </dl> </dd> </dl> <p> <span class="Bold">If you have HIV-1 and receive only APRETUDE, over time your HIV-1 may become harder to treat.</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What is APRETUDE?</span> </p> <p>APRETUDE is a prescription medicine used for HIV-1 PrEP to reduce the risk of getting HIV-1 infection in adults and adolescents who weigh at least 77 pounds (at least 35 kg). </p> <p>HIV-1 is the virus that causes acquired immune deficiency syndrome (AIDS).</p> <p>It is not known if APRETUDE is safe and effective in children younger than 12 years of age or weighing less than 77 pounds (less than 35 kg).</p> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Do not receive APRETUDE if you:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">already have HIV-1 infection. </span>If you are HIV-1 positive, you will need to take other medicines to treat HIV-1. APRETUDE is not approved for treatment of HIV-1.</dd> <dt>•</dt> <dd> <span class="Bold">do not know your HIV-1 infection status.</span> You may already be HIV-1 positive. You need to take other medicines to treat HIV-1. APRETUDE can only help reduce your risk of getting HIV-1 infection <span class="Bold">before</span> you are infected.</dd> <dt>•</dt> <dd>have ever had an allergic reaction to cabotegravir</dd> <dt>•</dt> <dd>are taking any of the following medicines:</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule" valign="top"></td><td class="Botrule" valign="top"> <dl> <dt> </dt> <dd>○   carbamazepine</dd> <dt> </dt> <dd>○   oxcarbazepine</dd> <dt> </dt> <dd>○   phenobarbital</dd> </dl> </td><td class="Botrule Rrule" valign="top"> <dl> <dt> </dt> <dd>○   phenytoin</dd> <dt> </dt> <dd>○   rifampin</dd> <dt> </dt> <dd>○   rifapentine</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Before receiving APRETUDE, tell your healthcare provider about all your medical conditions, including if you:</span> </p> <dl> <dt>•</dt> <dd>have ever had a skin rash or an allergic reaction to medicines that contain cabotegravir.</dd> <dt>•</dt> <dd>have or have had liver problems.</dd> <dt>•</dt> <dd>have ever had mental health problems. </dd> <dt>•</dt> <dd>are pregnant or plan to become pregnant. It is not known if APRETUDE will harm your unborn baby. APRETUDE can remain in your body for up to 12 months or longer after the last injection. Tell your healthcare provider if you become pregnant while or after receiving APRETUDE.<br/> <span class="Bold">Pregnancy Registry.</span> There is a pregnancy registry for those who receive APRETUDE during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry.</dd> <dt>•</dt> <dd>are breastfeeding or plan to breastfeed. APRETUDE may pass into your breast milk. Talk with your healthcare provider about the best way to feed your baby while or after receiving APRETUDE.</dd> </dl> <p> <span class="Bold">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements.</p> <p>Some medicines may interact with APRETUDE. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.</p> <p>You can ask your healthcare provider or pharmacist for a list of medicines that interact with APRETUDE.</p> <p> <span class="Bold">Do not start a new medicine without telling your healthcare provider.</span> Your healthcare provider can tell you if it is safe to receive APRETUDE with other medicines.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">How will I receive APRETUDE?</span> </p> <dl> <dt>•</dt> <dd>APRETUDE will be given to you as an injection by your healthcare provider.</dd> <dt>•</dt> <dd>APRETUDE is initially given as an injection into the muscle of your buttock 1 time every month for the first 2 months, then as an injection 1 time every 2 months.</dd> <dt>•</dt> <dd>Before receiving your first injection dose of APRETUDE, your healthcare provider may have you take 1 VOCABRIA (cabotegravir) tablet 1 time a day for 1 month (at least 28 days). This will allow your healthcare provider to assess how well you will tolerate cabotegravir.</dd> <dt>•</dt> <dd>APRETUDE is a long-acting medicine and may stay in your body for 12 months or longer after your last injection. </dd> <dt>•</dt> <dd>Stay under the care of a healthcare provider while receiving APRETUDE. It is important that you receive APRETUDE as scheduled.</dd> <dt>•</dt> <dd>If you miss or plan to miss a scheduled injection of APRETUDE by more than 7 days, call your healthcare provider right away to discuss your PrEP options.</dd> <dt>•</dt> <dd>If you stop receiving APRETUDE, talk to your healthcare provider about other options to reduce the risk of getting HIV-1 infection.</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What are the possible side effects of APRETUDE?</span> </p> <p> <span class="Bold">APRETUDE may cause serious side effects including:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Allergic reactions.</span> Call your healthcare provider right away if you develop a rash with APRETUDE. <span class="Bold">Stop receiving APRETUDE and get medical help right away if you develop a rash with any of the following signs or symptoms:</span> </dd> </dl> </td> </tr> <tr> <td class="Lrule" valign="top"></td><td valign="top"> <dl> <dt> </dt> <dd>○   fever</dd> <dt> </dt> <dd>○   generally ill feeling</dd> <dt> </dt> <dd>○   tiredness</dd> <dt> </dt> <dd>○   muscle or joint aches</dd> <dt> </dt> <dd>○   trouble breathing</dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt> </dt> <dd>○   blisters or sores in mouth </dd> <dt> </dt> <dd>○   blisters</dd> <dt> </dt> <dd>○   redness or swelling of the eyes</dd> <dt> </dt> <dd>○   swelling of the mouth, face, lips, or tongue</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">Liver problems.</span> Liver problems have happened in people with or without a history of liver problems or other risk factors. Your healthcare provider may do blood tests to check your liver function. <br/> <span class="Bold">Call your healthcare provider right away if you develop any of the following signs or symptoms of liver problems:</span> </dd> </dl> </td> </tr> <tr> <td class="Lrule" valign="top"></td><td valign="top"> <dl> <dt> </dt> <dd>○   your skin or the white part of your eyes turns yellow (jaundice)</dd> </dl> <dl> <dt> </dt> <dd>○   dark or “tea-colored” urine</dd> <dt> </dt> <dd>○   light-colored stools (bowel movements)</dd> <dt> </dt> <dd>○   nausea or vomiting</dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt> </dt> <dd>○   loss of appetite</dd> </dl> <dl> <dt> </dt> <dd>○   pain, aching, or tenderness on the right side of your stomach area</dd> </dl> <dl> <dt> </dt> <dd>○   itching</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">Depression or mood changes. Call your healthcare provider or get medical help right away if you develop any of the following symptoms:</span> <p class="First">○   feeling sad or hopeless</p> <p>○   feeling anxious or restless </p> <p>○   have thoughts of hurting yourself (suicide) or have tried to hurt yourself</p> </dd> </dl> <p class="First"> <span class="Bold">The most common side effects of APRETUDE include:</span> </p> </td> </tr> <tr> <td class="Lrule" colspan="2" valign="top"> <dl> <dt>•</dt> <dd>pain, tenderness, hardened mass or lump, swelling, bruising, redness, itching, warmth, loss of sensation at the injection site, abscess, and discoloration</dd> <dt>•</dt> <dd>diarrhea</dd> <dt>•</dt> <dd>headache</dd> <dt>•</dt> <dd>fever</dd> <dt>•</dt> <dd>tiredness</dd> <dt>•</dt> <dd>sleep problems</dd> <dt>•</dt> <dd>nausea</dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt>•</dt> <dd>dizziness</dd> <dt>•</dt> <dd>passing gas</dd> <dt>•</dt> <dd>stomach pain</dd> <dt>•</dt> <dd>vomiting</dd> <dt>•</dt> <dd>muscle pain</dd> <dt>•</dt> <dd>rash</dd> <dt>•</dt> <dd>loss of appetite</dd> <dt>•</dt> <dd>drowsiness</dd> <dt>•</dt> <dd>back pain</dd> <dt>•</dt> <dd>upper respiratory infection</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">These are not all the possible side effects of APRETUDE. </p> <p>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">General information about the safe and effective use of APRETUDE.</span> </p> <p>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about APRETUDE that is written for health professionals.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What are the ingredients in APRETUDE?</span> </p> <p> <span class="Bold">Active ingredient: </span>cabotegravir</p> <p> <span class="Bold">Inactive ingredients:</span> mannitol, polyethylene glycol (PEG) 3350, polysorbate 20, and Water for Injection.</p> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <p class="First">Manufactured for:</p> <p>ViiV Healthcare</p> <p>Durham, NC 27701</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">APRETUDE and VOCABRIA are trademarks owned by or licensed to the ViiV Healthcare group of companies.</p> <p>©2025 ViiV Healthcare group of companies or its licensor.</p> <p>APR:5PIL</p> <p>For more information, go to <a href="http://www.apretude.com">www.apretude.com</a> or call 1-877-844-8872.</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"3%\"/>\n<col width=\"47%\"/>\n<col width=\"50%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"3\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">PATIENT INFORMATION</span>\n</p>\n<p>\n<span class=\"Bold\">APRETUDE [AP-reh-tood]</span>\n</p>\n<p>\n<span class=\"Bold\">(cabotegravir extended-release injectable suspension)</span>\n</p>\n<p>\n<span class=\"Bold\">for intramuscular use</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is the most important information I should know about APRETUDE?</span>\n</p>\n<p>\n<span class=\"Bold\">Important information for people who receive APRETUDE to help reduce their risk of getting human immunodeficiency virus-1 (HIV-1) infection, also called pre-exposure prophylaxis or “PrEP”:</span>\n</p>\n<p>\n<span class=\"Bold\">Before receiving APRETUDE to reduce your risk of getting HIV-1:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">You must be HIV-1 negative to start APRETUDE. You must get tested to make sure that you do not already have HIV-1 infection.</span>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not receive APRETUDE for HIV-1 PrEP unless you are confirmed to be HIV-1 negative.</span>\n</dd>\n<dt>•</dt>\n<dd>Some HIV-1 tests can miss HIV-1 infection in a person who has recently become infected. If you have flu-like symptoms, you could have recently become infected with HIV-1. Tell your healthcare provider if you had a flu-like illness within the last month before starting APRETUDE or at any time while receiving APRETUDE. Symptoms of new HIV-1 infection include:</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"></td><td valign=\"top\">\n<dl>\n<dt> </dt>\n<dd>○   tiredness</dd>\n<dt> </dt>\n<dd>○   joint or muscle aches</dd>\n<dt> </dt>\n<dd>○   sore throat</dd>\n<dt> </dt>\n<dd>○   rash</dd>\n<dt> </dt>\n<dd>○   enlarged lymph nodes in the neck or groin</dd>\n</dl>\n</td><td class=\"Rrule\" valign=\"top\">\n<dl>\n<dt> </dt>\n<dd>○   fever</dd>\n<dt> </dt>\n<dd>○   headache</dd>\n<dt> </dt>\n<dd>○   vomiting or diarrhea</dd>\n<dt> </dt>\n<dd>○   night sweats</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">While you are receiving APRETUDE for HIV-1 PrEP:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">APRETUDE does not prevent other sexually transmitted infections. Practice safer sex by using a latex or polyurethane condom to reduce the risk of getting sexually transmitted infections.</span>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">You must stay HIV-1 negative to keep receiving APRETUDE for HIV-1 PrEP.</span>\n<dl>\n<dt>o</dt>\n<dd>Know your HIV-1 status and the HIV-1 status of your partners.</dd>\n<dt>o</dt>\n<dd>Ask your partners with HIV-1 if they are taking anti-HIV-1 medicines and have an undetectable viral load. An undetectable viral load is when the amount of virus in the blood is too low to be measured in a lab test. To maintain an undetectable viral load, your partners must keep taking HIV-1 medicine as prescribed. Your risk of getting HIV-1 is lower if your partners with HIV-1 are taking effective treatment.</dd>\n<dt>o</dt>\n<dd>Get tested for HIV-1 with each APRETUDE injection or when your healthcare provider tells you. You should not miss any HIV-1 tests. If you become HIV-1–infected and continue receiving APRETUDE because you do not know you are HIV-1–infected, the HIV-1 infection may become harder to treat.</dd>\n<dt>o</dt>\n<dd>Get tested for other sexually transmitted infections such as syphilis, chlamydia, and gonorrhea. These infections make it easier for HIV-1 to infect you.</dd>\n<dt>o</dt>\n<dd>If you think you were exposed to HIV-1, tell your healthcare provider right away. They may want to do more tests to be sure you are still HIV-1 negative.</dd>\n<dt>o</dt>\n<dd>Get information and support to help reduce sexual risk behaviors.</dd>\n<dt>o</dt>\n<dd>Do not miss any injections of APRETUDE. Missing injections increases your risk of getting HIV-1 infection.</dd>\n<dt>o</dt>\n<dd>If you do become HIV-1 positive, you will need to take other medicines to treat HIV-1. APRETUDE is not approved for treatment of HIV-1.</dd>\n</dl>\n</dd>\n</dl>\n<p>\n<span class=\"Bold\">If you have HIV-1 and receive only APRETUDE, over time your HIV-1 may become harder to treat.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is APRETUDE?</span>\n</p>\n<p>APRETUDE is a prescription medicine used for HIV-1 PrEP to reduce the risk of getting HIV-1 infection in adults and adolescents who weigh at least 77 pounds (at least 35 kg). </p>\n<p>HIV-1 is the virus that causes acquired immune deficiency syndrome (AIDS).</p>\n<p>It is not known if APRETUDE is safe and effective in children younger than 12 years of age or weighing less than 77 pounds (less than 35 kg).</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Do not receive APRETUDE if you:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">already have HIV-1 infection. </span>If you are HIV-1 positive, you will need to take other medicines to treat HIV-1. APRETUDE is not approved for treatment of HIV-1.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">do not know your HIV-1 infection status.</span> You may already be HIV-1 positive. You need to take other medicines to treat HIV-1. APRETUDE can only help reduce your risk of getting HIV-1 infection <span class=\"Bold\">before</span> you are infected.</dd>\n<dt>•</dt>\n<dd>have ever had an allergic reaction to cabotegravir</dd>\n<dt>•</dt>\n<dd>are taking any of the following medicines:</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule\" valign=\"top\"></td><td class=\"Botrule\" valign=\"top\">\n<dl>\n<dt> </dt>\n<dd>○   carbamazepine</dd>\n<dt> </dt>\n<dd>○   oxcarbazepine</dd>\n<dt> </dt>\n<dd>○   phenobarbital</dd>\n</dl>\n</td><td class=\"Botrule Rrule\" valign=\"top\">\n<dl>\n<dt> </dt>\n<dd>○   phenytoin</dd>\n<dt> </dt>\n<dd>○   rifampin</dd>\n<dt> </dt>\n<dd>○   rifapentine</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Before receiving APRETUDE, tell your healthcare provider about all your medical conditions, including if you:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>have ever had a skin rash or an allergic reaction to medicines that contain cabotegravir.</dd>\n<dt>•</dt>\n<dd>have or have had liver problems.</dd>\n<dt>•</dt>\n<dd>have ever had mental health problems. </dd>\n<dt>•</dt>\n<dd>are pregnant or plan to become pregnant. It is not known if APRETUDE will harm your unborn baby. APRETUDE can remain in your body for up to 12 months or longer after the last injection. Tell your healthcare provider if you become pregnant while or after receiving APRETUDE.<br/>\n<span class=\"Bold\">Pregnancy Registry.</span> There is a pregnancy registry for those who receive APRETUDE during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry.</dd>\n<dt>•</dt>\n<dd>are breastfeeding or plan to breastfeed. APRETUDE may pass into your breast milk. Talk with your healthcare provider about the best way to feed your baby while or after receiving APRETUDE.</dd>\n</dl>\n<p>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements.</p>\n<p>Some medicines may interact with APRETUDE. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.</p>\n<p>You can ask your healthcare provider or pharmacist for a list of medicines that interact with APRETUDE.</p>\n<p>\n<span class=\"Bold\">Do not start a new medicine without telling your healthcare provider.</span> Your healthcare provider can tell you if it is safe to receive APRETUDE with other medicines.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How will I receive APRETUDE?</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>APRETUDE will be given to you as an injection by your healthcare provider.</dd>\n<dt>•</dt>\n<dd>APRETUDE is initially given as an injection into the muscle of your buttock 1 time every month for the first 2 months, then as an injection 1 time every 2 months.</dd>\n<dt>•</dt>\n<dd>Before receiving your first injection dose of APRETUDE, your healthcare provider may have you take 1 VOCABRIA (cabotegravir) tablet 1 time a day for 1 month (at least 28 days). This will allow your healthcare provider to assess how well you will tolerate cabotegravir.</dd>\n<dt>•</dt>\n<dd>APRETUDE is a long-acting medicine and may stay in your body for 12 months or longer after your last injection. </dd>\n<dt>•</dt>\n<dd>Stay under the care of a healthcare provider while receiving APRETUDE. It is important that you receive APRETUDE as scheduled.</dd>\n<dt>•</dt>\n<dd>If you miss or plan to miss a scheduled injection of APRETUDE by more than 7 days, call your healthcare provider right away to discuss your PrEP options.</dd>\n<dt>•</dt>\n<dd>If you stop receiving APRETUDE, talk to your healthcare provider about other options to reduce the risk of getting HIV-1 infection.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of APRETUDE?</span>\n</p>\n<p>\n<span class=\"Bold\">APRETUDE may cause serious side effects including:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Allergic reactions.</span> Call your healthcare provider right away if you develop a rash with APRETUDE. <span class=\"Bold\">Stop receiving APRETUDE and get medical help right away if you develop a rash with any of the following signs or symptoms:</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"></td><td valign=\"top\">\n<dl>\n<dt> </dt>\n<dd>○   fever</dd>\n<dt> </dt>\n<dd>○   generally ill feeling</dd>\n<dt> </dt>\n<dd>○   tiredness</dd>\n<dt> </dt>\n<dd>○   muscle or joint aches</dd>\n<dt> </dt>\n<dd>○   trouble breathing</dd>\n</dl>\n</td><td class=\"Rrule\" valign=\"top\">\n<dl>\n<dt> </dt>\n<dd>○   blisters or sores in mouth </dd>\n<dt> </dt>\n<dd>○   blisters</dd>\n<dt> </dt>\n<dd>○   redness or swelling of the eyes</dd>\n<dt> </dt>\n<dd>○   swelling of the mouth, face, lips, or tongue</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Liver problems.</span> Liver problems have happened in people with or without a history of liver problems or other risk factors. Your healthcare provider may do blood tests to check your liver function. <br/>\n<span class=\"Bold\">Call your healthcare provider right away if you develop any of the following signs or symptoms of liver problems:</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"></td><td valign=\"top\">\n<dl>\n<dt> </dt>\n<dd>○   your skin or the white part of your eyes turns yellow (jaundice)</dd>\n</dl>\n<dl>\n<dt> </dt>\n<dd>○   dark or “tea-colored” urine</dd>\n<dt> </dt>\n<dd>○   light-colored stools (bowel movements)</dd>\n<dt> </dt>\n<dd>○   nausea or vomiting</dd>\n</dl>\n</td><td class=\"Rrule\" valign=\"top\">\n<dl>\n<dt> </dt>\n<dd>○   loss of appetite</dd>\n</dl>\n<dl>\n<dt> </dt>\n<dd>○   pain, aching, or tenderness on the right side of your stomach area</dd>\n</dl>\n<dl>\n<dt> </dt>\n<dd>○   itching</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Depression or mood changes. Call your healthcare provider or get medical help right away if you develop any of the following symptoms:</span>\n<p class=\"First\">○   feeling sad or hopeless</p>\n<p>○   feeling anxious or restless </p>\n<p>○   have thoughts of hurting yourself (suicide) or have tried to hurt yourself</p>\n</dd>\n</dl>\n<p class=\"First\">\n<span class=\"Bold\">The most common side effects of APRETUDE include:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>pain, tenderness, hardened mass or lump, swelling, bruising, redness, itching, warmth, loss of sensation at the injection site, abscess, and discoloration</dd>\n<dt>•</dt>\n<dd>diarrhea</dd>\n<dt>•</dt>\n<dd>headache</dd>\n<dt>•</dt>\n<dd>fever</dd>\n<dt>•</dt>\n<dd>tiredness</dd>\n<dt>•</dt>\n<dd>sleep problems</dd>\n<dt>•</dt>\n<dd>nausea</dd>\n</dl>\n</td><td class=\"Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>dizziness</dd>\n<dt>•</dt>\n<dd>passing gas</dd>\n<dt>•</dt>\n<dd>stomach pain</dd>\n<dt>•</dt>\n<dd>vomiting</dd>\n<dt>•</dt>\n<dd>muscle pain</dd>\n<dt>•</dt>\n<dd>rash</dd>\n<dt>•</dt>\n<dd>loss of appetite</dd>\n<dt>•</dt>\n<dd>drowsiness</dd>\n<dt>•</dt>\n<dd>back pain</dd>\n<dt>•</dt>\n<dd>upper respiratory infection</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">These are not all the possible side effects of APRETUDE. </p>\n<p>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of APRETUDE.</span>\n</p>\n<p>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about APRETUDE that is written for health professionals.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in APRETUDE?</span>\n</p>\n<p>\n<span class=\"Bold\">Active ingredient: </span>cabotegravir</p>\n<p>\n<span class=\"Bold\">Inactive ingredients:</span> mannitol, polyethylene glycol (PEG) 3350, polysorbate 20, and Water for Injection.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">Manufactured for:</p>\n<p>ViiV Healthcare</p>\n<p>Durham, NC 27701</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">APRETUDE and VOCABRIA are trademarks owned by or licensed to the ViiV Healthcare group of companies.</p>\n<p>©2025 ViiV Healthcare group of companies or its licensor.</p>\n<p>APR:5PIL</p>\n<p>For more information, go to <a href=\"http://www.apretude.com\">www.apretude.com</a> or call 1-877-844-8872.</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

{ "type": "", "children": [], "text": "" }

<div class="scrollingtable"><table width="100%"> <col width="69%"/> <col width="31%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"><a name="id229349695"></a><img alt="Instructions for Use header" src="/dailymed/image.cfm?name=apretude-spl-graphic-04.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Overview:</span> </p> <p>A complete dose of APRETUDE requires 1 injection: 600-mg (3 mL) of cabotegravir.</p> <p>APRETUDE is a suspension that does not need further dilution or reconstitution. Carefully follow these instructions when preparing the suspension for injection to avoid leakage.</p> <p>APRETUDE is for gluteal intramuscular use only.</p> <p> <span class="Bold">Note:</span> The ventrogluteal site is recommended.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <a name="id2116856876"></a><img alt="storage information" src="/dailymed/image.cfm?name=apretude-spl-graphic-05.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><span class="Bold"> Storage information</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First">Store at 2°C to 25°C (36°F to 77°F). Exposure up to 30°C (86°F) permitted.</p> <p> <span class="Bold">Do not </span>freeze.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">Prior to administration:</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <dl> <dt>•</dt> <dd>If the pack has been stored in the refrigerator, the vial should be brought to room temperature prior to administration (not to exceed 30°C [86°F]).</dd> <dt>•</dt> <dd>Once APRETUDE has been drawn into the syringe, the medicine can remain in the syringe for up to 2 hours before injection. The filled syringe should not be placed in the refrigerator. If the medicine remains in the syringe for more than 2 hours, the filled syringe and needle must be discarded.</dd> </dl> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" colspan="2" valign="top"><a name="id-1798057260"></a><img alt="Kit contents" src="/dailymed/image.cfm?name=apretude-spl-graphic-06.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">Your pack contains:</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="middle"> <dl> <dt>•</dt> <dd>1 vial of APRETUDE</dd> <dt>•</dt> <dd>1 vial adapter</dd> <dt>•</dt> <dd>1 syringe</dd> <dt>•</dt> <dd>1 injection needle (23 gauge, 1½ inch) </dd> </dl> <p class="First">Consider the individual’s build and use medical judgment to select an appropriate injection needle length.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">You will also need:</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="middle"> <dl> <dt>•</dt> <dd>Non-sterile gloves </dd> <dt>•</dt> <dd>2 alcohol wipes </dd> <dt>•</dt> <dd>2 gauze pads</dd> <dt>•</dt> <dd>A suitable sharps container</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">Preparation:</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">1. Inspect the vial.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-203090696"></a><img alt="Figure A" src="/dailymed/image.cfm?name=apretude-spl-graphic-07.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure A</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Check that the expiration date has not passed. <span class="Bold">See Figure A.</span> </dd> <dt>•</dt> <dd>Inspect the vial immediately. If you can see foreign matter, do not use the product.</dd> <dt> </dt> <dd> <span class="Bold">Note:</span> The vial has a brown tint to the glass.</dd> <dt> </dt> <dd> <span class="Bold">Do not</span> use if the expiration date has passed.</dd> <dt>•</dt> <dd>If the pack has been stored in the refrigerator, allow the medication to come to room temperature.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">2. Shake the vial vigorously.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id2084026179"></a><img alt="Figure B" src="/dailymed/image.cfm?name=apretude-spl-graphic-08.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure B</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Hold the vial firmly, and vigorously shake for a full 10 seconds. <span class="Bold">See Figure B.</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">3. Inspect suspension.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id282459184"></a><img alt="Figure C" src="/dailymed/image.cfm?name=apretude-spl-graphic-09.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure C</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Invert the vial and confirm the suspension is uniform. It should look uniform. <span class="Bold">See Figure C.</span> </dd> <dt>•</dt> <dd>If the suspension is not uniform, shake the vial again.</dd> <dt>•</dt> <dd>It is also normal to see small air bubbles.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">4. Remove the vial cap.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id548728332"></a><img alt="Figure D" src="/dailymed/image.cfm?name=apretude-spl-graphic-10.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure D</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Remove the cap from the vial. <span class="Bold">See Figure D.</span> </dd> <dt>•</dt> <dd>Wipe the rubber stopper with an alcohol wipe. </dd> <dt> </dt> <dd> <span class="Bold">Do not</span> allow anything to touch the rubber stopper after wiping it.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">5. Peel open the vial adapter.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id1189723626"></a><img alt="Figure E" src="/dailymed/image.cfm?name=apretude-spl-graphic-11.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure E</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Peel off the paper backing from the vial adapter packaging. <span class="Bold">See Figure E.</span> </dd> <dt> </dt> <dd> <span class="Bold">Note:</span> Do not remove the adapter from its packaging for the next step. The adapter <span class="Bold">will not</span> fall out when its packaging is turned upside down.</dd> <dt> </dt> <dd></dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">6. Place vial on flat surface and attach the vial adapter.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-1231218679"></a><img alt="Figure F" src="/dailymed/image.cfm?name=apretude-spl-graphic-12.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure F</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Ensure the vial is upright and on a flat surface. <span class="Bold">See Figure F.</span> </dd> <dt>•</dt> <dd>Press the vial adapter straight down onto the vial, as shown.</dd> <dt>•</dt> <dd>The vial adapter should click securely into place.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">7. Lift off the packaging.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id1706906927"></a><img alt="Figure G" src="/dailymed/image.cfm?name=apretude-spl-graphic-13.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure G</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Lift off the vial adapter packaging, as shown.<span class="Bold"> See Figure G.</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">8. Prepare the syringe.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-1994796004"></a><img alt="Figure H" src="/dailymed/image.cfm?name=apretude-spl-graphic-14.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure H</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Remove the syringe from its packaging.</dd> <dt>•</dt> <dd>Draw 1 mL of air into the syringe. This will make it easier to draw up the medicine later. <span class="Bold">See Figure H.</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">9. Attach the syringe.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-1949998177"></a><img alt="Figure I" src="/dailymed/image.cfm?name=apretude-spl-graphic-15.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure I</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Hold the vial adapter and vial firmly, as shown.</dd> <dt>•</dt> <dd>Screw the syringe firmly onto the vial adapter. <span class="Bold">See Figure I.</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">10. Press the plunger.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-147441965"></a><img alt="Figure J" src="/dailymed/image.cfm?name=apretude-spl-graphic-16.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure J</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Press the plunger all the way down to push the air into the vial. <span class="Bold">See Figure J.</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">11. Slowly draw up the dose.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-1160689931"></a><img alt="Figure K" src="/dailymed/image.cfm?name=apretude-spl-graphic-17.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure K</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Invert the syringe and vial and slowly withdraw as much of the medicine as possible into the syringe. There may be more medicine than the dose amount. <span class="Bold">See Figure K.</span> </dd> <dt> </dt> <dd> <span class="Bold">Note:</span> Keep the syringe upright to avoid leakage.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">12. Unscrew the syringe.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id774209232"></a><img alt="Figure L" src="/dailymed/image.cfm?name=apretude-spl-graphic-18.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure L</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Hold the syringe plunger firmly in place as shown to prevent leakage. It is normal to feel some back pressure.</dd> <dt>•</dt> <dd>Unscrew the syringe from the vial adapter, holding the vial adapter as shown. <span class="Bold">See Figure L.</span> </dd> <dt> </dt> <dd> <span class="Bold">Note:</span> Check that the suspension looks uniform and milky white.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">13. Attach the needle.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id2030066739"></a><img alt="Figure M" src="/dailymed/image.cfm?name=apretude-spl-graphic-19.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure M</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Peel open the needle packaging part way to expose the needle base.</dd> <dt>•</dt> <dd>Keeping the syringe upright, firmly twist the syringe onto the needle. </dd> <dt>•</dt> <dd>Remove the needle packaging from the needle. <span class="Bold">See Figure M.</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Injection:</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">14. Prepare the injection site.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-547227573"></a><img alt="Figure N" src="/dailymed/image.cfm?name=apretude-spl-graphic-20.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure N</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>APRETUDE must be administered to a gluteal site. <span class="Bold">See Figure N</span>.</dd> <dt> </dt> <dd>Select from the following areas for the injection:</dd> </dl> <dl> <dt>•</dt> <dd>Ventrogluteal, as shown (recommended)</dd> <dt>•</dt> <dd>Dorsogluteal, not shown (upper outer quadrant)</dd> <dt> </dt> <dd> <span class="Bold">Note: </span>For gluteal intramuscular use only.<br/> <span class="Bold">Do not</span> inject intravenously.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">15. Remove the cap.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id2125496266"></a><img alt="Figure O" src="/dailymed/image.cfm?name=apretude-spl-graphic-21.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure O</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Fold the needle guard away from the needle. <span class="Bold">See Figure O.</span> </dd> <dt>•</dt> <dd>Pull off the injection needle cap.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">16. Remove extra liquid from the syringe.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id1473947728"></a><img alt="Figure P" src="/dailymed/image.cfm?name=apretude-spl-graphic-22.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure P</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Hold the syringe with the needle pointing up. Press the plunger to the 3 mL dosing mark to remove extra liquid and any air bubbles. <span class="Bold">See Figure P.</span> </dd> <dt> </dt> <dd> <span class="Bold">Note:</span> Clean the injection site with an alcohol wipe. Allow the skin to air dry before continuing.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">17. Stretch the skin.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id2018657717"></a><img alt="Figure Q" src="/dailymed/image.cfm?name=apretude-spl-graphic-23.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure Q</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Use the z-track injection technique to minimize medicine leakage from the injection site.</dd> </dl> <dl> <dt>•</dt> <dd>Firmly drag the skin covering the injection site, displacing it by about an inch (2.5 cm). <span class="Bold">See Figure Q.</span> </dd> <dt>•</dt> <dd>Keep it held in this position for the injection.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">18. Insert the needle.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-1441684898"></a><img alt="Figure R" src="/dailymed/image.cfm?name=apretude-spl-graphic-24.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure R</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Insert the needle to its full depth, or deep enough to reach the muscle. <span class="Bold">See Figure R.</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">19. Inject the dose of medicine.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id1042252430"></a><img alt="Figure S" src="/dailymed/image.cfm?name=apretude-spl-graphic-25.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure S</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Still holding the skin stretched – slowly press the plunger all the way down. <span class="Bold">See Figure S.</span> </dd> <dt>•</dt> <dd>Ensure the syringe is empty.</dd> <dt>•</dt> <dd>Withdraw the needle and release the stretched skin immediately.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">20. Assess the injection site.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-554157893"></a><img alt="Figure T" src="/dailymed/image.cfm?name=apretude-spl-graphic-26.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure T</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Apply pressure to the injection site using a gauze pad. <span class="Bold">See Figure T.</span> </dd> <dt>•</dt> <dd>A small bandage may be used if bleeding occurs.</dd> <dt> </dt> <dd> <span class="Bold">Do not</span> massage the area.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">21. Make the needle safe.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id1486584380"></a><img alt="Figure U" src="/dailymed/image.cfm?name=apretude-spl-graphic-27.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure U</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Fold the needle guard over the needle. <span class="Bold">See Figure U.</span> </dd> </dl> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id1805812036"></a><img alt="Figure V" src="/dailymed/image.cfm?name=apretude-spl-graphic-28.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure V</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt>•</dt> <dd>Gently apply pressure using a hard surface to lock the needle guard in place.</dd> <dt>•</dt> <dd>The needle guard will make a click when it locks. <span class="Bold">See Figure V.</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">After injection:</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">22. Dispose safely.</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id1599445454"></a><img alt="Figure W" src="/dailymed/image.cfm?name=apretude-spl-graphic-29.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da"/><p class="First"> <span class="Bold">Figure W</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Dispose of used needle, syringe, vial, and vial adapter according to local health and safety laws. <span class="Bold">See Figure W.</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Questions and Answers</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <dl> <dt>1.</dt> <dd> <span class="Bold">If the pack has been stored in the refrigerator, is it safe to warm the vial up to room temperature more quickly?</span> <br/>The vial should be brought to room temperature before you are ready to give the injection, but make sure the vial does not get above 30°C (86°F).</dd> <dt> </dt> <dd> <span class="Bold">Do not</span> use any heating methods, other than using the warmth of your hands.</dd> <dt>2.</dt> <dd> <span class="Bold">How long can APRETUDE be left in the syringe?</span> <br/>It is best to inject (room temperature) APRETUDE as soon as possible after drawing it up. However, APRETUDE can remain in the syringe for up to 2 hours before injection.<br/>If the medicine remains in the syringe for more than 2 hours, the filled syringe and needle must be discarded.</dd> <dt>3.</dt> <dd> <span class="Bold">Why do I need to inject air into the vial?</span> <br/>Injecting 1 mL of air into the vial makes it easier to draw up the medicine into the syringe. Without the air, some liquid may flow back into the vial unintentionally, leaving less medicine than intended in the syringe.</dd> <dt>4.</dt> <dd> <span class="Bold">Why is the ventrogluteal administration approach recommended?</span> <br/>The ventrogluteal approach into the gluteus medius muscle is recommended because it is located away from major nerves and blood vessels. A dorsogluteal approach into the gluteus maximus muscle is acceptable, if preferred by the healthcare professional. The injection should not be administered in any other site.</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"> <p class="First">Manufactured for:</p> <p>ViiV Healthcare</p> <p>Durham, NC 27701</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First">Trademarks are owned by or licensed to the ViiV Healthcare group of companies.</p> <p>©2024 ViiV Healthcare group of companies or its licensor.</p> <p>APR:5IFU</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"69%\"/>\n<col width=\"31%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\" valign=\"top\"><a name=\"id229349695\"></a><img alt=\"Instructions for Use header\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-04.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Overview:</span>\n</p>\n<p>A complete dose of APRETUDE requires 1 injection: 600-mg (3 mL) of cabotegravir.</p>\n<p>APRETUDE is a suspension that does not need further dilution or reconstitution. Carefully follow these instructions when preparing the suspension for injection to avoid leakage.</p>\n<p>APRETUDE is for gluteal intramuscular use only.</p>\n<p>\n<span class=\"Bold\">Note:</span> The ventrogluteal site is recommended.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<a name=\"id2116856876\"></a><img alt=\"storage information\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-05.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><span class=\"Bold\"> Storage information</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">Store at 2°C to 25°C (36°F to 77°F). Exposure up to 30°C (86°F) permitted.</p>\n<p>\n<span class=\"Bold\">Do not </span>freeze.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">Prior to administration:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>If the pack has been stored in the refrigerator, the vial should be brought to room temperature prior to administration (not to exceed 30°C [86°F]).</dd>\n<dt>•</dt>\n<dd>Once APRETUDE has been drawn into the syringe, the medicine can remain in the syringe for up to 2 hours before injection. The filled syringe should not be placed in the refrigerator. If the medicine remains in the syringe for more than 2 hours, the filled syringe and needle must be discarded.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\"><a name=\"id-1798057260\"></a><img alt=\"Kit contents\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-06.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">Your pack contains:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<dl>\n<dt>•</dt>\n<dd>1 vial of APRETUDE</dd>\n<dt>•</dt>\n<dd>1 vial adapter</dd>\n<dt>•</dt>\n<dd>1 syringe</dd>\n<dt>•</dt>\n<dd>1 injection needle (23 gauge, 1½ inch) </dd>\n</dl>\n<p class=\"First\">Consider the individual’s build and use medical judgment to select an appropriate injection needle length.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">You will also need:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<dl>\n<dt>•</dt>\n<dd>Non-sterile gloves </dd>\n<dt>•</dt>\n<dd>2 alcohol wipes </dd>\n<dt>•</dt>\n<dd>2 gauze pads</dd>\n<dt>•</dt>\n<dd>A suitable sharps container</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">Preparation:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">1. Inspect the vial.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-203090696\"></a><img alt=\"Figure A\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-07.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure A</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Check that the expiration date has not passed. <span class=\"Bold\">See Figure A.</span>\n</dd>\n<dt>•</dt>\n<dd>Inspect the vial immediately. If you can see foreign matter, do not use the product.</dd>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Note:</span> The vial has a brown tint to the glass.</dd>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Do not</span> use if the expiration date has passed.</dd>\n<dt>•</dt>\n<dd>If the pack has been stored in the refrigerator, allow the medication to come to room temperature.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">2. Shake the vial vigorously.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id2084026179\"></a><img alt=\"Figure B\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-08.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure B</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Hold the vial firmly, and vigorously shake for a full 10 seconds. <span class=\"Bold\">See Figure B.</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">3. Inspect suspension.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id282459184\"></a><img alt=\"Figure C\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-09.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure C</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Invert the vial and confirm the suspension is uniform. It should look uniform. <span class=\"Bold\">See Figure C.</span>\n</dd>\n<dt>•</dt>\n<dd>If the suspension is not uniform, shake the vial again.</dd>\n<dt>•</dt>\n<dd>It is also normal to see small air bubbles.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">4. Remove the vial cap.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id548728332\"></a><img alt=\"Figure D\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-10.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure D</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Remove the cap from the vial. <span class=\"Bold\">See Figure D.</span>\n</dd>\n<dt>•</dt>\n<dd>Wipe the rubber stopper with an alcohol wipe. </dd>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Do not</span> allow anything to touch the rubber stopper after wiping it.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">5. Peel open the vial adapter.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id1189723626\"></a><img alt=\"Figure E\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-11.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure E</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Peel off the paper backing from the vial adapter packaging. <span class=\"Bold\">See Figure E.</span>\n</dd>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Note:</span> Do not remove the adapter from its packaging for the next step. The adapter <span class=\"Bold\">will not</span> fall out when its packaging is turned upside down.</dd>\n<dt> </dt>\n<dd></dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">6. Place vial on flat surface and attach the vial adapter.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-1231218679\"></a><img alt=\"Figure F\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-12.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure F</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Ensure the vial is upright and on a flat surface. <span class=\"Bold\">See Figure F.</span>\n</dd>\n<dt>•</dt>\n<dd>Press the vial adapter straight down onto the vial, as shown.</dd>\n<dt>•</dt>\n<dd>The vial adapter should click securely into place.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">7. Lift off the packaging.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id1706906927\"></a><img alt=\"Figure G\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-13.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure G</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Lift off the vial adapter packaging, as shown.<span class=\"Bold\"> See Figure G.</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">8. Prepare the syringe.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-1994796004\"></a><img alt=\"Figure H\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-14.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure H</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Remove the syringe from its packaging.</dd>\n<dt>•</dt>\n<dd>Draw 1 mL of air into the syringe. This will make it easier to draw up the medicine later. <span class=\"Bold\">See Figure H.</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">9. Attach the syringe.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-1949998177\"></a><img alt=\"Figure I\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-15.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure I</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Hold the vial adapter and vial firmly, as shown.</dd>\n<dt>•</dt>\n<dd>Screw the syringe firmly onto the vial adapter. <span class=\"Bold\">See Figure I.</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">10. Press the plunger.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-147441965\"></a><img alt=\"Figure J\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-16.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure J</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Press the plunger all the way down to push the air into the vial. <span class=\"Bold\">See Figure J.</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">11. Slowly draw up the dose.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-1160689931\"></a><img alt=\"Figure K\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-17.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure K</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Invert the syringe and vial and slowly withdraw as much of the medicine as possible into the syringe. There may be more medicine than the dose amount. <span class=\"Bold\">See Figure K.</span>\n</dd>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Note:</span> Keep the syringe upright to avoid leakage.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">12. Unscrew the syringe.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id774209232\"></a><img alt=\"Figure L\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-18.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure L</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Hold the syringe plunger firmly in place as shown to prevent leakage. It is normal to feel some back pressure.</dd>\n<dt>•</dt>\n<dd>Unscrew the syringe from the vial adapter, holding the vial adapter as shown. <span class=\"Bold\">See Figure L.</span>\n</dd>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Note:</span> Check that the suspension looks uniform and milky white.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">13. Attach the needle.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id2030066739\"></a><img alt=\"Figure M\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-19.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure M</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Peel open the needle packaging part way to expose the needle base.</dd>\n<dt>•</dt>\n<dd>Keeping the syringe upright, firmly twist the syringe onto the needle. </dd>\n<dt>•</dt>\n<dd>Remove the needle packaging from the needle. <span class=\"Bold\">See Figure M.</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Injection:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">14. Prepare the injection site.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-547227573\"></a><img alt=\"Figure N\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-20.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure N</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt> </dt>\n<dd>APRETUDE must be administered to a gluteal site. <span class=\"Bold\">See Figure N</span>.</dd>\n<dt> </dt>\n<dd>Select from the following areas for the injection:</dd>\n</dl>\n<dl>\n<dt>•</dt>\n<dd>Ventrogluteal, as shown (recommended)</dd>\n<dt>•</dt>\n<dd>Dorsogluteal, not shown (upper outer quadrant)</dd>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Note: </span>For gluteal intramuscular use only.<br/>\n<span class=\"Bold\">Do not</span> inject intravenously.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">15. Remove the cap.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id2125496266\"></a><img alt=\"Figure O\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-21.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure O</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Fold the needle guard away from the needle. <span class=\"Bold\">See Figure O.</span>\n</dd>\n<dt>•</dt>\n<dd>Pull off the injection needle cap.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">16. Remove extra liquid from the syringe.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id1473947728\"></a><img alt=\"Figure P\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-22.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure P</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Hold the syringe with the needle pointing up. Press the plunger to the 3 mL dosing mark to remove extra liquid and any air bubbles. <span class=\"Bold\">See Figure P.</span>\n</dd>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Note:</span> Clean the injection site with an alcohol wipe. Allow the skin to air dry before continuing.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">17. Stretch the skin.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id2018657717\"></a><img alt=\"Figure Q\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-23.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure Q</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt> </dt>\n<dd>Use the z-track injection technique to minimize medicine leakage from the injection site.</dd>\n</dl>\n<dl>\n<dt>•</dt>\n<dd>Firmly drag the skin covering the injection site, displacing it by about an inch (2.5 cm). <span class=\"Bold\">See Figure Q.</span>\n</dd>\n<dt>•</dt>\n<dd>Keep it held in this position for the injection.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">18. Insert the needle.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-1441684898\"></a><img alt=\"Figure R\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-24.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure R</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Insert the needle to its full depth, or deep enough to reach the muscle. <span class=\"Bold\">See Figure R.</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">19. Inject the dose of medicine.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id1042252430\"></a><img alt=\"Figure S\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-25.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure S</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Still holding the skin stretched – slowly press the plunger all the way down. <span class=\"Bold\">See Figure S.</span>\n</dd>\n<dt>•</dt>\n<dd>Ensure the syringe is empty.</dd>\n<dt>•</dt>\n<dd>Withdraw the needle and release the stretched skin immediately.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">20. Assess the injection site.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-554157893\"></a><img alt=\"Figure T\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-26.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure T</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Apply pressure to the injection site using a gauze pad. <span class=\"Bold\">See Figure T.</span>\n</dd>\n<dt>•</dt>\n<dd>A small bandage may be used if bleeding occurs.</dd>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Do not</span> massage the area.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">21. Make the needle safe.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id1486584380\"></a><img alt=\"Figure U\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-27.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure U</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Fold the needle guard over the needle. <span class=\"Bold\">See Figure U.</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id1805812036\"></a><img alt=\"Figure V\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-28.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure V</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Gently apply pressure using a hard surface to lock the needle guard in place.</dd>\n<dt>•</dt>\n<dd>The needle guard will make a click when it locks. <span class=\"Bold\">See Figure V.</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">After injection:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">22. Dispose safely.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id1599445454\"></a><img alt=\"Figure W\" src=\"/dailymed/image.cfm?name=apretude-spl-graphic-29.jpg&amp;setid=4338428e-43d4-4e02-ac9d-bd98e738a7da\"/><p class=\"First\">\n<span class=\"Bold\">Figure W</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Dispose of used needle, syringe, vial, and vial adapter according to local health and safety laws. <span class=\"Bold\">See Figure W.</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Questions and Answers</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>1.</dt>\n<dd>\n<span class=\"Bold\">If the pack has been stored in the refrigerator, is it safe to warm the vial up to room temperature more quickly?</span>\n<br/>The vial should be brought to room temperature before you are ready to give the injection, but make sure the vial does not get above 30°C (86°F).</dd>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Do not</span> use any heating methods, other than using the warmth of your hands.</dd>\n<dt>2.</dt>\n<dd>\n<span class=\"Bold\">How long can APRETUDE be left in the syringe?</span>\n<br/>It is best to inject (room temperature) APRETUDE as soon as possible after drawing it up. However, APRETUDE can remain in the syringe for up to 2 hours before injection.<br/>If the medicine remains in the syringe for more than 2 hours, the filled syringe and needle must be discarded.</dd>\n<dt>3.</dt>\n<dd>\n<span class=\"Bold\">Why do I need to inject air into the vial?</span>\n<br/>Injecting 1 mL of air into the vial makes it easier to draw up the medicine into the syringe. Without the air, some liquid may flow back into the vial unintentionally, leaving less medicine than intended in the syringe.</dd>\n<dt>4.</dt>\n<dd>\n<span class=\"Bold\">Why is the ventrogluteal administration approach recommended?</span>\n<br/>The ventrogluteal approach into the gluteus medius muscle is recommended because it is located away from major nerves and blood vessels. A dorsogluteal approach into the gluteus maximus muscle is acceptable, if preferred by the healthcare professional. The injection should not be administered in any other site.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">Manufactured for:</p>\n<p>ViiV Healthcare</p>\n<p>Durham, NC 27701</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">Trademarks are owned by or licensed to the ViiV Healthcare group of companies.</p>\n<p>©2024 ViiV Healthcare group of companies or its licensor.</p>\n<p>APR:5IFU</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

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Principal Display Panel

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NDC 49702-264-23

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Apretude

{ "type": "p", "children": [], "text": "\nApretude\n" }

(cabotegravir extended-release injectable suspension)

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600 mg/3 mL

{ "type": "p", "children": [], "text": "\n600 mg/3 mL\n" }

(200 mg/mL)

{ "type": "p", "children": [], "text": "\n(200 mg/mL)\n" }

Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n" }

For gluteal intramuscular use only.

{ "type": "p", "children": [], "text": "\nFor gluteal intramuscular use only.\n" }

Healthcare Professional Administration Only.

{ "type": "p", "children": [], "text": "\nHealthcare Professional Administration Only.\n" }

Contents:

{ "type": "p", "children": [], "text": "\nContents:\n" }

1 Single-dose vial

{ "type": "p", "children": [], "text": "\n1 Single-dose vial\n" }

1 Vial adapter

{ "type": "p", "children": [], "text": "\n1 Vial adapter\n" }

1 Syringe

{ "type": "p", "children": [], "text": "\n1 Syringe\n" }

1 Injection needle (23 gauge, 1 ½ inch)

{ "type": "p", "children": [], "text": "\n1 Injection needle (23 gauge, 1 ½ inch)\n" }

Prescribing Information

{ "type": "p", "children": [], "text": "\nPrescribing Information\n" }

Patient Information

{ "type": "p", "children": [], "text": "\nPatient Information\n" }

Instructions for Use

{ "type": "p", "children": [], "text": "\nInstructions for Use\n" }

Ensure vial adapter is used correctly.

{ "type": "p", "children": [], "text": "\nEnsure vial adapter is used correctly.\n" }

ViiV Healthcare

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600 mg/ 3 mL Kit

{ "type": "p", "children": [], "text": "\n600 mg/ 3 mL Kit\n" }

Made in Singapore and Belgium

{ "type": "p", "children": [], "text": "Made in Singapore and Belgium" }

Rev. 2/24

{ "type": "p", "children": [], "text": "Rev. 2/24" }

©2024 ViiV Healthcare group of companies or its licensor.

{ "type": "p", "children": [], "text": "©2024 ViiV Healthcare group of companies or its licensor. " }

62000000092471

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Principal Display Panel

{ "type": "p", "children": [], "text": "\nPrincipal Display Panel\n" }

NDC 49702-280-63

{ "type": "p", "children": [], "text": "\nNDC 49702-280-63\n" }

Apretude

{ "type": "p", "children": [], "text": "\nApretude\n" }

(cabotegravir extended-release injectable suspension)

{ "type": "p", "children": [], "text": "\n(cabotegravir extended-release injectable suspension)\n" }

600 mg/3 mL

{ "type": "p", "children": [], "text": "\n600 mg/3 mL\n" }

(200 mg/mL)

{ "type": "p", "children": [], "text": "\n(200 mg/mL)\n" }

Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n" }

Sample-Not for Sale

{ "type": "p", "children": [], "text": "\nSample-Not for Sale\n" }

For gluteal intramuscular use only.

{ "type": "p", "children": [], "text": "\nFor gluteal intramuscular use only.\n" }

Healthcare Professional Administration Only.

{ "type": "p", "children": [], "text": "\nHealthcare Professional Administration Only.\n" }

Contents:

{ "type": "p", "children": [], "text": "\nContents:\n" }

1 Single-dose vial

{ "type": "p", "children": [], "text": "\n1 Single-dose vial\n" }

1 Vial adapter

{ "type": "p", "children": [], "text": "\n1 Vial adapter\n" }

1 Syringe

{ "type": "p", "children": [], "text": "\n1 Syringe\n" }

1 Injection needle (23 gauge, 1 ½ inch)

{ "type": "p", "children": [], "text": "\n1 Injection needle (23 gauge, 1 ½ inch)\n" }

Prescribing Information

{ "type": "p", "children": [], "text": "\nPrescribing Information\n" }

Patient Information

{ "type": "p", "children": [], "text": "\nPatient Information\n" }

Instructions for Use

{ "type": "p", "children": [], "text": "\nInstructions for Use\n" }

Ensure vial adapter is used correctly.

{ "type": "p", "children": [], "text": "\nEnsure vial adapter is used correctly.\n" }

ViiV Healthcare

{ "type": "p", "children": [], "text": "\nViiV Healthcare\n" }

600 mg/ 3 mL Kit

{ "type": "p", "children": [], "text": "\n600 mg/ 3 mL Kit\n" }

Made in Singapore and Belgium

{ "type": "p", "children": [], "text": "Made in Singapore and Belgium" }

Rev. 5/24

{ "type": "p", "children": [], "text": "Rev. 5/24" }

©2024 ViiV Healthcare group of companies or its licensor.

{ "type": "p", "children": [], "text": "©2024 ViiV Healthcare group of companies or its licensor. " }

62000000094179

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VOCABRIA is indicated in combination with EDURANT (rilpivirine) tablets for short-term treatment of HIV-1 infection in adults and adolescents 12 years of age and older and weighing at least 35 kg who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine, for use as [see Microbiology (12.4), Clinical Studies (14.1)]:

VOCABRIA is indicated for short-term pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating VOCABRIA for HIV-1 PrEP. VOCABRIA may be used as [see Dosage and Administration (2.2), Contraindications (4), Warnings and Precautions (5.1), Clinical Studies (14.2)]:

Oral Lead-In Dosing to Assess Tolerability of Cabotegravir

Consult the prescribing information for CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) before initiating VOCABRIA to ensure therapy with CABENUVA is appropriate. See full prescribing information for CABENUVA.

Oral lead-in may be used to assess the tolerability of cabotegravir prior to the initiation of CABENUVA. The recommended oral lead-in daily dose is one 30-mg tablet of VOCABRIA with one 25-mg tablet of EDURANT for approximately 1 month (at least 28 days). The last oral dose should be taken on the same day injections with CABENUVA are started.

Take VOCABRIA once daily with EDURANT at approximately the same time each day with a meal [see Clinical Pharmacology (12.3)].

Because VOCABRIA is indicated in combination with EDURANT tablets, the prescribing information for EDURANT should also be consulted.

Recommended Oral Dosing to Replace Planned Missed Injections of CABENUVA

Planned Missed Injections for Patients on the Monthly Dosing Schedule: If a patient plans to miss a monthly scheduled injection of CABENUVA by more than 7 days, take daily oral therapy for up to 2 months to replace missed injection visits. For oral therapy with VOCABRIA and EDURANT, the recommended oral daily dose is one 30‑mg tablet of VOCABRIA and one 25-mg tablet of EDURANT. Take VOCABRIA with EDURANT at approximately the same time each day with a meal.

The first dose of oral therapy should be taken 1 month (+/-7 days) after the last injection dose of CABENUVA and continued until the day injection dosing is restarted. For oral therapy with VOCABRIA and EDURANT of durations greater than 2 months, an alternative oral regimen is recommended. See full prescribing information for CABENUVA to resume monthly injection dosing.

Planned Missed Injections for Patients on the Every-2-Month Dosing Schedule: If a patient plans to miss a scheduled every-2-month injection of CABENUVA by more than 7 days, take daily oral therapy for up to 2 months to replace 1 missed scheduled every-2-month injection. For oral therapy with VOCABRIA and EDURANT of durations greater than 2 months, the recommended oral daily dose is one 30-mg tablet of VOCABRIA and one 25-mg tablet of EDURANT. Take VOCABRIA with EDURANT at approximately the same time each day with a meal.

The first dose of oral therapy should be taken approximately 2 months after the last injection dose of CABENUVA and continued until the day injection dosing is restarted. For oral therapy with VOCABRIA and EDURANT of durations greater than 2 months, an alternative oral regimen is recommended. See full prescribing information for CABENUVA to resume every-2-month injection dosing.

HIV-1 Screening for Individuals for HIV-1 Pre-Exposure Prophylaxis

Individuals must be tested for HIV-1 infection prior to initiating VOCABRIA and APRETUDE for HIV-1 PrEP, and with each subsequent injection of APRETUDE, using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection. If an antigen/antibody-specific test is used and provides negative results, then such negative results should be confirmed using an RNA-specific assay, even if the results of the RNA-assay are available after VOCABRIA or APRETUDE administration [see Contraindications (4), Warnings and Precautions (5.1)].

Oral Lead-In Dosing to Assess Tolerability of Cabotegravir for HIV-1 Pre-Exposure Prophylaxis

Consult the prescribing information for APRETUDE before initiating VOCABRIA to ensure use of APRETUDE is appropriate. See full prescribing information for APRETUDE.

Oral lead-in may be used to assess the tolerability of cabotegravir prior to the initiation of APRETUDE. The recommended oral daily dose is one 30-mg tablet of VOCABRIA for approximately 1 month (at least 28 days). Following oral lead-in, start initiation injection of APRETUDE on the last day of oral lead-in or within 3 days.

Oral Dosing to Replace a Planned Missed Injection of APRETUDE (One Every-2-Month Injection)

If an individual plans to miss a scheduled injection of APRETUDE by more than 7 days, take daily oral VOCABRIA to replace one every-2-month injection visit. The recommended oral daily dose is one 30-mg tablet of VOCABRIA. The first dose of oral VOCABRIA should be taken approximately 2 months after the last injection dose of APRETUDE. Restart injection with APRETUDE on the day oral dosing completes or within 3 days. See full prescribing information for APRETUDE to resume every-2-month injection dosing.

Tablets: 30 mg.

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Treatment of HIV-1 Infection

{ "type": "p", "children": [], "text": "\nTreatment of HIV-1 Infection\n" }

VOCABRIA is contraindicated in patients:

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Prior to initiation of VOCABRIA, note that use of CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) with rifabutin is contraindicated.

{ "type": "p", "children": [], "text": "Prior to initiation of VOCABRIA, note that use of CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) with rifabutin is contraindicated." }

Since VOCABRIA is taken in combination with EDURANT tablets, the prescribing information for EDURANT should be consulted for additional contraindications.

{ "type": "p", "children": [], "text": "Since VOCABRIA is taken in combination with EDURANT tablets, the prescribing information for EDURANT should be consulted for additional contraindications." }

HIV-1 Pre-Exposure Prophylaxis

{ "type": "p", "children": [], "text": "\nHIV-1 Pre-Exposure Prophylaxis\n" }

VOCABRIA is contraindicated in individuals:

{ "type": "p", "children": [], "text": "VOCABRIA is contraindicated in individuals:" }

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Use of VOCABRIA for HIV-1 PrEP should be part of a comprehensive prevention strategy including adherence to the dosing schedule and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs). VOCABRIA is not always effective in preventing HIV-1 acquisition [see Clinical Studies (14.2)]. The time from initiation of VOCABRIA for HIV-1 PrEP to maximal protection against HIV-1 infection is unknown.

Risk for HIV-1 acquisition includes behavioral, biological, or epidemiologic factors including, but not limited to, condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high prevalence area or network.

Counsel individuals on the use of other prevention measures (e.g., consistent and correct condom use; knowledge of partner(s)’ HIV-1 status, including viral suppression status; regular testing for STIs that can facilitate HIV-1 transmission). Inform individuals about and support their efforts in reducing sexual risk behavior.

VOCABRIA for HIV-1 PrEP to reduce the risk of acquiring HIV-1 should be used only in individuals confirmed to be HIV-1 negative [see Contraindications (4)]. HIV-1 resistance substitutions may emerge in individuals with undiagnosed HIV-1 infection who are taking only VOCABRIA, because VOCABRIA alone does not constitute a complete regimen for HIV-1 treatment [see Microbiology (12.4)]; therefore, care should be taken to minimize the risk of initiating or continuing VOCABRIA before confirming the individual is HIV-1 negative.

Counsel individuals without HIV-1 to strictly adhere to the recommended dosing schedule for VOCABRIA in order to reduce the risk of HIV-1 acquisition and the potential development of resistance [see Dosage and Administration (2.2), Microbiology (12.4)]. Some individuals, such as adolescents, may benefit from frequent visits and counseling to support adherence to the dosing schedule [see Use in Specific Populations (8.4), Microbiology (12.4), Clinical Studies (14.2)].

Serious or severe hypersensitivity reactions have been reported with cabotegravir and include Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) [see Adverse Reactions (6.2)]. Administration of oral lead-in dosing was used in clinical studies to help identify participants who may be at risk of a hypersensitivity reaction. Remain vigilant and discontinue VOCABRIA if a hypersensitivity reaction is suspected [see Dosage and Administration (2.2), Contraindications (4), Adverse Reactions (6)].

Discontinue VOCABRIA immediately if signs or symptoms of hypersensitivity reactions develop (including, but not limited to, severe rash, or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, mucosal involvement [oral blisters or lesions], conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing). Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated.

Hepatotoxicity has been reported in a limited number of patients receiving cabotegravir with or without known pre-existing hepatic disease or identifiable risk factors [see Adverse Reactions (6.1)].

When VOCABRIA is Used for Treatment HIV-1 Infection

Patients with underlying liver disease or marked elevations in transaminases prior to treatment with VOCABRIA may be at increased risk for worsening or development of transaminase elevations.

Monitoring of liver chemistries is recommended and treatment with VOCABRIA should be discontinued if hepatotoxicity is suspected.

When VOCABRIA is Used for HIV-1 Pre-Exposure Prophylaxis

Clinical and laboratory monitoring should be considered and VOCABRIA should be discontinued if hepatotoxicity is suspected, and individuals managed as clinically indicated.

When VOCABRIA is Used for Treatment HIV-1 Infection

Depressive disorders (including depressed mood, depression, mood altered, mood swings, suicidal ideation/suicide attempt) have been reported with VOCABRIA when used with EDURANT for treatment of HIV-1 infection [see Adverse Reactions (6.1)]. Promptly evaluate patients with depressive symptoms to assess whether the symptoms are related to VOCABRIA and to determine whether the risks of continued therapy outweigh the benefits.

When VOCABRIA is Used for HIV-1 Pre-Exposure Prophylaxis

Depressive disorders (including depression, depressed mood, persistent depressive disorder, suicidal ideation/suicide attempt) have been reported with VOCABRIA [see Adverse Reactions (6.1)]. Promptly evaluate individuals with depressive symptoms to assess whether the symptoms are related to VOCABRIA and to determine whether the risks of continued therapy outweigh the benefits.

The concomitant use of VOCABRIA and other drugs may result in known or potentially significant drug interactions, some of which may lead to adverse events, loss of efficacy from VOCABRIA when used for treatment of HIV-1 infection or HIV-1 PrEP, and possible development of viral resistance [see Contraindications (4), Drug Interactions (7.2, 7.3)].

See Table 1 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during use of VOCABRIA; review concomitant medications during use of VOCABRIA [see Drug Interactions (7.3)].

VOCABRIA is indicated for use in combination with EDURANT (rilpivirine) for treatment of HIV-1 infection [see Indications and Usage (1.1), Dosage and Administration (2.1)]. Review the prescribing information for EDURANT for information on rilpivirine prior to initiation of VOCABRIA in combination with EDURANT.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect rates observed in practice. See full prescribing information for CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) for additional safety information. Since VOCABRIA is taken in combination with EDURANT tablets, the prescribing information for EDURANT (rilpivirine) should be consulted for relevant information on rilpivirine.

Adverse Reactions of VOCABRIA in Clinical Trials for the Treatment of HIV-1 Infection

Clinical Trials Experience in Adults: The safety assessment of VOCABRIA for oral lead-in therapy prior to therapy with CABENUVA is based on the analysis of 48-week data from virologically suppressed participants with HIV-1 infection in 3 international, multicenter, open-label trials, where 590 of 1,182 participants received oral lead-in within the pivotal trials FLAIR and ATLAS (pooled analysis) and 655 of 1,045 participants received oral lead-in within ATLAS-2M [see Clinical Studies (14.1)].

Adverse reactions were reported following exposure to VOCABRIA tablets and EDURANT tablets administered in combination as oral lead-in therapy (median time exposure: 5.3 weeks). Adverse reactions included those attributable to the oral formulation of cabotegravir and rilpivirine administered as a combination regimen. Refer to the prescribing information for EDURANT for other adverse reactions associated with oral rilpivirine.

The most common adverse reactions during the oral lead-in period in the pooled analyses of FLAIR and ATLAS at Week 48 were headache, nausea, abnormal dreams, anxiety, and insomnia, all of which occurred in at least 3 participants with an incidence ≤1%. The most common adverse reactions during the oral lead-in period for ATLAS-2M were fatigue, diarrhea, headache, nausea, dizziness, abdominal discomfort, abdominal distension, insomnia, and asthenia, all of which occurred in at least 3 participants across both arms, with an incidence ≤2%.

During the oral lead-in period for FLAIR and ATLAS, 6 (1%) participants discontinued due to adverse events, including asthenia, myalgia, depression suicidal, and headache. During the oral lead-in period for ATLAS-2M, 4 (<1%) participants discontinued due to adverse events, including asthenia, skin lesion, fatigue, transaminases increased, and depression.

In the extension phase of the FLAIR study at Week 124, the overall safety profile was consistent with that observed at Week 48 and when injection therapy with CABENUVA was initiated directly without the oral lead-in phase.

Clinical Trial Experience in Adolescents: Based on data from the Week 24 analysis of the MOCHA study in 144 adolescents (aged 12 to younger than 18 years and weighing ≥35 kg), the safety profile of oral cabotegravir and oral rilpivirine administered in combination during the oral lead-in period in adolescents was consistent with the safety profile established with cabotegravir plus rilpivirine in adults.

Adverse Reactions of VOCABRIA in Clinical Trials for HIV-1 Pre-Exposure Prophylaxis

Clinical Trial Experience in Adults: In trial HPTN 083, adverse reactions were reported while participants were on blinded study product following exposure to VOCABRIA tablets as oral lead-in for HIV-1 PrEP (median time exposure: 4.1 weeks). The most common adverse reactions reported at ≥1% during the oral lead-in period were diarrhea (4% and 4%), nausea (3% and 5%), dizziness (2% and 2%), headache (2% and 2%), fatigue (1% and 2%), and abnormal dreams (1% and 2%) for VOCABRIA and TRUVADA (emtricitabine and tenofovir disoproxil fumarate), respectively. During the oral lead-in period, 24 (1%) participants receiving VOCABRIA discontinued due to adverse events, including increased alanine aminotransferase, increased aspartate aminotransferase, suicide attempt, and dizziness, which were observed in ≥2 participants.

In Trial HPTN 084, adverse reactions were reported while participants were on blinded study product following exposure to VOCABRIA tablets as oral lead-in for HIV-1 PrEP (median time exposure: 4.1 weeks). The most common adverse reactions reported at ≥1% during the oral lead-in period were headache (6% and 7%), nausea (3% and 7%), dizziness (3% and 4%), diarrhea (2% and 4%), upper respiratory tract infection (2% and 2%), somnolence (2% and 1%), fatigue (1% and 2%), abdominal pain (1% and 1%), vomiting (<1% and 3%), decreased appetite (<1% and 2%), and pruritus (<1% and 1%) for VOCABRIA and TRUVADA, respectively. During the oral lead-in period, 4 (<1%) participants receiving VOCABRIA discontinued due to adverse events of increased alanine aminotransferase (n = 3) and sleep disorders (n = 1).

Clinical Trials Experience in Adolescents: In adolescents receiving VOCABRIA for HIV-1 PrEP, the safety data were comparable to the safety data reported in adults receiving VOCABRIA for HIV-1 PrEP [see Use in Specific Populations (8.4)].

Less Common Adverse Reactions

The following select adverse reactions (regardless of severity) occurred in <1% of participants receiving VOCABRIA in clinical trials for the treatment of HIV-1 infection or for HIV-1 PrEP.

Psychiatric Disorders: Suicidal ideation, and suicide attempt (these events were observed primarily in participants with a pre‑existing history of depression or other psychiatric illness).

The following adverse reactions have been identified during postmarketing use of VOCABRIA or cabotegravir-containing regimens. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders

Hypersensitivity reactions (including angioedema and urticaria) [see Warnings and Precautions (5.2)].

Skin and Subcutaneous Tissue Disorders

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) [see Warnings and Precautions (5.2)].

VOCABRIA in combination with EDURANT (rilpivirine) is a complete regimen for the treatment of HIV-1 infection. Refer to the prescribing information for EDURANT for relevant information on rilpivirine.

Coadministration of VOCABRIA with other antiretroviral medications for PrEP is not recommended [see Drug Interactions (7.4), Clinical Pharmacology (12.3)].

Prior to initiating dosing with VOCABRIA, the prescribing information for CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) or APRETUDE should be consulted to ensure use of CABENUVA or APRETUDE will be appropriate for either the treatment of HIV-1 infection or HIV-1 PrEP, respectively.

Cabotegravir is primarily metabolized by UGT1A1 with some contribution from UGT1A9. Drugs that are strong inducers of UGT1A1 or UGT1A9 are expected to decrease cabotegravir plasma concentrations and may result in loss of efficacy; therefore, coadministration of VOCABRIA with these drugs is contraindicated [see Contraindications (4)].

Coadministration of oral cabotegravir with polyvalent cation-containing products may lead to decreased absorption of cabotegravir [see Drug Interactions (7.3)].

Information regarding potential drug interactions with cabotegravir are provided in Table 1. These recommendations are based on either drug interaction trials or predicted interactions due to the expected magnitude of the interaction and potential for loss of efficacy [see Contraindications (4), Warnings and Precautions (5.5), Clinical Pharmacology (12.3)]. Table 1 includes potentially significant interactions but is not all inclusive.

Refer to the prescribing information for EDURANT (rilpivirine) for established or potentially significant interactions that should be considered during concomitant administration of VOCABRIA and EDURANT for HIV-1 treatment.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1. Drug Interactions with VOCABRIA</span> </caption> <col width="31%"/> <col width="26%"/> <col width="43%"/> <tfoot> <tr class="First"> <td align="left" colspan="3" valign="top">↓ = Decrease; PrEP = Pre-exposure prophylaxis.</td> </tr> <tr class="Last"> <td align="left" colspan="3" valign="top"><span class="Sup">a</span> Rifabutin can be coadministered with cabotegravir; however, it is contraindicated with CABENUVA for HIV-1 treatment. Dosage modification is recommended with APRETUDE for HIV-1 PrEP.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Concomitant Drug Class: </span> </p> <p> <span class="Bold">Drug Name</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Effect on Concentration</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Clinical Comment</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Antacids </span>containing polyvalent cations (e.g., aluminum or magnesium hydroxide, calcium carbonate)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">↓Cabotegravir</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">Administer antacid products at least 2 hours before or 4 hours after taking VOCABRIA.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Anticonvulsants:</span> </p> <p>Carbamazepine </p> <p>Oxcarbazepine</p> <p>Phenobarbital</p> <p>Phenytoin</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">↓Cabotegravir</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Coadministration is contraindicated with VOCABRIA due to potential for loss of efficacy and development of resistance <span class="Italics">[see Contraindications (<a href="#ID_ebed8212-ac53-4117-8d63-0ffb552a19e6">4</a>)]</span>. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Antimycobacterials<span class="Sup">a</span>:</span> </p> <p>Rifampin</p> <p>Rifapentine</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">↓Cabotegravir</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Antimycobacterial:</span> </p> <p>Rifabutin</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">↓Cabotegravir</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">Dose modification is not required for VOCABRIA. Dose modification is recommended for APRETUDE for HIV-1 PrEP. Coadministration is contraindicated with CABENUVA for HIV-1 treatment.</p> </td> </tr> </tbody> </table></div>

Based on drug interaction study results, the following drugs can be coadministered with cabotegravir without a dose adjustment: etravirine, midazolam, oral contraceptives containing levonorgestrel and ethinyl estradiol, rifabutin, and rilpivirine [see Clinical Pharmacology (12.3)].

Prior to initiating oral therapy, note that use of CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) with rifabutin is contraindicated for the treatment of HIV-1 infection. Dosage modification is recommended when APRETUDE is used with rifabutin for HIV-1 PrEP.

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to VOCABRIA during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.

Risk Summary

There are insufficient human data on the use of VOCABRIA during pregnancy to adequately assess a drug-associated risk of birth defects and miscarriage. Discuss the benefit-risk of using VOCABRIA with individuals of childbearing potential or during pregnancy.

The APR has been established to monitor for birth defects following prenatal exposure to antiretrovirals. The rate of miscarriage is not reported in the APR. The background risk for major birth defects and miscarriage for the indicated population is unknown. The background rate for major birth defects in a United States (U.S.) reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) is 2.7%. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15% to 20%. The APR uses the MACDP as the U.S. reference population for birth defects in the general population. The MACDP evaluates mothers and infants from a limited geographic area and does not include outcomes for births that occurred at <20 weeks’ gestation.

In animal reproduction studies with oral cabotegravir, a delay in the onset of parturition and increased stillbirths and neonatal deaths were observed in a rat pre- and postnatal development study at >28 times the exposure at the recommended human dose (RHD). No evidence of adverse developmental outcomes was observed with oral cabotegravir in rats or rabbits (>28 times or similar to the exposure at the RHD, respectively) given during organogenesis (see Data).

Data

Animal Data: Cabotegravir was administered orally to pregnant rats at 0, 0.5, 5, or 1,000 mg/kg/day from 15 days before cohabitation, during cohabitation, and from Gestation Days 0 to 17. There were no effects on fetal viability when fetuses were delivered by caesarean, although a minor decrease in fetal body weight was observed at 1,000 mg/kg/day (>28 times the exposure in humans at the RHD). No drug-related fetal toxicities were observed at 5 mg/kg/day (approximately 13 times the exposure in humans at the RHD), and no drug-related fetal malformations were observed at any dose.

Cabotegravir was administered orally to pregnant rabbits at 0, 30, 500, or 2,000 mg/kg/day from Gestation Days 7 to 19. No drug-related fetal toxicities were observed at 2,000 mg/kg/day (approximately 0.7 times the exposure in humans at the RHD).

In a rat pre- and postnatal development study, cabotegravir was administered orally to pregnant rats at 0, 0.5, 5, or 1,000 mg/kg/day from Gestation Day 6 to Lactation Day 21. A delay in the onset of parturition and increases in the number of stillbirths and neonatal deaths by Lactation Day 4 were observed at 1,000 mg/kg/day (>28 times the exposure in humans at the RHD); there were no alterations to growth and development of surviving offspring. In a cross-fostering study, similar incidences of stillbirths and early postnatal deaths were observed when rat pups born to cabotegravir-treated mothers were nursed from birth by control mothers. There was no effect on neonatal survival of control pups nursed from birth by cabotegravir-treated mothers. A lower dose of 5 mg/kg/day (13 times the exposure at the RHD) was not associated with delayed parturition or neonatal mortality in rats. Studies in pregnant rats showed that cabotegravir crosses the placenta and can be detected in fetal tissue.

Risk Summary

There are no data on the presence of cabotegravir in human milk, the effects on the breastfed infant, or the effects on milk production. Cabotegravir is present in animal milk (see Data). When a drug is present in animal milk, it is likely that the drug will be present in human milk. Potential risks of breastfeeding include: (1) HIV-1 transmission (in HIV-1–negative infants), (2) developing viral resistance (in HIV-1–positive infants), and (3) adverse reactions in a breastfed infant similar to those seen in adults.

In mothers without HIV-1, breastfeeding should only be considered if the expected benefit justifies the potential risk to the infant, including the potential risk for adverse reaction in the breastfed child, along with the risk of HIV-1 acquisition due to nonadherence and subsequent vertical transmission to the child. Breastfeeding is not recommended if acute HIV-1 infection is suspected to avoid the risk of postnatal transmission of HIV-1 infection.

Data

Animal lactation studies with cabotegravir have not been conducted. However, cabotegravir was detected in the plasma of nursing pups on Lactation Day 10 in the rat pre- and postnatal development study.

Treatment of HIV-1 Infection

The safety and effectiveness of VOCABRIA have been established in adolescents aged 12 to younger than 18 years and weighing at least 35 kg, which is supported by the following:

The safety and efficacy of VOCABRIA in adolescents (aged 12 to younger than 18 years and weighing at least 35 kg) were similar to that in adults and there was no clinically significant change in drug exposure [see Adverse Reactions (6.1), Clinical Pharmacology (12.3)].

Please refer to the CABENUVA prescribing information for additional information.

The safety, efficacy, and pharmacokinetics of VOCABRIA have not been established in pediatric patients younger than 12 years of age or weighing <35 kg.

HIV-1 Pre-Exposure Prophylaxis

The safety and effectiveness of VOCABRIA for HIV-1 PrEP in adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition is supported by data from 2 adequate and well-controlled trials of VOCABRIA for HIV-1 PrEP in adults with additional safety and pharmacokinetic data from studies in adults with HIV-1 who were administered CABENUVA and in adolescent participants with HIV-1 who were administered separate components of CABENUVA in addition to their current antiretroviral therapy [see Dosage and Administration (2.2), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.2)].

APRETUDE for HIV-1 PrEP was evaluated in 2 open-label multicenter clinical trials, HPTN 083-01 and HPTN 084-01, in adolescent individuals 12 to less than 18 years of age weighing at least 35 kg who are at risk for HIV-1 acquisition. Sixty-four adolescents were enrolled. Of these, 62 adolescent participants received one or more injections after receiving VOCABRIA. In adolescents receiving VOCABRIA and APRETUDE for HIV-1 PrEP, the safety data were comparable to the safety data reported in adults receiving APRETUDE for HIV-1 PrEP.

While using APRETUDE, HIV-1 testing should be conducted prior to initiating APRETUDE (with or without an oral lead-in with oral cabotegravir) and prior to each injection of APRETUDE. Adolescents may benefit from more frequent visits and counseling to support adherence to the dosing schedule [see Dosage and Administration (2.2), Warnings and Precautions (5.1)].

The safety, efficacy, and pharmacokinetics of VOCABRIA in pediatric participants younger than 12 years of age or weighing <35 kg have not been established.

Clinical trials of VOCABRIA did not include sufficient numbers of participants aged 65 years and older to determine whether they respond differently from younger participants. In general, caution should be exercised in administration of VOCABRIA in elderly patients, reflecting greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy [see Clinical Pharmacology (12.3)].

No dosage adjustment of VOCABRIA is necessary for patients with mild to moderate (creatinine clearance equal to 30 mL/min to <90 mL/min) or severe renal impairment (creatinine clearance equal to 15 mL/min to <30 mL/min) [see Clinical Pharmacology (12.3)]. The effect of end-stage renal disease (creatinine clearance <15 mL/min) on the pharmacokinetics of cabotegravir is unknown. As cabotegravir is >99% protein bound, dialysis is not expected to alter exposures of cabotegravir.

Since VOCABRIA is taken in combination with EDURANT for the treatment of HIV-1 infection, the prescribing information for EDURANT should be consulted for additional recommendations in patients with severe impairment or end-stage renal disease.

No dosage adjustment of VOCABRIA is necessary for patients with mild or moderate hepatic impairment (Child-Pugh A or B). The effect of severe hepatic impairment (Child-Pugh C) on the pharmacokinetics of cabotegravir is unknown [see Clinical Pharmacology (12.3)].

There is no known specific treatment for overdose with VOCABRIA. If overdose occurs, monitor the patient and apply standard supportive treatment as required as well as observation of the clinical status of the individual. As cabotegravir is highly bound to plasma proteins, it is unlikely that it will be significantly removed by dialysis.

{ "type": "p", "children": [], "text": "There is no known specific treatment for overdose with VOCABRIA. If overdose occurs, monitor the patient and apply standard supportive treatment as required as well as observation of the clinical status of the individual. As cabotegravir is highly bound to plasma proteins, it is unlikely that it will be significantly removed by dialysis." }

VOCABRIA contains cabotegravir, as cabotegravir sodium, an HIV integrase strand transfer inhibitor (INSTI). The chemical name of cabotegravir sodium is sodium (3S,11aR)-N-[(2,4-difluorophenyl)methyl]-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido [1,2-d]pyrazine-8-carboxamide. The empirical formula is C19H16F2N3NaO5 and the molecular weight is 427.34 g/mol. It has the following structural formula:

{ "type": "p", "children": [], "text": "VOCABRIA contains cabotegravir, as cabotegravir sodium, an HIV integrase strand transfer inhibitor (INSTI). The chemical name of cabotegravir sodium is sodium (3S,11aR)-N-[(2,4-difluorophenyl)methyl]-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido [1,2-d]pyrazine-8-carboxamide. The empirical formula is C19H16F2N3NaO5 and the molecular weight is 427.34 g/mol. It has the following structural formula:" }

Cabotegravir sodium is a white to almost white crystalline solid that is slightly soluble in water.

{ "type": "p", "children": [], "text": "Cabotegravir sodium is a white to almost white crystalline solid that is slightly soluble in water. " }

Each immediate-release film-coated tablet of VOCABRIA for oral administration contains 30 mg of cabotegravir (equivalent to 31.62 mg cabotegravir sodium) and the inactive ingredients: hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The tablet film-coating contains hypromellose, polyethylene glycol, and titanium dioxide.

{ "type": "p", "children": [], "text": "Each immediate-release film-coated tablet of VOCABRIA for oral administration contains 30 mg of cabotegravir (equivalent to 31.62 mg cabotegravir sodium) and the inactive ingredients: hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The tablet film-coating contains hypromellose, polyethylene glycol, and titanium dioxide." }

Cabotegravir is an HIV-1 antiretroviral drug [see Microbiology (12.4)].

Cardiac Electrophysiology

At a dose of cabotegravir 150 mg orally every 12 hours (10 times the recommended total daily oral lead-in dosage of VOCABRIA), the QT interval is not prolonged to any clinically relevant extent. Administration of 3 doses of cabotegravir 150 mg orally every 12 hours resulted in a geometric mean Cmax approximately 2.8-fold above the geometric mean steady-state Cmax associated with the recommended 30-mg dose of oral cabotegravir.

For additional QT information related to the injectable formulations of cabotegravir and rilpivirine (CABENUVA), the injectable formulation of cabotegravir (APRETUDE), and the oral formulation of rilpivirine (EDURANT), refer to the prescribing information for CABENUVA, APRETUDE, and EDURANT.

Absorption, Distribution, and Elimination

The pharmacokinetic properties of cabotegravir are provided in Table 2. The multiple-dose pharmacokinetic parameters are provided in Table 3.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 2. Pharmacokinetic Properties of Cabotegravir</span> </caption> <col width="66%"/> <col width="34%"/> <tfoot> <tr class="First"> <td align="left" colspan="2" valign="top">CSF = Cerebrospinal fluid.</td> </tr> <tr> <td align="left" colspan="2" valign="top"><span class="Sup">a</span> Geometric mean ratio (fed/fasted) in pharmacokinetic parameters and 90% confidence interval. High‑calorie/high-fat meal = 870 kcal, 53% fat. </td> </tr> <tr class="Last"> <td align="left" colspan="2" valign="top"><span class="Sup">b</span> Dosing in mass balance studies: single-dose oral administration of [<span class="Sup">14</span>C] cabotegravir.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Toprule" valign="top"> <p class="First"> <span class="Bold">Absorption</span> </p> </td><td class="Botrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">T<span class="Sub">max</span> (h), median</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Effect of high-fat meal (relative to fasting): </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.14</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">AUC<span class="Sub">(0-inf)</span> ratio<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(1.02, 1.28)</p> </td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First"> <span class="Bold">Distribution</span> </p> </td><td class="Botrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">% Bound to human plasma proteins</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&gt;99.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Blood-to-plasma ratio</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.52</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">CSF-to-plasma concentration ratio (median [range])<span class="Sup">b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.003</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.002 to 0.004)</p> </td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First"> <span class="Bold">Elimination</span> </p> </td><td class="Botrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">t<span class="Sub">1/2</span> (h), mean</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">41</p> </td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First"> <span class="Italics">Metabolism</span> </p> </td><td class="Botrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">     Metabolic pathways</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">UGT1A1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">UGT1A9 (minor)</p> </td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First"> <span class="Italics">Excretion</span> </p> </td><td class="Botrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Major route of elimination</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">Metabolism</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     % of dose excreted as total <span class="Sup">14</span>C (unchanged drug) in urine<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">27 (0)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     % of dose excreted as total <span class="Sup">14</span>C (unchanged drug) in feces<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">59 (47)</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 3. Multiple-Dose Pharmacokinetic Parameters of Oral Cabotegravir in Adults</span> </caption> <col width="45%"/> <col width="55%"/> <tfoot> <tr class="First"> <td align="left" colspan="2" valign="top"><span class="Sup">a</span> Pharmacokinetic parameter values were based on individual post-hoc estimates from the final population pharmacokinetic model for participants receiving 30 mg of oral cabotegravir once daily in FLAIR and ATLAS trials.</td> </tr> <tr class="Last"> <td align="left" colspan="2" valign="top"><span class="Sup">b</span> tau is dosing interval: 24 hours for oral cabotegravir.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Parameter </span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Geometric Mean (5<span class="Sup">th</span>, 95<span class="Sup">th</span> Percentile)<span class="Sup">a</span></span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">C<span class="Sub">max</span> (mcg/mL)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">8.0 (5.3, 11.9)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">AUC<span class="Sub">(0-tau)</span> (mcg•h/mL)<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">145 (93.5, 224)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">C<span class="Sub">tau</span> (mcg/mL)<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4.6 (2.8, 7.5)</p> </td> </tr> </tbody> </table></div>

Specific Populations

No clinically significant differences in the pharmacokinetics of cabotegravir were observed based on age, sex, race/ethnicity, body mass index, or UGT1A1 polymorphisms. The effect of hepatitis B and C virus co-infection on the pharmacokinetics of cabotegravir is unknown.

Renal Impairment: No clinically significant differences in the pharmacokinetics of cabotegravir are expected with mild, moderate, or severe renal impairment. Cabotegravir has not been studied in patients with end-stage renal disease not on dialysis. As cabotegravir is >99% protein bound, dialysis is not expected to alter exposures of cabotegravir [see Use in Specific Populations (8.6)].

Hepatic Impairment: No clinically significant differences in the pharmacokinetics of cabotegravir are expected in mild to moderate (Child-Pugh A or B) hepatic impairment. The effect of severe hepatic impairment (Child-Pugh C) on the pharmacokinetics of cabotegravir has not been studied [see Use in Specific Populations (8.7)].

Gender: Population pharmacokinetic analyses revealed no clinically relevant effect of gender on the exposure of cabotegravir. In addition, no clinically relevant differences in plasma cabotegravir concentrations were observed in PrEP studies by gender, including cisgender men and transgender women (+/-hormone use). Therefore, no dose adjustment is necessary based on gender.

Geriatric Patients: No dose adjustment is required in elderly individuals. There are limited data available on the use of cabotegravir in individuals aged 65 years and older. In general, caution should be exercised in administration of cabotegravir in elderly individuals, reflecting greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy [see Use in Specific Populations (8.5)].

Pediatric Patients: Population pharmacokinetic analyses revealed no clinically relevant differences in exposure between adolescent participants (weighing ≥35 kg) and adult participants with and without HIV-1 from the cabotegravir development program; therefore, no dosage adjustment is needed for adolescents weighing ≥35 kg (Table 4).

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 4. Pharmacokinetic Parameters following Once-Daily Oral Cabotegravir in Adolescents Aged 12 to Younger than 18 Years (≥35 kg)</span> </caption> <col width="45%"/> <col width="55%"/> <tfoot> <tr class="First"> <td align="left" colspan="2" valign="top"><span class="Sup">a</span> Pharmacokinetic parameter values were based on individual post-hoc estimates from population pharmacokinetic models in both adolescents with HIV-1 (n = 147) weighing 35.2 to 98.5 kg and adolescents without HIV-1 (n = 62) weighing 39.9 to 167 kg.</td> </tr> <tr class="Last"> <td align="left" colspan="2" valign="top"><span class="Sup">b</span> tau is dosing interval: 24 hours for oral administration.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Parameter </span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Geometric Mean (5<span class="Sup">th</span>, 95<span class="Sup">th</span> Percentile)<span class="Sup">a</span></span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">C<span class="Sub">max</span> (mcg/mL)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">10.7 (7.36, 16.6)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">AUC<span class="Sub">(0-tau)</span> (mcg•h/mL)<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">203 (136, 320)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">C<span class="Sub">tau</span> (mcg/mL)<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">6.43 (4.15, 10.5)</p> </td> </tr> </tbody> </table></div>

Drug Interaction Studies

Cabotegravir is not a clinically relevant inhibitor of the following enzymes and transporters: cytochrome P450 (CYP)1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4; UGT1A1, 1A3, 1A4, 1A6, 1A9, 2B4, 2B7, 2B15, and 2B17; P-glycoprotein (P-gp); breast cancer resistance protein (BCRP); bile salt export pump (BSEP); organic cation transporter (OCT)1, OCT2; organic anion transporter polypeptide (OATP)1B1, OATP1B3; multidrug and toxin extrusion transporter (MATE) 1, MATE 2-K; and multidrug resistance protein (MRP)2 or MRP4.

In vitro, cabotegravir inhibited renal OAT1 (IC50 = 0.81 microM) and OAT3 (IC50 = 0.41 microM). Based on physiologically based pharmacokinetic (PBPK) modeling, cabotegravir may increase the AUC of OAT1/3 substrates up to approximately 80%.

In vitro, cabotegravir did not induce CYP1A2, CYP2B6, or CYP3A4.

Simulations using PBPK modeling show that no clinically significant interaction is expected during coadministration of cabotegravir with drugs that inhibit UGT1A1.

In vitro, cabotegravir was not a substrate of OATP1B1, OATP1B3, OATP2B1, or OCT1.

Cabotegravir is a substrate of P-gp and BCRP in vitro; however, because of its high permeability, no alteration in cabotegravir absorption is expected with coadministration of P-gp or BCRP inhibitors.

The effects of coadministered drugs on the exposure of cabotegravir are summarized in Table 5, and the effects of cabotegravir on the exposure of coadministered drugs are summarized in Table 6.

<div class="scrollingtable"><table cellpadding="5.75pt" width="100%"> <caption> <span>Table 5. Effect of Coadministered Drugs on the Pharmacokinetics of Cabotegravir</span> </caption> <col width="25%"/> <col width="16%"/> <col width="5%"/> <col width="25%"/> <col width="16%"/> <col width="14%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="6" valign="top">n = Maximum number of participants with data, CI = Confidence Interval.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Coadministered Drug(s) and Dose(s)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Dose of Cabotegravir</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">n</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="bottom"> <p class="First"> <span class="Bold">Geometric Mean Ratio (90% CI) of Cabotegravir Pharmacokinetic Parameters with/without Coadministered Drugs</span> </p> <p> <span class="Bold">No Effect = 1.00</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">C<span class="Sub">max</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">AUC</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">C<span class="Sub">tau</span> or C<span class="Sub">24</span></span> </p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Etravirine </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30 mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">12</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.04</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.01</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.00</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">      200 mg twice daily</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">once daily</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.99, 1.09)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.96, 1.06)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.94, 1.06)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Rifabutin </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30 mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">12</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.83</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.79</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.74</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">      300 mg once daily</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">once daily</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.76, 0.90)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.74, 0.83)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.70, 0.78)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Rifampin </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30-mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">15</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.94</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.41</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.50</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">      600 mg once daily</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">single dose</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.87, 1.02)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.36, 0.46)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.44, 0.57)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Rilpivirine </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30 mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">11</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.05</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.12</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.14</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">      25 mg once daily</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">once daily</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.96, 1.15)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(1.05, 1.19)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(1.04, 1.24)</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table cellpadding="5.75pt" width="100%"> <caption> <span>Table 6. Effect of Cabotegravir on the Pharmacokinetics of Coadministered Drugs</span> </caption> <col width="25%"/> <col width="16%"/> <col width="5%"/> <col width="25%"/> <col width="16%"/> <col width="14%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="6" valign="top">n = Maximum number of participants with data, CI = Confidence Interval, NA = Not available.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Coadministered Drug(s) and Dose(s)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Dose of Cabotegravir</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">n</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="bottom"> <p class="First"> <span class="Bold">Geometric Mean Ratio (90% CI) of Pharmacokinetic Parameters of Coadministered Drug with/without Cabotegravir</span> </p> <p> <span class="Bold">No Effect = 1.00</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">C<span class="Sub">max</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">AUC</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">C<span class="Sub">tau</span> or C<span class="Sub">24</span></span> </p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Ethinyl estradiol</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30 mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">19</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.92</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.02</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.00</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">      0.03 mg once daily</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">once daily</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.83, 1.03)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.97, 1.08)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.92, 1.10)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Levonorgestrel</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30 mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">19</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.05</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.12</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.07</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">      0.15 mg once daily</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">once daily</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.96, 1.15)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(1.07, 1.18)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(1.01, 1.15)</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Midazolam </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30 mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">12</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.09</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">1.10</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">NA</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">      3 mg</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">once daily</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.94, 1.26)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.95, 1.26)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Rilpivirine</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">30 mg</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">11</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.96</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.99</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.92</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">      25 mg once daily</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">once daily</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.85, 1.09)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.89, 1.09)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(0.79, 1.07)</p> </td> </tr> </tbody> </table></div>

Mechanism of Action

Cabotegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration that is essential for the HIV replication cycle. The mean 50% inhibitory concentration (IC50) value of cabotegravir in a strand transfer assay using purified recombinant HIV-1 integrase was 3.0 nM.

Antiviral Activity in Cell Culture

Cabotegravir exhibited antiviral activity against laboratory strains of HIV-1 (subtype B, n = 4) with mean 50 percent effective concentration (EC50) values of 0.22 to 1.7 nM in peripheral blood mononuclear cells (PBMCs) and 293 cells. Cabotegravir demonstrated antiviral activity in PBMCs against a panel of 24 HIV-1 clinical isolates (3 in each of group M subtypes A, B, C, D, E, F, and G and 3 in group O) with a median EC50 value of 0.19 nM (range: 0.02 to 1.06 nM, n = 24). The median EC50 value against subtype B clinical isolates was 0.05 nM (range: 0.02 to 0.50 nM, n = 3). Against clinical HIV-2 isolates, the median EC50 value was 0.12 nM (range: 0.10 to 0.14 nM, n = 3).

In cell culture, cabotegravir was not antagonistic in combination with the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine, or the nucleoside reverse transcriptase inhibitors (NRTIs) emtricitabine (FTC), lamivudine (3TC), or tenofovir disoproxil fumarate (TDF).

Resistance

Cell Culture: Cabotegravir-resistant viruses were selected during passage of HIV-1 strain IIIB in MT-2 cells in the presence of cabotegravir. Amino acid substitutions in integrase that emerged and conferred decreased susceptibility to cabotegravir included Q146L (fold change: 1.3 to 4.6), S153Y (fold change: 2.8 to 8.4), and I162M (fold change: 2.8). The integrase substitution T124A also emerged alone (fold change: 1.1 to 7.4 in cabotegravir susceptibility), in combination with S153Y (fold change: 3.6 to 6.6 in cabotegravir susceptibility) or I162M (2.8-fold change in cabotegravir susceptibility). Cell culture passage of virus harboring integrase substitutions Q148H, Q148K, or Q148R selected for additional substitutions (C56S, V72I, L74M, V75A, T122N, E138K, G140S, G149A, and M154I), with substituted viruses having reduced susceptibility to cabotegravir of 2.0- to 410-fold change. The combinations of E138K+Q148K and V72I+E138K+Q148K conferred the greatest reductions of 53- to 260-fold change and 410-fold change, respectively.

Clinical Trials: Treatment of HIV-1 Infection: In the pooled Phase 3 FLAIR (Week 124) and ATLAS (Week 96) analysis, there were 8 confirmed virologic failures (2 consecutive HIV-1 RNA ≥200 copies/mL) on cabotegravir plus rilpivirine (8/591, 1.4%) and 8 confirmed virologic failures on current antiretroviral regimen (8/591, 1.4%). Of the 8 confirmed virologic failures in the cabotegravir plus rilpivirine arm, 7 (88%) had treatment-emergent NNRTI resistance-associated substitutions K101E, V106V/A, V108I, E138A, E138G, E138K, H221H/L, or M230L in reverse transcriptase, and 6 of them showed reduced phenotypic susceptibility to rilpivirine (range: 2- to 27-fold). One additional participant in the ATLAS Extension Switch on cabotegravir plus rilpivirine had emergent NNRTI resistance substitution E138A at Week 80 with HIV-1 RNA >50 copies/mL and <200 copies/mL.

Additionally, 5 of the 8 (63%) cabotegravir plus rilpivirine confirmed virologic failures had treatment-emergent INSTI resistance-associated substitutions and reduced phenotypic susceptibility to cabotegravir: Q148R (n = 2; 5- and 9-fold decreased susceptibility to cabotegravir), G140R (n = 1; 7-fold decreased susceptibility to cabotegravir), N155H (n = 1; 3-fold decreased susceptibility to cabotegravir), or N155H+R263K (n = 1; 9-fold decreased susceptibility to cabotegravir).

There was another confirmed virologic failure participant at Week 112 in FLAIR who had switched to cabotegravir plus rilpivirine direct to injection at Week 100; there were no INSTI resistance-associated substitutions detected at failure.

In comparison, in the current antiretroviral regimen arm with 8 confirmed virologic failures, 2 of 7 (29%) who had post‑baseline resistance data had treatment-emergent resistance substitutions and phenotypic resistance to their antiretroviral drugs; both had treatment-emergent NRTI substitutions, M184V or I, which conferred resistance to emtricitabine or lamivudine in their regimen, and one of them also had the treatment-emergent NNRTI resistance substitution G190S, which conferred resistance to efavirenz in their regimen.

In the ATLAS-2M trial, there were 11 confirmed virologic failures (2 consecutive HIV-1 RNA ≥200 copies/mL) through Week 48: 9 participants (1.7%) in the every-2-month treatment arm and 2 participants (0.4%) in the monthly treatment arm. Of note, 8 of the 11 (73%) participants met confirmed virologic failure criteria at or before the Week 24 injection visit.

Four of the 9 confirmed virologic failure participants in the every-2-month arm transitioned from the oral current antiretroviral regimen arm of ATLAS into this trial.

In the every-2-month treatment arm, 8 of 9 (89%) confirmed virologic failure participants had NNRTI resistance-associated substitutions (E138E/K+V179V/I, K101E+E138A, A98G+K103N, E138K, V179I+Y188L+P225H, Y188L, K103N+E138A, or K101E) at virologic failure. Decreases in rilpivirine susceptibility for these 8 participant isolates ranged from 2- to 30-fold. Six of the 8 participants with NNRTI resistance-associated substitutions also had INSTI resistance-associated substitutions (L74I+Q148Q/R+N155N/H (n = 2), L74I+T97A+N155H, L74I+N155H, N155H, or L74I+Q148R) at failure with cabotegravir fold changes ranging from 1- to 9-fold. The INSTI polymorphism L74I was detected at baseline in 5 of the virologic failure participants by a HIV-1 proviral DNA assay.

In the monthly treatment arm, both of the confirmed virologic failure participants had NNRTI resistance-associated substitutions (K101E+M230L or Y188F+G190Q) at virologic failure with decreased susceptibility to rilpivirine of 17- and >119.2-fold, respectively. Both participants also had INSTI resistance-associated substitutions (N155N/H or Q148R+E138E/K) at failure with decreased susceptibility to cabotegravir of 2- and 5-fold, respectively. Neither participant had the L74I integrase polymorphism at baseline.

Genotypic Baseline Factors Associated with Virologic Failure

An increased risk of cabotegravir plus rilpivirine confirmed virologic failure is associated with baseline virological factors: HIV-1 subtype A1, the presence of baseline integrase L74I polymorphism, and archived NNRTI resistance-associated substitutions.

Association of Subtype A1 and Baseline L74I Polymorphism in Integrase with Cabotegravir plus Rilpivirine Virologic Failure

Eight of the 18 (44%) cabotegravir plus rilpivirine confirmed virologic failures in FLAIR, ATLAS, and ATLAS-2M had HIV-1 subtype A1 with 7 of the 8 subtype A1 failures having the integrase polymorphism L74I detected at baseline and failure timepoints (Table 7). There was no detectable phenotypic resistance to cabotegravir conferred by the presence of L74I at baseline.

Subtype A1 is uncommon in the U.S.

The presence of the integrase polymorphism L74I in subtype B commonly seen in the U.S. was not associated with virologic failure. In contrast to FLAIR and ATLAS, where all virologic failures were subtype A, A1, or AG, subtypes of the cabotegravir plus rilpivirine virologic failures in ATLAS-2M included A (n = 1), A1 (n = 3), B (n = 4), C (n = 2), and complex/A1 (n = 1).

Association of Archived Baseline NNRTI Substitutions with Cabotegravir plus Rilpivirine Virologic Failure

The presence of archived NNRTI resistance-associated substitutions at baseline detected using an exploratory HIV-1 proviral DNA assay was associated with a higher virologic failure rate in the every-2-month arm of ATLAS-2M and in the cabotegravir plus rilpivirine arm (monthly) of ATLAS compared to without archived NNRTI resistance-associated substitutions (Table 7). However, in clinical practice, it is unlikely baseline resistance testing will be performed on virologically suppressed patients (HIV-1 RNA <50 copies/mL). Thus, in patients with an incomplete or uncertain NNRTI treatment history, consideration should be given before starting cabotegravir plus rilpivirine treatment.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 7. Rate of Confirmed Virologic Failure in FLAIR, ATLAS, and ATLAS-2M: Baseline<span class="Sup">a</span> Analysis (Subtype Al, Presence of lntegrase Polymorphism L74I, and Presence of Archived NNRTI Resistance-Associated Substitutions)</span> </caption> <col width="20%"/> <col width="13%"/> <col width="12%"/> <col width="13%"/> <col width="13%"/> <col width="14%"/> <col width="14%"/> <tfoot> <tr class="First"> <td align="left" colspan="7" valign="top">NNRTI = Non-Nucleoside Reverse Transcriptase Inhibitor, CAB+RPV = Cabotegravir + Rilpivirine, CAR = Current Antiretroviral Regimen, RAS = resistance-associated substitutions, NA = Not available.</td> </tr> <tr> <td align="left" colspan="7" valign="top"><span class="Sup">a </span>Baseline and/or Screening result used.</td> </tr> <tr> <td align="left" colspan="7" valign="top"><span class="Sup">b </span>Per Standard Monogram Nomenclature Reports. Based on June 2020 Los Alamos National Library panel, the majority of HIV-1 subtype A1 was reclassified as HIV-1 subtype A6.</td> </tr> <tr> <td align="left" colspan="7" valign="top"><span class="Sup">c </span>L74I and L74L/I mixture.</td> </tr> <tr class="Last"> <td align="left" colspan="7" valign="top"><span class="Sup">d </span>Baseline/Screening NNRTI substitutions at L100, K101, K103, V106, V108, E138, V179, Y181, Y188, G190, H221, P225, M230.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">FLAIR</span> <br/> <span class="Bold">CAB+RPV</span> <br/> <span class="Bold">N = 283</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">FLAIR</span> <br/> <span class="Bold">CAR</span> <br/> <span class="Bold">N = 283</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">ATLAS</span> <br/> <span class="Bold">CAB+RPV</span> <br/> <span class="Bold">N = 308</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">ATLAS</span> <br/> <span class="Bold">CAR</span> <br/> <span class="Bold">N = 308</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">ATLAS</span>‑<span class="Bold">2M Q4W</span> <br/> <span class="Bold">N = 523</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">ATLAS</span>‑<span class="Bold">2M</span> <br/> <span class="Bold">Q8W</span> <br/> <span class="Bold">N = 522</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Total confirmed virologic failures</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Subtype A1<span class="Sup">b</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4/8 (50%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1/4 (25%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1/17 (6%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0/21 (0%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0/30 (0%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4/31 (13%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     <span class="Bold">+L74I<span class="Sup">c</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4/5 (80%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1/3 (33%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1/16 (6%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0/19 (0%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2/28 (0%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3/26 (12%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     <span class="Bold">-L74I</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0/3 (0%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0/1 (0%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0/1 (0%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0/2 (0%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0/2 (0%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1/5 (20%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Other subtypes</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2/268<br/>(0.7%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3/272<br/>(1%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2/240<br/>(0.8%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4/252<br/>(1.6%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2/409<br/>(0.5%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5/415<br/>(1.2%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     <span class="Bold">+L74I<span class="Sup">c</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0/49 (0%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1/43 (2.3%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1/29 (3%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1/39 (2.6%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0/42 (0%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2/48 (4%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     <span class="Bold">-L74I</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0/219<br/>(2.5%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2/229<br/>(0.9%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1/211<br/>(0.5%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3/213<br/>(1.4%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2/367<br/>(0.5%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3/367<br/>(0.8%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Missing data</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">51</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">35</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">84</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">76</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">With NNRTI RAS<span class="Sup">d</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">NA</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">NA</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3/78 <br/>(4%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2/83 <br/>(2%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1/128<br/>(0.8%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">7/117 <br/>(6%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Without NNRTI RAS</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">NA</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">NA</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0/179 <br/>(0%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2/190<br/>(1%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1/310<br/>(0.3%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2/327<br/>(0.6%)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Missing data</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">NA</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">NA</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">51</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">35</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">84</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">76</p> </td> </tr> </tbody> </table></div>

HIV-1 PrEP: There were 12 incident infections and 4 prevalent infections among participants receiving cabotegravir injection for HIV-1 PrEP in HPTN 083. Genotypic data were generated for viruses from 13 of these 16 participants (4 participants with prevalent infections and 9 participants with incident infections) and phenotypic data were generated for 3 of these viruses. INSTI resistance-associated substitutions were detected in 5 viruses from participants who achieved target plasma concentrations of cabotegravir (≥0.65 mcg/mL [1.6 microM]) and included R263K (2-fold less susceptible to cabotegravir), E138A+Q148R (6-fold less susceptible to cabotegravir), E138K+Q148K, G140A+Q148R (13-fold less susceptible to cabotegravir), and L74I+E138E/K+G140G/S+Q148R+E157Q.

There were 3 incident infections and 1 prevalent infection among participants receiving cabotegravir injection for HIV-1 PrEP in HPTN 084. All 3 incident infections occurred during periods with cabotegravir exposures below the target concentration. No variants expressing INSTI resistance-associated substitutions were detected.

Cross-Resistance

Cross-resistance has been observed among INSTIs. Cabotegravir had reduced susceptibility (>5-fold change) to recombinant HIV-1 strain NL432 viruses harboring the following integrase amino acid substitutions: G118R, Q148K, Q148R, T66K+L74M, E92Q+N155H, E138A+Q148R, E138K+Q148K/R, G140C+Q148R, G140S+Q148H/K/R, Y143H+N155H, and Q148R+N155H (range: 5.1- to 81-fold). The substitutions E138K+Q148K and Q148R+N155H conferred the greatest reductions in susceptibility of 81- and 61-fold, respectively.

Cabotegravir was active against viruses harboring the NNRTI substitutions K103N or Y188L, or the NRTI substitutions M184V, D67N/K70R/T215Y, or V75I/F77L/F116Y/Q151M.

Virologic failure isolates from cabotegravir plus rilpivirine treatment in FLAIR, ATLAS, and ATLAS-2M exhibited cross-resistance to INSTIs and NNRTIs. All confirmed virologic isolates with genotypic evidence of cabotegravir resistance had cross-resistance to elvitegravir and raltegravir but retained phenotypic susceptibility to dolutegravir and when tested bictegravir.

Viruses harboring E138A+Q148R or G140A+Q148R with reduced susceptibility to cabotegravir were isolated from participants using cabotegravir injection for HIV-1 PrEP in HPTN 083. These viruses remained susceptible to bictegravir and dolutegravir but had cross-resistance to elvitegravir and raltegravir.

Carcinogenesis

Two-year carcinogenicity studies in mice and rats were conducted with cabotegravir. In mice, no drug-related increases in tumor incidence were observed at cabotegravir exposures (AUC) up to approximately 8 times (males) and 7 times (females) higher than those in humans at the RHD. In rats, no drug-related increases in tumor incidence were observed at cabotegravir exposures up to approximately 26 times higher than those in humans at the RHD.

Mutagenesis

Cabotegravir was not genotoxic in the bacterial reverse mutation assay, mouse lymphoma assay, or in the in vivo rodent micronucleus assay.

Impairment of Fertility

In rats, no effects on fertility were observed at cabotegravir exposures (AUC) >20 times (male) and 28 times (female) the exposure in humans at the RHD.

The use of VOCABRIA in combination with EDURANT as an oral lead-in and in patients who miss planned injections with CABENUVA was evaluated in 3 Phase 3 randomized, multicenter, active-controlled, parallel-arm, open-label, non-inferiority trials (Trial 201584: FLAIR [NCT02938520], Trial 201585: ATLAS [NCT02951052], and Trial 207966: ATLAS‑2M [NCT03299049]) in participants who were virologically suppressed (HIV-1 RNA <50 copies/mL). Please refer to the CABENUVA prescribing information for additional information.

In the FLAIR study during the Extension Phase (Week 100 to Week 124), the efficacy of CABENUVA was evaluated in participants who switched (at Week 100) from their current antiretroviral regimen to CABENUVA, with and without an oral lead-in phase. A total of 121 participants chose to start the treatment with oral lead-in and 111 participants chose direct to injection. Participants were not randomized during the Extension Phase. At Week 124, the proportion of participants with HIV-1 RNA ≥50 copies/mL was 0.8% and 0.9% for the oral lead-in and direct to injection groups, respectively. The rates of virologic suppression (HIV-1 RNA <50 copies/mL) were similar in both the oral lead-in (93%) and direct to injection (99%) groups.

The use of VOCABRIA as an oral lead-in and in participants who miss planned injections with APRETUDE to reduce the risk of acquiring HIV-1 infection were evaluated in 2 randomized, double-blind, controlled, multinational trials, Trial 201738 (HPTN 083 [NCT02720094]) in men and transgender women without HIV-1 who have sex with men and have evidence of high-risk behavior for HIV-1 infection and Trial 201739 (HPTN 084 [NCT03164564]) in cisgender women without HIV-1 at risk of acquiring HIV-1. Please refer to the APRETUDE prescribing information for additional information.

Trial 208580 (MOCHA, [NCT03497676])

The safety, tolerability, and pharmacokinetics of oral and injectable cabotegravir and oral and injectable rilpivirine were assessed in an ongoing Phase 1/2 multicenter, open-label, non‑comparative study, MOCHA (IMPAACT 2017), in virologically suppressed adolescents with HIV-1 aged 12 to younger than 18 years and weighing ≥35 kg [see Adverse Reactions (6.1), Clinical Pharmacology (12.3)].

The primary objective at Week 24 was to confirm the safety of injectable cabotegravir plus injectable rilpivirine in virologically suppressed adolescents with HIV-1. Antiviral activity was assessed as a secondary objective. A total of 144 adolescent participants with HIV-1 received oral cabotegravir in combination with oral rilpivirine as an oral lead-in. Please refer to the CABENUVA prescribing information for additional information.

Each VOCABRIA tablet contains 30 mg of cabotegravir and is a white, oval, film-coated, biconvex tablet debossed with “SV CTV” on one side.

{ "type": "p", "children": [], "text": "Each VOCABRIA tablet contains 30 mg of cabotegravir and is a white, oval, film-coated, biconvex tablet debossed with “SV CTV” on one side." }

Bottle of 30 tablets with child-resistant closure NDC 49702-248-13.

{ "type": "p", "children": [], "text": "Bottle of 30 tablets with child-resistant closure NDC 49702-248-13." }

Store below 30°C (86°F).

{ "type": "p", "children": [], "text": "Store below 30°C (86°F)." }

Advise the patient to read the FDA-approved patient labeling (Patient Information).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Patient Information)." }

Important Information for Individuals without HIV-1 Taking VOCABRIA for HIV-1 PrEP

{ "type": "p", "children": [], "text": "\nImportant Information for Individuals without HIV-1 Taking VOCABRIA for HIV-1 PrEP \n" }

Advise individuals without HIV-1 about the following [see Warnings and Precautions (5.1)]:

{ "type": "p", "children": [], "text": "Advise individuals without HIV-1 about the following [see Warnings and Precautions (5.1)]:" }

{ "type": "", "children": [], "text": "" }

Hypersensitivity Reactions

{ "type": "p", "children": [], "text": "\nHypersensitivity Reactions \n" }

Advise patients to immediately contact their healthcare provider if they develop a rash. Instruct patients to immediately stop taking VOCABRIA and seek medical attention if they develop a rash associated with any of the following symptoms as it may be a sign of a more serious reaction such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN): fever; generally ill feeling; extreme tiredness; muscle or joint aches; blisters; oral blisters or lesions; eye inflammation; facial swelling; swelling of the eyes, lips, tongue, or mouth; difficulty breathing; and/or signs and symptoms of liver problems (e.g., yellowing of the skin or whites of the eyes; dark or tea-colored urine; pale-colored stools or bowel movements; nausea; vomiting; loss of appetite; or pain, aching, or sensitivity on the right side below the ribs). Advise patients that if hypersensitivity occurs, they will be closely monitored, laboratory tests will be ordered, and appropriate therapy will be initiated [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Advise patients to immediately contact their healthcare provider if they develop a rash. Instruct patients to immediately stop taking VOCABRIA and seek medical attention if they develop a rash associated with any of the following symptoms as it may be a sign of a more serious reaction such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN): fever; generally ill feeling; extreme tiredness; muscle or joint aches; blisters; oral blisters or lesions; eye inflammation; facial swelling; swelling of the eyes, lips, tongue, or mouth; difficulty breathing; and/or signs and symptoms of liver problems (e.g., yellowing of the skin or whites of the eyes; dark or tea-colored urine; pale-colored stools or bowel movements; nausea; vomiting; loss of appetite; or pain, aching, or sensitivity on the right side below the ribs). Advise patients that if hypersensitivity occurs, they will be closely monitored, laboratory tests will be ordered, and appropriate therapy will be initiated [see Warnings and Precautions (5.2)]." }

Hepatotoxicity

{ "type": "p", "children": [], "text": "\nHepatotoxicity\n" }

Inform patients that hepatotoxicity has been reported with cabotegravir [see Warnings and Precautions (5.3), Adverse Reactions (6.1)]. Inform patients that monitoring for liver transaminases is recommended when VOCABRIA is used for HIV-1 treatment. Inform individuals that clinical and laboratory monitoring should be considered and APRETUDE should be discontinued if hepatoxicity is confirmed when VOCABRIA is used for HIV-1 PrEP [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Inform patients that hepatotoxicity has been reported with cabotegravir [see Warnings and Precautions (5.3), Adverse Reactions (6.1)]. Inform patients that monitoring for liver transaminases is recommended when VOCABRIA is used for HIV-1 treatment. Inform individuals that clinical and laboratory monitoring should be considered and APRETUDE should be discontinued if hepatoxicity is confirmed when VOCABRIA is used for HIV-1 PrEP [see Warnings and Precautions (5.3)]." }

Depressive Disorders

{ "type": "p", "children": [], "text": "\nDepressive Disorders \n" }

Inform patients that depressive disorders (including depressed mood, depression, mood altered, mood swings, suicidal ideation/suicide attempt) have been reported with VOCABRIA for treatment of HIV-1. Inform patients that depressive disorders (including depression, depressed mood, persistent depressive disorder, suicidal ideation/suicide attempt) have been reported with VOCABRIA for HIV-1 PrEP. Promptly evaluate patients with severe depressive symptoms to assess whether the symptoms are related to VOCABRIA and to determine whether the risks of continued therapy outweigh the benefits [see Warnings and Precautions (5.4), Adverse Reactions (6.1)].

{ "type": "p", "children": [], "text": "Inform patients that depressive disorders (including depressed mood, depression, mood altered, mood swings, suicidal ideation/suicide attempt) have been reported with VOCABRIA for treatment of HIV-1. Inform patients that depressive disorders (including depression, depressed mood, persistent depressive disorder, suicidal ideation/suicide attempt) have been reported with VOCABRIA for HIV-1 PrEP. Promptly evaluate patients with severe depressive symptoms to assess whether the symptoms are related to VOCABRIA and to determine whether the risks of continued therapy outweigh the benefits [see Warnings and Precautions (5.4), Adverse Reactions (6.1)]." }

Drug Interactions

{ "type": "p", "children": [], "text": "\nDrug Interactions\n" }

Inform patients that VOCABRIA may interact with other drugs and may reduce exposure of VOCABRIA; therefore, advise patients to report to their healthcare provider the use of any other prescription or nonprescription medication or herbal products [see Contraindications (4), Warnings and Precautions (5.5), Drug Interactions (7.2, 7.3)].

{ "type": "p", "children": [], "text": "Inform patients that VOCABRIA may interact with other drugs and may reduce exposure of VOCABRIA; therefore, advise patients to report to their healthcare provider the use of any other prescription or nonprescription medication or herbal products [see Contraindications (4), Warnings and Precautions (5.5), Drug Interactions (7.2, 7.3)]." }

Dosage and Administration

{ "type": "p", "children": [], "text": "\nDosage and Administration\n" }

Inform patients that it is important to take VOCABRIA once daily on a regular dosing schedule with a meal at the same time as EDURANT for HIV-1 treatment and to avoid missing doses, as this can result in development of resistance. Instruct patients that if they miss a dose of VOCABRIA to take it as soon as they remember [see Dosage and Administration (2.1), Clinical Pharmacology (12.3)].

{ "type": "p", "children": [], "text": "Inform patients that it is important to take VOCABRIA once daily on a regular dosing schedule with a meal at the same time as EDURANT for HIV-1 treatment and to avoid missing doses, as this can result in development of resistance. Instruct patients that if they miss a dose of VOCABRIA to take it as soon as they remember [see Dosage and Administration (2.1), Clinical Pharmacology (12.3)]." }

Pregnancy Registry

{ "type": "p", "children": [], "text": "\nPregnancy Registry\n" }

Inform patients that there is an antiretroviral pregnancy registry to monitor fetal outcomes in those exposed to VOCABRIA during pregnancy [see Use in Specific Populations (8.1)].

{ "type": "p", "children": [], "text": "Inform patients that there is an antiretroviral pregnancy registry to monitor fetal outcomes in those exposed to VOCABRIA during pregnancy [see Use in Specific Populations (8.1)]." }

Lactation

{ "type": "p", "children": [], "text": "\nLactation\n" }

Inform individuals with HIV-1 infection that the potential risks of breastfeeding include: (1) HIV-1 transmission (in HIV-1–negative infants), (2) developing viral resistance (in HIV‑1‑positive infants), and (3) adverse reactions in a breastfed infant similar to those seen in adults.

{ "type": "p", "children": [], "text": "Inform individuals with HIV-1 infection that the potential risks of breastfeeding include: (1) HIV-1 transmission (in HIV-1–negative infants), (2) developing viral resistance (in HIV‑1‑positive infants), and (3) adverse reactions in a breastfed infant similar to those seen in adults." }

In mothers without HIV-1, the benefits and risks of VOCABRIA while breastfeeding should be evaluated, including the risk of HIV-1 acquisition due to medication nonadherence and subsequent mother to child transmission. Instruct mothers not to breastfeed if acute HIV‑1 infection is suspected because of the risk of passing the HIV-1 virus to the baby [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "In mothers without HIV-1, the benefits and risks of VOCABRIA while breastfeeding should be evaluated, including the risk of HIV-1 acquisition due to medication nonadherence and subsequent mother to child transmission. Instruct mothers not to breastfeed if acute HIV‑1 infection is suspected because of the risk of passing the HIV-1 virus to the baby [see Use in Specific Populations (8.2)]." }

APRETUDE, CABENUVA, and VOCABRIA are trademarks owned by or licensed to the ViiV Healthcare group of companies.

{ "type": "p", "children": [], "text": "APRETUDE, CABENUVA, and VOCABRIA are trademarks owned by or licensed to the ViiV Healthcare group of companies." }

The other brands listed are trademarks owned by or licensed to their respective owners and are not trademarks owned by or licensed to the ViiV Healthcare group of companies. The makers of these brands are not affiliated with and do not endorse the ViiV Healthcare group of companies or its products.

{ "type": "p", "children": [], "text": "The other brands listed are trademarks owned by or licensed to their respective owners and are not trademarks owned by or licensed to the ViiV Healthcare group of companies. The makers of these brands are not affiliated with and do not endorse the ViiV Healthcare group of companies or its products." }

Manufactured for:

{ "type": "p", "children": [], "text": "Manufactured for:" }

ViiV HealthcareDurham, NC 27701

{ "type": "p", "children": [], "text": "ViiV HealthcareDurham, NC 27701" }

©2025 ViiV Healthcare group of companies or its licensor.

{ "type": "p", "children": [], "text": "©2025 ViiV Healthcare group of companies or its licensor." }

VCB:10PI

{ "type": "p", "children": [], "text": "VCB:10PI" }

<div class="scrollingtable"><table width="99.84%"> <col width="2%"/> <col width="48%"/> <col width="50%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="middle"> <p class="First"> <span class="Bold">PATIENT INFORMATION</span> </p> <p> <span class="Bold">VOCABRIA [voe-KAB-ree-ah]</span> </p> <p> <span class="Bold">(cabotegravir)</span> </p> <p> <span class="Bold">tablets, for oral use</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">This Patient Information provides information about two different ways that VOCABRIA may be used. See the section <span class="Bold">“What is VOCABRIA?”</span> for detailed information about how VOCABRIA may be used.</p> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What is the most important information I should know about VOCABRIA?</span> </p> <p> <span class="Bold">Important information for people who take VOCABRIA to help reduce their risk of getting human immunodeficiency virus-1 (HIV-1) infection, also called pre-exposure prophylaxis or “PrEP”:</span> </p> <p> <span class="Bold">Before taking VOCABRIA to reduce your risk of getting HIV-1:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">You must be HIV-1 negative to start VOCABRIA. You must get tested to make sure that you do not already have HIV-1 infection.</span> </dd> <dt>•</dt> <dd> <span class="Bold">Do not take VOCABRIA for HIV-1 PrEP unless you are confirmed to be HIV-1 negative.</span> </dd> <dt>•</dt> <dd>Some HIV-1 tests can miss HIV-1 infection in a person who has recently become infected. If you have flu-like symptoms, you could have recently become infected with HIV-1. Tell your healthcare provider if you had a flu‑like illness within the last month before starting VOCABRIA or at any time while taking VOCABRIA. Symptoms of new HIV-1 infection include:</dd> </dl> </td> </tr> <tr> <td class="Lrule" valign="top"></td><td valign="top"> <dl> <dt>o</dt> <dd>tiredness</dd> <dt>o</dt> <dd>joint or muscle aches</dd> <dt>o</dt> <dd>sore throat</dd> <dt>o</dt> <dd>rash</dd> <dt>o</dt> <dd>enlarged lymph nodes in the neck or groin</dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt>o</dt> <dd>fever </dd> <dt>o</dt> <dd>headache</dd> <dt>o</dt> <dd>vomiting or diarrhea</dd> <dt>o</dt> <dd>night sweats</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">While you are taking VOCABRIA for HIV-1 PrEP:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">VOCABRIA does not prevent other sexually transmitted infections. Practice safer sex by using a latex or polyurethane condom to reduce the risk of getting sexually transmitted infections.</span> </dd> <dt>•</dt> <dd> <span class="Bold">You must stay HIV-1 negative to keep taking VOCABRIA for HIV-1 PrEP.</span> <dl> <dt>o</dt> <dd>Know your HIV-1 status and the HIV-1 status of your partners.</dd> <dt>o</dt> <dd>Ask your partners with HIV-1 if they are taking anti-HIV-1 medicines and have an undetectable viral load. An undetectable viral load is when the amount of virus in the blood is too low to be measured in a lab test. To maintain an undetectable viral load, your partners must keep taking HIV-1 medicine as prescribed. Your risk of getting HIV-1 is lower if your partners with HIV-1 are taking effective treatment.</dd> <dt>o</dt> <dd>Get tested for HIV-1 when your healthcare provider tells you.</dd> <dt>o</dt> <dd>Get tested for other sexually transmitted infections such as syphilis, chlamydia, and gonorrhea. These infections make it easier for HIV-1 to infect you.</dd> <dt>o</dt> <dd>If you think you were exposed to HIV-1, tell your healthcare provider right away. They may want to do more tests to be sure you are still HIV-1 negative.</dd> <dt>o</dt> <dd>Get information and support to help reduce sexual risk behaviors.</dd> <dt>o</dt> <dd>Do not miss any doses of VOCABRIA. Missing doses increases your risk of getting HIV-1 infection.</dd> <dt>o</dt> <dd>If you do become HIV-1 positive, you will need to take other medicines to treat HIV-1. VOCABRIA by itself is not a complete treatment for HIV-1.</dd> </dl> </dd> </dl> <p> <span class="Bold">If you have HIV-1 and take only VOCABRIA, over time your HIV-1 may become harder to treat.</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What is VOCABRIA?</span> </p> <p>VOCABRIA is a prescription medicine that may be used in two different ways when a person’s healthcare provider determines that they meet certain requirements. VOCABRIA is used:</p> <dl> <dt>•</dt> <dd>to treat HIV-1 infection<dl> <dt>o</dt> <dd>in combination with another HIV-1 medicine called EDURANT (rilpivirine) for short-term treatment of HIV-1 infection in people 12 years of age and older who weigh at least 77 pounds (35 kg) to replace their current HIV-1 medicines to assess the tolerability of cabotegravir before receiving the long-acting medicine called CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension).</dd> <dt>o</dt> <dd>as oral therapy for people who will miss planned injection dosing with CABENUVA.</dd> </dl> </dd> <dt>•</dt> <dd>for HIV-1 PrEP to reduce the risk of getting HIV-1 infection<dl> <dt>o</dt> <dd>for short-term PrEP in adults and adolescents who weigh at least 77 pounds (at least 35 kg) to assess the tolerability of cabotegravir before receiving the long-acting medicine called APRETUDE (cabotegravir extended-release injectable suspension).</dd> <dt>o</dt> <dd>as oral dosing for people who will miss planned injection dosing with APRETUDE.</dd> </dl> </dd> </dl> <p>HIV-1 is the virus that causes Acquired Immune Deficiency Syndrome (AIDS).</p> <p>If you are taking VOCABRIA to treat HIV-1 infection, you should also read the Patient Information for EDURANT.</p> <p>It is not known if VOCABRIA for treatment of HIV-1 infection is safe and effective in children younger than 12 years of age or weighing less than 77 pounds (35 kg).</p> <p>It is not known if VOCABRIA is safe and effective in reducing the risk of HIV-1 infection in children younger than 12 years of age or weighing less than 77 pounds (less than 35 kg).</p> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Do not take VOCABRIA if you:</span> </p> <dl> <dt>•</dt> <dd>have ever had an allergic reaction to cabotegravir.</dd> <dt>•</dt> <dd>are taking any of the following medicines:</dd> </dl> </td> </tr> <tr> <td class="Lrule" valign="top"></td><td valign="top"> <dl> <dt>o</dt> <dd>carbamazepine</dd> <dt>o</dt> <dd>oxcarbazepine </dd> <dt>o</dt> <dd>phenobarbital</dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt>o</dt> <dd>phenytoin</dd> <dt>o</dt> <dd>rifampin</dd> <dt>o</dt> <dd>rifapentine</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">For people taking VOCABRIA for treatment of HIV-1 infection:</span> </p> <p> <span class="Bold">Do not take VOCABRIA for HIV-1 infection if you are taking rifabutin.</span> </p> <p> <span class="Bold">For people taking VOCABRIA for HIV-1 PrEP:</span> </p> <p> <span class="Bold">Do not take VOCABRIA for HIV-1 PrEP if you:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">already have HIV-1 infection.</span> If you are HIV-1 positive, you will need to take other medicines to treat HIV-1. VOCABRIA by itself is not a complete treatment for HIV-1.</dd> <dt>•</dt> <dd> <span class="Bold">do not know your HIV-1 infection status.</span> You may already be HIV-1 positive. You need to take other medicines to treat HIV-1. VOCABRIA can only help reduce your risk of getting HIV-1 infection <span class="Bold">before</span> you are infected. </dd> <dt>•</dt> <dd>are allergic to cabotegravir.</dd> <dt>•</dt> <dd>are taking any of the medicines listed above. See <span class="Bold">“Do not take VOCABRIA for HIV-1 infection if you:”</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Before taking VOCABRIA, tell your healthcare provider about all your medical conditions, including if you:</span> </p> <dl> <dt>•</dt> <dd>have ever had a skin rash or an allergic reaction to medicines that contain cabotegravir.</dd> <dt>•</dt> <dd>have or have had liver problems, including hepatitis B or C infection.</dd> <dt>•</dt> <dd>have ever had mental health problems.</dd> <dt>•</dt> <dd>are pregnant or plan to become pregnant. It is not known if VOCABRIA will harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with VOCABRIA. <br/> <span class="Bold">Pregnancy Registry.</span> There is a pregnancy registry for those who take VOCABRIA during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry.</dd> <dt>•</dt> <dd>are breastfeeding or plan to breastfeed. VOCABRIA may pass into your breast milk.<dl> <dt>o</dt> <dd>If you take VOCABRIA to treat HIV-1 infection, talk to your healthcare provider about the following risks to your baby from breastfeeding during treatment with VOCABRIA:<dl> <dt>▪</dt> <dd>the HIV-1 virus may pass to your baby if your baby does not have HIV-1 infection.</dd> <dt>▪</dt> <dd>the HIV-1 virus may become harder to treat if your baby has HIV-1 infection.</dd> <dt>▪</dt> <dd>your baby may get side effects from VOCABRIA.</dd> </dl> </dd> <dt>o</dt> <dd>If you take VOCABRIA for HIV-1 PrEP, talk with your healthcare provider about the best way to feed your baby while receiving VOCABRIA.</dd> </dl> </dd> </dl> <p> <span class="Bold">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements.</p> <p>Some medicines may interact with VOCABRIA. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine. </p> <p>You can ask your healthcare provider or pharmacist for a list of medicines that interact with VOCABRIA.</p> <p> <span class="Bold">Do not start taking a new medicine without telling your healthcare provider.</span> Your healthcare provider can tell you if it is safe to take VOCABRIA with other medicines.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">How should I take VOCABRIA?</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">For treatment of HIV-1 infection:</span> <dl> <dt>o</dt> <dd>Take 1 VOCABRIA tablet and 1 EDURANT tablet 1 time a day for 1 month (at least 28 days) exactly as your healthcare provider tells you. </dd> <dt>o</dt> <dd>Your healthcare provider may have you take VOCABRIA tablets in combination with EDURANT tablets for 1 month (at least 28 days) before you receive CABENUVA for the first time. This will allow your healthcare provider to assess how well you will tolerate these medicines.</dd> <dt>o</dt> <dd>Your final dose of VOCABRIA and EDURANT should be taken on the same day you receive your first injections of CABENUVA.</dd> <dt>o</dt> <dd>If you miss or plan to miss a scheduled monthly or every-2-month injections of CABENUVA by more than 7 days, call your healthcare provider right away to discuss your options. </dd> <dt>o</dt> <dd>If you take VOCABRIA at the same time as EDURANT, you should take it with a meal.</dd> <dt>o</dt> <dd>Do not run out of VOCABRIA. The virus in your blood may increase and the virus may become harder to treat when using VOCABRIA to treat HIV-1 infection. </dd> </dl> </dd> <dt>•</dt> <dd> <span class="Bold">For HIV-1 PrEP:</span> <dl> <dt>o</dt> <dd>Take 1 VOCABRIA tablet 1 time a day for 1 month (at least 28 days) exactly as your healthcare provider tells you.</dd> <dt>o</dt> <dd>Your healthcare provider may have you take VOCABRIA tablets for 1 month (at least 28 days) before you receive APRETUDE for the first time. This will allow your healthcare provider to assess how well you will tolerate APRETUDE.</dd> <dt>o</dt> <dd>You should receive your first injection of APRETUDE on the day of your last dose of VOCABRIA or within 3 days.</dd> <dt>o</dt> <dd>If you miss or plan to miss a scheduled every-2-month injection of APRETUDE by more than 7 days, call your healthcare provider right away to discuss your options.</dd> </dl> </dd> <dt>•</dt> <dd>VOCABRIA may be taken with or without food.</dd> <dt>•</dt> <dd>If you take antacid products that contain aluminum or magnesium hydroxide or calcium carbonate, they should be taken at least 2 hours before or 4 hours after you take VOCABRIA.</dd> <dt>•</dt> <dd>Stay under the care of a healthcare provider while taking VOCABRIA.</dd> <dt>•</dt> <dd>Do not change your dose or stop taking VOCABRIA without talking to your healthcare provider.</dd> <dt>•</dt> <dd>Do not miss a dose of VOCABRIA. If you miss a dose of VOCABRIA, take it as soon as you remember.</dd> <dt>•</dt> <dd>If you take too much VOCABRIA, call your healthcare provider or go to the nearest hospital emergency room right away.</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What are the possible side effects of VOCABRIA?</span> </p> <p> <span class="Bold">VOCABRIA may cause serious side effects including:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Allergic reactions.</span> Call your healthcare provider right away if you develop a rash with VOCABRIA. <span class="Bold"> <br/>Stop taking VOCABRIA and get medical help right away if you develop a rash with any of the following signs or symptoms:</span> </dd> </dl> </td> </tr> <tr> <td class="Lrule" valign="top"></td><td valign="top"> <dl> <dt>o</dt> <dd>fever</dd> <dt>o</dt> <dd>generally ill feeling</dd> <dt>o</dt> <dd>tiredness</dd> <dt>o</dt> <dd>muscle or joint aches</dd> <dt>o</dt> <dd>trouble breathing</dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt>o</dt> <dd>blisters or sores in mouth</dd> <dt>o</dt> <dd>blisters </dd> <dt>o</dt> <dd>redness or swelling of the eyes</dd> <dt>o</dt> <dd>swelling of the mouth, face, lips, or tongue</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">Liver problems</span>. Liver problems have happened in people with or without history of liver problems or other risk factors. Your healthcare provider may do blood tests to check your liver function. People with a history of liver problems or people who have certain liver function test changes may have an increased risk of developing new or worsening changes in certain liver tests during treatment with VOCABRIA. <br/> <span class="Bold">Call your healthcare provider right away if you develop any of the following signs or symptoms of liver problems:</span> </dd> </dl> </td> </tr> <tr> <td class="Lrule" valign="top"></td><td valign="top"> <dl> <dt>o</dt> <dd>your skin or the white part of your eyes turns yellow (jaundice)</dd> <dt>o</dt> <dd>dark or “tea-colored” urine</dd> <dt>o</dt> <dd>light-colored stools (bowel movements)</dd> <dt>o</dt> <dd>nausea or vomiting</dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt>o</dt> <dd>loss of appetite </dd> <dt>o</dt> <dd>pain, aching, or tenderness on the right side of your stomach area</dd> <dt>o</dt> <dd>itching</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">Depression or mood changes. Call your healthcare provider or get medical help right away if you develop any of the following symptoms:</span> <dl> <dt>o</dt> <dd>feeling sad or hopeless</dd> <dt>o</dt> <dd>feeling anxious or restless</dd> <dt>o</dt> <dd>have thoughts of hurting yourself (suicide) or have tried to hurt yourself</dd> </dl> </dd> </dl> <p class="First"> <span class="Bold">The most common side effects of VOCABRIA for HIV-1 treatment include:</span> </p> </td> </tr> <tr> <td class="Lrule" colspan="2" valign="top"> <dl> <dt>•</dt> <dd>fatigue</dd> <dt>•</dt> <dd>headache </dd> <dt>•</dt> <dd>diarrhea</dd> <dt>•</dt> <dd>nausea</dd> <dt>•</dt> <dd>dizziness</dd> <dt>•</dt> <dd>abnormal dreams</dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt>•</dt> <dd>anxiety</dd> <dt>•</dt> <dd>sleep disorders</dd> <dt>•</dt> <dd>stomach pain</dd> <dt>•</dt> <dd>stomach bloating</dd> <dt>•</dt> <dd>weakness</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">The most common side effects of VOCABRIA for HIV-1 PrEP include:</span> </p> </td> </tr> <tr> <td class="Lrule" colspan="2" valign="top"> <dl> <dt>•</dt> <dd>headache</dd> <dt>•</dt> <dd>diarrhea</dd> <dt>•</dt> <dd>nausea</dd> <dt>•</dt> <dd>dizziness</dd> <dt>•</dt> <dd>upper respiratory tract infection</dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt>•</dt> <dd>tiredness</dd> <dt>•</dt> <dd>drowsiness</dd> <dt>•</dt> <dd>abnormal dreams</dd> <dt>•</dt> <dd>stomach pain</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">These are not all the possible side effects of VOCABRIA. </p> <p>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800‑FDA‑1088.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">How should I store VOCABRIA?</span> </p> <p>Store VOCABRIA below 86°F (30°C).</p> <p> <span class="Bold">Keep VOCABRIA and all medicines out of the reach of children.</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">General information about the safe and effective use of VOCABRIA.</span> </p> <p>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use VOCABRIA for a condition for which it was not prescribed. Do not give VOCABRIA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about VOCABRIA that is written for health professionals.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What are the ingredients in VOCABRIA?</span> </p> <p> <span class="Bold">Active ingredient:</span> cabotegravir</p> <p> <span class="Bold">Inactive ingredients:</span> hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. </p> <p> <span class="Bold">The tablet film-coating contains:</span> hypromellose, polyethylene glycol and titanium dioxide.</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="3" valign="top"> <p class="First">   Manufactured for:</p> <p>   ViiV Healthcare</p> <p>   Durham, NC 27701</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">APRETUDE, CABENUVA, and VOCABRIA are trademarks owned by or licensed to the ViiV Healthcare group of companies.</p> <p>The other brand listed is a trademark owned by or licensed to its respective owner and is not a trademark owned by or licensed to the ViiV Healthcare group of companies. The maker of this brand is not affiliated with and does not endorse the ViiV Healthcare group of companies or its products.</p> <p>©2025 ViiV Healthcare group of companies or its licensor.</p> <p>VCB:7PIL</p> <p>For more information call 1-877-844-8872.</p> </td> </tr> <tr class="Last"> <td class="Botrule" colspan="3" valign="top"> <dl> <dt> </dt> <dd>           This Patient Information has been approved by the U.S. Food and Drug Administration.                Revised: 4/2025</dd> </dl> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"99.84%\">\n<col width=\"2%\"/>\n<col width=\"48%\"/>\n<col width=\"50%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"3\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">PATIENT INFORMATION</span>\n</p>\n<p>\n<span class=\"Bold\">VOCABRIA [voe-KAB-ree-ah]</span>\n</p>\n<p>\n<span class=\"Bold\">(cabotegravir)</span>\n</p>\n<p>\n<span class=\"Bold\">tablets, for oral use</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">This Patient Information provides information about two different ways that VOCABRIA may be used. See the section <span class=\"Bold\">“What is VOCABRIA?”</span> for detailed information about how VOCABRIA may be used.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is the most important information I should know about VOCABRIA?</span>\n</p>\n<p>\n<span class=\"Bold\">Important information for people who take VOCABRIA to help reduce their risk of getting human immunodeficiency virus-1 (HIV-1) infection, also called pre-exposure prophylaxis or “PrEP”:</span>\n</p>\n<p>\n<span class=\"Bold\">Before taking VOCABRIA to reduce your risk of getting HIV-1:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">You must be HIV-1 negative to start VOCABRIA. You must get tested to make sure that you do not already have HIV-1 infection.</span>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not take VOCABRIA for HIV-1 PrEP unless you are confirmed to be HIV-1 negative.</span>\n</dd>\n<dt>•</dt>\n<dd>Some HIV-1 tests can miss HIV-1 infection in a person who has recently become infected. If you have flu-like symptoms, you could have recently become infected with HIV-1. Tell your healthcare provider if you had a flu‑like illness within the last month before starting VOCABRIA or at any time while taking VOCABRIA. Symptoms of new HIV-1 infection include:</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"></td><td valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>tiredness</dd>\n<dt>o</dt>\n<dd>joint or muscle aches</dd>\n<dt>o</dt>\n<dd>sore throat</dd>\n<dt>o</dt>\n<dd>rash</dd>\n<dt>o</dt>\n<dd>enlarged lymph nodes in the neck or groin</dd>\n</dl>\n</td><td class=\"Rrule\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>fever </dd>\n<dt>o</dt>\n<dd>headache</dd>\n<dt>o</dt>\n<dd>vomiting or diarrhea</dd>\n<dt>o</dt>\n<dd>night sweats</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">While you are taking VOCABRIA for HIV-1 PrEP:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">VOCABRIA does not prevent other sexually transmitted infections. Practice safer sex by using a latex or polyurethane condom to reduce the risk of getting sexually transmitted infections.</span>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">You must stay HIV-1 negative to keep taking VOCABRIA for HIV-1 PrEP.</span>\n<dl>\n<dt>o</dt>\n<dd>Know your HIV-1 status and the HIV-1 status of your partners.</dd>\n<dt>o</dt>\n<dd>Ask your partners with HIV-1 if they are taking anti-HIV-1 medicines and have an undetectable viral load. An undetectable viral load is when the amount of virus in the blood is too low to be measured in a lab test. To maintain an undetectable viral load, your partners must keep taking HIV-1 medicine as prescribed. Your risk of getting HIV-1 is lower if your partners with HIV-1 are taking effective treatment.</dd>\n<dt>o</dt>\n<dd>Get tested for HIV-1 when your healthcare provider tells you.</dd>\n<dt>o</dt>\n<dd>Get tested for other sexually transmitted infections such as syphilis, chlamydia, and gonorrhea. These infections make it easier for HIV-1 to infect you.</dd>\n<dt>o</dt>\n<dd>If you think you were exposed to HIV-1, tell your healthcare provider right away. They may want to do more tests to be sure you are still HIV-1 negative.</dd>\n<dt>o</dt>\n<dd>Get information and support to help reduce sexual risk behaviors.</dd>\n<dt>o</dt>\n<dd>Do not miss any doses of VOCABRIA. Missing doses increases your risk of getting HIV-1 infection.</dd>\n<dt>o</dt>\n<dd>If you do become HIV-1 positive, you will need to take other medicines to treat HIV-1. VOCABRIA by itself is not a complete treatment for HIV-1.</dd>\n</dl>\n</dd>\n</dl>\n<p>\n<span class=\"Bold\">If you have HIV-1 and take only VOCABRIA, over time your HIV-1 may become harder to treat.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is VOCABRIA?</span>\n</p>\n<p>VOCABRIA is a prescription medicine that may be used in two different ways when a person’s healthcare provider determines that they meet certain requirements. VOCABRIA is used:</p>\n<dl>\n<dt>•</dt>\n<dd>to treat HIV-1 infection<dl>\n<dt>o</dt>\n<dd>in combination with another HIV-1 medicine called EDURANT (rilpivirine) for short-term treatment of HIV-1 infection in people 12 years of age and older who weigh at least 77 pounds (35 kg) to replace their current HIV-1 medicines to assess the tolerability of cabotegravir before receiving the long-acting medicine called CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension).</dd>\n<dt>o</dt>\n<dd>as oral therapy for people who will miss planned injection dosing with CABENUVA.</dd>\n</dl>\n</dd>\n<dt>•</dt>\n<dd>for HIV-1 PrEP to reduce the risk of getting HIV-1 infection<dl>\n<dt>o</dt>\n<dd>for short-term PrEP in adults and adolescents who weigh at least 77 pounds (at least 35 kg) to assess the tolerability of cabotegravir before receiving the long-acting medicine called APRETUDE (cabotegravir extended-release injectable suspension).</dd>\n<dt>o</dt>\n<dd>as oral dosing for people who will miss planned injection dosing with APRETUDE.</dd>\n</dl>\n</dd>\n</dl>\n<p>HIV-1 is the virus that causes Acquired Immune Deficiency Syndrome (AIDS).</p>\n<p>If you are taking VOCABRIA to treat HIV-1 infection, you should also read the Patient Information for EDURANT.</p>\n<p>It is not known if VOCABRIA for treatment of HIV-1 infection is safe and effective in children younger than 12 years of age or weighing less than 77 pounds (35 kg).</p>\n<p>It is not known if VOCABRIA is safe and effective in reducing the risk of HIV-1 infection in children younger than 12 years of age or weighing less than 77 pounds (less than 35 kg).</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Do not take VOCABRIA if you:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>have ever had an allergic reaction to cabotegravir.</dd>\n<dt>•</dt>\n<dd>are taking any of the following medicines:</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"></td><td valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>carbamazepine</dd>\n<dt>o</dt>\n<dd>oxcarbazepine </dd>\n<dt>o</dt>\n<dd>phenobarbital</dd>\n</dl>\n</td><td class=\"Rrule\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>phenytoin</dd>\n<dt>o</dt>\n<dd>rifampin</dd>\n<dt>o</dt>\n<dd>rifapentine</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">For people taking VOCABRIA for treatment of HIV-1 infection:</span>\n</p>\n<p>\n<span class=\"Bold\">Do not take VOCABRIA for HIV-1 infection if you are taking rifabutin.</span>\n</p>\n<p>\n<span class=\"Bold\">For people taking VOCABRIA for HIV-1 PrEP:</span>\n</p>\n<p>\n<span class=\"Bold\">Do not take VOCABRIA for HIV-1 PrEP if you:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">already have HIV-1 infection.</span> If you are HIV-1 positive, you will need to take other medicines to treat HIV-1. VOCABRIA by itself is not a complete treatment for HIV-1.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">do not know your HIV-1 infection status.</span> You may already be HIV-1 positive. You need to take other medicines to treat HIV-1. VOCABRIA can only help reduce your risk of getting HIV-1 infection <span class=\"Bold\">before</span> you are infected. </dd>\n<dt>•</dt>\n<dd>are allergic to cabotegravir.</dd>\n<dt>•</dt>\n<dd>are taking any of the medicines listed above. See <span class=\"Bold\">“Do not take VOCABRIA for HIV-1 infection if you:”</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Before taking VOCABRIA, tell your healthcare provider about all your medical conditions, including if you:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>have ever had a skin rash or an allergic reaction to medicines that contain cabotegravir.</dd>\n<dt>•</dt>\n<dd>have or have had liver problems, including hepatitis B or C infection.</dd>\n<dt>•</dt>\n<dd>have ever had mental health problems.</dd>\n<dt>•</dt>\n<dd>are pregnant or plan to become pregnant. It is not known if VOCABRIA will harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with VOCABRIA. <br/>\n<span class=\"Bold\">Pregnancy Registry.</span> There is a pregnancy registry for those who take VOCABRIA during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry.</dd>\n<dt>•</dt>\n<dd>are breastfeeding or plan to breastfeed. VOCABRIA may pass into your breast milk.<dl>\n<dt>o</dt>\n<dd>If you take VOCABRIA to treat HIV-1 infection, talk to your healthcare provider about the following risks to your baby from breastfeeding during treatment with VOCABRIA:<dl>\n<dt>▪</dt>\n<dd>the HIV-1 virus may pass to your baby if your baby does not have HIV-1 infection.</dd>\n<dt>▪</dt>\n<dd>the HIV-1 virus may become harder to treat if your baby has HIV-1 infection.</dd>\n<dt>▪</dt>\n<dd>your baby may get side effects from VOCABRIA.</dd>\n</dl>\n</dd>\n<dt>o</dt>\n<dd>If you take VOCABRIA for HIV-1 PrEP, talk with your healthcare provider about the best way to feed your baby while receiving VOCABRIA.</dd>\n</dl>\n</dd>\n</dl>\n<p>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements.</p>\n<p>Some medicines may interact with VOCABRIA. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine. </p>\n<p>You can ask your healthcare provider or pharmacist for a list of medicines that interact with VOCABRIA.</p>\n<p>\n<span class=\"Bold\">Do not start taking a new medicine without telling your healthcare provider.</span> Your healthcare provider can tell you if it is safe to take VOCABRIA with other medicines.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I take VOCABRIA?</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">For treatment of HIV-1 infection:</span>\n<dl>\n<dt>o</dt>\n<dd>Take 1 VOCABRIA tablet and 1 EDURANT tablet 1 time a day for 1 month (at least 28 days) exactly as your healthcare provider tells you. </dd>\n<dt>o</dt>\n<dd>Your healthcare provider may have you take VOCABRIA tablets in combination with EDURANT tablets for 1 month (at least 28 days) before you receive CABENUVA for the first time. This will allow your healthcare provider to assess how well you will tolerate these medicines.</dd>\n<dt>o</dt>\n<dd>Your final dose of VOCABRIA and EDURANT should be taken on the same day you receive your first injections of CABENUVA.</dd>\n<dt>o</dt>\n<dd>If you miss or plan to miss a scheduled monthly or every-2-month injections of CABENUVA by more than 7 days, call your healthcare provider right away to discuss your options. </dd>\n<dt>o</dt>\n<dd>If you take VOCABRIA at the same time as EDURANT, you should take it with a meal.</dd>\n<dt>o</dt>\n<dd>Do not run out of VOCABRIA. The virus in your blood may increase and the virus may become harder to treat when using VOCABRIA to treat HIV-1 infection. </dd>\n</dl>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">For HIV-1 PrEP:</span>\n<dl>\n<dt>o</dt>\n<dd>Take 1 VOCABRIA tablet 1 time a day for 1 month (at least 28 days) exactly as your healthcare provider tells you.</dd>\n<dt>o</dt>\n<dd>Your healthcare provider may have you take VOCABRIA tablets for 1 month (at least 28 days) before you receive APRETUDE for the first time. This will allow your healthcare provider to assess how well you will tolerate APRETUDE.</dd>\n<dt>o</dt>\n<dd>You should receive your first injection of APRETUDE on the day of your last dose of VOCABRIA or within 3 days.</dd>\n<dt>o</dt>\n<dd>If you miss or plan to miss a scheduled every-2-month injection of APRETUDE by more than 7 days, call your healthcare provider right away to discuss your options.</dd>\n</dl>\n</dd>\n<dt>•</dt>\n<dd>VOCABRIA may be taken with or without food.</dd>\n<dt>•</dt>\n<dd>If you take antacid products that contain aluminum or magnesium hydroxide or calcium carbonate, they should be taken at least 2 hours before or 4 hours after you take VOCABRIA.</dd>\n<dt>•</dt>\n<dd>Stay under the care of a healthcare provider while taking VOCABRIA.</dd>\n<dt>•</dt>\n<dd>Do not change your dose or stop taking VOCABRIA without talking to your healthcare provider.</dd>\n<dt>•</dt>\n<dd>Do not miss a dose of VOCABRIA. If you miss a dose of VOCABRIA, take it as soon as you remember.</dd>\n<dt>•</dt>\n<dd>If you take too much VOCABRIA, call your healthcare provider or go to the nearest hospital emergency room right away.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of VOCABRIA?</span>\n</p>\n<p>\n<span class=\"Bold\">VOCABRIA may cause serious side effects including:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Allergic reactions.</span> Call your healthcare provider right away if you develop a rash with VOCABRIA. <span class=\"Bold\">\n<br/>Stop taking VOCABRIA and get medical help right away if you develop a rash with any of the following signs or symptoms:</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"></td><td valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>fever</dd>\n<dt>o</dt>\n<dd>generally ill feeling</dd>\n<dt>o</dt>\n<dd>tiredness</dd>\n<dt>o</dt>\n<dd>muscle or joint aches</dd>\n<dt>o</dt>\n<dd>trouble breathing</dd>\n</dl>\n</td><td class=\"Rrule\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>blisters or sores in mouth</dd>\n<dt>o</dt>\n<dd>blisters </dd>\n<dt>o</dt>\n<dd>redness or swelling of the eyes</dd>\n<dt>o</dt>\n<dd>swelling of the mouth, face, lips, or tongue</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Liver problems</span>. Liver problems have happened in people with or without history of liver problems or other risk factors. Your healthcare provider may do blood tests to check your liver function. People with a history of liver problems or people who have certain liver function test changes may have an increased risk of developing new or worsening changes in certain liver tests during treatment with VOCABRIA. <br/>\n<span class=\"Bold\">Call your healthcare provider right away if you develop any of the following signs or symptoms of liver problems:</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"></td><td valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>your skin or the white part of your eyes turns yellow (jaundice)</dd>\n<dt>o</dt>\n<dd>dark or “tea-colored” urine</dd>\n<dt>o</dt>\n<dd>light-colored stools (bowel movements)</dd>\n<dt>o</dt>\n<dd>nausea or vomiting</dd>\n</dl>\n</td><td class=\"Rrule\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>loss of appetite </dd>\n<dt>o</dt>\n<dd>pain, aching, or tenderness on the right side of your stomach area</dd>\n<dt>o</dt>\n<dd>itching</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Depression or mood changes. Call your healthcare provider or get medical help right away if you develop any of the following symptoms:</span>\n<dl>\n<dt>o</dt>\n<dd>feeling sad or hopeless</dd>\n<dt>o</dt>\n<dd>feeling anxious or restless</dd>\n<dt>o</dt>\n<dd>have thoughts of hurting yourself (suicide) or have tried to hurt yourself</dd>\n</dl>\n</dd>\n</dl>\n<p class=\"First\">\n<span class=\"Bold\">The most common side effects of VOCABRIA for HIV-1 treatment include:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>fatigue</dd>\n<dt>•</dt>\n<dd>headache </dd>\n<dt>•</dt>\n<dd>diarrhea</dd>\n<dt>•</dt>\n<dd>nausea</dd>\n<dt>•</dt>\n<dd>dizziness</dd>\n<dt>•</dt>\n<dd>abnormal dreams</dd>\n</dl>\n</td><td class=\"Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>anxiety</dd>\n<dt>•</dt>\n<dd>sleep disorders</dd>\n<dt>•</dt>\n<dd>stomach pain</dd>\n<dt>•</dt>\n<dd>stomach bloating</dd>\n<dt>•</dt>\n<dd>weakness</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">The most common side effects of VOCABRIA for HIV-1 PrEP include:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>headache</dd>\n<dt>•</dt>\n<dd>diarrhea</dd>\n<dt>•</dt>\n<dd>nausea</dd>\n<dt>•</dt>\n<dd>dizziness</dd>\n<dt>•</dt>\n<dd>upper respiratory tract infection</dd>\n</dl>\n</td><td class=\"Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>tiredness</dd>\n<dt>•</dt>\n<dd>drowsiness</dd>\n<dt>•</dt>\n<dd>abnormal dreams</dd>\n<dt>•</dt>\n<dd>stomach pain</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">These are not all the possible side effects of VOCABRIA. </p>\n<p>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800‑FDA‑1088.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I store VOCABRIA?</span>\n</p>\n<p>Store VOCABRIA below 86°F (30°C).</p>\n<p>\n<span class=\"Bold\">Keep VOCABRIA and all medicines out of the reach of children.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of VOCABRIA.</span>\n</p>\n<p>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use VOCABRIA for a condition for which it was not prescribed. Do not give VOCABRIA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about VOCABRIA that is written for health professionals.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in VOCABRIA?</span>\n</p>\n<p>\n<span class=\"Bold\">Active ingredient:</span> cabotegravir</p>\n<p>\n<span class=\"Bold\">Inactive ingredients:</span> hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. </p>\n<p>\n<span class=\"Bold\">The tablet film-coating contains:</span> hypromellose, polyethylene glycol and titanium dioxide.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">   Manufactured for:</p>\n<p>   ViiV Healthcare</p>\n<p>   Durham, NC 27701</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">APRETUDE, CABENUVA, and VOCABRIA are trademarks owned by or licensed to the ViiV Healthcare group of companies.</p>\n<p>The other brand listed is a trademark owned by or licensed to its respective owner and is not a trademark owned by or licensed to the ViiV Healthcare group of companies. The maker of this brand is not affiliated with and does not endorse the ViiV Healthcare group of companies or its products.</p>\n<p>©2025 ViiV Healthcare group of companies or its licensor.</p>\n<p>VCB:7PIL</p>\n<p>For more information call 1-877-844-8872.</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule\" colspan=\"3\" valign=\"top\">\n<dl>\n<dt> </dt>\n<dd>           This Patient Information has been approved by the U.S. Food and Drug Administration.                Revised: 4/2025</dd>\n</dl>\n</td>\n</tr>\n</tbody>\n</table></div>" }

PRINCIPAL DISPLAY PANEL

{ "type": "p", "children": [], "text": "\nPRINCIPAL DISPLAY PANEL\n" }

NDC 49702-248-13

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VOCABRIA

{ "type": "p", "children": [], "text": "\nVOCABRIA\n" }

(cabotegravir)

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Tablets

{ "type": "p", "children": [], "text": "\nTablets\n" }

30 mg

{ "type": "p", "children": [], "text": "\n30 mg\n" }

Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n" }

Note to pharmacist:

{ "type": "p", "children": [], "text": "\nNote to pharmacist:\n" }

Do not cover ALERT box with pharmacy label.

{ "type": "p", "children": [], "text": "\nDo not cover ALERT box with pharmacy label.\n" }

ALERT: Find out about medicines that should NOT be taken with VOCABRIA.

{ "type": "p", "children": [], "text": "\nALERT: Find out about medicines that should NOT be taken with VOCABRIA.\n" }

30 tablets

{ "type": "p", "children": [], "text": "30 tablets" }

Each tablet contains 30 mg of cabotegravir equivalent to 31.62 mg of cabotegravir sodium.

{ "type": "p", "children": [], "text": "Each tablet contains 30 mg of cabotegravir equivalent to 31.62 mg of cabotegravir sodium." }

This package is child-resistant.

{ "type": "p", "children": [], "text": "This package is child-resistant." }

Keep out of reach of children.

{ "type": "p", "children": [], "text": "\nKeep out of reach of children.\n" }

Store below 30°C (86°F).

{ "type": "p", "children": [], "text": "Store below 30°C (86°F)." }

Do not accept if safety seal under cap is missing or broken.

{ "type": "p", "children": [], "text": "\nDo not accept if safety seal under cap is missing or broken.\n" }

See prescribing information for dosage information.

{ "type": "p", "children": [], "text": "See prescribing information for dosage information." }

ViiV Healthcare

{ "type": "p", "children": [], "text": "ViiV Healthcare" }

Mfd for:

{ "type": "p", "children": [], "text": "Mfd for:" }

ViiV Healthcare

{ "type": "p", "children": [], "text": "\nViiV Healthcare\n" }

Durham, NC 27701

{ "type": "p", "children": [], "text": "Durham, NC 27701" }

by:

{ "type": "p", "children": [], "text": "by:" }

GlaxoSmithKline

{ "type": "p", "children": [], "text": "\nGlaxoSmithKline\n" }

Durham, NC 27701

{ "type": "p", "children": [], "text": "Durham, NC 27701" }

Trademarks owned or licensed by ViiV Healthcare.

{ "type": "p", "children": [], "text": "Trademarks owned or licensed by ViiV Healthcare." }

©2023 ViiV Healthcare of licensor.

{ "type": "p", "children": [], "text": "©2023 ViiV Healthcare of licensor." }

Made in Singapore

{ "type": "p", "children": [], "text": "Made in Singapore" }

Rev.4/23

{ "type": "p", "children": [], "text": "Rev.4/23" }

{ "type": "", "children": [], "text": "" }