XYOSTED (testosterone enanthate) injection is an androgen indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone.

{ "type": "p", "children": [], "text": "XYOSTED (testosterone enanthate) injection is an androgen indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone." }

{ "type": "ul", "children": [ "Primary hypogonadism (congenital or acquired): testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range.", "Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations but have gonadotropins in the normal or low range." ], "text": "" }

Limitations of Use:

{ "type": "p", "children": [], "text": "\nLimitations of Use:\n" }

{ "type": "ul", "children": [ "Safety and efficacy of XYOSTED in men with “age-related hypogonadism” has not been established.", "Safety and efficacy of XYOSTED in males less than 18 years old have not been established [see Use in Specific Populations (8.4)]." ], "text": "" }

Prior to initiating XYOSTED, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range.

The starting dose of XYOSTED is 75 mg, administered subcutaneously in the abdominal region once a week.

Dose adjustment

Measure total testosterone trough concentrations (measured 7 days after the most recent dose) following 6 weeks of dosing, following 6 weeks after dose adjustment, and periodically while on treatment with XYOSTED. A trough concentration between 350 ng/dL and 650 ng/dL generally provides testosterone exposures in the normal range during the entire dosing interval.

Decrease the dose by 25 mg if the total testosterone trough concentration (Ctrough) is ≥650 ng/dL.Increase the dose by 25 mg if the total testosterone Ctrough is <350 ng/dL.Maintain the same dose if the total testosterone Ctrough is ≥350 ng/dL and <650 ng/dL.

XYOSTED is for subcutaneous injection in the abdominal region only. Avoid intramuscular or intravascular injection.

Instruct patients on the proper use of XYOSTED and direct them to use the proper injection site. Refer to the Instructions for Use for proper use of XYOSTED.

Visually inspect XYOSTED for particulate matter and discoloration prior to administration. Do not use if the liquid is cloudy or if visible particles are present.

Do not use XYOSTED if the seal is broken. Discard unused portion.

XYOSTED injection is available as 0.5 mL of a sterile, preservative-free and nonpyrogenic, clear, colorless to yellow solution containing testosterone enanthate. It is supplied in a single-dose syringe assembled in an autoinjector for subcutaneous administration. XYOSTED is available in three dosage strengths:

{ "type": "p", "children": [], "text": "XYOSTED injection is available as 0.5 mL of a sterile, preservative-free and nonpyrogenic, clear, colorless to yellow solution containing testosterone enanthate. It is supplied in a single-dose syringe assembled in an autoinjector for subcutaneous administration. XYOSTED is available in three dosage strengths:" }

50 mg/0.5 mL

{ "type": "p", "children": [], "text": "50 mg/0.5 mL" }

75 mg/0.5 mL

{ "type": "p", "children": [], "text": "75 mg/0.5 mL" }

100 mg/0.5 mL

{ "type": "p", "children": [], "text": "100 mg/0.5 mL" }

XYOSTED is contraindicated in:

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

{ "type": "ul", "children": [ "Men with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precautions (5.3)].", "Women who are pregnant. Testosterone can cause virilization of the female fetus when administered to a pregnant woman [see Use in Specific Populations (8.1)].", "Men with known hypersensitivity to XYOSTED or any of its ingredients (testosterone enanthate and sesame oil)." ], "text": "" }

Increases in hematocrit reflective of increases in red blood cell mass may require discontinuation of XYOSTED.

Check that hematocrit is not elevated prior to initiating XYOSTED. Evaluate hematocrit approximately every 3 months while the patient is on XYOSTED. If hematocrit becomes elevated, stop XYOSTED until the hematocrit decreases to an acceptable level. If XYOSTED is restarted and again causes hematocrit to become elevated, stop XYOSTED permanently. An increase in red blood cell mass may increase the risk of thromboembolic events.

There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as XYOSTED.

In the Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) Study, a randomized, double-blind, placebo-controlled, cardiovascular (CV) outcomes study, compared to placebo, topical testosterone gel was associated with a higher risk of VTE (1.7% vs 1.2%) which included DVT (0.6% vs 0.5%) and PE (0.9% vs 0.5%) [see Adverse Reactions (6.1)].

Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with XYOSTED and initiate appropriate workup and management.

Patients with BPH treated with androgens are at an increased risk of worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms.

Patients treated with androgens may be at an increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating and during treatment with androgens [see Contraindications (4)].

XYOSTED can increase blood pressure. Ambulatory blood pressure monitoring (ABPM) demonstrated XYOSTED increased systolic/diastolic BP by an average of 3.9/1.5 mmHg from baseline after 12 weeks of treatment in clinical trials [see Adverse Reactions (6.1)]. In patients with hypertension on antihypertensive therapy, XYOSTED increased the mean systolic/diastolic BP by 3.9/1.3 mm Hg from baseline.

The CV risk associated with topical testosterone gel was evaluated in TRAVERSE, a randomized, double-blind, placebo-controlled, CV outcomes study in men with a history of CV disease or multiple CV risk factors. In TRAVERSE, topical testosterone gel increased mean systolic blood pressure by 1.8 mmHg from baseline. However, the incidences of major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction [MI] and non-fatal stroke, were similar between treatment groups (7% for topical testosterone gel vs 7.3% for placebo) [see Adverse Reactions (6.1)].

Monitor blood pressure periodically in men using XYOSTED, especially men with hypertension. XYOSTED is not recommended for use in patients with uncontrolled hypertension.

Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids.  Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions [see Drug Abuse and Dependence (9)].

If testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range.  However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids.  Conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events.

Due to lack of controlled studies in women and potential virilizing effects, XYOSTED is not indicated for use in women [see Contraindications (4) and Use in Specific Populations (8.1, 8.2)].

With large doses of exogenous androgens, including XYOSTED, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (FSH) which could possibly lead to adverse effects on semen parameters including sperm count [see Use in Specific Populations (8.3)]. Patients should be informed of this possible risk when deciding whether to use or to continue to use XYOSTED.

Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate, which elevates blood levels for prolonged periods, has produced multiple hepatic adenomas. XYOSTED is not known to produce these adverse effects. Nonetheless, patients should be instructed to report any signs or symptoms of hepatic dysfunction (e.g., jaundice). If these occur, promptly discontinue XYOSTED while the cause is evaluated.

Androgens, including XYOSTED, may promote retention of sodium and water. Edema with or without congestive heart failure may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic therapy may be required.

Gynecomastia may develop and may persist in patients being treated for hypogonadism.

Treatment with testosterone products including XYOSTED may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung disease.

Changes in the serum lipid profile may require dose adjustment of lipid lowering drugs or discontinuation of testosterone therapy. Monitor the lipid profile periodically, particularly after starting testosterone therapy.

Androgens, including XYOSTED, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Monitor serum calcium concentrations regularly during treatment with XYOSTED in these patients.

Androgens, including XYOSTED, may decrease concentrations of thyroxine-binding globulin, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.

Depression and suicidal ideation and behavior, including completed suicide, have occurred during clinical trials in patients treated with XYOSTED. Advise patients and caregivers to seek medical attention for manifestations of suicidal ideation or behavior, new onset or worsening depression, anxiety, or other mood changes.

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 the rates observed in practice.

The safety of XYOSTED was evaluated in 2 clinical studies in a total of 283 men who received weekly subcutaneous doses for up to one year. All patients were started on 75 mg weekly, then the dose was titrated to 50 mg or 100 mg weekly, as needed, to achieve pre-dose total testosterone concentrations of ≥350 ng/dL and <650 ng/dL.

Table 1 summarizes adverse reactions (≥2%) reported in a one-year study with XYOSTED.

Table 1. Number (%) of Patients with Adverse Reactions ≥2% in a 1 Year study with XYOSTED

<div class="scrollingtable"><table border="1" cellpadding="2" cellspacing="0" width="75%"> <colgroup> <col width="50%"/> <col width="50%"/> </colgroup> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Preferred Term</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Overall (N=150)</span> </p> <p> <span class="Bold">n (%)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Hematocrit increased</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">21 (14.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Hypertension</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">19 (12.7)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Prostatic specific antigen (PSA) increased</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">18 (12.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Injection site bruising</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10 (6.7)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Headache</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8 (5.3)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Back pain</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5 (3.3)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Blood creatine phosphokinase increased</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5 (3.3)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Injection site hemorrhage</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5 (3.3)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Acne</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4 (2.7)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Blood testosterone increased</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4 (2.7)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Cough</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4 (2.7)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Edema peripheral</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4 (2.7)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Injection site erythema</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4 (2.7)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Prostatitis</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4 (2.7)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Urinary tract infection</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4 (2.7)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Abdominal pain</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (2.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Arthralgia</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (2.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Fatigue</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (2.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Hematuria</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (2.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Polycythemia</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (2.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Sleep apnea syndrome</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (2.0)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First">Note: Includes events that started on or after the first dosing, or existed prior to the first dose and worsened in severity or relatedness after dosing. Percentage was calculated using the number of patients in the column heading as the denominator.</p> </td> </tr> </tbody> </table></div>

Table 2 summarizes the adverse reactions (≥2%) reported in a 6-month study with XYOSTED.

Table 2. Number (%) of Patients with Adverse Reactions ≥2% in a 6-Month Study with XYOSTED

<div class="scrollingtable"><table border="1" cellpadding="2" cellspacing="0" width="75%"> <colgroup> <col width="50%"/> <col width="50%"/> </colgroup> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Preferred Term</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Overall (N = 133)</span> </p> <p> <span class="Bold">n (%)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Hematocrit increased</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">11 (8.3)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Injection site hemorrhage</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8 (6.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Blood creatine phosphokinase increased</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5 (3.8)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Injection site bruising</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5 (3.8)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Prostatitis</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4 (3.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Prostatic specific antigen (PSA) increased</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4 (3.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Urinary tract infection</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4 (3.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Fatigue</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (2.3)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Hypertension</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (2.3)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Insomnia</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (2.3)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Nausea</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (2.3)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First">Note: Includes events that started on or after the first dosing, or existed prior to the first dose and worsened in severity or relatedness after dosing. Percentage was calculated using the number of patients in the column heading as the denominator.</p> </td> </tr> </tbody> </table></div>

BP Increases

In the 6-month clinical study, 24-hour ambulatory blood pressure monitoring (ABPM) was conducted in 133 patients, 113 of whom completed the study. ABPM was conducted at 3 distinct 24-hour time periods: at Baseline and following 6 and 12 weeks of XYOSTED therapy. A total of 62 patients had acceptable ABPM recordings at baseline and Week 12. In that group, the mean change in systolic and diastolic BP from baseline to Week 12 was + 3.9 mmHg (95% CI 1.4-6.4) and + 1.5 mmHg (95% CI 0.4-2.6), respectively. In patients with a history of hypertension who were receiving antihypertensive therapy, the mean ABPM systolic and diastolic BP increased by +3.9 mmHg [95% CI 0.19-7.7] and +1.3 mmHg [95% CI -0.37-3.0], respectively [n=33]). In patients with no history of hypertension, the mean ABPM systolic and diastolic blood pressure increased by +4.1 mmHg [95% CI 0.43-7.8] and +1.9 mmHg [95% CI 0.055-3.7], respectively [n=28]).

10% of XYOSTED-treated patients were either started on antihypertensive medications or required changes to their antihypertensive medication regimen during the 1-year study.

A total of 3 patients were reported to have an adverse reaction of hypertension (2 patients with hypertension and 1 patient with worsening hypertension), and 1 was reported to have an adverse reaction of increased blood pressure.

Increases in Hematocrit

Increases in hematocrit to ≥55% were reported for 12 of the 283 patients in the 2 clinical studies, representing 4.2% of patients who received XYOSTED for up to one year. While the studies did not pre-define clinical adverse events related to increased hematocrit, polycythemia was reported as a medically significant adverse event in the investigator’s clinical judgment in 1.8% of treated patients. XYOSTED dosing resulted in mean hemoglobin increases of 1.0 ± 1.1 g/dL at 6 months and 1.1 ± 1.4 g/dL at 1 year and mean hematocrit increases of 3.8 ± 3.4% at 6 months and 5.4 ± 3.4% at 1 year.

Injection Site Reactions

Injection site reactions, including injection site bruising, injection site hemorrhage, injection site erythema and injection site induration were reported in 36 of the 283 patients in the 2 clinical studies, representing 12.7% of patients who received XYOSTED for up to one year. No patients discontinued XYOSTED because of injection site reactions.

Depression and Suicide Attempts

Depression requiring discontinuation was reported in 2 of the 283 patients in the two clinical studies and suicide attempts (one complete and one incomplete) were reported in 2 additional patients, comprising a total of 4 patients, representing 1.4% of patients who received XYOSTED for up to one year.

Increases in Serum PSA

Increases in serum PSA concentrations, defined as an increase from baseline of at least 1.4 ng/mL, or PSA greater than 4 ng/mL, led to discontinuation in 4.6% of the 283 patients in the 2 clinical studies.

Cardiovascular Outcomes

TRAVERSE was a randomized, double-blind, cardiovascular outcomes study to assess the cardiovascular (CV) safety of topical testosterone gel compared to placebo in 5198 hypogonadal men aged 45 to 80 years with a history of CV disease or with multiple CV risk factors. The primary outcome was the incidence of the composite endpoint of major adverse cardiovascular events (MACE), consisting of CV death, non-fatal myocardial infarction (MI), and non-fatal stroke.

The mean duration of therapy was approximately 22 months. The mean duration of follow-up was 33 months. Approximately 61% of all patients discontinued topical testosterone gel or placebo therapy.

The mean patient age (±SD) was 63.3 (7.9) years. Approximately 80% of patients were White, 17% were Black, and 3% were of other races or ethnic groups. Approximately 69%, 84%, and 93% had diabetes mellitus, hyperlipidemia, and hypertension, respectively. Approximately 55% had preexisting cardiovascular disease.

The mean serum testosterone concentration at baseline in patients receiving topical testosterone gel was 220.4 ng/dL (n=2129). The mean serum testosterone concentrations at 12 months, 24 months, 36 months, and 48 months in patients receiving topical testosterone gel were 440.5 ng/dL (n=1683), 420.9 ng/dl (n=1125), 428.7 ng/dL (n=731), and 365.2 ng/dL (n=220), respectively.

For patients treated with topical testosterone gel, the incidence of MACE was 7.0% (n=182 events) and for those receiving placebo, the incidence of MACE was 7.3% (n=190 events). The study demonstrated noninferiority of topical testosterone gel versus placebo because the upper bound of 95% CI was less than the prespecified risk margin, of 1.5 for MACE (Hazard Ratio 0.96 [95% CI: 0.78, 1.17]).

Additional Adverse Reactions Reported in TRAVERSE

Additional adverse reactions reported in TRAVERSE at an incidence rate >2% in either treatment group and greater in topical testosterone gel versus placebo included: nonfatal arrythmias warranting intervention (5.2% vs 3.3%), atrial fibrillation (3.5% vs 2.4%), acute kidney injury (2.3% vs 1.5%) and bone fracture (3.5% vs 2.5%). For the adverse reaction of bone fracture, each event was adjudicated by clinical review.

Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may necessitate a decrease in the dose of anti-diabetic medication.

Changes in anticoagulant activity may be seen with androgens, therefore more frequent monitoring of international normalized ratio (INR) and prothrombin time are recommended in patients taking warfarin, especially at the initiation and termination of androgen therapy.

The concurrent use of testosterone with corticosteroids may result in increased fluid retention and requires careful monitoring, particularly in patients with cardiac, renal or hepatic disease.

Some prescription medications and nonprescription analgesic and cold medications contain drugs known to increase blood pressure. Concomitant administration of these medications with XYOSTED may lead to additional increases in blood pressure.

Risk Summary

XYOSTED is contraindicated in pregnant women. Testosterone is teratogenic and may cause fetal harm when administered to a pregnant woman based on data from animal studies and its mechanism of action [see Contraindications (4) and Clinical Pharmacology (12.1)]. Exposure of a female fetus to androgens may result in varying degrees of virilization. In animal developmental studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural impairments of reproductive tissues in female and male offspring. These studies did not meet current standards for nonclinical development toxicity studies.

Data Animal Data

In developmental studies conducted in rats, rabbits, pigs, sheep and rhesus monkeys, pregnant animals received intramuscular injection of testosterone during the period of organogenesis. Testosterone treatment at doses that were comparable to those used for testosterone replacement therapy resulted in structural impairments in both female and male offspring. Structural impairments observed in females included increased ano-genital distance, phallus development, empty scrotum, no external vagina, intrauterine growth retardation, reduced ovarian reserve, and increased ovarian follicular recruitment. Structural impairments seen in male offspring included increased testicular weight, larger seminal tubular lumen diameter, and higher frequency of occluded tubule lumen. Increased pituitary weight was seen in both sexes.

Testosterone exposure in utero also resulted in hormonal and behavioral changes in offspring. Hypertension was observed in pregnant females and offspring in rats exposed to doses approximately twice those used for testosterone replacement therapy.

Risk Summary

XYOSTED is not indicated for use in females.

Infertility

During treatment with large doses of exogenous androgens, including XYOSTED, spermatogenesis may be suppressed through feedback inhibition of the hypothalamic-pituitary-testicular axis [see Warnings and Precautions (5.8)]. Reduced fertility is observed in some men taking testosterone replacement therapy. The impact on fertility may be irreversible.

Safety and effectiveness of XYOSTED in pediatric patients less than 18 years old have not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses.

There have not been sufficient numbers of geriatric patients in controlled clinical studies with XYOSTED to determine whether efficacy or safety in those over 65 years of age differs from younger subjects. Of the 283 patients enrolled in the 6-month and one-year efficacy and safety clinical study utilizing XYOSTED, 49 (17%) were over 65 years of age. Additionally, there are insufficient long-term safety data in geriatric patients to assess the potentially increased risk of cardiovascular disease and prostate cancer.

Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of BPH [see Warnings and Precautions (5.4)].

XYOSTED contains testosterone, a Schedule III controlled substance in the Controlled Substances Act.

Drug abuse is intentional non-therapeutic use of a drug, even once, for its rewarding psychological and physiological effects. Abuse and misuse of testosterone are seen in male and female adults and adolescents. Testosterone, often in combination with other anabolic androgenic steroids (AAS), and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. There have been reports of misuse of men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice.

Abuse-Related Adverse Reactions

Serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids, and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility and aggression.

The following adverse reactions have also been reported in men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility.

The following additional adverse reactions have been reported in women: hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities.

The following adverse reactions have been reported in male and female adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty.

Because these reactions are reported voluntarily from a population of uncertain size and may include abuse of other agents, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Behaviors Associated with Addiction

Continued abuse of testosterone and other anabolic steroids, leading to addiction is characterized by the following behaviors:

Physical dependence is characterized by withdrawal symptoms after abrupt drug discontinuation or a significant dose reduction of a drug. Individuals taking supratherapeutic doses of testosterone may experience withdrawal symptoms lasting for weeks or months which include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido and hypogonadotropic hypogonadism.

Drug dependence in individuals using approved doses of testosterone for approved indications has not been documented.

There have been no reports of overdosage in the XYOSTED clinical trials. There is a single report of acute overdosage with use of an approved injectable testosterone product. This subject had serum testosterone concentrations of up to 11,400 ng/dL, which were implicated in a cerebrovascular accident.

{ "type": "p", "children": [], "text": "There have been no reports of overdosage in the XYOSTED clinical trials. There is a single report of acute overdosage with use of an approved injectable testosterone product. This subject had serum testosterone concentrations of up to 11,400 ng/dL, which were implicated in a cerebrovascular accident." }

Treatment of overdosage consists of discontinuation of XYOSTED together with appropriate symptomatic and supportive care.

{ "type": "p", "children": [], "text": "Treatment of overdosage consists of discontinuation of XYOSTED together with appropriate symptomatic and supportive care." }

XYOSTED (testosterone enanthate) injection contains testosterone enanthate, an ester derivative of an endogenous androgen, testosterone. Testosterone enanthate is a white to creamy white crystalline powder described by the chemical name (17β)-17-[(1-Oxoheptyl) oxy]-androst-4-en-3-one.  Testosterone enanthate has the molecular formula C26H40O3, the molecular weight 400.59, and the molecular structure with the chemical formula:

{ "type": "p", "children": [], "text": "XYOSTED (testosterone enanthate) injection contains testosterone enanthate, an ester derivative of an endogenous androgen, testosterone. Testosterone enanthate is a white to creamy white crystalline powder described by the chemical name (17β)-17-[(1-Oxoheptyl) oxy]-androst-4-en-3-one.  Testosterone enanthate has the molecular formula C26H40O3, the molecular weight 400.59, and the molecular structure with the chemical formula:" }

XYOSTED (testosterone enanthate) injection is a sterile, preservative-free, and nonpyrogenic colorless to pale yellow solution supplied in a single-dose syringe assembled in a pressure-assisted autoinjector for subcutaneous administration. Each XYOSTED autoinjector contains 50 mg, 75 mg, or 100 mg of testosterone in sesame oil to form 0.5mL solution providing three product strengths of 50 mg/0.5 mL, 75 mg/0.5 mL, and 100 mg/0.5 mL.

{ "type": "p", "children": [], "text": "XYOSTED (testosterone enanthate) injection is a sterile, preservative-free, and nonpyrogenic colorless to pale yellow solution supplied in a single-dose syringe assembled in a pressure-assisted autoinjector for subcutaneous administration. Each XYOSTED autoinjector contains 50 mg, 75 mg, or 100 mg of testosterone in sesame oil to form 0.5mL solution providing three product strengths of 50 mg/0.5 mL, 75 mg/0.5 mL, and 100 mg/0.5 mL." }

Endogenous androgens, including testosterone and dihydrotestosterone (DHT) are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of the prostate, seminal vesicles, penis, and scrotum; the development of male hair distribution, such as facial, pubic, chest, and axillary hair; laryngeal enlargement, vocal cord thickening, and alterations in body musculature and fat distribution.

Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter’s syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).

No specific pharmacodynamic studies were conducted using XYOSTED.

Absorption and Bioavailability

XYOSTED delivers physiologic amounts of testosterone, producing circulating testosterone concentrations that approximate normal concentrations (300-1100 ng/dL) seen in healthy men.

Following weekly subcutaneous injection of XYOSTED for 12 weeks, serum testosterone concentrations reached a maximum after a median of 11.9 hours post-dose (range: 5.8-168.7 hours) then slowly declined (Figure 1). In this study, the starting dose of XYOSTED was 75 mg weekly then the XYOSTED dose was adjusted based upon total testosterone trough concentrations obtained following 6 weeks of dosing [see Dosage and Administration (2.2)].  Steady state serum testosterone concentration was achieved by Week 6.

Figure 1. Mean (±SD) of Total Testosterone (TT) Concentration (ng/dL) Following Weekly Administration of XYOSTED for 12 Weeks (N=137)

At Week 12, total testosterone concentrations were measured before and at specified times up to 168 hours after XYOSTED administration then analyzed for pharmacokinetic (PK) parameters (Table 3).

Table 3.  Arithmetic Mean (SD) and Range for Total Testosterone Pharmacokinetic Parameters at Week 12 Following Weekly Administration of 50 mg, 75 mg, or 100 mg XYOSTED (N=137)

<div class="scrollingtable"><table border="1" cellpadding="2" cellspacing="0" width="75%"> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First First Paragraph">C<span class="Sub">avg (0-168 hr)</span> </p> <p class="Paragraph">(ng/dL)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First First Paragraph">C<span class="Sub">max</span> </p> <p class="Paragraph">(ng/dL)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First First Paragraph">T<span class="Sub">max</span> </p> <p class="Paragraph">(hr)<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First First Paragraph">C<span class="Sub">min</span> </p> <p class="Paragraph">(ng/dL)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First First Paragraph">AUC (0-168 hr)</p> <p class="Paragraph">(ng·hr/dL)</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First First Paragraph">Mean (SD)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First First Paragraph">553 (127)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First First Paragraph">790 (215)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First First Paragraph">11.9</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First First Paragraph">436 (109)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First First Paragraph">92,955 (21,385)</p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First First Paragraph">Min - Max</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">276 - 1036</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">389 - 1410</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First First Paragraph">6 - 168</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First First Paragraph">166 - 788</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First First Paragraph">46432 - 173,987</p> </td> </tr> </tbody> </table></div>

a Reported as median

Distribution

Circulating testosterone is primarily bound in serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free), and the rest is loosely bound to albumin and other proteins.

Elimination

Metabolism

Testosterone enanthate is metabolized to testosterone via ester cleavage of the enanthate group. The mean (SD) maximum concentration of testosterone enanthate was 169 (68) ng/dL at Week 12 following weekly administration of XYOSTED.

Testosterone is metabolized to various 17-keto steroids through two different pathways. The major active metabolites of testosterone are estradiol and dihydrotestosterone (DHT). At pre-dose of Week 12 treatment, the mean DHT/testosterone ratio was 0.07 which was within the normal range.

Excretion

About 90% of a testosterone dose given intramuscularly is excreted in the urine as glucuronic and sulfuric acid-conjugates of testosterone or as metabolites. About 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver.

Carcinogenicity

Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, the implant induced cervical-uterine tumors, which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats.

Mutagenicity

Testosterone was negative in the in vitro Ames and in the in vivo mouse micronucleus assays.

Impairment of Fertility

The administration of exogenous testosterone suppresses spermatogenesis in the rat, dog and non-human primates, which was reversible on cessation of the treatment.

XYOSTED was evaluated in a 52-week, open-label study (NCT02159469) to evaluate its efficacy and safety when administered subcutaneously once weekly to 150 adult males with hypogonadism. The study included a Screening Phase, a Treatment Titration Phase, and an Extended Treatment Phase.

{ "type": "p", "children": [], "text": "XYOSTED was evaluated in a 52-week, open-label study (NCT02159469) to evaluate its efficacy and safety when administered subcutaneously once weekly to 150 adult males with hypogonadism. The study included a Screening Phase, a Treatment Titration Phase, and an Extended Treatment Phase.\n " }

Patients were trained on proper use of XYOSTED to self-administer the initial dose of 75 mg once weekly on the same day of the week and at approximately the same time (7:00 am ± 2 hours). The dose was increased by 25 mg at Week 7 if the Week 6 serum total testosterone concentration at the end of the dosing interval (Ctrough) was <350 ng/dL, and was decreased by 25 mg if the Ctrough was ≥650 ng/dL.

{ "type": "p", "children": [], "text": "Patients were trained on proper use of XYOSTED to self-administer the initial dose of 75 mg once weekly on the same day of the week and at approximately the same time (7:00 am ± 2 hours). The dose was increased by 25 mg at Week 7 if the Week 6 serum total testosterone concentration at the end of the dosing interval (Ctrough) was <350 ng/dL, and was decreased by 25 mg if the Ctrough was ≥650 ng/dL.\n " }

The primary endpoint was the percentage of patients with a time-averaged serum total testosterone concentration (Cavg) over the 7-day dosing interval (0 to 168 hours) within the normal range (300 to 1100 ng/dL) at Week 12.

{ "type": "p", "children": [], "text": "The primary endpoint was the percentage of patients with a time-averaged serum total testosterone concentration (Cavg) over the 7-day dosing interval (0 to 168 hours) within the normal range (300 to 1100 ng/dL) at Week 12. \n " }

Secondary endpoints were the percentage of patients with a maximum total testosterone concentration (Cmax) above three predetermined limits: greater than 1500 ng/dL, between 1800 and 2500 ng/dL, and greater than 2500 ng/dL.

{ "type": "p", "children": [], "text": "Secondary endpoints were the percentage of patients with a maximum total testosterone concentration (Cmax) above three predetermined limits: greater than 1500 ng/dL, between 1800 and 2500 ng/dL, and greater than 2500 ng/dL." }

One hundred and thirty five (90%) of the 150 hypogonadal men who received XYOSTED had a serum total testosterone concentration Cavg(0-168h) within the normal range (300 to 1100 ng/dL) at Week 12. There were no patients (0%) with Cmax >1500 ng/dL at Week 12.

{ "type": "p", "children": [], "text": "One hundred and thirty five (90%) of the 150 hypogonadal men who received XYOSTED had a serum total testosterone concentration Cavg(0-168h) within the normal range (300 to 1100 ng/dL) at Week 12. There were no patients (0%) with Cmax >1500 ng/dL at Week 12.\n " }

XYOSTED (testosterone enanthate) injection is provided as 0.5 mL of a sterile, preservative-free, and nonpyrogenic colorless to pale yellow solution in a single-dose syringe pre-assembled in an autoinjector for a single subcutaneous administration. XYOSTED is packaged in cartons containing four (4) or one (1) autoinjectors. XYOSTED is available in the following strengths and configurations.

Before use, each autoinjector should be visually inspected. XYOSTED should be clear to light yellow in color and free of visible particles. Do not use if the liquid is cloudy or if visible particles are present. You may notice an air bubble, this is normal.

Do Not refrigerate or freeze. Use at room temperature.

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

{ "type": "p", "children": [], "text": "\nAdvise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).\n" }

Venous Thromboembolism

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

{ "type": "ul", "children": [ "Inform patients that XYOSTED can cause venous thromboembolism. Advise patients of the signs and symptoms of venous thromboembolism, which may include the following: lower limb pain, edema, or erythema; and dyspnea or chest pain. Advise patients to promptly report the signs and symptoms of venous thromboembolism, discontinue use of XYOSTED, and seek urgent medical care." ], "text": "" }

Increased Blood Pressure

{ "type": "p", "children": [], "text": "\nIncreased Blood Pressure\n" }

{ "type": "ul", "children": [ "Inform patients that XYOSTED can increase BP which can increase cardiovascular risk over time.", "Instruct patients about the importance of monitoring BP periodically while on XYOSTED. If BP increases while on XYOSTED, antihypertensive medications may need to be started, added, or adjusted to control BP, or XYOSTED may need to be discontinued." ], "text": "" }

Other Adverse Reactions Inform patients that treatment with androgens may lead to adverse reactions which include:

{ "type": "p", "children": [], "text": "\nOther Adverse Reactions\nInform patients that treatment with androgens may lead to adverse reactions which include:" }

{ "type": "ul", "children": [ "Changes in urinary habits related to effects on prostate size, such as increased urination at night, hesitancy, urinary frequency, urinary urgency, having a urine accident, or being unable to pass urine or weak urine flow.", "Breathing disturbances that may reflect obstructive sleep apnea, including those associated with sleep or excessive daytime sleepiness.", "Too frequent or persistent erections of the penis.", "Ankle swelling that may reflect peripheral edema.", "Red blood cell count increase, PSA increase, injection site bruising, injection site bleeding.Instruct patients to report any changes in their state of health, such as changes in urinary habits, breathing, sleep, and mood, including new onset or worsening of depression, or suicidal ideation." ], "text": "" }

Keep XYOSTED out of the reach of children

{ "type": "p", "children": [], "text": "Keep XYOSTED out of the reach of children" }

For more information call: 1-844-XYOSTED (1-844-996-7833) or visit www.XYOSTED.com

{ "type": "p", "children": [], "text": "For more information call: 1-844-XYOSTED (1-844-996-7833) or visit www.XYOSTED.com\n" }

Manufactured For: Antares Pharma, Inc. Ewing, NJ 08628

{ "type": "p", "children": [], "text": "Manufactured For: Antares Pharma, Inc. Ewing, NJ 08628" }

XYOSTED is a trademark of Antares Pharma, Inc.

{ "type": "p", "children": [], "text": "XYOSTED is a trademark of Antares Pharma, Inc." }

©2022 Antares Pharma, Inc. All rights reserved

{ "type": "p", "children": [], "text": "©2022 Antares Pharma, Inc. All rights reserved" }

<div class="scrollingtable"><table border="1" cellpadding="2" cellspacing="0" width="85%"> <colgroup> <col align="left" valign="top" width="80%"/> <col align="right" valign="top" width="20%"/> </colgroup> <tfoot> <tr class="First First Last Last"> <td align="left">This Medication Guide has been approved by the U.S. Food and Drug Administration.<br/> <br/>For Controlled Substances, Antares Pharma will authorize a one-time reimbursement.</td><td align="right">Issued: 03/2025</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First">MEDICATION GUIDE</p> <p>XYOSTED<span class="Sup">®</span> (ZYE-oh-sted)</p> <p>(testosterone enanthate) injection, for subcutaneous use CIII</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">What is XYOSTED?</span> </p> <p>XYOSTED is a prescription medicine that contains testosterone. XYOSTED is used to treat adult men who have low or no testosterone due to certain medical conditions.</p> <p>It is not known if XYOSTED is safe and effective in children younger than 18 years old. Improper use of XYOSTED may affect bone growth in children.</p> <p>It is not known if XYOSTED is safe or effective to treat men who have low testosterone due to aging.</p> <p>XYOSTED is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your XYOSTED in a safe place to protect it. Never give your XYOSTED to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and it is against the law.</p> <p>XYOSTED is not meant for use by women.</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Do not take XYOSTED if you:</span> </p> <ul> <li>are a man who has breast cancer.</li> <li>have or might have prostate cancer.</li> <li>are a woman who is pregnant. XYOSTED may harm your unborn baby.</li> <li>are allergic to XYOSTED or to any ingredients in XYOSTED including testosterone or sesame oil. </li> <li>have low testosterone without certain medical conditions.  For example, do not take XYOSTED if you have low testosterone due to age.</li> </ul> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Before you use XYOSTED, tell your healthcare provider about all your medical conditions, including, if you:</span> </p> <ul> <li>have high blood pressure or are being treated for high blood pressure.</li> <li>have heart problems.</li> <li>have high red blood cell count (hematocrit) or high hemoglobin laboratory value.</li> <li>have urinary problems due to an enlarged prostate.</li> <li>have kidney or liver problems.</li> <li>have a history of mental health illness including suicidal thoughts or actions, depression, anxiety or mood disorder.</li> <li>have problems breathing while you sleep (sleep apnea).</li> </ul> <p></p> <p>Tell your healthcare provider about all the medicines you take, including prescription and non­prescription medicines, vitamins, and herbal supplements.</p> <p>Using XYOSTED with other medicines can affect each other. Especially, tell your healthcare provider if you take:</p> <ul> <li>insulin</li> <li>medicines that decrease blood clotting (blood thinners)</li> <li>corticosteroids</li> <li>medicines for pain and cold.</li> </ul> <p>Know the medicines you take. Ask your healthcare provider or pharmacist for a list of all your medicines if you are not sure. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">How should I use XYOSTED?</span> </p> <ul> <li> <span class="Bold">See the detailed Instructions for Use for information about how to use XYOSTED.</span> </li> <li>Use XYOSTED exactly as your healthcare provider tells you to take it.</li> <li>Your healthcare provider will show you or your caregiver how to inject XYOSTED. You should not inject XYOSTED until you have been trained on the proper way to use it.</li> </ul> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">What are the possible side effects of XYOSTED?</span> </p> <p> <span class="Bold">XYOSTED can cause serious side effects including:</span> </p> <ul> <li> <span class="Bold">Increase in red blood cell count (hematocrit) or hemoglobin. </span> <ul> <li>XYOSTED increases red blood cell counts in some patients. High red blood cell counts increase the risk of clots, strokes, and heart attacks.</li> <li>You may need to stop XYOSTED if your red blood cell count increases.</li> <li>Your healthcare provider should check your red blood cell count and hemoglobin while you use XYOSTED.</li> </ul> </li> </ul> <ul> <li> <span class="Bold">If you already have an enlarged prostate, your signs and symptoms may get worse while using XYOSTED. This can include:</span> <ul> <li>increased urination at night</li> <li>trouble starting your urine stream</li> <li>having to pass urine many times during the day</li> <li>having an urge that you have to go to the bathroom right away</li> <li>having a urine accident</li> <li>being unable to pass urine or weak urine flow</li> </ul> </li> </ul> <ul> <li> <span class="Bold">Increased risk of prostate cancer</span>. Your healthcare provider should check you for prostate cancer or any other prostate problems before you start and while you use XYOSTED.</li> <li> <span class="Bold">Blood clots in the legs or lungs. </span>Signs and symptoms of a blood clot in your leg can include leg pain, swelling or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain.</li> <li> <span class="Bold">Increase in blood pressure. </span>XYOSTED can increase your blood pressure. Increases in blood pressure can increase the risk of heart attack or stroke over time. Your risk may be greater if you have already had a heart attack or stroke or if you have other risk factors for heart attack or stroke. If your blood pressure increases while on XYOSTED, blood pressure medicines may need to be started. If you are taking blood pressure medicines, new blood pressure medicines may need to be added or your current blood pressure medicines may need to be adjusted to control your blood pressure. If your blood pressure cannot be controlled, XYOSTED may need to be stopped. Your healthcare provider will monitor your blood pressure while you are being treated with XYOSTED.</li> <li> <span class="Bold">Abuse.</span> Testosterone can be abused, when taken at higher than prescribed doses and when used with other anabolic androgenic steroids. Abuse can cause serious heart and psychological side effects. Your healthcare provider should check you for signs of abuse before and during treatment with XYOSTED.</li> <li> <span class="Bold">In large doses XYOSTED may lower your sperm count.</span> </li> <li> <span class="Bold">Liver problems</span>. Symptoms of liver problems may include:<ul> <li>nausea or vomiting</li> <li>yellowing of your skin or whites of your eyes</li> <li>dark urine</li> <li>pain on the right side of your stomach area (abdominal pain)</li> </ul> </li> </ul> <ul> <li> <span class="Bold">Swelling of your ankles, feet, or body, with or without heart failure.</span> </li> <li> <span class="Bold">Enlarged or painful breasts.</span> </li> <li> <span class="Bold">Problems breathing while you sleep (sleep apnea).</span> </li> <li> <span class="Bold">Change in mood. </span>Talk to your healthcare provide if you have changes in mood or behavior including, new or worsening depression, or suicidal thoughts.</li> </ul> <p> <span class="Bold">Call your healthcare provider right away if you have any of the serious side effects listed above.</span> </p> <p> <span class="Bold">The most common side effects of XYOSTED include:</span> </p> <ul> <li>red blood cell count increase</li> <li>prostatic specific antigen (PSA) increase (a test used to screen for prostate cancer)</li> <li>high blood pressure</li> <li>injection site reactions including:<ul> <li>bruising</li> <li>bleeding</li> <li>redness</li> <li>hardness</li> </ul> </li> </ul> <p> <span class="Bold">Other side effects include </span>more erections than are normal for you or erections that last a long time.</p> <p>Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</p> <p>These are not all the possible side effects of XYOSTED. For more information, ask your healthcare provider or pharmacist.  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 align="left" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">How should I store XYOSTED?</span> </p> <p> <span class="Bold">Do not refrigerate or freeze. Use at room temperature.</span> </p> <p>Store at controlled room temperature, 68°F to 77°F (20°C to 25°C).  Protect from light (keep in carton until time of use). Discard unused portion.</p> <p> <span class="Bold">Keep XYOSTED and all medicines out of the reach of children.</span> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">General information about the safe and effective use of XYOSTED.</span> </p> <p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use XYOSTED for a condition for which it was not prescribed. Do not give XYOSTED to other people, even they have the same symptoms that you have. It may harm them.  You can ask your pharmacist or healthcare provider for information about XYOSTED that is written for health professionals.</p> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">What are the ingredients in XYOSTED?</span> </p> <p> <span class="Bold">Active ingredient: </span>testosterone enanthate</p> <p> <span class="Bold">Inactive ingredients: </span>sesame oil</p> <br/> <p>Manufactured by:</p> <p>Antares Pharma, Inc. Ewing, NJ 08628 XYOSTED is a trademark of Antares Pharma, Inc.  ©2018 Antares Pharma, Inc. All rights reserved</p> <p>For more information, go to <a href="http://www.xyosted.com">www.XYOSTED.com</a> or call 1-844-XYOSTED (1-844-996-7833).    </p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"2\" cellspacing=\"0\" width=\"85%\">\n<colgroup>\n<col align=\"left\" valign=\"top\" width=\"80%\"/>\n<col align=\"right\" valign=\"top\" width=\"20%\"/>\n</colgroup>\n<tfoot>\n<tr class=\"First First Last Last\">\n<td align=\"left\">This Medication Guide has been approved by the U.S. Food and Drug Administration.<br/>\n<br/>For Controlled Substances, Antares Pharma will authorize a one-time reimbursement.</td><td align=\"right\">Issued: 03/2025</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">MEDICATION GUIDE</p>\n<p>XYOSTED<span class=\"Sup\">®</span> (ZYE-oh-sted)</p>\n<p>(testosterone enanthate) injection, for subcutaneous use CIII</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is XYOSTED?</span>\n</p>\n<p>XYOSTED is a prescription medicine that contains testosterone. XYOSTED is used to treat adult men who have low or no testosterone due to certain medical conditions.</p>\n<p>It is not known if XYOSTED is safe and effective in children younger than 18 years old. Improper use of XYOSTED may affect bone growth in children.</p>\n<p>It is not known if XYOSTED is safe or effective to treat men who have low testosterone due to aging.</p>\n<p>XYOSTED is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your XYOSTED in a safe place to protect it. Never give your XYOSTED to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and it is against the law.</p>\n<p>XYOSTED is not meant for use by women.</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Do not take XYOSTED if you:</span>\n</p>\n<ul>\n<li>are a man who has breast cancer.</li>\n<li>have or might have prostate cancer.</li>\n<li>are a woman who is pregnant. XYOSTED may harm your unborn baby.</li>\n<li>are allergic to XYOSTED or to any ingredients in XYOSTED including testosterone or sesame oil. </li>\n<li>have low testosterone without certain medical conditions.  For example, do not take XYOSTED if you have low testosterone due to age.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Before you use XYOSTED, tell your healthcare provider about all your medical conditions, including, if you:</span>\n</p>\n<ul>\n<li>have high blood pressure or are being treated for high blood pressure.</li>\n<li>have heart problems.</li>\n<li>have high red blood cell count (hematocrit) or high hemoglobin laboratory value.</li>\n<li>have urinary problems due to an enlarged prostate.</li>\n<li>have kidney or liver problems.</li>\n<li>have a history of mental health illness including suicidal thoughts or actions, depression, anxiety or mood disorder.</li>\n<li>have problems breathing while you sleep (sleep apnea).</li>\n</ul>\n<p></p>\n<p>Tell your healthcare provider about all the medicines you take, including prescription and non­prescription medicines, vitamins, and herbal supplements.</p>\n<p>Using XYOSTED with other medicines can affect each other. Especially, tell your healthcare provider if you take:</p>\n<ul>\n<li>insulin</li>\n<li>medicines that decrease blood clotting (blood thinners)</li>\n<li>corticosteroids</li>\n<li>medicines for pain and cold.</li>\n</ul>\n<p>Know the medicines you take. Ask your healthcare provider or pharmacist for a list of all your medicines if you are not sure. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I use XYOSTED?</span>\n</p>\n<ul>\n<li>\n<span class=\"Bold\">See the detailed Instructions for Use for information about how to use XYOSTED.</span>\n</li>\n<li>Use XYOSTED exactly as your healthcare provider tells you to take it.</li>\n<li>Your healthcare provider will show you or your caregiver how to inject XYOSTED. You should not inject XYOSTED until you have been trained on the proper way to use it.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of XYOSTED?</span>\n</p>\n<p>\n<span class=\"Bold\">XYOSTED can cause serious side effects including:</span>\n</p>\n<ul>\n<li>\n<span class=\"Bold\">Increase in red blood cell count (hematocrit) or hemoglobin. </span>\n<ul>\n<li>XYOSTED increases red blood cell counts in some patients. High red blood cell counts increase the risk of clots, strokes, and heart attacks.</li>\n<li>You may need to stop XYOSTED if your red blood cell count increases.</li>\n<li>Your healthcare provider should check your red blood cell count and hemoglobin while you use XYOSTED.</li>\n</ul>\n</li>\n</ul>\n<ul>\n<li>\n<span class=\"Bold\">If you already have an enlarged prostate, your signs and symptoms may get worse while using XYOSTED. This can include:</span>\n<ul>\n<li>increased urination at night</li>\n<li>trouble starting your urine stream</li>\n<li>having to pass urine many times during the day</li>\n<li>having an urge that you have to go to the bathroom right away</li>\n<li>having a urine accident</li>\n<li>being unable to pass urine or weak urine flow</li>\n</ul>\n</li>\n</ul>\n<ul>\n<li>\n<span class=\"Bold\">Increased risk of prostate cancer</span>. Your healthcare provider should check you for prostate cancer or any other prostate problems before you start and while you use XYOSTED.</li>\n<li>\n<span class=\"Bold\">Blood clots in the legs or lungs. </span>Signs and symptoms of a blood clot in your leg can include leg pain, swelling or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain.</li>\n<li>\n<span class=\"Bold\">Increase in blood pressure. </span>XYOSTED can increase your blood pressure. Increases in blood pressure can increase the risk of heart attack or stroke over time. Your risk may be greater if you have already had a heart attack or stroke or if you have other risk factors for heart attack or stroke. If your blood pressure increases while on XYOSTED, blood pressure medicines may need to be started. If you are taking blood pressure medicines, new blood pressure medicines may need to be added or your current blood pressure medicines may need to be adjusted to control your blood pressure. If your blood pressure cannot be controlled, XYOSTED may need to be stopped. Your healthcare provider will monitor your blood pressure while you are being treated with XYOSTED.</li>\n<li>\n<span class=\"Bold\">Abuse.</span> Testosterone can be abused, when taken at higher than prescribed doses and when used with other anabolic androgenic steroids. Abuse can cause serious heart and psychological side effects. Your healthcare provider should check you for signs of abuse before and during treatment with XYOSTED.</li>\n<li>\n<span class=\"Bold\">In large doses XYOSTED may lower your sperm count.</span>\n</li>\n<li>\n<span class=\"Bold\">Liver problems</span>. Symptoms of liver problems may include:<ul>\n<li>nausea or vomiting</li>\n<li>yellowing of your skin or whites of your eyes</li>\n<li>dark urine</li>\n<li>pain on the right side of your stomach area (abdominal pain)</li>\n</ul>\n</li>\n</ul>\n<ul>\n<li>\n<span class=\"Bold\">Swelling of your ankles, feet, or body, with or without heart failure.</span>\n</li>\n<li>\n<span class=\"Bold\">Enlarged or painful breasts.</span>\n</li>\n<li>\n<span class=\"Bold\">Problems breathing while you sleep (sleep apnea).</span>\n</li>\n<li>\n<span class=\"Bold\">Change in mood. </span>Talk to your healthcare provide if you have changes in mood or behavior including, new or worsening depression, or suicidal thoughts.</li>\n</ul>\n<p>\n<span class=\"Bold\">Call your healthcare provider right away if you have any of the serious side effects listed above.</span>\n</p>\n<p>\n<span class=\"Bold\">The most common side effects of XYOSTED include:</span>\n</p>\n<ul>\n<li>red blood cell count increase</li>\n<li>prostatic specific antigen (PSA) increase (a test used to screen for prostate cancer)</li>\n<li>high blood pressure</li>\n<li>injection site reactions including:<ul>\n<li>bruising</li>\n<li>bleeding</li>\n<li>redness</li>\n<li>hardness</li>\n</ul>\n</li>\n</ul>\n<p>\n<span class=\"Bold\">Other side effects include </span>more erections than are normal for you or erections that last a long time.</p>\n<p>Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</p>\n<p>These are not all the possible side effects of XYOSTED. For more information, ask your healthcare provider or pharmacist.  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 align=\"left\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I store XYOSTED?</span>\n</p>\n<p>\n<span class=\"Bold\">Do not refrigerate or freeze. Use at room temperature.</span>\n</p>\n<p>Store at controlled room temperature, 68°F to 77°F (20°C to 25°C).  Protect from light (keep in carton until time of use). Discard unused portion.</p>\n<p>\n<span class=\"Bold\">Keep XYOSTED and all medicines out of the reach of children.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of XYOSTED.</span>\n</p>\n<p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use XYOSTED for a condition for which it was not prescribed. Do not give XYOSTED to other people, even they have the same symptoms that you have. It may harm them.  You can ask your pharmacist or healthcare provider for information about XYOSTED that is written for health professionals.</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in XYOSTED?</span>\n</p>\n<p>\n<span class=\"Bold\">Active ingredient: </span>testosterone enanthate</p>\n<p>\n<span class=\"Bold\">Inactive ingredients: </span>sesame oil</p>\n<br/>\n<p>Manufactured by:</p>\n<p>Antares Pharma, Inc. Ewing, NJ 08628 XYOSTED is a trademark of Antares Pharma, Inc.  ©2018 Antares Pharma, Inc. All rights reserved</p>\n<p>For more information, go to <a href=\"http://www.xyosted.com\">www.XYOSTED.com</a> or call 1-844-XYOSTED (1-844-996-7833).    </p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

​XYOSTED​® Testosterone Enanthate Injection USP CIII

{ "type": "p", "children": [], "text": "\n​XYOSTED​®\n\nTestosterone Enanthate Injection USP CIII\n" }

Single-dose auto-injector.For a single subcutaneous administration.Administer one device weekly.

{ "type": "p", "children": [], "text": "Single-dose auto-injector.For a single subcutaneous administration.Administer one device weekly." }

Read this Instructions for Use before you start using XYOSTED (ZYE-oh-sted) and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or treatment.

{ "type": "p", "children": [], "text": "Read this Instructions for Use before you start using XYOSTED (ZYE-oh-sted) and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or treatment." }

Important Information about XYOSTED:

{ "type": "p", "children": [], "text": "\nImportant Information about XYOSTED:\n" }

{ "type": "ul", "children": [ "Use XYOSTED exactly as your healthcare provider tells you to take it.", "Inject XYOSTED only 1 time each week. Do not use XYOSTED every day.", "Your healthcare provider will show you or your caregiver how to inject XYOSTED. You should not inject XYOSTED until you have been trained on the proper way to use it.", "Check XYOSTED before you inject it. XYOSTED should be clear to light yellow in color and should be free of visible particles.", "\nDo not use if the liquid is cloudy or if visible particles are present. You may see air bubble(s), this is normal.", "\nDo not use XYOSTED if the safety seal is broken or if the Auto-Injector appears broken, damaged or changed in any way.", "XYOSTED should be injected in the stomach (abdomen) area after cleaning the skin.", "\nDo not inject XYOSTED within 2 inches of the belly button (navel).", "\nDo not inject XYOSTED in any other areas of the body.", "\nDo not inject XYOSTED in areas where the skin is tender, bruised, red, scaly, hard, or has scars or stretch marks.", "Discard unused portion." ], "text": "" }

If you are not sure if XYOSTED was injected, or if you have a hard time giving the injection, do not inject another dose. Call your pharmacist or healthcare provider right away.

{ "type": "p", "children": [], "text": "If you are not sure if XYOSTED was injected, or if you have a hard time giving the injection, do not inject another dose. Call your pharmacist or healthcare provider right away." }

<div class="scrollingtable"><table border="1" cellpadding="2" cellspacing="0" width="30%"> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">If you need help or instructions, call:<br/>1-844-996-7833</span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <ul> <li>Carefully read all steps before beginning injection.</li> <li>Injection process must be completed without interruption.</li> </ul> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"2\" cellspacing=\"0\" width=\"30%\">\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">If you need help or instructions, call:<br/>1-844-996-7833</span>\n</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<ul>\n<li>Carefully read all steps before beginning injection.</li>\n<li>Injection process must be completed without interruption.</li>\n</ul>\n</td>\n</tr>\n</tbody>\n</table></div>" }

​Supplies You Will Need

{ "type": "p", "children": [], "text": "\n​Supplies You Will Need\n" }

{ "type": "ul", "children": [ "1 XYOSTED Auto-Injector", "1 alcohol swab", "1 cotton ball or gauze" ], "text": "" }

​Storage Conditions

{ "type": "p", "children": [], "text": "\n​Storage Conditions\n" }

{ "type": "ul", "children": [ "Do not refrigerate or freeze.", "Protect from light.", "Use at room temperature.", "Store at 68° - 77° F (20° - 25° C).", "Keep XYOSTED and all medicines away from children." ], "text": "" }

​Inspect Auto-Injector

{ "type": "p", "children": [], "text": "\n​Inspect Auto-Injector\n" }

{ "type": "ul", "children": [ "\nDo not remove Cap until ready to inject.", "Inspect Auto-Injector for any visible damage. Do not use if it appears damaged or broken.", "Check the expiration date. Do not use if the expiration date has passed.", "Inspect the medicine through the Viewing Window; it should be clear to light yellow and free of visible particles (see Figure 2)." ], "text": "" }

Do not use if the medicine is cloudy or if visible particles are present. You may notice an air bubble, this is normal.

{ "type": "p", "children": [], "text": "\nDo not use if the medicine is cloudy or if visible particles are present. You may notice an air bubble, this is normal." }

​Select & Prep Injection Site

{ "type": "p", "children": [], "text": "\n​Select & Prep Injection Site\n" }

Wash your hands with soap and water.Wipe the abdomen injection site with an alcohol swab.

{ "type": "p", "children": [], "text": "Wash your hands with soap and water.Wipe the abdomen injection site with an alcohol swab." }

Allow the site to dry on its own. Do not fan or blow on the injection site. Do not touch the site again before injecting.

{ "type": "p", "children": [], "text": "\nAllow the site to dry on its own.\nDo not fan or blow on the injection site.\nDo not touch the site again before injecting." }

Only use the left or right side of the abdomen (belly) for injection sites. Do not use the area within 2 inches around your navel (belly button). See Figure 3.

{ "type": "p", "children": [], "text": "\nOnly use the left or right side of the abdomen (belly) for injection sites.\nDo not use the area within 2 inches around your navel (belly button). \nSee Figure 3.\n" }

Do not use in areas where the skin is tender, bruised, red, scaly, or hard. Avoid areas with scars, tattoos, or stretch marks.

{ "type": "p", "children": [], "text": "\nDo not use in areas where the skin is tender, bruised, red, scaly, or hard. Avoid areas with scars, tattoos, or stretch marks." }

​Administering Injection

{ "type": "p", "children": [], "text": "\n​Administering Injection\n" }

1. Remove Cap

{ "type": "p", "children": [], "text": "\n1. Remove Cap\n" }

Twist the Cap to remove (this will also break the red safety seal). See Figure 4.

{ "type": "p", "children": [], "text": "Twist the Cap to remove (this will also break the red safety seal). See Figure 4.\n" }

After the Cap is removed, a few drops of liquid may appear, this is normal.The Auto-Injector should be used or discarded after the Cap is removed. Do not re-Cap for later use.

{ "type": "p", "children": [], "text": "After the Cap is removed, a few drops of liquid may appear, this is normal.The Auto-Injector should be used or discarded after the Cap is removed.\nDo not re-Cap for later use." }

<div class="scrollingtable"><table border="1" cellpadding="2" cellspacing="0" width="40%"> <tbody class="Headless"> <tr class="First First Last Last"> <td align="left" class="Botrule Lrule Toprule" valign="middle"><img alt="Warning symbol" src="/dailymed/image.cfm?name=warning.jpg&amp;setid=8a3d204c-be26-49e0-8599-0ac12a272e81"/></td><td align="left" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Do not</span> touch the Needle End of the Auto-Injector with your hand or fingers after the Cap is removed, doing so can cause injection and injury to your hands.</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"2\" cellspacing=\"0\" width=\"40%\">\n<tbody class=\"Headless\">\n<tr class=\"First First Last Last\">\n<td align=\"left\" class=\"Botrule Lrule Toprule\" valign=\"middle\"><img alt=\"Warning symbol\" src=\"/dailymed/image.cfm?name=warning.jpg&amp;setid=8a3d204c-be26-49e0-8599-0ac12a272e81\"/></td><td align=\"left\" class=\"Botrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Do not</span> touch the Needle End of the Auto-Injector with your hand or fingers after the Cap is removed, doing so can cause injection and injury to your hands.</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

​2. Position Auto-Injector

{ "type": "p", "children": [], "text": "\n​2. Position Auto-Injector\n" }

Gently squeeze the abdomen injection site to create a raised area and hold that area firmly until after the injection is complete (see Figure 5).

{ "type": "p", "children": [], "text": "Gently squeeze the abdomen injection site to create a raised area and hold that area firmly until after the injection is complete (see Figure 5)." }

Place the Needle End of the Auto-Injector on the abdomen injection site.

{ "type": "p", "children": [], "text": "Place the Needle End of the Auto-Injector on the abdomen injection site." }

Keep the Auto-Injector straight at a 90 degree angle to the abdomen injection site. (see Figure 6).

{ "type": "p", "children": [], "text": "Keep the Auto-Injector straight at a 90 degree angle to the abdomen injection site. (see Figure 6)." }

3. Inject & Hold Down

{ "type": "p", "children": [], "text": "\n3. Inject & Hold Down\n" }

Firmly push the Auto-Injector down on the abdomen site and continue to hold down after you hear the “CLICK” (see Figure 7).

{ "type": "p", "children": [], "text": "Firmly push the Auto-Injector down on the abdomen site and continue to hold down after you hear the “CLICK” (see Figure 7)." }

While holding the XYOSTED Auto-Injector down, slowly count from 1 to 10 to allow all of the medicine to be delivered (see Figure 8).

{ "type": "p", "children": [], "text": "While holding the XYOSTED Auto-Injector down, slowly count from 1 to 10 to allow all of the medicine to be delivered (see Figure 8)." }

Keep holding the XYOSTED Auto-Injector down for a total of 10 seconds even if your injection is complete and the viewing window turns orange sooner.

{ "type": "p", "children": [], "text": "Keep holding the XYOSTED Auto-Injector down for a total of 10 seconds even if your injection is complete and the viewing window turns orange sooner." }

It is normal if there is slight bleeding from the site after injection. If this occurs, hold a cotton ball or gauze on the area for a few seconds. Do not rub the area.

{ "type": "p", "children": [], "text": "It is normal if there is slight bleeding from the site after injection. If this occurs, hold a cotton ball or gauze on the area for a few seconds. Do not rub the area." }

​4. Inspect Viewing Window

{ "type": "p", "children": [], "text": "\n​4. Inspect Viewing Window\n" }

After injecting, inspect the Viewing Window. It should be orange, confirming the dose was administered (see Figure 9).

{ "type": "p", "children": [], "text": "After injecting, inspect the Viewing Window. It should be orange, confirming the dose was administered (see Figure 9)." }

If the Viewing Window is not orange:

{ "type": "p", "children": [], "text": "If the Viewing Window is not orange:" }

{ "type": "ul", "children": [ "\nDo not use another Auto-Injector.", "\nDo not attempt another injection.", "\nCall your healthcare provider or 1-844-996-7833 for assistance." ], "text": "" }

​Disposal After Injection

{ "type": "p", "children": [], "text": "\n​Disposal After Injection\n" }

<div class="scrollingtable"><table border="1" cellpadding="2" cellspacing="0" width="20%"> <tbody class="Headless"> <tr class="First First Last Last"> <td align="left" class="Botrule Lrule Toprule" valign="top"><img alt="IFU Disposal after injection" src="/dailymed/image.cfm?name=ifu10.jpg&amp;setid=8a3d204c-be26-49e0-8599-0ac12a272e81"/></td><td align="left" class="Botrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">After completing your injection, dispose of the XYOSTED Auto-Injector and Cap in an FDA-cleared sharps disposal container immediately after use.</span> </p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"2\" cellspacing=\"0\" width=\"20%\">\n<tbody class=\"Headless\">\n<tr class=\"First First Last Last\">\n<td align=\"left\" class=\"Botrule Lrule Toprule\" valign=\"top\"><img alt=\"IFU Disposal after injection\" src=\"/dailymed/image.cfm?name=ifu10.jpg&amp;setid=8a3d204c-be26-49e0-8599-0ac12a272e81\"/></td><td align=\"left\" class=\"Botrule Rrule Toprule\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">After completing your injection, dispose of the XYOSTED Auto-Injector and Cap in an FDA-cleared sharps disposal container immediately after use.</span>\n</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Do not dispose of the XYOSTED Auto-Injector in your household trash.

{ "type": "p", "children": [], "text": "\nDo not dispose of the XYOSTED Auto-Injector in your household trash." }

If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:

{ "type": "p", "children": [], "text": "If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:" }

{ "type": "ul", "children": [ "made of a heavy-duty plastic", "can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out", "upright and stable during use", "leak-resistant", "properly labeled to warn of hazardous waste inside the container" ], "text": "" }

When your sharps disposal container is almost full, you will need to follow your community guidelines for the proper way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal in the state that you live in, go to the FDA’s website at: http://www.fda.gov/safesharpsdisposal.

{ "type": "p", "children": [], "text": "When your sharps disposal container is almost full, you will need to follow your community guidelines for the proper way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal in the state that you live in, go to the FDA’s website at: http://www.fda.gov/safesharpsdisposal." }

Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

{ "type": "p", "children": [], "text": "\nDo not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container." }

This Instructions for Use has been approved by the U.S. Food and Drug Administration

{ "type": "p", "children": [], "text": "This Instructions for Use has been approved by the U.S. Food and Drug Administration" }

LB-0118 V08

{ "type": "p", "children": [], "text": "LB-0118 V08" }

Manufactured for:Antares Pharma, Inc.Ewing, NJ 0862803/2025

{ "type": "p", "children": [], "text": "Manufactured for:Antares Pharma, Inc.Ewing, NJ 0862803/2025" }

XYOSTED® (testosterone enathate injection, USP) CIII

{ "type": "p", "children": [], "text": "\nXYOSTED® (testosterone enathate injection, USP) CIII\n" }

50 mg/0.5 mL

{ "type": "p", "children": [], "text": "\n50 mg/0.5 mL\n" }

NDC 54436-250-02

{ "type": "p", "children": [], "text": "NDC 54436-250-02" }

For subcutaneous injections only.Single-dose autoinjector. Discard after use. ​DO NOT​ reuse. Rx ONLY

{ "type": "p", "children": [], "text": "For subcutaneous injections only.Single-dose autoinjector. Discard after use. ​DO NOT​ reuse. Rx ONLY" }

XYOSTED® (testosterone enathate injection, USP) CIII

{ "type": "p", "children": [], "text": "\nXYOSTED® (testosterone enathate injection, USP) CIII\n" }

75 mg/0.5 mL

{ "type": "p", "children": [], "text": "\n75 mg/0.5 mL\n" }

NDC 54436-275-02

{ "type": "p", "children": [], "text": "NDC 54436-275-02" }

For subcutaneous injections only.Single-dose autoinjector.Discard after use. DO NOT reuse. Rx ONLY

{ "type": "p", "children": [], "text": "For subcutaneous injections only.Single-dose autoinjector.Discard after use. DO NOT reuse. Rx ONLY" }

XYOSTED® (testosterone enathate injection, USP) CIII

{ "type": "p", "children": [], "text": "\nXYOSTED® (testosterone enathate injection, USP) CIII\n" }

100 mg/0.5 mL

{ "type": "p", "children": [], "text": "\n100 mg/0.5 mL\n" }

NDC 54436-200-02

{ "type": "p", "children": [], "text": "NDC 54436-200-02" }

For subcutaneous injections only.Single-dose autoinjector. Discard after use. ​DO NOT​ reuse. Rx ONLY

{ "type": "p", "children": [], "text": "For subcutaneous injections only.Single-dose autoinjector. Discard after use. ​DO NOT​ reuse. Rx ONLY" }

XYOSTED® (testosterone enathate injection, USP)

{ "type": "p", "children": [], "text": "\nXYOSTED® (testosterone enathate injection, USP)" }

NDC 54436-250-04

{ "type": "p", "children": [], "text": "NDC 54436-250-04" }

50 mg/0.5 mL

{ "type": "p", "children": [], "text": "\n50 mg/0.5 mL\n" }

CIII

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

For subcutaneous injections only

{ "type": "p", "children": [], "text": "For subcutaneous injections only" }

Four Single-dose autoinjectors

{ "type": "p", "children": [], "text": "Four Single-dose autoinjectors" }

Discard after use. DO NOT reuse.

{ "type": "p", "children": [], "text": "\nDiscard after use. DO NOT reuse." }

Dispense the enclosed Medication Guide to each patient.

{ "type": "p", "children": [], "text": "\nDispense the enclosed Medication Guide to each patient.\n" }

Rx ONLY

{ "type": "p", "children": [], "text": "Rx ONLY" }

XYOSTED® (testosterone enathate injection, USP)

{ "type": "p", "children": [], "text": "\nXYOSTED® (testosterone enathate injection, USP)\n" }

NDC 54436-275-04

{ "type": "p", "children": [], "text": "\nNDC 54436-275-04\n" }

75 mg/0.5 mL

{ "type": "p", "children": [], "text": "\n75 mg/0.5 mL\n" }

CIII

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

For subcutaneous injections only

{ "type": "p", "children": [], "text": "For subcutaneous injections only" }

Four Single-dose autoinjectors

{ "type": "p", "children": [], "text": "Four Single-dose autoinjectors" }

Discard after use. DO NOT reuse.

{ "type": "p", "children": [], "text": "\nDiscard after use. DO NOT reuse." }

Dispense the enclosed Medication Guide to each patient.

{ "type": "p", "children": [], "text": "\nDispense the enclosed Medication Guide to each patient.\n" }

Rx ONLY

{ "type": "p", "children": [], "text": "Rx ONLY" }

XYOSTED® (testosterone enathate injection, USP)

{ "type": "p", "children": [], "text": "\nXYOSTED® (testosterone enathate injection, USP)" }

NDC 54436-200-04

{ "type": "p", "children": [], "text": "NDC 54436-200-04" }

100 mg/0.5 mL

{ "type": "p", "children": [], "text": "\n100 mg/0.5 mL\n" }

CIII

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

For subcutaneous injections only

{ "type": "p", "children": [], "text": "For subcutaneous injections only" }

Four Single-dose autoinjectors

{ "type": "p", "children": [], "text": "Four Single-dose autoinjectors" }

Discard after use. DO NOT reuse.

{ "type": "p", "children": [], "text": "\nDiscard after use. DO NOT reuse." }

Dispense the enclosed Medication Guide to each patient.

{ "type": "p", "children": [], "text": "\nDispense the enclosed Medication Guide to each patient.\n" }

Rx ONLY

{ "type": "p", "children": [], "text": "Rx ONLY" }

JATENZO (testosterone undecanoate) is an androgen indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone:

{ "type": "p", "children": [], "text": "JATENZO (testosterone undecanoate) is an androgen indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone:\n" }

{ "type": "ul", "children": [ "Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range.\n ", "Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from causes such as tumors, trauma, or radiation. These men have low testosterone serum concentrations but have gonadotropins in the normal or low range.\n " ], "text": "" }

Limitations of use:

{ "type": "p", "children": [], "text": "\nLimitations of use:\n" }

{ "type": "ul", "children": [ "Safety and efficacy of JATENZO in men with “age-related hypogonadism” have not been established.", "Safety and efficacy of JATENZO in males less than 18 years old have not been established [see Use in Specific Populations (8.4)]." ], "text": "" }

Prior to initiating JATENZO, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these testosterone concentrations are below the normal range.

Individualize the dosage of JATENZO based on the patient's serum testosterone concentration response to the drug. The recommended starting dose is 237 mg taken orally twice daily, once in the morning and once in the evening. Take JATENZO with food.

Dose Adjustment

To ensure proper dose adjustment, measure serum testosterone concentrations 6 hours after the morning dose in plain tubes, clotted at room temperature for 30 minutes prior to centrifugation. Adjust the JATENZO dose based on this serum testosterone measurement as shown in Table 1. Wait seven days after starting treatment or adjusting the dose before checking the serum testosterone concentration. Thereafter, periodically monitor serum testosterone concentrations 6 hours after the morning dose.

Administer the same dose in the morning and evening. The minimum recommended dose is 158 mg twice daily. The maximum recommended dose is 396 mg (two 198 mg capsules) twice daily.

<div class="scrollingtable"><table width="863.748px"> <caption> <span>Table 1: JATENZO Dose Adjustment Scheme</span> </caption> <col width="39.4%"/> <col width="30.3%"/> <col width="30.3%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Testosterone Concentration in Serum From Plain Tube Drawn 6 hours After Morning Dose</span></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Current JATENZO Dose<br/>(mg, twice daily)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">New JATENZO Dose<br/>(mg, twice daily)</span></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="4">Less than 425 ng/dL </td><td align="center" class="Botrule Lrule Rrule Toprule">158 </td><td align="center" class="Botrule Lrule Rrule Toprule">198 </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule">198 </td><td align="center" class="Botrule Lrule Rrule Toprule">237 </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule">237 </td><td align="center" class="Botrule Lrule Rrule Toprule">316 (two 158 mg capsules) </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule">316 (two 158 mg capsules) </td><td align="center" class="Botrule Lrule Rrule Toprule">396 (two 198 mg capsules) </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule">425 ng/dL – 970 ng/dL </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2">No Dose Change </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="5">More than 970 ng/dL<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">396 (two 198 mg capsules) </td><td align="center" class="Botrule Lrule Rrule Toprule">316 (two 158 mg capsules) </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule">316 (two 158 mg capsules) </td><td align="center" class="Botrule Lrule Rrule Toprule">237 </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule">237 </td><td align="center" class="Botrule Lrule Rrule Toprule">198 </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule">198 </td><td align="center" class="Botrule Lrule Rrule Toprule">158 </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule">158 </td><td align="center" class="Botrule Lrule Rrule Toprule">Discontinue Treatment </td> </tr> </tbody> </table></div>

JATENZO capsules for oral use are available in three strengths:

{ "type": "p", "children": [], "text": "JATENZO capsules for oral use are available in three strengths:\n" }

{ "type": "ul", "children": [ "The 158 mg testosterone undecanoate capsules are opaque red and imprinted with “158” in white ink.\n", "The 198 mg testosterone undecanoate capsules are opaque white and imprinted with “198” in red ink.\n", "The 237 mg testosterone undecanoate capsules are opaque orange and imprinted with “237” in white ink.\n" ], "text": "" }

JATENZO is contraindicated in:

{ "type": "p", "children": [], "text": "JATENZO is contraindicated in:\n" }

{ "type": "ul", "children": [ "Men with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precautions (5.3)].\n ", "Women who are pregnant. Testosterone can cause virilization of the female fetus when administered to a pregnant woman [see Use in Specific Populations (8.1)].\n ", "Men with known hypersensitivity to JATENZO or any of its ingredients [see Description (11)].\n " ], "text": "" }

Increases in hematocrit reflective of increases in red blood cell mass, may require lowering the dose or discontinuation of JATENZO. Check that hematocrit is not elevated prior to initiating JATENZO. Evaluate hematocrit approximately every 3 months while the patient is on JATENZO. If hematocrit becomes elevated, stop JATENZO until the hematocrit decreases to an acceptable concentration. If JATENZO is restarted and again causes hematocrit to become elevated, stop JATENZO permanently. An increase in red blood cell mass may increase the risk of thromboembolic events [see Warnings and Precautions (5.2)].

There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone replacement products such as JATENZO.  

In the Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) Study, a randomized, double-blind, placebo-controlled, cardiovascular (CV) outcomes study, compared to placebo, topical testosterone gel was associated with a higher risk of VTE (1.7% vs 1.2%) which included DVT (0.6% vs 0.5%) and PE (0.9% vs 0.5%) [see Adverse Reactions (6.1)].

Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE.  If a venous thromboembolic event is suspected, discontinue treatment with JATENZO and initiate appropriate workup and management [see Adverse Reactions (6.2)].

Patients with BPH treated with androgens are at an increased risk for worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms.

Patients treated with androgens may be at increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating and during treatment with androgens [see Contraindications (4)].

JATENZO can increase blood pressure. Ambulatory blood pressure monitoring (ABPM) demonstrated JATENZO increased systolic /diastolic BP by an average of 4.9/2.5 mmHg from baseline after 4 months of treatment in a clinical trial [see Adverse Reactions (6.1)].  In patients with hypertension on antihypertensive therapy, JATENZO increased the mean systolic/diastolic BP by 5.4/3.2 mmHg from baseline.  Average blood pressures had not plateaued at the end of the trial.

The CV risk associated with topical testosterone gel was evaluated in TRAVERSE, a randomized, double-blind, placebo-controlled, CV outcomes study in men with a history of CV disease or multiple CV risk factors.  In TRAVERSE, topical testosterone gel increased mean systolic blood pressure by 1.8 mmHg from baseline.  However, the incidences of major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction [MI] and non-fatal stroke, were similar between treatment groups (7% for topical testosterone gel vs 7.3% for placebo) [See Adverse Reactions (6.1)].

Monitor blood pressure periodically in men using JATENZO, especially men with hypertension.  JATENZO is not recommended for use in patients with uncontrolled hypertension.

Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions [see Drug Abuse and Dependence (9)].

If testosterone abuse is suspected, check testosterone concentrations to ensure they are within therapeutic range [see Dose and Administration (2)]. However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids. Conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events.

Due to lack of controlled studies in women and potential virilizing effects, JATENZO is not indicated for use in women [see Contraindications (4) and Use in Specific Populations (8.1, 8.2)].

With large doses of exogenous androgens, including JATENZO, spermatogenesis may be suppressed through feedback inhibition of pituitary FSH possibly leading to adverse effects on semen parameters including sperm count [see Use in Specific Populations (8.3)]. Patients should be informed of this possible risk when deciding whether to use or to continue to use JATENZO.

Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate has produced multiple hepatic adenomas. JATENZO is not known to cause these adverse effects. Nonetheless, patients should be instructed to report any signs or symptoms of hepatic dysfunction (e.g. jaundice). If these occur, promptly discontinue JATENZO while the cause is evaluated.

Androgens, including JATENZO, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic therapy may be required.

Gynecomastia may develop and persist in patients being treated for hypogonadism.

The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung disease.

Changes in the serum lipid profile may require dose adjustment of lipid lowering drugs or discontinuation of testosterone therapy. Monitor the lipid profile periodically, particularly after starting testosterone therapy.

Androgens, including JATENZO, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Monitor serum calcium concentrations regularly during treatment with JATENZO in these patients.

Androgens, including JATENZO, may decrease concentrations of thyroxin-binding globulin, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.

Depression and suicidal ideation has been reported in patients treated with JATENZO in clinical trials. Advise patients and caregivers to seek medical attention for manifestations of new onset or worsening depression, suicidal ideation or behavior, anxiety, or other mood changes [see Adverse Events (6.1)].

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

The safety of JATENZO was evaluated in a randomized, controlled clinical study with 166 patients treated with JATENZO twice daily with morning and evening meals for approximately 4 months. All patients were started on 237 mg twice daily, then the dose was titrated to 158 mg, 198 mg, 316 mg, or 396 mg twice daily to achieve testosterone concentrations in the eugonadal range.

Table 2 summarizes adverse reactions (≥2%) reported in this 4-month study.

<div class="scrollingtable"><table> <caption> <span>Table 2: Number (%) of Patients with Adverse Reactions ≥ 2% in a 4-Month Study with JATENZO </span> </caption> <col width="70.65%"/> <col width="29.35%"/> <tfoot> <tr class="First"> <td colspan="2" valign="top"> <p class="First">Among the 569 patients who received JATENZO in all Phase 2 and 3 trials combined, the following adverse reactions were reported in &gt;2% of patients: polycythemia, diarrhea, dyspepsia, eructation, peripheral edema, nausea, increased hematocrit, headache, prostatomegaly, and hypertension. </p> </td> </tr> <tr class="Last"> <td colspan="2" valign="top"> <p class="First">Three of the 166 patients (1.8%) in the 4-month study experienced adverse reactions that led to premature discontinuation from the study, including rash (n=1) and headache (n=2). </p> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="bottom">    <span class="Bold">Preferred Term</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Overall (N = 166)</span> <br/> <span class="Bold">n (%)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top">   Headache </td><td align="center" class="Botrule Lrule Rrule Toprule">8 (4.8) </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top">   Hematocrit increased </td><td align="center" class="Botrule Lrule Rrule Toprule">8 (4.8) </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top">   Hypertension </td><td align="center" class="Botrule Lrule Rrule Toprule">6 (3.6) </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top">   High-density lipoprotein decreased </td><td align="center" class="Botrule Lrule Rrule Toprule">5 (3.0) </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top">   Nausea </td><td align="center" class="Botrule Lrule Rrule Toprule">4 (2.4) </td> </tr> </tbody> </table></div>

BP Increases

In the 4-month clinical study, 24-hour ABPM was conducted on 166 patients.  ABPM was conducted at baseline and at Day 139 of JATENZO therapy.  A total of 135 patients had acceptable ABPM recordings at both time periods and were at least 85% compliant with study drug.  In that group, the mean change in 24-hour systolic BP and diastolic BP from baseline to final on-treatment visit on Day 139 (n=135) was +4.9 mmHg (95% CI 3.5, 6.4) and +2.5 mmHg (95% CI 1.5, 3.6), respectively.

In patients with a history of hypertension who were receiving antihypertensive therapy, the mean ABPM systolic and diastolic BP increased by 5.4 mmHg [95% CI 3.3, 7.6] and 3.2 mmHg [95% CI 1.7, 4.7], respectively [n=67]. In patients with no history of hypertension, the mean ABPM systolic and diastolic blood pressure increased by 4.4 mmHg [95% CI 2.3, 6.4] and 1.8 mmHg [95% CI 0.2, 3.3], respectively [n=63].  

Twelve (7.2%) patients on JATENZO either started antihypertensive medications or had their antihypertensive regimen increased during the study. 

A total of 6 patients were reported to have an adverse reaction of hypertension (2 patients with hypertension and 4 patients with worsening hypertension), and 3 were reported to have an adverse reaction of increased blood pressure.

HR Increases

JATENZO increased mean heart rate by an average of 2.2 beats per minute (bpm) [95% CI (1.0, 3.3), N=135] during the study. Patients without a history of hypertension had a greater average increase in mean heart rate (2.7 bpm [95% CI (0.8, 4.6), N=63]) compared to patients with treated hypertension (1.9 bpm [95% CI (0.3, 3.5), N=67)]).

Increases in Hematocrit

Increases in hematocrit were reported in 8 of the 166 (4.8%) patients, which occurred in the second half of the study. None of these increases led to premature discontinuation of JATENZO.

Headaches

Headaches were reported in 8 of the 166 patients (4.8%) of which three required treatment with analgesics or non-steroidal anti-inflammatory drugs and 2 led to premature discontinuation from the study. Five of these 8 patients had headache events that resolved within 1 to 2 days.

Depression and suicidal ideation

Two of the 166 patients (1.2%) reported either worsening depression (n=1) or new-onset depression (n=1). One of the 569 patients (0.2%) in clinical trials had suicidal ideation. Each patient completed the study.

Increases in Serum PSA

The mean increase from baseline in PSA was 0.2 ng/mL (n=161). Increases in serum PSA concentrations, defined as an increase from baseline of at least 1.4 ng/mL or PSA greater than 4 ng/mL, occurred in 3 (1.9%) of the patients at the final visit.

Cardiovascular Outcomes

TRAVERSE was a randomized, double-blind, cardiovascular outcomes study to assess the cardiovascular (CV) safety of topical testosterone gel compared to placebo in 5198 hypogonadal men aged 45 to 80 years with a history of CV disease or with multiple CV risk factors.  The primary outcome was the incidence of the composite endpoint of major adverse cardiovascular events (MACE), consisting of CV death, non-fatal myocardial infarction (MI), and non-fatal stroke. 

The mean duration of therapy was approximately 22 months. The mean duration of follow-up was 33 months. Approximately 61% of all patients discontinued topical testosterone gel or placebo therapy.

The mean patient age (±SD) was 63.3 (7.9) years.  Approximately 80% of patients were White, 17% were Black, and 3% were of other races or ethnic groups.  Approximately 69%, 84%, and 93% had diabetes mellitus, hyperlipidemia, and hypertension, respectively. Approximately 55% had preexisting cardiovascular disease. 

The mean serum testosterone concentration at baseline in patients receiving topical testosterone gel was 220.4 ng/dL (n=2129).  The mean serum testosterone concentrations at 12 months, 24 months, 36 months, and 48 months in patients receiving topical testosterone gel were 440.5 ng/dL (n=1683), 420.9 ng/dl (n=1125), 428.7 ng/dL (n=731), and 365.2 ng/dL (n=220), respectively.

For patients treated with topical testosterone gel, the incidence of MACE was 7.0% (n=182 events) and for those receiving placebo, the incidence of MACE was 7.3% (n=190 events). The study demonstrated non-inferiority of topical testosterone gel versus placebo because the upper bound of 95% CI was less than the pre-specified risk margin, of 1.5 for MACE (Hazard Ratio 0.96 [95% CI: 0.78, 1.17]). 

Additional Adverse Reactions Reported in TRAVERSE

Additional adverse reactions reported in TRAVERSE at an incidence rate >2% in either treatment group and greater in topical testosterone gel versus placebo included: nonfatal arrythmias warranting intervention (5.2% vs 3.3%), atrial fibrillation (3.5% vs 2.4%), acute kidney injury (2.3% vs 1.5%) and bone fracture (3.5% vs 2.5%). For the adverse reaction of bone fracture, each event was adjudicated by clinical review.

The following adverse reactions have been identified during post-approval use of testosterone. 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.

Cardiovascular Disorders: myocardial infarction, stroke [see Warnings and Precautions (5.4), Clinical Trial Experience (6.1)]

Vascular Disorders: Venous thromboembolism [see Warnings and Precautions (5.1)]

Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may necessitate a decrease in the dose of anti-diabetic medication.

Changes in anticoagulant activity may be seen with androgens; therefore, more frequent monitoring of international normalized ratio (INR) and prothrombin time are recommended in patients taking warfarin, especially at the initiation and termination of androgen therapy.

The concurrent use of testosterone with corticosteroids may result in increased fluid retention and requires careful monitoring particularly in patients with cardiac, renal or hepatic disease.

Some prescription medications and nonprescription analgesic and cold medications contain drugs known to increase blood pressure. Concomitant administration of these medications with JATENZO may lead to additional increases in blood pressure [see Warnings and Precautions (5.4)].

Risk Summary

JATENZO is contraindicated in pregnant women. Testosterone is teratogenic and may cause fetal harm based on data from animal studies and its mechanism of action [see Contraindications (4) and Clinical Pharmacology (12.1)]. Exposure of a female fetus to androgens may result in varying degrees of virilization. In animal developmental studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural impairments of reproductive tissues in female and male offspring. These studies did not meet current standards for nonclinical development toxicity studies.

Data

Animal Data

In developmental studies conducted in rats, rabbits, pigs, sheep and rhesus monkeys, pregnant animals received intramuscular injection of testosterone during the period of organogenesis. Testosterone treatment at doses that were comparable to those used for testosterone replacement therapy resulted in structural impairments in both female and male offspring. Structural impairments observed in females included increased anogenital distance, phallus development, empty scrotum, no external vagina, intrauterine growth retardation, reduced ovarian reserve, and increased ovarian follicular recruitment. Structural impairments seen in male offspring included increased testicular weight, larger seminal tubular lumen diameter, and higher frequency of occluded tubule lumen. Increased pituitary weight was seen in both sexes.

Testosterone exposure in utero also resulted in hormonal and behavioral changes in offspring. Hypertension was observed in pregnant female rats and their offspring exposed to doses approximately twice those used for testosterone replacement therapy.

Risk Summary

JATENZO is not indicated for use in women.

Infertility

During treatment with large doses of exogenous androgens, including JATENZO, spermatogenesis may be suppressed through feedback inhibition of the hypothalamic-pituitary-testicular axis [see Warnings and Precautions (5.7)], possibly leading to adverse effects on semen parameters including sperm count. Reduced fertility is observed in some men taking testosterone replacement therapy. Testicular atrophy, subfertility, and infertility have also been reported in men who abuse anabolic androgenic steroids [see Drug Abuse and Dependence (9.2)]. With either type of use, the impact on fertility may be irreversible.

The safety and efficacy of JATENZO in pediatric patients less than 18 years old have not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses.

There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing JATENZO to determine whether efficacy or safety in those over 65 years of age differs from younger subjects. No patients over 65 years of age were enrolled in the 4-month efficacy and safety clinical study utilizing JATENZO. Additionally, there is insufficient long-term safety data in geriatric patients utilizing JATENZO to assess the potentially increased risk of cardiovascular disease and prostate cancer.

Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of BPH [see Warnings and Precautions (5.3)].

JATENZO contains testosterone undecanoate, which is a Schedule III controlled substance as defined under the Controlled Substances Act.

Drug abuse is intentional non-therapeutic use of a drug, even once, for its rewarding psychological and physiological effects. Abuse and misuse of testosterone are seen in male and female adults and adolescents. Testosterone, often in combination with other anabolic androgenic steroids (AAS), and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. There have been reports of misuse by men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice.

Abuse-Related Adverse Reactions

Serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility and aggression.

The following adverse reactions have also been reported in men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility.

The following additional adverse reactions have been reported in women: hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities.

The following adverse reactions have been reported in male and female adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty.

Because these reactions are reported voluntarily from a population of uncertain size and may include abuse of other agents, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Behaviors Associated with Addiction

Continued abuse of testosterone and other anabolic steroids, leading to addiction is characterized by the following behaviors:

Physical dependence is characterized by withdrawal symptoms after abrupt drug discontinuation or a significant dose reduction of a drug. Individuals taking supratherapeutic doses of testosterone may experience withdrawal symptoms lasting for weeks or months which include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido and hypogonadotropic hypogonadism.

Drug dependence in individuals using approved doses of testosterone for approved indications has not been documented.

There is a single report of acute overdosage with use of an approved injectable testosterone product: this subject had serum testosterone concentrations of up to 11,400 ng/dL which were implicated in a cerebrovascular accident.

{ "type": "p", "children": [], "text": "There is a single report of acute overdosage with use of an approved injectable testosterone product: this subject had serum testosterone concentrations of up to 11,400 ng/dL which were implicated in a cerebrovascular accident.\n" }

One case of overdose with JATENZO was reported in clinical trials. This patient inadvertently took a higher dose than prescribed (474 mg twice daily, which is 20% higher than the maximum recommended dose). He did not report any adverse reactions associated with the overdose.

{ "type": "p", "children": [], "text": "One case of overdose with JATENZO was reported in clinical trials. This patient inadvertently took a higher dose than prescribed (474 mg twice daily, which is 20% higher than the maximum recommended dose). He did not report any adverse reactions associated with the overdose.\n" }

Treatment of overdosage consists of discontinuation of JATENZO and appropriate symptomatic and supportive care.

{ "type": "p", "children": [], "text": "Treatment of overdosage consists of discontinuation of JATENZO and appropriate symptomatic and supportive care.\n" }

JATENZO (testosterone undecanoate) for oral use is provided as a gelatin capsule containing testosterone undecanoate, a fatty-acid ester of testosterone. Testosterone undecanoate is a white to off-white yellow crystalline powder. Testosterone, an androgen, is formed by cleavage of the ester side chain of testosterone undecanoate.

{ "type": "p", "children": [], "text": "JATENZO (testosterone undecanoate) for oral use is provided as a gelatin capsule containing testosterone undecanoate, a fatty-acid ester of testosterone. Testosterone undecanoate is a white to off-white yellow crystalline powder. Testosterone, an androgen, is formed by cleavage of the ester side chain of testosterone undecanoate.\n" }

Testosterone undecanoate is chemically described as 17β-hydroxyandrost-4-en-3-one undecanoate. It has the empirical formula of C30H48O3 and the molecular weight of 456.7. The structural formula for testosterone undecanoate is presented in Figure 1.

{ "type": "p", "children": [], "text": "Testosterone undecanoate is chemically described as 17β-hydroxyandrost-4-en-3-one undecanoate. It has the empirical formula of C30H48O3 and the molecular weight of 456.7. The structural formula for testosterone undecanoate is presented in\nFigure 1.\n" }

Figure 1: Testosterone Undecanoate

{ "type": "p", "children": [], "text": "\nFigure 1: Testosterone Undecanoate\n" }

JATENZO capsules are available in three strengths of 158 mg, 198 mg, and 237 mg.

{ "type": "p", "children": [], "text": "JATENZO capsules are available in three strengths of 158 mg, 198 mg, and 237 mg.\n" }

The 158 mg strength is an opaque red capsule that contains 158 mg of testosterone undecanoate and is imprinted with “158” in white ink. The 198 mg strength is an opaque white capsule that contains 198 mg of testosterone undecanoate and is imprinted with “198” in red ink. The 237 mg strength is an opaque orange capsule that contains 237 mg of testosterone undecanoate and is imprinted with “237” in white ink. All capsule strengths also contain oleic acid, polyoxyl 40 hydrogenated castor oil (Cremophor RH 40), borage seed oil, peppermint oil, and butylated hydroxytoluene as inactive ingredients.

{ "type": "p", "children": [], "text": "The 158 mg strength is an opaque red capsule that contains 158 mg of testosterone undecanoate and is imprinted with “158” in white ink. The 198 mg strength is an opaque white capsule that contains 198 mg of testosterone undecanoate and is imprinted with “198” in red ink. The 237 mg strength is an opaque orange capsule that contains 237 mg of testosterone undecanoate and is imprinted with “237” in white ink. All capsule strengths also contain oleic acid, polyoxyl 40 hydrogenated castor oil (Cremophor RH 40), borage seed oil, peppermint oil, and butylated hydroxytoluene as inactive ingredients.\n" }

Gelatin capsule shells are composed of the following inactive ingredients: Gelatin, sorbitol, glycerin, purified water, iron oxide red, FD&C Yellow #6, and titanium dioxide.

{ "type": "p", "children": [], "text": "Gelatin capsule shells are composed of the following inactive ingredients: Gelatin, sorbitol, glycerin, purified water, iron oxide red, FD&C Yellow #6, and titanium dioxide.\n" }

Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement, vocal cord thickening, alterations in body musculature and fat distribution.

Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter syndrome or Leydig cell aplasia, whereas secondary hypogonadism (also known as hypogonadotropic hypogonadism) is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).

No specific pharmacodynamic studies were conducted using JATENZO.

Absorption

JATENZO delivers physiologic amounts of testosterone, producing testosterone concentrations that approximate normal concentrations seen in healthy men.

JATENZO was taken orally at a starting dose of 237 mg twice per day with meals in a multicenter, open-label, randomized, 2-arm, active-controlled trial in hypogonadal males. The dose was adjusted, as needed, on Days 14 and 56 between a minimum of 158 mg twice per day and a maximum of 396 mg twice per day based on the average plasma testosterone concentration obtained over 24 hours after the morning dose. The average daily NaF-EDTA plasma testosterone concentration was 403 (± 128) ng/dL at the end of treatment, where the normal eugonadal range in NaF-EDTA plasma was 252-907 ng/dL in this study. Note that the titration scheme for use in clinical practice is based on serum total testosterone [see Dosage and Administration (2.2)].

Table 3 summarizes the pharmacokinetic (PK) parameters for plasma total testosterone in patients completing at least 105 days of JATENZO treatment administered twice daily.

<div class="scrollingtable"><table> <caption> <span>Table 3: NaF-EDTA Plasma Testosterone C<span class="Sub">avg</span> and C<span class="Sub">max</span> at Final PK Visit </span> </caption> <col width="33.133%"/> <col width="19.133%"/> <col width="47.733%"/> <tfoot> <tr class="First Last"> <td colspan="3" valign="top"> <p class="First">PK = pharmacokinetic; C<span class="Sub">avg</span> = 24-hour average concentration; C<span class="Sub">max</span> = maximum concentration </p> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="top"><span class="Bold">PK Parameter</span></td><td align="center" class="Rrule Toprule" valign="top"></td><td align="center" class="Botrule Rrule Toprule" rowspan="2" valign="top"><span class="Bold">All Doses</span> <br/> <span class="Bold">(N=151)</span></td> </tr> <tr> <td align="center" class="Botrule Rrule" valign="top"></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" rowspan="2" valign="top">C<span class="Sub">avg</span> (ng/dL) </td><td align="center" class="Botrule Rrule" valign="top">Mean </td><td align="center" class="Botrule Rrule" valign="top">403 </td> </tr> <tr> <td align="center" class="Botrule Rrule" valign="top">SD </td><td align="center" class="Botrule Rrule" valign="top">128 </td> </tr> <tr> <td align="center" class="Lrule Rrule" valign="top">C<span class="Sub">max</span> (ng/dL) </td><td align="center" class="Botrule Rrule" valign="top">Mean </td><td align="center" class="Botrule Rrule" valign="top">1008 </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Rrule" valign="top">SD </td><td align="center" class="Botrule Rrule" valign="top">581 </td> </tr> </tbody> </table></div>

Figure 2 summarizes the mean plasma total testosterone profile for the patients at the final PK visit.

<div class="scrollingtable"><table> <col width="100.000%"/> <tbody class="Headless"> <tr class="First Last"> <td align="center" valign="top"> <p class="First"> <span class="Bold">Figure 2: Mean (±SEM) Concentration-Time Profile for NaF-EDTA Plasma Total Testosterone in JATENZO Treated Subjects at Final PK Visit</span> </p> <img alt="Figure 2" src="/dailymed/image.cfm?name=jatenzo-2.jpg&amp;setid=ed7b5d41-7475-4c10-99b9-b62b3434ae60"/><p>SEM = standard error of the mean; T = testosterone </p> </td> </tr> </tbody> </table></div>

When JATENZO was dosed with different breakfasts containing various amounts of fat, the bioavailability with the 30 g fat, 45 g fat, and high-calorie high-fat breakfasts was comparable, but there was a food effect with the 15 g fat breakfast compared to the 30 g fat breakfast. The 15 g fat breakfast had a 25% decrease in testosterone exposure compared to the 30 g fat breakfast.

Distribution

Circulating testosterone is primarily bound in serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is loosely bound to albumin and other proteins.

Metabolism

The androgenic activity of testosterone undecanoate occurs after the ester bond linking the testosterone to the undecanoic acid is cleaved by endogenous non-specific esterases. Undecanoic acid is metabolized like all fatty acids via the beta-oxidation pathway.

Testosterone is metabolized to various 17-keto steroids through two different pathways. The major active metabolites of testosterone are dihydrotestosterone (DHT) and estradiol.

Excretion

About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites. About 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver.

Carcinogenesis

Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, the implant induced cervical-uterine tumors, which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats.

Mutagenesis

Testosterone was negative in the in vitro Ames and in the in vivo mouse micronucleus assays.

Impairment of Fertility

The administration of exogenous testosterone suppresses spermatogenesis in the rat, dog and non-human primates, which was reversible on cessation of the treatment.

JATENZO has been evaluated in 3- and 9-month repeat-dose oral toxicity studies in male eugonadal dogs. JATENZO caused exaggerated pharmacological effects on androgen-responsive tissues including testes, epididymis, prostate and adrenals at exposures to testosterone or testosterone undecanoate, comparable to the maximum human exposure based on AUC comparisons. Following a 4-week drug-free period, a reduced severity of these findings was observed, suggesting partial reversibility.

In adrenal glands, moderate to severe atrophy, characterized as thinning of the zona fasciculata, was observed with reduced adrenal weights and reduced circulating levels of cortisol in testosterone undecanoate-treated dogs after 3 months of treatment. Following 9-month treatment, there were dose-related decreases in adrenal weights in testosterone undecanoate-treated male dogs and moderate adrenal vacuolation in one testosterone undecanoate-treated male dog. The clinical significance of these adrenal and cortisol findings is unknown.

The efficacy and safety of JATENZO was evaluated in 166 adult hypogonadal males in an open-label study of approximately 4 months duration (NCT02722278). The study included a Screening Phase, a Treatment Titration Phase, and a Treatment Maintenance Phase.

JATENZO was taken orally at a starting dose of 237 mg twice per day with meals. The dose was adjusted on Days 21 and 56 between a minimum of 158 mg twice per day and a maximum of 396 mg twice per day on the basis of the average testosterone concentration obtained over 24 hours post-morning dose.

The primary endpoint was the percentage of patients with mean plasma total testosterone concentration (Cavg) over 24-hours within the normal eugonadal range on the final PK visit of the study.

Secondary endpoints were the percentage of patients with a maximum total testosterone concentration (Cmax) above three predetermined limits: less than or equal to 1500 ng/dL, between 1800 and 2500 ng/dL, and greater than 2500 ng/dL.

One hundred and forty-five (87%) of the 166 hypogonadal men who received JATENZO had a mean total testosterone concentration (Cavg) within the normal eugonadal range at the end of treatment.

The percentage of patients who received JATENZO and had Cmax less than or equal to 1500 ng/dL, between 1800 and 2500 ng/dL, and greater than 2500 ng/dL at the final PK visit were 83%, 3%, and 3%, respectively. Note that the testosterone concentrations were not measured in serum but the effects of different sample preparation conditions were accounted for in data analysis of the results shown here. The titration scheme for use in clinical practice is based on serum total testosterone [see Dosage and Administration (2.2)].

JATENZO (testosterone undecanoate) capsules are available in three strengths of 158 mg, 198 mg, and 237 mg. Capsules are packaged as 120 units in wide-mouth, round, white HDPE bottles with white, polypropylene, child resistant caps and induction-sealed liner.

{ "type": "p", "children": [], "text": "JATENZO (testosterone undecanoate) capsules are available in three strengths of 158 mg, 198 mg, and 237 mg. Capsules are packaged as 120 units in wide-mouth, round, white HDPE bottles with white, polypropylene, child resistant caps and induction-sealed liner.\n" }

158 mg capsules are opaque red capsules imprinted with “158” in white ink and are supplied in bottles: NDC 69087-158-12.

{ "type": "p", "children": [], "text": "158 mg capsules are opaque red capsules imprinted with “158” in white ink and are supplied in bottles: NDC 69087-158-12.\n" }

198 mg capsules are opaque white capsules imprinted with “198” in red ink and are supplied in bottles: NDC 69087-198-12.

{ "type": "p", "children": [], "text": "198 mg capsules are opaque white capsules imprinted with “198” in red ink and are supplied in bottles: NDC 69087-198-12.\n" }

237 mg capsules are opaque orange capsules imprinted with “237” in white ink and are supplied in bottles: NDC 69087-237-12.

{ "type": "p", "children": [], "text": "237 mg capsules are opaque orange capsules imprinted with “237” in white ink and are supplied in bottles: NDC 69087-237-12.\n" }

Keep JATENZO out of reach of children.

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

Store at 20°C to 25ºC (68°F to 77ºF), excursions permitted to 15ºC to 30ºC (59ºF to 86ºF). Avoid exposing the capsules to moisture (store in a dry place).

{ "type": "p", "children": [], "text": "Store at 20°C to 25ºC (68°F to 77ºF), excursions permitted to 15ºC to 30ºC (59ºF to 86ºF). Avoid exposing the capsules to moisture (store in a dry place).\n" }

Increased Blood Pressure

Other Adverse Reactions

Inform patients that treatment with androgens may lead to adverse reactions which include:

Instruct patients to report any changes in their state of health, such as changes in urinary habits, breathing, sleep, and mood including new onset or worsening of depression, or suicidal ideation.

Keep JATENZO out of the reach of children.

Distributed by: Tolmar, Inc. Fort Collins, CO 80526

131924 Rev. 1 03/2025

<div class="scrollingtable"><table> <col/> <col/> <col/> <tfoot> <tr class="First Last"> <td colspan="2" valign="top"> <p class="First">This Medication Guide has been approved by the U.S. Food and Drug Administration</p> </td><td valign="top"> <p class="First">Issued: 03/2025</p> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">MEDICATION GUIDE</span> <br/> <span class="Bold">JATENZO</span><span class="Bold"><span class="Sup">® </span></span><span class="Bold">(juh-TEN-zoh)</span> <br/> <span class="Bold">(testosterone undecanoate) capsules, for oral use CIII</span></td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What is JATENZO?</span> <br/> JATENZO is a prescription medicine that contains testosterone. JATENZO is used to treat adult men who have low or no testosterone due to certain medical conditions.<br/> It is not known if JATENZO is safe or effective to treat men who have low testosterone due to aging.<br/> It is not known if JATENZO is safe or effective in children younger than 18 years old. Improper use of JATENZO may affect bone growth in children.</p> <p> JATENZO is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your JATENZO in a safe place to protect it. Never give your JATENZO to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and is against the law.<br/> JATENZO is not meant for use by women. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Do not take JATENZO if you:</span> </p> <ul class="Disk"> <li>have breast cancer.</li> <li>have or might have prostate cancer.</li> <li>are a woman who is pregnant. JATENZO may harm your unborn baby.</li> <li>are allergic to JATENZO or any ingredients in JATENZO. See the end of this Medication Guide for a complete list of ingredients in JATENZO.</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"><span class="Bold">Before you take JATENZO, tell your healthcare provider about all of your medical conditions, including if you:</span> <ul class="Disk"> <li>have high blood pressure or are treated for high blood pressure.</li> <li>have heart problems.</li> <li>have high red blood cell count (hematocrit) or high hemoglobin laboratory value.</li> <li>have urinary problems due to an enlarged prostate.</li> <li>have liver or kidney problems.</li> <li>have a history of mental health illness including suicidal thoughts or actions, depression, anxiety or mood disorder.</li> <li>have problems breathing while you sleep (sleep apnea).</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"><span class="Bold">Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.</span> <br/> Using JATENZO with certain other medicines can affect each other. Especially, tell your healthcare provider if you take: <ul class="Disk"> <li>insulin</li> <li>medicines that decrease blood clotting (blood thinners)</li> <li>corticosteroids.</li> <li>medicines that increase blood pressure such as some cold medicines and pain medicines.</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top">Know the medicines you take. Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.</td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"><span class="Bold">How should I take JATENZO?</span> <ul class="Disk"> <li>Take JATENZO exactly as your healthcare provider tells you take it.</li> <li>Take JATENZO by mouth two times daily. Take 1 time in the morning and take 1 time in the evening.</li> <li>Take JATENZO with food.</li> <li>Your healthcare provider may change your JATENZO dose. Do not change your JATENZO dose without talking to your healthcare provider.</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"><span class="Bold">What are the possible side effects of JATENZO?</span> <br/> <span class="Bold">JATENZO may cause serious side effects including:</span> <ul class="Disk"> <li> <span class="Bold">Increase in blood pressure.</span> <ul class="Circle"> <li>JATENZO can increase your blood pressure, which can increase your risk of having a heart attack or stroke over time. Your risk may be greater if you already have heart disease or if you have had a heart attack or stroke.</li> <li>You may need to start new blood pressure medicines or have your medicines adjusted to control your blood pressure while on JATENZO.</li> <li>If your blood pressure cannot be controlled, JATENZO may need to be stopped.</li> <li>Your healthcare provider should check your blood pressure while you use JATENZO.</li> </ul> </li> <li> <span class="Bold">Increase in red blood cell count (hematocrit) or hemoglobin.</span> <ul class="Circle"> <li>JATENZO increases red blood cell counts in some patients. High red blood cell counts increase the risk of blood clots, strokes, and heart attacks.</li> <li>You may need to stop JATENZO if your red blood cell count increases.</li> <li>Your healthcare provider should check your red blood cell count and hemoglobin while you use JATENZO.</li> </ul> </li> <li> <span class="Bold">If you already have an enlarged prostate, your signs and symptoms may worsen while using JATENZO.</span> <br/> These may include: <ul class="Circle"> <li>increased urination at night</li> <li>trouble starting your urine stream</li> <li>urinating many times during the day</li> <li>urge to go to the bathroom right away</li> <li>a urine accident</li> <li>inability to pass urine or weak urine flow</li> </ul> </li> <li> <span class="Bold">Increased risk of prostate cancer</span>. Your healthcare provider should check you for prostate cancer or any other prostate problems before you start and while you use JATENZO. </li> <li> <span class="Bold">Blood clots in the legs or lungs</span>. Signs and symptoms of a blood clot in your leg can include pain, swelling or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain. </li> <li> <span class="Bold">Abuse</span>. Testosterone can be abused, when taken at higher than prescribed doses and when used with other anabolic androgenic steroids. Abuse can cause serious heart and psychological side effects. Your healthcare provider should check you for signs of abuse before and during treatment with JATENZO. </li> <li> <span class="Bold">In large doses JATENZO may lower your sperm count.</span> </li> <li> <span class="Bold">Liver problems.</span> Symptoms of liver problems may include: <ul class="Circle"> <li>nausea or vomiting</li> <li>yellowing of your skin or whites of your eyes</li> <li>dark urine</li> <li>pain on the right side of your stomach area (abdominal pain)</li> </ul> </li> <li> <span class="Bold">Swelling of your ankles, feet, or body (edema), with or without heart failure.</span> </li> <li> <span class="Bold">Enlarged or painful breasts.</span> </li> <li> <span class="Bold">Breathing problems while you sleep (sleep apnea).</span> </li> <li> <span class="Bold">Changes in mood.</span> Talk to your healthcare provider if you have changes in mood or behavior including, new or worsening depression, or suicidal thoughts. </li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"><span class="Bold">Call your healthcare provider right away if you have any of the serious side effects listed above.</span> <br/> <br/> <span class="Bold">The most common side effects of JATENZO include:</span></td> </tr> <tr> <td class="Lrule" valign="top"> <ul class="Disk"> <li>increased red blood cell count</li> <li>diarrhea</li> <li>heart burn</li> </ul> </td><td valign="top"> <ul class="Disk"> <li>burping</li> <li>foot, leg and ankle swelling</li> <li>nausea</li> </ul> </td><td class="Rrule" valign="top"> <ul class="Disk"> <li>enlarged prostate gland</li> <li>high blood pressure</li> <li>headache</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"><span class="Bold">Other side effects include</span> more erections than are normal for you or erections that last a long time. <br/> <br/> Tell your healthcare provider if you have any side effect that bothers you or that does not go away. <br/> <br/> These are not all the possible side effects of JATENZO. For more information, ask your healthcare provider or pharmacist. <br/> <br/> Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"><span class="Bold">How should I store JATENZO?</span> <ul class="Disk"> <li>Store JATENZO at room temperature between 68°F to 77°F (20°C to 25°C).</li> <li>Store JATENZO in a dry place.</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"><span class="Bold">Keep JATENZO and all medicines out of the reach of children.</span></td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"><span class="Bold">General information about the safe and effective use of JATENZO</span> <br/> <br/> Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use JATENZO for a condition for which it was not prescribed. Do not give JATENZO to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about JATENZO that is written for health professionals. </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" colspan="3" valign="top"><span class="Bold">What are the ingredients in JATENZO?</span> <br/> <br/> <span class="Bold">Active ingredient:</span> testosterone undecanoate <br/> <br/> <span class="Bold">Inactive ingredients:</span> oleic acid, polyoxyl 40 hydrogenated castor oil (Cremophor RH 40), borage seed oil, peppermint oil, and butylated hydroxytoluene. The ingredients of the soft gelatin capsule shells are gelatin, sorbitol, glycerin, purified water, iron oxide red, FD&amp;C Yellow #6, and titanium dioxide. <br/> <br/> Distributed by:<br/> Tolmar, Inc. Fort Collins, CO 80526      <br/> <br/> For more information, go to www.JATENZO.com or call 1-844-4TO-LMAR. </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col/>\n<col/>\n<col/>\n<tfoot>\n<tr class=\"First Last\">\n<td colspan=\"2\" valign=\"top\">\n<p class=\"First\">This Medication Guide has been approved by the U.S. Food and Drug Administration</p>\n</td><td valign=\"top\">\n<p class=\"First\">Issued: 03/2025</p>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"3\" valign=\"top\"><span class=\"Bold\">MEDICATION GUIDE</span>\n<br/>\n<span class=\"Bold\">JATENZO</span><span class=\"Bold\"><span class=\"Sup\">® </span></span><span class=\"Bold\">(juh-TEN-zoh)</span>\n<br/>\n<span class=\"Bold\">(testosterone undecanoate) capsules, for oral use CIII</span></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 JATENZO?</span>\n<br/>\n JATENZO is a prescription medicine that contains testosterone. JATENZO is used to treat adult men who have low or no testosterone due to certain medical conditions.<br/>\n It is not known if JATENZO is safe or effective to treat men who have low testosterone due to aging.<br/>\n It is not known if JATENZO is safe or effective in children younger than 18 years old. Improper use of JATENZO may affect bone growth in children.</p>\n<p>\n JATENZO is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your JATENZO in a safe place to protect it. Never give your JATENZO to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and is against the law.<br/>\n JATENZO is not meant for use by women.\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\">Do not take JATENZO if you:</span>\n</p>\n<ul class=\"Disk\">\n<li>have breast cancer.</li>\n<li>have or might have prostate cancer.</li>\n<li>are a woman who is pregnant. JATENZO may harm your unborn baby.</li>\n<li>are allergic to JATENZO or any ingredients in JATENZO. See the end of this Medication Guide for a complete list of ingredients in JATENZO.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\"><span class=\"Bold\">Before you take JATENZO, tell your healthcare provider about all of your medical conditions, including if you:</span>\n<ul class=\"Disk\">\n<li>have high blood pressure or are treated for high blood pressure.</li>\n<li>have heart problems.</li>\n<li>have high red blood cell count (hematocrit) or high hemoglobin laboratory value.</li>\n<li>have urinary problems due to an enlarged prostate.</li>\n<li>have liver or kidney problems.</li>\n<li>have a history of mental health illness including suicidal thoughts or actions, depression, anxiety or mood disorder.</li>\n<li>have problems breathing while you sleep (sleep apnea).</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\"><span class=\"Bold\">Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.</span>\n<br/>\n Using JATENZO with certain other medicines can affect each other. Especially, tell your healthcare provider if you take:\n <ul class=\"Disk\">\n<li>insulin</li>\n<li>medicines that decrease blood clotting (blood thinners)</li>\n<li>corticosteroids.</li>\n<li>medicines that increase blood pressure such as some cold medicines and pain medicines.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">Know the medicines you take. Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\"><span class=\"Bold\">How should I take JATENZO?</span>\n<ul class=\"Disk\">\n<li>Take JATENZO exactly as your healthcare provider tells you take it.</li>\n<li>Take JATENZO by mouth two times daily. Take 1 time in the morning and take 1 time in the evening.</li>\n<li>Take JATENZO with food.</li>\n<li>Your healthcare provider may change your JATENZO dose. Do not change your JATENZO dose without talking to your healthcare provider.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\"><span class=\"Bold\">What are the possible side effects of JATENZO?</span>\n<br/>\n<span class=\"Bold\">JATENZO may cause serious side effects including:</span>\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\">Increase in blood pressure.</span>\n<ul class=\"Circle\">\n<li>JATENZO can increase your blood pressure, which can increase your risk of having a heart attack or stroke over time. Your risk may be greater if you already have heart disease or if you have had a heart attack or stroke.</li>\n<li>You may need to start new blood pressure medicines or have your medicines adjusted to control your blood pressure while on JATENZO.</li>\n<li>If your blood pressure cannot be controlled, JATENZO may need to be stopped.</li>\n<li>Your healthcare provider should check your blood pressure while you use JATENZO.</li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">Increase in red blood cell count (hematocrit) or hemoglobin.</span>\n<ul class=\"Circle\">\n<li>JATENZO increases red blood cell counts in some patients. High red blood cell counts increase the risk of blood clots, strokes, and heart attacks.</li>\n<li>You may need to stop JATENZO if your red blood cell count increases.</li>\n<li>Your healthcare provider should check your red blood cell count and hemoglobin while you use JATENZO.</li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">If you already have an enlarged prostate, your signs and symptoms may worsen while using JATENZO.</span>\n<br/>\n These may include:\n <ul class=\"Circle\">\n<li>increased urination at night</li>\n<li>trouble starting your urine stream</li>\n<li>urinating many times during the day</li>\n<li>urge to go to the bathroom right away</li>\n<li>a urine accident</li>\n<li>inability to pass urine or weak urine flow</li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">Increased risk of prostate cancer</span>. Your healthcare provider should check you for prostate cancer or any other prostate problems before you start and while you use JATENZO.\n </li>\n<li>\n<span class=\"Bold\">Blood clots in the legs or lungs</span>. Signs and symptoms of a blood clot in your leg can include pain, swelling or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain.\n </li>\n<li>\n<span class=\"Bold\">Abuse</span>. Testosterone can be abused, when taken at higher than prescribed doses and when used with other anabolic androgenic steroids. Abuse can cause serious heart and psychological side effects. Your healthcare provider should check you for signs of abuse before and during treatment with JATENZO.\n </li>\n<li>\n<span class=\"Bold\">In large doses JATENZO may lower your sperm count.</span>\n</li>\n<li>\n<span class=\"Bold\">Liver problems.</span> Symptoms of liver problems may include:\n <ul class=\"Circle\">\n<li>nausea or vomiting</li>\n<li>yellowing of your skin or whites of your eyes</li>\n<li>dark urine</li>\n<li>pain on the right side of your stomach area (abdominal pain)</li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">Swelling of your ankles, feet, or body (edema), with or without heart failure.</span>\n</li>\n<li>\n<span class=\"Bold\">Enlarged or painful breasts.</span>\n</li>\n<li>\n<span class=\"Bold\">Breathing problems while you sleep (sleep apnea).</span>\n</li>\n<li>\n<span class=\"Bold\">Changes in mood.</span> Talk to your healthcare provider if you have changes in mood or behavior including, new or worsening depression, or suicidal thoughts.\n </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\"><span class=\"Bold\">Call your healthcare provider right away if you have any of the serious side effects listed above.</span>\n<br/>\n<br/>\n<span class=\"Bold\">The most common side effects of JATENZO include:</span></td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\">\n<ul class=\"Disk\">\n<li>increased red blood cell count</li>\n<li>diarrhea</li>\n<li>heart burn</li>\n</ul>\n</td><td valign=\"top\">\n<ul class=\"Disk\">\n<li>burping</li>\n<li>foot, leg and ankle swelling</li>\n<li>nausea</li>\n</ul>\n</td><td class=\"Rrule\" valign=\"top\">\n<ul class=\"Disk\">\n<li>enlarged prostate gland</li>\n<li>high blood pressure</li>\n<li>headache</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\"><span class=\"Bold\">Other side effects include</span> more erections than are normal for you or erections that last a long time.\n <br/>\n<br/>\n Tell your healthcare provider if you have any side effect that bothers you or that does not go away.\n <br/>\n<br/>\n These are not all the possible side effects of JATENZO. For more information, ask your healthcare provider or pharmacist.\n <br/>\n<br/>\n Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.\n </td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\"><span class=\"Bold\">How should I store JATENZO?</span>\n<ul class=\"Disk\">\n<li>Store JATENZO at room temperature between 68°F to 77°F (20°C to 25°C).</li>\n<li>Store JATENZO in a dry place.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\"><span class=\"Bold\">Keep JATENZO and all medicines out of the reach of children.</span></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\"><span class=\"Bold\">General information about the safe and effective use of JATENZO</span>\n<br/>\n<br/>\n Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use JATENZO for a condition for which it was not prescribed. Do not give JATENZO to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about JATENZO that is written for health professionals.\n </td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\"><span class=\"Bold\">What are the ingredients in JATENZO?</span>\n<br/>\n<br/>\n<span class=\"Bold\">Active ingredient:</span> testosterone undecanoate\n <br/>\n<br/>\n<span class=\"Bold\">Inactive ingredients:</span> oleic acid, polyoxyl 40 hydrogenated castor oil (Cremophor RH 40), borage seed oil, peppermint oil, and butylated hydroxytoluene. The ingredients of the soft gelatin capsule shells are gelatin, sorbitol, glycerin, purified water, iron oxide red, FD&amp;C Yellow #6, and titanium dioxide.\n <br/>\n<br/>\n Distributed by:<br/>\n Tolmar, Inc. Fort Collins, CO 80526      <br/>\n<br/>\n For more information, go to www.JATENZO.com or call 1-844-4TO-LMAR.\n </td>\n</tr>\n</tbody>\n</table></div>" }

Testosterone gel 1.62% is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone:

{ "type": "p", "children": [], "text": "Testosterone gel 1.62% is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone:" }

• Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range.

{ "type": "p", "children": [], "text": "• Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range." }

• Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations, but have gonadotropins in the normal or low range.

{ "type": "p", "children": [], "text": "• Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations, but have gonadotropins in the normal or low range." }

Limitations of use:

{ "type": "p", "children": [], "text": "Limitations of use:" }

• Safety and efficacy of testosterone gel 1.62% in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established.

{ "type": "p", "children": [], "text": "• Safety and efficacy of testosterone gel 1.62% in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established." }

• Safety and efficacy of testosterone gel 1.62% in males less than 18 years old have not been established [see Use in Specific Populations (8.4)].

{ "type": "p", "children": [], "text": "• Safety and efficacy of testosterone gel 1.62% in males less than 18 years old have not been established [see Use in Specific Populations (8.4)]." }

• Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure [see Indications and Usage (1), and Clinical Pharmacology (12.3)].

{ "type": "p", "children": [], "text": "• Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure [see Indications and Usage (1), and Clinical Pharmacology (12.3)]." }

The recommended starting dose of testosterone gel 1.62% is 40.5 mg of testosterone (2 pump actuations or a single 40.5 mg packet) applied topically once daily in the morning to the shoulders and upper arms.

The dose can be adjusted between a minimum of 20.25 mg of testosterone (1 pump actuation or a single 20.25 mg packet) and a maximum of 81 mg of testosterone (4 pump actuations or two 40.5 mg packets). To ensure proper dosing, the dose should be titrated based on the pre-dose morning serum testosterone concentration from a single blood draw at approximately 14 days and 28 days after starting treatment or following dose adjustment. In addition, serum testosterone concentration should be assessed periodically thereafter. Table 1 describes the dose adjustments required at each titration step.

<div class="scrollingtable"><table cellpadding="5" cellspacing="0" width="800px"> <caption> <span>Table 1: Dose Adjustment Criteria</span> </caption> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">Pre-Dose Morning Total Serum Testosterone Concentration</span></td><td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">Dose Titration</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Greater than 750 ng/dL</td><td class="Botrule Lrule Rrule Toprule"> Decrease daily dose by 20.25 mg (1 pump actuation or the equivalent of one 20.25 mg packet)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Equal to or greater than 350 and equal to <br/>or less than 750 ng/dL</td><td class="Botrule Lrule Rrule Toprule"> No change: continue on current dose</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> Less than 350 ng/dL</td><td class="Botrule Lrule Rrule Toprule"> Increase daily dose by 20.25 mg (1 pump actuation or the equivalent of one 20.25 mg packet)</td> </tr> </tbody> </table></div>

The application site and dose of testosterone gel 1.62% are not interchangeable with other topical testosterone products.

Testosterone gel 1.62% should be applied to clean, dry, intact skin of the upper arms and shoulders. Do not apply testosterone gel 1.62% to any other parts of the body, including the abdomen, genitals, chest, armpits (axillae), or knees [see Clinical Pharmacology (12.3)]. Area of application should be limited to the area that will be covered by the patient's short sleeve t-shirt. Patients should be instructed to use the palm of the hand to apply testosterone gel 1.62% and spread across the maximum surface area as directed in Table 2 (for pump) and Table 3 (for packets) and in Figure 1.

<div class="scrollingtable"><table cellpadding="5" cellspacing="0" width="800px"> <caption> <span>Table 2: Application Sites for Testosterone Gel 1.62%, Pump</span> </caption> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">Total Dose of </span><span class="Bold">Testosterone</span></td><td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">Total Pump </span><span class="Bold">Actuations</span></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"> <span class="Bold">Pump Actuations Per Upper Arm and </span><span class="Bold">Shoulder</span></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"> </td><td align="center" class="Botrule Lrule Rrule Toprule"> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">Upper Arm and </span><span class="Bold">Shoulder #1</span></td><td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">Upper Arm and </span><span class="Bold">Shoulder #2</span></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"> 20.25 mg</td><td align="center" class="Botrule Lrule Rrule Toprule"> 1</td><td align="center" class="Botrule Lrule Rrule Toprule"> 1</td><td align="center" class="Botrule Lrule Rrule Toprule"> 0</td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"> 40.5 mg</td><td align="center" class="Botrule Lrule Rrule Toprule"> 2</td><td align="center" class="Botrule Lrule Rrule Toprule"> 1</td><td align="center" class="Botrule Lrule Rrule Toprule"> 1</td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"> 60.75 mg</td><td align="center" class="Botrule Lrule Rrule Toprule"> 3</td><td align="center" class="Botrule Lrule Rrule Toprule"> 2</td><td align="center" class="Botrule Lrule Rrule Toprule"> 1</td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule"> 81 mg</td><td align="center" class="Botrule Lrule Rrule Toprule"> 4</td><td align="center" class="Botrule Lrule Rrule Toprule"> 2</td><td align="center" class="Botrule Lrule Rrule Toprule"> 2</td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table cellpadding="5" cellspacing="0" width="800px"> <caption> <span>Table 3: Application Sites for Testosterone Gel 1.62%, Packets</span> </caption> <col width="90.75pt"/> <col width="90.75pt"/> <col width="90.75pt"/> <col/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Total Dose of Testosterone</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Total packets</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Gel Applications Per Upper Arm and Shoulder</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Upper Arm and Shoulder #1</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Upper Arm and Shoulder #2</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"> 20.25 mg</td><td align="center" class="Botrule Lrule Rrule Toprule"> One 20.25 mg packet</td><td align="center" class="Botrule Lrule Rrule Toprule">One 20.25 mg packet </td><td align="center" class="Botrule Lrule Rrule Toprule">0 </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">40.5 mg</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">One 40.5 mg packet</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">Half of contents of One 40.5 mg packet</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">Half of contents of One 40.5 mg packet</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"> 60.75 mg</td><td align="center" class="Botrule Lrule Rrule Toprule">One 20.25 mg packet and One 40.5 mg packet </td><td align="center" class="Botrule Lrule Rrule Toprule">One 40.5 mg packet </td><td align="center" class="Botrule Lrule Rrule Toprule">One 20.25 mg packet </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">81 mg</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">Two 40.5 mg packets</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">One 40.5 mg packet</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">One 40.5 mg packet</p> </td> </tr> </tbody> </table></div>

The prescribed daily dose of testosterone gel 1.62% should be applied to the right and left upper arms and shoulders as shown in the shaded areas in Figure 1.

Once the application site is dry, the site should be covered with clothing [see Clinical Pharmacology (12.3)]. Wash hands thoroughly with soap and water. Avoid fire, flames or smoking until the gel has dried since alcohol based products, including testosterone gel 1.62%, are flammable.

The patient should avoid swimming or showering or washing the administration site for a minimum of 2 hours after application [see Clinical Pharmacology (12.3)].

To obtain a full first dose, it is necessary to prime the canister pump. To do so, with the canister in the upright position, slowly and fully depress the actuator three times. Safely discard the gel from the first three actuations. It is only necessary to prime the pump before the first dose.

After the priming procedure, fully depress the actuator once for every 20.25 mg of testosterone gel 1.62%. Testosterone gel 1.62% should be delivered directly into the palm of the hand and then applied to the application sites.

When using packets, the entire contents should be squeezed into the palm of the hand and immediately applied to the application sites. When 40.5 mg packets need to be split between the left and right shoulder, patients may squeeze a portion of the gel from the packet into the palm of the hand and apply to application sites. Repeat until entire contents have been applied. Alternatively, Testosterone gel 1.62% can be applied directly to the application sites from the pump or packets.

Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from testosterone gel 1.62%-treated skin:

Testosterone gel 1.62% for topical use only, is available as follows:

{ "type": "p", "children": [], "text": "Testosterone gel 1.62% for topical use only, is available as follows:" }

{ "type": "ul", "children": [ "A metered-dose pump. Each pump actuation delivers 20.25 mg of testosterone in 1.25 g of gel.", "A unit dose packet containing 20.25 mg of testosterone in 1.25 g of gel.", "A unit dose packet containing 40.5 mg of testosterone in 2.5 g of gel." ], "text": "" }

{ "type": "ul", "children": [ "Testosterone gel 1.62% is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].\n", "Testosterone gel 1.62% is contraindicated in women who are pregnant. Testosterone gel 1.62% can cause virilization of the female fetus when administered to a pregnant woman. Pregnant women need to be aware of the potential for transfer of testosterone from men treated with testosterone gel 1.62%. If a pregnant woman is exposed to testosterone gel 1.62%, she should be apprised of the potential hazard to the fetus [see Warnings and Precautions (5.2) and Use in Specific Populations (8.1)]." ], "text": "" }

Cases of secondary exposure resulting in virilization of children have been reported in postmarketing surveillance of testosterone gel products. Signs and symptoms have included enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases, these signs and symptoms regressed with removal of the exposure to testosterone gel. In a few cases, however, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age. The risk of transfer was increased in some of these cases by not adhering to precautions for the appropriate use of the topical testosterone product. Children and women should avoid contact with unwashed or unclothed application sites in men using testosterone gel 1.62% [see Dosage and Administration (2.2), Use in Specific Populations (8.1) and Clinical Pharmacology (12.3)].

Inappropriate changes in genital size or development of pubic hair or libido in children, or changes in body hair distribution, significant increase in acne, or other signs of virilization in adult women should be brought to the attention of a physician and the possibility of secondary exposure to testosterone gel should also be brought to the attention of a physician. Testosterone gel should be promptly discontinued until the cause of virilization has been identified.

Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating treatment. It would also be appropriate to re-evaluate the hematocrit 3 to 6 months after starting treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable concentration. An increase in red blood cell mass may increase the risk of thromboembolic events.

There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products such as testosterone gel 1.62%. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with testosterone gel 1.62% and initiate appropriate workup and management [see Adverse Reactions (6.2)].

Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use testosterone gel 1.62%.

Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions [see Drug Abuse and Dependence (9)].

If testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range. However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids. Conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events.

Due to the lack of controlled evaluations in women and potential virilizing effects, testosterone gel 1.62% is not indicated for use in women [see Contraindications (4) and Use in Specific Populations (8.1, 8.2)].

With large doses of exogenous androgens, including testosterone gel 1.62%, spermatogenesis may be suppressed through feedback inhibition of pituitary FSH possibly leading to adverse effects on semen parameters including sperm count.

Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate has produced multiple hepatic adenomas. Testosterone gel 1.62% is not known to cause these adverse effects.

Androgens, including testosterone gel 1.62%, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease [see Adverse Reactions (6.2)].

Gynecomastia may develop and persist in patients being treated with androgens, including testosterone gel 1.62%, for hypogonadism.

The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases.

Changes in serum lipid profile may require dose adjustment or discontinuation of testosterone therapy.

Androgens, including testosterone gel 1.62 %, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is recommended in these patients.

Androgens, including testosterone gel 1.62%, may decrease concentrations of thyroxin-binding globulins, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.

Alcohol based products, including testosterone gel 1.62%, are flammable; therefore, patients should be advised to avoid fire, flame or smoking until the testosterone gel 1.62% has dried.

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

Testosterone gel 1.62% was evaluated in a two-phase, 364-day, controlled clinical study. The first phase was a multi-center, randomized, double-blind, parallel-group, placebo-controlled period of 182 days, in which 234 hypogonadal men were treated with testosterone gel 1.62% and 40 received placebo. Patients could continue in an open-label, non-comparative, maintenance period for an additional 182 days [see Clinical Studies (14.1)].

The most common adverse reaction reported in the double-blind period was increased prostate specific antigen (PSA) reported in 26 testosterone gel 1.62%-treated patients (11.1%). In 17 patients, increased PSA was considered an adverse event by meeting one of the two pre-specified criteria for abnormal PSA values, defined as (1) average serum PSA >4 ng/mL based on two separate determinations, or (2) an average change from baseline in serum PSA of greater than 0.75 ng/mL on two determinations.

During the 182-day, double-blind period of the clinical trial, the mean change in serum PSA value was 0.14 ng/mL for patients receiving testosterone gel 1.62% and -0.12 ng/mL for the patients in the placebo group. During the double-blind period, seven patients had a PSA value >4.0 ng/mL, four of these seven patients had PSA less than or equal to 4.0 ng/mL upon repeat testing. The other three patients did not undergo repeat PSA testing.

During the 182-day, open-label period of the study, the mean change in serum PSA values was 0.10 ng/mL for both patients continuing on active therapy and patients transitioning onto active from placebo. During the open-label period, three patients had a serum PSA value > 4.0 ng/mL, two of whom had a serum PSA less than or equal to 4.0 ng/mL upon repeated testing. The other patient did not undergo repeat PSA testing. Among previous placebo patients, 3 of 28 (10.7%), had increased PSA as an adverse event in the open-label period.

Table 4 shows adverse reactions reported by > 2% of patients in the 182-day, double-blind period of the testosterone gel 1.62% clinical trial and more frequent in the testosterone gel 1.62% treated group versus placebo.

<div class="scrollingtable"><table> <caption> <span>Table 4: Adverse Reactions Reported in &gt;2% of Patients in the 182-Day, Double-Blind Period of Testosterone Gel 1.62% Clinical Trial</span> </caption> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule"> </td><td align="center" class="Lrule Rrule Toprule" colspan="2"> <span class="Bold">Number (%) of Patients</span></td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Adverse Reaction</span></td><td align="center" class="Lrule Rrule Toprule"> <span class="Bold">Testosterone Gel 1.62%</span> <br/> <span class="Bold">N=234</span></td><td align="center" class="Lrule Rrule Toprule"> <span class="Bold">Placebo</span> <br/> <span class="Bold">N=40</span></td> </tr> <tr> <td class="Lrule Rrule Toprule"> PSA increased*</td><td align="center" class="Lrule Rrule Toprule"> 26 (11.1%)</td><td align="center" class="Lrule Rrule Toprule"> 0%</td> </tr> <tr> <td class="Lrule Rrule Toprule"> Emotional lability**</td><td align="center" class="Lrule Rrule Toprule"> 6 (2.6%)</td><td align="center" class="Lrule Rrule Toprule"> 0%</td> </tr> <tr> <td class="Lrule Rrule Toprule"> Hypertension</td><td align="center" class="Lrule Rrule Toprule"> 5 (2.1%)</td><td align="center" class="Lrule Rrule Toprule"> 0%</td> </tr> <tr> <td class="Lrule Rrule Toprule"> Hematocrit or hemoglobin increased</td><td align="center" class="Lrule Rrule Toprule"> 5 (2.1%)</td><td align="center" class="Lrule Rrule Toprule"> 0%</td> </tr> <tr> <td class="Lrule Rrule Toprule"> Contact dermatitis***</td><td align="center" class="Lrule Rrule Toprule"> 5 (2.1%)</td><td align="center" class="Lrule Rrule Toprule"> 0%</td> </tr> <tr> <td class="Toprule" colspan="3"> <span class="Bold">*</span><span class="Bold"><span class="Italics">PSA increased</span></span> includes: PSA values that met pre-specified criteria for abnormal PSA values (an average change from baseline &gt; 0.75 ng/mL and/or an average PSA value &gt;4.0 ng/mL based on two measurements) as well as those reported as adverse events.</td> </tr> <tr> <td colspan="3"> <span class="Bold">**</span><span class="Bold"><span class="Italics">Emotional lability</span></span> includes: mood swings, affective disorder, impatience, anger, and aggression.</td> </tr> <tr class="Last"> <td colspan="3"> <span class="Bold">***</span><span class="Bold"><span class="Italics">Contact dermatitis</span></span><span class="Bold"> </span>includes: 4 patients with dermatitis at non-application sites.</td> </tr> </tbody> </table></div>

Other adverse reactions occurring in less than or equal to 2% of testosterone gel 1.62%-treated patients and more frequently than placebo included: frequent urination, and hyperlipidemia.

In the open-label period of the study (N=191), the most commonly reported adverse reaction (experienced by greater than 2% of patients) was increased PSA (n=13; 6.2%) and sinusitis. Other adverse reactions reported by less than or equal to 2% of patients included increased hemoglobin or hematocrit, hypertension, acne, libido decreased, insomnia, and benign prostatic hypertrophy.

During the 182-day, double-blind period of the clinical trial, 25 testosterone gel 1.62%-treated patients (10.7%) discontinued treatment because of adverse reactions. These adverse reactions included 17 patients with PSA increased and 1 report each of: hematocrit increased, blood pressure increased, frequent urination, diarrhea, fatigue, pituitary tumor, dizziness, skin erythema and skin nodule (same patient – neither at application site), vasovagal syncope, and diabetes mellitus. During the 182-day, open-label period, 9 patients discontinued treatment because of adverse reactions. These adverse reactions included 6 reports of PSA increased, 2 of hematocrit increased, and 1 each of triglycerides increased and prostate cancer.

Application Site Reactions

In the 182-day double-blind period of the study, application site reactions were reported in two (2/234; 0.9%) patients receiving testosterone gel 1.62%, both of which resolved. Neither of these patients discontinued the study due to application site adverse reactions. In the open-label period of the study, application site reactions were reported in three (3/219; 1.4%) additional patients that were treated with testosterone gel 1.62%. None of these subjects were discontinued from the study due to application site reactions.

The following adverse reactions have been identified during post approval use of testosterone gel 1%. Because the 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 (Table 5).

<div class="scrollingtable"><table> <caption> <span>Table 5: Adverse Reactions from Post Approval Experience of Testosterone Gel 1% by System Organ Class</span> </caption> <col width="169"/> <col width="534"/> <tbody class="Headless"> <tr class="First"> <td class="Lrule Rrule Toprule"> <span class="Bold">System Organ Class</span></td><td class="Lrule Rrule Toprule"> <span class="Bold">Adverse Reaction</span></td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Blood and lymphatic system disorders:</span></td><td class="Lrule Rrule Toprule"> Elevated hemoglobin or hematocrit, polycythemia, anemia</td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Cardiovascular disorders:</span></td><td class="Lrule Rrule Toprule"> Myocardial infarction, stroke</td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Endocrine disorders:</span></td><td class="Lrule Rrule Toprule"> Hirsutism</td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Gastrointestinal disorders:</span></td><td class="Lrule Rrule Toprule"> Nausea</td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">General disorders:</span></td><td class="Lrule Rrule Toprule"> Asthenia, edema, malaise</td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Genitourinary disorders:</span></td><td class="Lrule Rrule Toprule"> Impaired urination*</td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Hepatobiliary disorders:</span></td><td class="Lrule Rrule Toprule"> Abnormal liver function tests</td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Investigations:</span></td><td class="Lrule Rrule Toprule"> Lab test abnormal**, elevated PSA, electrolyte changes (nitrogen, calcium, potassium [includes hypokalemia], phosphorus, sodium), impaired glucose tolerance, hyperlipidemia, HDL, fluctuating testosterone levels, weight increase</td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Neoplasms:</span></td><td class="Lrule Rrule Toprule"> Prostate cancer</td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Nervous system disorders:</span></td><td class="Lrule Rrule Toprule"> Dizziness, headache, insomnia, sleep apnea</td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Psychiatric disorders:</span></td><td class="Lrule Rrule Toprule"> Amnesia, anxiety, depression, hostility, emotional lability, decreased libido, nervousness</td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Reproductive system and breast disorders:</span></td><td class="Lrule Rrule Toprule"> Gynecomastia, mastodynia, oligospermia, priapism (frequent or prolonged erections), prostate enlargement, BPH, testis disorder***</td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Respiratory disorders:</span></td><td class="Lrule Rrule Toprule"> Dyspnea</td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Skin and subcutaneous tissue disorders:</span></td><td class="Lrule Rrule Toprule"> Acne, alopecia, application site reaction (discolored hair, dry skin, erythema, paresthesia, pruritus, rash), skin dry, pruritus, sweating</td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Vascular disorders:</span></td><td class="Lrule Rrule Toprule"> Hypertension, vasodilation (hot flushes), venous thromboembolism</td> </tr> <tr> <td class="Toprule" colspan="2"> <span class="Bold">* </span><span class="Bold"><span class="Italics">Impaired urination</span></span><span class="Bold"> includes</span> nocturia, urinary hesitancy, urinary incontinence, urinary retention, urinary urgency and weak urinary stream</td> </tr> <tr> <td colspan="2"> <span class="Bold">**</span><span class="Bold"><span class="Italics">Lab test abnormal</span></span><span class="Bold"> includes</span> elevated AST, elevated ALT, elevated testosterone, elevated hemoglobin or hematocrit, elevated cholesterol, elevated cholesterol/LDL ratio, elevated triglycerides, or elevated serum creatinine</td> </tr> <tr class="Last"> <td colspan="2"> <span class="Bold">***</span><span class="Bold"><span class="Italics">Testis disorder</span></span><span class="Bold"> includes</span> atrophy or non-palpable testis, varicocele, testis sensitivity or tenderness</td> </tr> </tbody> </table></div>

Secondary Exposure to Testosterone in Children

Cases of secondary exposure to testosterone resulting in virilization of children have been reported in postmarketing surveillance of testosterone gel products. Signs and symptoms of these reported cases have included enlargement of the clitoris (with surgical intervention) or the penis, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases with a reported outcome, these signs and symptoms were reported to have regressed with removal of the testosterone gel exposure. In a few cases, however, enlarged genitalia did not fully return to age appropriate normal size, and bone age remained modestly greater than chronological age. In some of the cases, direct contact with the sites of application on the skin of men using testosterone gel was reported. In at least one reported case, the reporter considered the possibility of secondary exposure from items such as the testosterone gel user's shirts and/or other fabric, such as towels and sheets [see Warnings and Precautions (5.2)].

Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease insulin requirements.

Changes in anticoagulant activity may be seen with androgens, therefore more frequent monitoring of international normalized ratio (INR) and prothrombin time are recommended in patients taking anticoagulants, especially at the initiation and termination of androgen therapy.

The concurrent use of testosterone with adrenocorticotropic hormone (ACTH) or corticosteroids may result in increased fluid retention and requires careful monitoring particularly in patients with cardiac, renal or hepatic disease.

Risk Summary

Testosterone gel 1.62% is contraindicated in pregnant women. Testosterone is teratogenic and may cause fetal harm when administered to a pregnant woman based on data from animal studies and its mechanism of action [see Contraindications (4) and Clinical Pharmacology (12.1)]. Exposure of a female fetus to androgens may result in varying degrees of virilization. In animal developmental studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural impairments of reproductive tissues in female and male offspring. These studies did not meet current standards for nonclinical development toxicity studies.

Data

Animal Data

In developmental studies conducted in rats, rabbits, pigs, sheep and rhesus monkeys, pregnant animals received intramuscular injection of testosterone during the period of organogenesis. Testosterone treatment at doses that were comparable to those used for testosterone replacement therapy resulted in structural impairments in both female and male offspring. Structural impairments observed in females included increased ano-genital distance, phallus development, empty scrotum, no external vagina, intrauterine growth retardation, reduced ovarian reserve, and increased ovarian follicular recruitment. Structural impairments seen in male offspring included increased testicular weight, larger seminal tubular lumen diameter, and higher frequency of occluded tubule lumen. Increased pituitary weight was seen in both sexes.

Testosterone exposure in utero also resulted in hormonal and behavioral changes in offspring. Hypertension was observed in pregnant female rats and their offspring exposed to doses approximately twice those used for testosterone replacement therapy.

Risk Summary

Testosterone gel 1.62% is not indicated for use in women.

Infertility

Testis disorder, testicular atrophy, and oligospermia have been identified during use of testosterone gel 1.62% [see Adverse Reactions (6.1, 6.2)].

During treatment with large doses of exogenous androgens, including testosterone gel 1.62%, spermatogenesis may be suppressed through feedback inhibition of the hypothalamic-pituitary-testicular axis [see Warnings and Precautions (5.8)]. Reduced fertility is observed in some men taking testosterone replacement therapy. Testicular atrophy, subfertility, and infertility have also been reported in men who abuse anabolic androgenic steroids [see Drug Abuse and Dependence (9.2)]. With either type of use, the impact on fertility may be irreversible.

The safety and effectiveness of testosterone gel 1.62% in pediatric patients less than 18 years old has not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses.

There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing testosterone gel 1.62% to determine whether efficacy in those over 65 years of age differs from younger subjects. Of the 234 patients enrolled in the clinical trial utilizing testosterone gel 1.62%, 21 were over 65 years of age. Additionally, there is insufficient long-term safety data in geriatric patients to assess the potentially increased risks of cardiovascular disease and prostate cancer.

Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of BPH.

No studies were conducted involving patients with renal impairment.

No studies were conducted in patients with hepatic impairment.

Testosterone gel 1.62% contains testosterone, a Schedule III controlled substance in the Controlled Substances Act.

Drug abuse is intentional non-therapeutic use of a drug, even once, for its rewarding psychological and physiological effects. Abuse and misuse of testosterone are seen in male and female adults and adolescents. Testosterone, often in combination with other anabolic androgenic steroids (AAS), and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. There have been reports of misuse by men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice.

Abuse-Related Adverse Reactions

Serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility and aggression.

The following adverse reactions have also been reported in men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility.

The following additional adverse reactions have been reported in women: hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities.

The following adverse reactions have been reported in male and female adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty.

Because these reactions are reported voluntarily from a population of uncertain size and may include abuse of other agents, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Behaviors Associated with Addiction

Continued abuse of testosterone and other anabolic steroids, leading to addiction is characterized by the following behaviors:

Physical dependence is characterized by withdrawal symptoms after abrupt drug discontinuation or a significant dose reduction of a drug. Individuals taking supratherapeutic doses of testosterone may experience withdrawal symptoms lasting for weeks or months which include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido and hypogonadotropic hypogonadism.

Drug dependence in individuals using approved doses of testosterone for approved indications has not been documented.

There is a single report of acute overdosage after parenteral administration of an approved testosterone product in the literature. This subject had serum testosterone concentrations of up to 11,400 ng/dL, which were implicated in a cerebrovascular accident. There were no reports of overdosage in the testosterone gel 1.62% clinical trial.

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Treatment of overdosage would consist of discontinuation of testosterone gel 1.62%, washing the application site with soap and water, and appropriate symptomatic and supportive care.

{ "type": "p", "children": [], "text": "Treatment of overdosage would consist of discontinuation of testosterone gel 1.62%, washing the application site with soap and water, and appropriate symptomatic and supportive care." }

Testosterone gel 1.62% for topical use is a clear, colorless gel containing testosterone, USP. Testosterone is an androgen. Testosterone gel 1.62% is available in a metered-dose pump or unit dose packets.

{ "type": "p", "children": [], "text": "Testosterone gel 1.62% for topical use is a clear, colorless gel containing testosterone, USP. Testosterone is an androgen. Testosterone gel 1.62% is available in a metered-dose pump or unit dose packets." }

The active pharmacologic ingredient in testosterone gel 1.62% is testosterone. Testosterone, USP is a white to almost white powder chemically described as 17-beta hydroxyandrost-4-en-3-one. The structural formula is:

{ "type": "p", "children": [], "text": "The active pharmacologic ingredient in testosterone gel 1.62% is testosterone. Testosterone, USP is a white to almost white powder chemically described as 17-beta hydroxyandrost-4-en-3-one. The structural formula is:" }

The inactive ingredients in testosterone gel 1.62% are: carbomer homopolymer type C (carbopol 980), ethyl alcohol, isopropyl myristate, purified water, and sodium hydroxide.

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Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement; vocal chord thickening; and alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics.

Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter's syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).

No specific pharmacodynamic studies were conducted using testosterone gel 1.62%.

Absorption

Testosterone gel 1.62% delivers physiologic amounts of testosterone, producing circulating testosterone concentrations that approximate normal levels (300 ng/dL to 1000 ng/dL) seen in healthy men. Testosterone gel 1.62% provides continuous transdermal delivery of testosterone for 24 hours following once daily application to clean, dry, intact skin of the shoulders and upper arms. Average serum testosterone concentrations over 24 hours (Cavg) observed when testosterone gel 1.62% was applied to the upper arms/shoulders were comparable to average serum testosterone concentrations (Cavg) when testosterone gel 1.62% was applied using a rotation method utilizing the abdomen and upper arms/shoulders. The rotation of abdomen and upper arms/shoulders was a method used in the pivotal clinical trial [see Clinical Studies (14.1)].

Distribution

Circulating testosterone is primarily bound in the serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is loosely bound to albumin and other proteins.

Metabolism

Testosterone is metabolized to various 17-keto steroids through two different pathways. The major active metabolites of testosterone are estradiol and DHT.

Excretion

There is considerable variation in the half-life of testosterone concentration as reported in the literature, ranging from 10 to 100 minutes. About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic acid and sulfuric acid conjugates of testosterone and its metabolites. About 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver.

When testosterone gel 1.62% treatment is discontinued, serum testosterone concentrations return to approximately baseline concentrations within 48 to 72 hours after administration of the last dose.

Potential for testosterone transfer

The potential for testosterone transfer following administration of testosterone gel 1.62% when it was applied only to upper arms/shoulders was evaluated in two clinical studies of males dosed with testosterone gel 1.62% and their untreated female partners. In one study, 8 male subjects applied a single dose of testosterone gel 1.62% 81 mg to their shoulders and upper arms. Two (2) hours after application, female subjects rubbed their hands, wrists, arms, and shoulders to the application site of the male subjects for 15 minutes. Serum concentrations of testosterone were monitored in female subjects for 24 hours after contact occurred. After direct skin-to-skin contact with the site of application, mean testosterone Cavg and Cmax in female subjects increased by 280% and 267%, respectively, compared to mean baseline testosterone concentrations. In a second study evaluating transfer of testosterone, 12 male subjects applied a single dose of testosterone gel 1.62% 81 mg to their shoulders and upper arms. Two (2) hours after application, female subjects rubbed their hands, wrists, arms, and shoulders to the application site of the male subjects for 15 minutes while the site of application was covered by a t-shirt. When a t-shirt was used to cover the site of application, mean testosterone Cavg and Cmax in female subjects increased by 6% and 11%, respectively, compared to mean baseline testosterone concentrations.

A separate study was conducted to evaluate the potential for testosterone transfer from 16 males dosed with testosterone gel 1.62% 81 mg when it was applied to abdomen only for 7 days, a site of application not approved for testosterone gel 1.62%. Two (2) hours after application to the males on each day, the female subjects rubbed their abdomens for 15 minutes to the abdomen of the males. The males had covered the application area with a T-shirt. The mean testosterone Cavg and Cmax in female subjects on day 1 increased by 43% and 47%, respectively, compared to mean baseline testosterone concentrations. The mean testosterone Cavg and Cmax in female subjects on day 7 increased by 60% and 58%, respectively, compared to mean baseline testosterone concentrations.

Effect of showering

In a randomized, 3-way (3 treatment periods without washout period) crossover study in 24 hypogonadal men, the effect of showering on testosterone exposure was assessed after once daily application of testosterone gel 1.62% 81 mg to upper arms/shoulders for 7 days in each treatment period. On the 7th day of each treatment period, hypogonadal men took a shower with soap and water at either 2, 6, or 10 hours after drug application. The effect of showering at 2 or 6 hours post-dose on Day 7 resulted in 13% and 12% decreases in mean Cavg, respectively, compared to Day 6 when no shower was taken after drug application. Showering at 10 hours after drug application had no effect on bioavailability. The amount of testosterone remaining in the outer layers of the skin at the application site on the 7th day was assessed using a tape stripping procedure and was reduced by at least 80% after showering 2 to 10 hours post-dose compared to on the 6th day when no shower was taken after drug application.

Effect of hand washing

In a randomized, open-label, single-dose, 2-way crossover study in 16 healthy male subjects, the effect of hand washing on the amount of residual testosterone on the hands was evaluated. Subjects used their hands to apply the maximum dose (81 mg testosterone) of testosterone gel 1.62% to their upper arms and shoulders. Within 1 minute of applying the gel, subjects either washed or did not wash their hands prior to study personnel wiping the subjects’ hands with ethanol dampened gauze pads. The gauze pads were then analyzed for residual testosterone content. A mean (SD) of 0.1 (0.04) mg of residual testosterone (0.12% of the actual applied dose of testosterone, and a 96% reduction compared to when hands were not washed) was recovered after washing hands with water and soap.

Effect of sunscreen or moisturizing lotion on absorption of testosterone 

In a randomized, 3-way (3 treatment periods without washout period) crossover study in 18 hypogonadal males, the effect of applying a moisturizing lotion or a sunscreen on the absorption of testosterone was evaluated with the upper arms/shoulders as application sites. For 7 days, moisturizing lotion or sunscreen (SPF 50) was applied daily to the testosterone gel 1.62% application site 1 hour after the application of testosterone gel 1.62% 40.5 mg. Application of moisturizing lotion increased mean testosterone Cavg and Cmax by 14% and 17%, respectively, compared to testosterone gel 1.62% administered alone. Application of sunscreen increased mean testosterone Cavg and Cmax by 8% and 13%, respectively, compared to testosterone gel 1.62% applied alone.

Carcinogenesis

Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, the implant induced cervical-uterine tumors which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats.

Mutagenesis

Testosterone was negative in the in vitro Ames and in the in vivo mouse micronucleus assays. 

Impairment of Fertility

The administration of exogenous testosterone has been reported to suppress spermatogenesis in rats, dogs, and non-human primates, which was reversible on cessation of the treatment.

Testosterone gel 1.62% was evaluated in a multi-center, randomized, double-blind, parallel-group, placebo-controlled study (182-day double-blind period) in 274 hypogonadal men with body mass index (BMI) 18 kg/m2 to 40 kg/m2 and 18 to 80 years of age (mean age 53.8 years). The patients had an average serum testosterone concentration of <300 ng/dL, as determined by two morning samples collected on the same visit. Patients were Caucasian 83%, Black 13%, Asian or Native American 4%. 7.5% of patients were Hispanic.

Patients were randomized to receive active treatment or placebo using a rotation method utilizing the abdomen and upper arms/shoulders for 182 days. All patients were started at a daily dose of 40.5 mg (two pump actuations) testosterone gel 1.62% or matching placebo on Day 1 of the study. Patients returned to the clinic on Day 14, Day 28, and Day 42 for predose serum total testosterone assessments. The patient's daily dose was titrated up or down in 20.25 mg increments if the predose serum testosterone value was outside the range of 350 ng/dL to 750 ng/dL. The study included four active testosterone gel 1.62% doses: 20.25 mg, 40.5 mg, 60.75 mg, and 81 mg daily.

The primary endpoint was the percentage of patients with Cavg within the normal range of 300 ng/dL to 1000 ng/dL on Day 112. In patients treated with testosterone gel 1.62%, 81.6% (146/179) had Cavg within the normal range at Day 112. The secondary endpoint was the percentage of patients, with Cmax above three pre-determined limits. The percentages of patients with Cmax greater than 1500 ng/dL, and between 1800 and 2499 ng/dL on Day 112 were 11.2% and 5.5%, respectively. Two patients had a Cmax >2500 ng/dL on Day 112 (2510 ng/dL and 2550 ng/dL, respectively); neither of these 2 patients demonstrated an abnormal Cmax on prior or subsequent assessments at the same dose.

Patients could agree to continue in an open-label, active treatment maintenance period of the study for an additional 182 days.

Dose titrations on Days 14, 28, and 42 resulted in final doses of 20.25 mg to 81 mg on Day 112 as shown in Table 6.

<div class="scrollingtable"><table> <caption> <span>Table 6: Mean (SD) Testosterone Concentrations (C<span class="Sub">avg</span> and C<span class="Sub">max</span>) by final dose on Days 112 and 364</span> </caption> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule"> </td><td align="center" class="Lrule Rrule Toprule" colspan="5"> <span class="Bold">Final Dose on Day 112</span></td><td align="center" class="Lrule Rrule Toprule"> </td> </tr> <tr> <td align="center" class="Lrule Rrule"> <span class="Bold">Parameter</span></td><td align="center" class="Lrule Rrule Toprule"> <span class="Bold">Placebo</span> <br/> <span class="Bold">(n=27)</span></td><td align="center" class="Lrule Rrule Toprule"> <span class="Bold">20.25 mg</span> <br/> <span class="Bold">(n=12)</span></td><td align="center" class="Lrule Rrule Toprule"> <span class="Bold">40.5 mg</span> <br/> <span class="Bold">(n=34)</span></td><td align="center" class="Lrule Rrule Toprule"> <span class="Bold">60.75 mg</span> <br/> <span class="Bold">(n=54)</span></td><td align="center" class="Lrule Rrule Toprule"> <span class="Bold">81 mg</span> <br/> <span class="Bold">(n=79)</span></td><td align="center" class="Lrule Rrule Toprule"> <span class="Bold">All Active</span> <br/> <span class="Bold">(n=179)</span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule"> <span class="Bold">C</span><span class="Bold"><span class="Sub">avg</span></span><span class="Bold"> (ng/dL)</span></td><td align="center" class="Lrule Rrule Toprule"> 303 (135)</td><td align="center" class="Lrule Rrule Toprule"> 457 (275)</td><td align="center" class="Lrule Rrule Toprule"> 524 (228)</td><td align="center" class="Lrule Rrule Toprule"> 643 (285)</td><td align="center" class="Lrule Rrule Toprule"> 537 (240)</td><td align="center" class="Lrule Rrule Toprule"> 561 (259)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule"> <span class="Bold">C</span><span class="Bold"><span class="Sub">max</span></span><span class="Bold"> (ng/dL)</span></td><td align="center" class="Lrule Rrule Toprule"> 450 (349)</td><td align="center" class="Lrule Rrule Toprule"> 663 (473)</td><td align="center" class="Lrule Rrule Toprule"> 798 (439)</td><td align="center" class="Lrule Rrule Toprule"> 958 (497)</td><td align="center" class="Lrule Rrule Toprule"> 813 (479)</td><td align="center" class="Lrule Rrule Toprule"> 845 (480)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule"> </td><td align="center" class="Lrule Rrule Toprule" colspan="5"> <span class="Bold">Final Dose on Day 364</span></td><td align="center" class="Lrule Rrule Toprule"> </td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule"> </td><td align="center" class="Lrule Rrule Toprule"> </td><td align="center" class="Lrule Rrule Toprule"> <span class="Bold">20.25 mg</span> <br/> <span class="Bold">(n=7)</span></td><td align="center" class="Lrule Rrule Toprule"> <span class="Bold">40.5 mg</span> <br/> <span class="Bold">(n=26)</span></td><td align="center" class="Lrule Rrule Toprule"> <span class="Bold">60.75 mg</span> <br/> <span class="Bold">(n=29)</span></td><td align="center" class="Lrule Rrule Toprule"> <span class="Bold">81 mg</span> <br/> <span class="Bold">(n=74)</span></td><td align="center" class="Lrule Rrule Toprule"> <span class="Bold">Continuing Active</span> <br/> <span class="Bold">(n=136)</span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule"> <span class="Bold">C</span><span class="Bold"><span class="Sub">avg</span></span><span class="Bold"> (ng/dL)</span></td><td align="center" class="Lrule Rrule Toprule"> </td><td align="center" class="Lrule Rrule Toprule"> 386 (130)</td><td align="center" class="Lrule Rrule Toprule"> 474 (176)</td><td align="center" class="Lrule Rrule Toprule"> 513 (222)</td><td align="center" class="Lrule Rrule Toprule"> 432 (186)</td><td align="center" class="Lrule Rrule Toprule"> 455 (192)</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule Toprule"> <span class="Bold">C</span><span class="Bold"><span class="Sub">max</span></span><span class="Bold"> (ng/dL)</span></td><td align="center" class="Lrule Rrule Toprule"> </td><td align="center" class="Lrule Rrule Toprule"> 562 (187)</td><td align="center" class="Lrule Rrule Toprule"> 715 (306)</td><td align="center" class="Lrule Rrule Toprule"> 839 (568)</td><td align="center" class="Lrule Rrule Toprule"> 649 (329)</td><td align="center" class="Lrule Rrule Toprule"> 697 (389)</td> </tr> </tbody> </table></div>

Figure 3 summarizes the pharmacokinetic profile of total testosterone in patients completing 112 days of testosterone gel 1.62% treatment administered as a starting dose of 40.5 mg of testosterone (2 pump actuations) for the initial 14 days followed by possible titration according to the follow-up testosterone measurements.

Efficacy was maintained in the group of men that received testosterone gel 1.62% for one full year. In that group, 78% (106/136) had average serum testosterone concentrations in the normal range at Day 364. Figure 4 summarizes the mean total testosterone profile for these patients on Day 364.

Figure 4: Mean (±SD) Steady-State Serum Total Testosterone Concentrations on Day 364

The mean estradiol and DHT concentration profiles paralleled the changes observed in testosterone. The levels of LH and FSH decreased with testosterone treatment. The decreases in levels of LH and FSH are consistent with reports published in the literature of long-term treatment with testosterone.

Testosterone gel 1.62% is supplied in non-aerosol, metered-dose pumps that deliver 20.25 mg of testosterone per complete pump actuation. The pumps are composed of plastic and stainless steel and an LDPE/aluminum foil inner liner encased in rigid plastic with a polypropylene cap. Each 88 g metered-dose pump is capable of dispensing 75 g of gel or 60-metered pump actuations; each pump actuation dispenses 1.25 g of gel.

{ "type": "p", "children": [], "text": "Testosterone gel 1.62% is supplied in non-aerosol, metered-dose pumps that deliver 20.25 mg of testosterone per complete pump actuation. The pumps are composed of plastic and stainless steel and an LDPE/aluminum foil inner liner encased in rigid plastic with a polypropylene cap. Each 88 g metered-dose pump is capable of dispensing 75 g of gel or 60-metered pump actuations; each pump actuation dispenses 1.25 g of gel." }

Testosterone gel 1.62% is also supplied in unit-dose aluminum foil packets in cartons of 30. Each packet of 1.25 g or 2.5 g gel contains 20.25 mg or 40.5 mg testosterone, respectively.

{ "type": "p", "children": [], "text": "Testosterone gel 1.62% is also supplied in unit-dose aluminum foil packets in cartons of 30. Each packet of 1.25 g or 2.5 g gel contains 20.25 mg or 40.5 mg testosterone, respectively." }

<div class="scrollingtable"><table cellpadding="5" cellspacing="0" width="800px"> <col width="150px"/> <col width="650px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <span class="Bold">NDC Number</span></td><td class="Botrule Lrule Rrule Toprule"> <span class="Bold">Package Size</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> 0591-2924-18</td><td class="Botrule Lrule Rrule Toprule"> 88 g pump (each pump dispenses 60 metered pump actuations with each pump actuation containing 20.25 mg of testosterone in 1.25 g of gel)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> 0591-2925-32</td><td class="Botrule Lrule Rrule Toprule"> Each unit dose packet contains 20.25 mg of testosterone provided in 1.25 g of gel</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> 0591-2925-30</td><td class="Botrule Lrule Rrule Toprule"> 30 packets (each unit dose packet contains 20.25 mg of testosterone provided in 1.25 g of gel)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> 0591-2926-25</td><td class="Botrule Lrule Rrule Toprule"> Each unit dose packet contains 40.5 mg of testosterone provided in 2.5 g of gel</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> 0591-2926-30</td><td class="Botrule Lrule Rrule Toprule"> 30 packets (each unit dose packet contains 40.5 mg of testosterone provided in 2.5 g of gel)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"5\" cellspacing=\"0\" width=\"800px\">\n<col width=\"150px\"/>\n<col width=\"650px\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\"> <span class=\"Bold\">NDC Number</span></td><td class=\"Botrule Lrule Rrule Toprule\"> <span class=\"Bold\">Package Size</span></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"> 0591-2924-18</td><td class=\"Botrule Lrule Rrule Toprule\"> 88 g pump (each pump dispenses 60 metered pump actuations with each pump actuation containing 20.25 mg of testosterone in 1.25 g of gel)</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"> 0591-2925-32</td><td class=\"Botrule Lrule Rrule Toprule\"> Each unit dose packet contains 20.25 mg of testosterone provided in 1.25 g of gel</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"> 0591-2925-30</td><td class=\"Botrule Lrule Rrule Toprule\"> 30 packets (each unit dose packet contains 20.25 mg of testosterone provided in 1.25 g of gel)</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"> 0591-2926-25</td><td class=\"Botrule Lrule Rrule Toprule\"> Each unit dose packet contains 40.5 mg of testosterone provided in 2.5 g of gel</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\"> 0591-2926-30</td><td class=\"Botrule Lrule Rrule Toprule\"> 30 packets (each unit dose packet contains 40.5 mg of testosterone provided in 2.5 g of gel)</td>\n</tr>\n</tbody>\n</table></div>" }

Store at controlled room temperature 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "Store at controlled room temperature 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]." }

Used testosterone gel 1.62% pumps or used testosterone gel 1.62% packets should be discarded in household trash in a manner that prevents accidental application or ingestion by children or pets.

{ "type": "p", "children": [], "text": "Used testosterone gel 1.62% pumps or used testosterone gel 1.62% packets should be discarded in household trash in a manner that prevents accidental application or ingestion by children or pets." }

Men with known or suspected prostate or breast cancer should not use testosterone gel 1.62% [see Contraindications (4) and Warnings and Precautions (5.1)].

Secondary exposure to testosterone in children and women can occur with the use of testosterone gel in men [see Warnings and Precautions (5.2)]. Cases of secondary exposure to testosterone have been reported in children.

Physicians should advise patients of the reported signs and symptoms of secondary exposure, which may include the following:

Strict adherence to the following precautions is advised to minimize the potential for secondary exposure to testosterone from testosterone gel 1.62% in men [see Medication Guide]: 

Patients should be informed that treatment with androgens may lead to adverse reactions which include:

Teva Pharmaceuticals USA, Inc. North Wales, PA 19454

Iss. 8/2019

<div class="scrollingtable"><table border="0" cellpadding="5" cellspacing="0" width="1000px"> <col width="7.65in"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <br/> </p> <p> <span class="Bold">Testosterone (tes tosʹ ter one) Gel 1.62%  </span><span class="Bold">CIII</span> </p> <p> <span class="Bold">for topical use</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">What is the most important information I should know about testosterone gel 1.62%?</span> </p> <p> <span class="Bold">1. Testosterone gel</span><span class="Bold"> 1.62% can transfer from your body to others including, children and women. </span>Children and women should avoid contact with the unwashed or not covered (unclothed) areas where testosterone gel 1.62% has been applied to your skin. Early signs and symptoms of puberty have occurred in young children who have come in direct contact with testosterone by touching areas where men have used testosterone gel 1.62%.</p> <p> <span class="Bold"><span class="Underline">Children</span></span> </p> <p> <span class="Bold">Signs and symptoms of early puberty in a child when they come in direct contact with testosterone gel</span><span class="Bold"> 1.62% may include:</span> </p> <p> <span class="Bold">Abnormal sexual changes:</span> </p> <ul class="Disk"> <li>enlarged penis or clitoris.</li> <li>early growth of hair near the vagina or around the penis (pubic hair).</li> <li>erections or acting out sexual urges (sex drive).</li> </ul> <p> <span class="Bold">Behavior problems:</span> </p> <ul class="Disk"> <li>acting aggressively, behaving in an angry or violent way.</li> </ul> <p> <span class="Bold"><span class="Underline">Women</span></span> </p> <p> <span class="Bold">Signs and symptoms in women when they come in direct contact with testosterone gel 1.62% may include:</span> </p> <ul class="Disk"> <li>changes in body hair.</li> <li>an abnormal increase in pimples (acne).</li> </ul> <p> <span class="Bold">Stop using testosterone gel 1.62% and call your healthcare provider right away if you see any signs and symptoms</span> in a child or a woman that may have happened through accidental touching of the area where you have applied testosterone gel 1.62%.</p> <p> <span class="Bold">2. To lower the risk of transfer of testosterone gel 1.62% from your body to others, follow these important instructions:</span> </p> <ul class="Circle"> <li>Apply testosterone gel 1.62% only to your shoulders and upper arms that will be covered by a short sleeve t-shirt.</li> <li>Wash your hands right away with soap and water after applying testosterone gel 1.62%.</li> <li>After the gel has dried, cover the application area with clothing. Keep the area covered until you have washed the application area well or have showered.</li> <li>If you expect to have skin-to-skin contact with another person, first wash the application area well with soap and water.</li> <li>If a child or woman touches the area where you have applied testosterone gel 1.62%, that area on the child or woman should be washed well with soap and water right away.</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">What is testosterone gel 1.62%?</span> </p> <p>Testosterone gel 1.62% is a prescription medicine that contains testosterone. Testosterone gel 1.62% is used to treat adult males who have low or no testosterone due to certain medical conditions.</p> <ul class="Disk"> <li>Your healthcare provider will test your blood before you start and while you are using testosterone gel 1.62%.</li> <li>It is not known if testosterone gel 1.62% is safe or effective to treat men who have low testosterone due to aging.</li> <li>It is not known if testosterone gel 1.62% is safe or effective in children younger than 18 years old. Improper use of testosterone gel 1.62% may affect bone growth in children.</li> </ul> <p>Testosterone gel 1.62% is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your testosterone gel 1.62% in a safe place to protect it. Never give your testosterone gel 1.62% to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and is against the law.</p> <p>Testosterone gel 1.62% is not meant for use in women.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Do not use testosterone gel 1.62% if you:</span> </p> <ul class="Disk"> <li>have breast cancer.</li> <li>have or might have prostate cancer.</li> <li>are pregnant. Testosterone gel 1.62% may harm your unborn baby.</li> <li>Women who are pregnant should avoid contact with the area of skin where testosterone gel 1.62% has been applied.</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Before using testosterone gel 1.62%, tell your healthcare provider about all of your medical conditions, including if you:</span> </p> <ul class="Disk"> <li>have breast cancer.</li> <li>have or might have prostate cancer.</li> <li>have urinary problems due to an enlarged prostate.</li> <li>have heart problems.</li> <li>have kidney or liver problems.</li> <li>have problems breathing while you sleep (sleep apnea).</li> </ul> <p>Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Using testosterone gel 1.62% with certain other medicines can affect each other. </p> <p>Especially, tell your healthcare provider if you take:</p> <ul class="Disk"> <li>insulin</li> <li>medicines that decrease blood clotting (blood thinners)</li> <li>corticosteroids</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">How should I use testosterone gel 1.62%?</span> </p> <ul class="Disk"> <li>See the detailed <span class="Bold">Instructions for Use </span>about how to use testosterone gel 1.62% at the end of this Medication Guide.</li> <li>It is important that you apply testosterone gel 1.62% exactly as your healthcare provider tells you to.</li> <li>Your healthcare provider may change your testosterone gel 1.62% dose. <span class="Bold">Do not </span>change your testosterone gel 1.62% dose without talking to your healthcare provider.</li> <li>Apply testosterone gel 1.62% at the same time each morning. Testosterone gel 1.62% should be applied after showering or bathing.</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">What are the possible side effects of testosterone gel 1.62%?</span> </p> <p> <span class="Bold">Testosterone gel</span><span class="Bold"> 1.62% can cause serious side effects including:</span> </p> <p>See<span class="Bold"> “What is the most important information I should know about testosterone gel 1.62%?” </span> </p> <ul class="Disk"> <li> <span class="Bold">If you already have enlargement of your prostate gland your signs and symptoms can get worse while using testosterone gel 1.62%. </span>This can include:</li> </ul> <ul class="Circle"> <li>increased urination at night.</li> <li>trouble starting your urine stream.</li> <li>having to pass urine many times during the day.</li> <li>having an urge to go to the bathroom right away.</li> <li>having a urine accident.</li> <li>being unable to pass urine or weak urine flow.</li> </ul> <ul class="Disk"> <li> <span class="Bold">Possible increased risk of prostate cancer. </span>Your healthcare provider should check you for prostate cancer or any other prostate problems before you start and while you use testosterone gel 1.62%.</li> <li> <span class="Bold">Blood clots in the legs or lungs. </span>Signs and symptoms of a blood clot in your leg can include leg pain, swelling, or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain.</li> <li> <span class="Bold">Possible increased risk of heart attack or stroke.</span> </li> <li> <span class="Bold">In large doses testosterone gel 1.62% may lower your sperm count.</span> </li> <li> <span class="Bold">Swelling of your ankles, feet, or body, with or without heart failure.</span> </li> <li> <span class="Bold">Enlarged or painful breasts.</span> </li> <li> <span class="Bold">Have problems breathing while you sleep (sleep apnea).</span> </li> </ul> <p> <span class="Bold">Call your healthcare provider right away if you have any of the serious side effects listed above.</span> </p> <p> <span class="Bold">The most common side effects of testosterone gel 1.62% include:</span> </p> <ul class="Disk"> <li>increased prostate specific antigen (a test used to screen for prostate cancer)</li> <li>mood swings</li> <li>hypertension</li> <li>increased red blood cell count</li> <li>skin irritation where testosterone gel 1.62% is applied</li> </ul> <p> <span class="Bold">Other side effects include </span>more erections than are normal for you or erections that last a long time.</p> <p>Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</p> <p>These are not all the possible side effects of testosterone gel 1.62%. For more information, ask your healthcare provider or pharmacist.</p> <p> <span class="Bold">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">General information about the safe and effective use of testosterone gel 1.62% </span> </p> <p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use testosterone gel 1.62% for a condition for which it was not prescribed. Do not give testosterone gel 1.62% to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about testosterone gel 1.62% that is written for health professionals.</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">What are the ingredients in testosterone gel 1.62%? </span> </p> <p> <span class="Bold">Active ingredient:</span> testosterone</p> <p> <span class="Bold">Inactive ingredients:</span> carbomer homopolymer type C (carbopol 980), ethyl alcohol, isopropyl myristate, purified water and sodium hydroxide.</p> <p>For more information, contact Teva Pharmaceuticals USA, Inc. at 1-888-838-2872.</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" width=\"1000px\">\n<col width=\"7.65in\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<br/>\n</p>\n<p>\n<span class=\"Bold\">Testosterone (tes tosʹ ter one) Gel 1.62%  </span><span class=\"Bold\">CIII</span>\n</p>\n<p>\n<span class=\"Bold\">for topical use</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">What is the most important information I should know about testosterone gel 1.62%?</span>\n</p>\n<p>\n<span class=\"Bold\">1. Testosterone gel</span><span class=\"Bold\"> 1.62% can transfer from your body to others including, children and women. </span>Children and women should avoid contact with the unwashed or not covered (unclothed) areas where testosterone gel 1.62% has been applied to your skin. Early signs and symptoms of puberty have occurred in young children who have come in direct contact with testosterone by touching areas where men have used testosterone gel 1.62%.</p>\n<p>\n<span class=\"Bold\"><span class=\"Underline\">Children</span></span>\n</p>\n<p>\n<span class=\"Bold\">Signs and symptoms of early puberty in a child when they come in direct contact with testosterone gel</span><span class=\"Bold\"> 1.62% may include:</span>\n</p>\n<p>\n<span class=\"Bold\">Abnormal sexual changes:</span>\n</p>\n<ul class=\"Disk\">\n<li>enlarged penis or clitoris.</li>\n<li>early growth of hair near the vagina or around the penis (pubic hair).</li>\n<li>erections or acting out sexual urges (sex drive).</li>\n</ul>\n<p>\n<span class=\"Bold\">Behavior problems:</span>\n</p>\n<ul class=\"Disk\">\n<li>acting aggressively, behaving in an angry or violent way.</li>\n</ul>\n<p>\n<span class=\"Bold\"><span class=\"Underline\">Women</span></span>\n</p>\n<p>\n<span class=\"Bold\">Signs and symptoms in women when they come in direct contact with testosterone gel 1.62% may include:</span>\n</p>\n<ul class=\"Disk\">\n<li>changes in body hair.</li>\n<li>an abnormal increase in pimples (acne).</li>\n</ul>\n<p>\n<span class=\"Bold\">Stop using testosterone gel 1.62% and call your healthcare provider right away if you see any signs and symptoms</span> in a child or a woman that may have happened through accidental touching of the area where you have applied testosterone gel 1.62%.</p>\n<p>\n<span class=\"Bold\">2. To lower the risk of transfer of testosterone gel 1.62% from your body to others, follow these important instructions:</span>\n</p>\n<ul class=\"Circle\">\n<li>Apply testosterone gel 1.62% only to your shoulders and upper arms that will be covered by a short sleeve t-shirt.</li>\n<li>Wash your hands right away with soap and water after applying testosterone gel 1.62%.</li>\n<li>After the gel has dried, cover the application area with clothing. Keep the area covered until you have washed the application area well or have showered.</li>\n<li>If you expect to have skin-to-skin contact with another person, first wash the application area well with soap and water.</li>\n<li>If a child or woman touches the area where you have applied testosterone gel 1.62%, that area on the child or woman should be washed well with soap and water right away.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">What is testosterone gel 1.62%?</span>\n</p>\n<p>Testosterone gel 1.62% is a prescription medicine that contains testosterone. Testosterone gel 1.62% is used to treat adult males who have low or no testosterone due to certain medical conditions.</p>\n<ul class=\"Disk\">\n<li>Your healthcare provider will test your blood before you start and while you are using testosterone gel 1.62%.</li>\n<li>It is not known if testosterone gel 1.62% is safe or effective to treat men who have low testosterone due to aging.</li>\n<li>It is not known if testosterone gel 1.62% is safe or effective in children younger than 18 years old. Improper use of testosterone gel 1.62% may affect bone growth in children.</li>\n</ul>\n<p>Testosterone gel 1.62% is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your testosterone gel 1.62% in a safe place to protect it. Never give your testosterone gel 1.62% to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and is against the law.</p>\n<p>Testosterone gel 1.62% is not meant for use in women.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Do not use testosterone gel 1.62% if you:</span>\n</p>\n<ul class=\"Disk\">\n<li>have breast cancer.</li>\n<li>have or might have prostate cancer.</li>\n<li>are pregnant. Testosterone gel 1.62% may harm your unborn baby.</li>\n<li>Women who are pregnant should avoid contact with the area of skin where testosterone gel 1.62% has been applied.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Before using testosterone gel 1.62%, tell your healthcare provider about all of your medical conditions, including if you:</span>\n</p>\n<ul class=\"Disk\">\n<li>have breast cancer.</li>\n<li>have or might have prostate cancer.</li>\n<li>have urinary problems due to an enlarged prostate.</li>\n<li>have heart problems.</li>\n<li>have kidney or liver problems.</li>\n<li>have problems breathing while you sleep (sleep apnea).</li>\n</ul>\n<p>Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Using testosterone gel 1.62% with certain other medicines can affect each other. </p>\n<p>Especially, tell your healthcare provider if you take:</p>\n<ul class=\"Disk\">\n<li>insulin</li>\n<li>medicines that decrease blood clotting (blood thinners)</li>\n<li>corticosteroids</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">How should I use testosterone gel 1.62%?</span>\n</p>\n<ul class=\"Disk\">\n<li>See the detailed <span class=\"Bold\">Instructions for Use </span>about how to use testosterone gel 1.62% at the end of this Medication Guide.</li>\n<li>It is important that you apply testosterone gel 1.62% exactly as your healthcare provider tells you to.</li>\n<li>Your healthcare provider may change your testosterone gel 1.62% dose. <span class=\"Bold\">Do not </span>change your testosterone gel 1.62% dose without talking to your healthcare provider.</li>\n<li>Apply testosterone gel 1.62% at the same time each morning. Testosterone gel 1.62% should be applied after showering or bathing.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of testosterone gel 1.62%?</span>\n</p>\n<p>\n<span class=\"Bold\">Testosterone gel</span><span class=\"Bold\"> 1.62% can cause serious side effects including:</span>\n</p>\n<p>See<span class=\"Bold\"> “What is the most important information I should know about testosterone gel 1.62%?” </span>\n</p>\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\">If you already have enlargement of your prostate gland your signs and symptoms can get worse while using testosterone gel 1.62%. </span>This can include:</li>\n</ul>\n<ul class=\"Circle\">\n<li>increased urination at night.</li>\n<li>trouble starting your urine stream.</li>\n<li>having to pass urine many times during the day.</li>\n<li>having an urge to go to the bathroom right away.</li>\n<li>having a urine accident.</li>\n<li>being unable to pass urine or weak urine flow.</li>\n</ul>\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\">Possible increased risk of prostate cancer. </span>Your healthcare provider should check you for prostate cancer or any other prostate problems before you start and while you use testosterone gel 1.62%.</li>\n<li>\n<span class=\"Bold\">Blood clots in the legs or lungs. </span>Signs and symptoms of a blood clot in your leg can include leg pain, swelling, or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain.</li>\n<li>\n<span class=\"Bold\">Possible increased risk of heart attack or stroke.</span>\n</li>\n<li>\n<span class=\"Bold\">In large doses testosterone gel 1.62% may lower your sperm count.</span>\n</li>\n<li>\n<span class=\"Bold\">Swelling of your ankles, feet, or body, with or without heart failure.</span>\n</li>\n<li>\n<span class=\"Bold\">Enlarged or painful breasts.</span>\n</li>\n<li>\n<span class=\"Bold\">Have problems breathing while you sleep (sleep apnea).</span>\n</li>\n</ul>\n<p>\n<span class=\"Bold\">Call your healthcare provider right away if you have any of the serious side effects listed above.</span>\n</p>\n<p>\n<span class=\"Bold\">The most common side effects of testosterone gel 1.62% include:</span>\n</p>\n<ul class=\"Disk\">\n<li>increased prostate specific antigen (a test used to screen for prostate cancer)</li>\n<li>mood swings</li>\n<li>hypertension</li>\n<li>increased red blood cell count</li>\n<li>skin irritation where testosterone gel 1.62% is applied</li>\n</ul>\n<p>\n<span class=\"Bold\">Other side effects include </span>more erections than are normal for you or erections that last a long time.</p>\n<p>Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</p>\n<p>These are not all the possible side effects of testosterone gel 1.62%. For more information, ask your healthcare provider or pharmacist.</p>\n<p>\n<span class=\"Bold\">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of testosterone gel 1.62% </span>\n</p>\n<p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use testosterone gel 1.62% for a condition for which it was not prescribed. Do not give testosterone gel 1.62% to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about testosterone gel 1.62% that is written for health professionals.</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in testosterone gel 1.62%? </span>\n</p>\n<p>\n<span class=\"Bold\">Active ingredient:</span> testosterone</p>\n<p>\n<span class=\"Bold\">Inactive ingredients:</span> carbomer homopolymer type C (carbopol 980), ethyl alcohol, isopropyl myristate, purified water and sodium hydroxide.</p>\n<p>For more information, contact Teva Pharmaceuticals USA, Inc. at 1-888-838-2872.</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

This Medication Guide has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Medication Guide has been approved by the U.S. Food and Drug Administration." }

Teva Pharmaceuticals USA, Inc.

{ "type": "p", "children": [], "text": "\nTeva Pharmaceuticals USA, Inc.\n\n" }

North Wales, PA 19454

{ "type": "p", "children": [], "text": "North Wales, PA 19454" }

Rev. A 5/2019

{ "type": "p", "children": [], "text": "Rev. A 5/2019" }

Testosterone (tes tosʹ ter one) Gel 1.62%  CIII

{ "type": "p", "children": [], "text": "\nTestosterone (tes tosʹ ter one) Gel 1.62%  CIII\n" }

for topical use

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

Read this Instructions for Use for testosterone gel 1.62% before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment.

{ "type": "p", "children": [], "text": "Read this Instructions for Use for testosterone gel 1.62% before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment." }

Applying testosterone gel 1.62%:

{ "type": "p", "children": [], "text": "\nApplying testosterone gel 1.62%:\n" }

Testosterone gel 1.62% comes in a pump or in packets.

{ "type": "p", "children": [], "text": "\nTestosterone gel 1.62% comes in a pump or in packets.\n" }

{ "type": "ul", "children": [ "Before applying testosterone gel 1.62% make sure that your shoulders and upper arms are clean, dry, and that there is no broken skin.", "\nTestosterone gel 1.62% is to be applied to the area of your shoulders and upper arms that will be covered by a short sleeve t-shirt (See Figure A). Do not apply testosterone gel 1.62% to any other parts of your body such as your stomach area (abdomen), penis, scrotum, chest, armpits (axillae), or knees." ], "text": "" }

(Figure A)

{ "type": "p", "children": [], "text": "\n(Figure A)\n" }

If you are using testosterone gel 1.62% pump:

{ "type": "p", "children": [], "text": "\nIf you are using testosterone gel 1.62% pump:\n" }

{ "type": "ul", "children": [ "Before using a new bottle of testosterone gel 1.62 % for the first time, you will need to remove the cap and then prime the pump. To prime the testosterone gel 1.62% pump, slowly push the pump all the way down 3 times, over the sink drain. Do not use any testosterone gel 1.62% that came out while priming. Wash it down the sink to avoid accidental exposure to others. Your testosterone gel 1.62% pump is now ready to use.", "Remove the cap from the pump. Then, put the spout opening at the top of the pump where the medicine comes out over the palm of your hand and slowly push the pump all the way down. Apply testosterone gel 1.62% to the application site. You may also apply testosterone gel 1.62% directly to the application site. Your healthcare provider will tell you the number of times to press the pump for each dose.\n", "Wash your hands with soap and water right away." ], "text": "" }

<div class="scrollingtable"><table> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Find Your Dose as Prescribed by Your<br/> </span><span class="Bold">Healthcare Provider</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Application Method</span></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule">1 PUMP</td><td align="center" class="Botrule Lrule Rrule Toprule">20.25 mg</td><td class="Botrule Lrule Rrule Toprule">Apply 1 pump of testosterone gel 1.62% to 1 upper arm and shoulder.</td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule">2 PUMPS</td><td align="center" class="Botrule Lrule Rrule Toprule">40.5 mg</td><td class="Botrule Lrule Rrule Toprule">Apply 1 pump of testosterone gel 1.62% to 1 upper arm and shoulder and then apply 1 pump of testosterone gel 1.62% to the opposite upper arm and shoulder.</td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule">3 PUMPS</td><td align="center" class="Botrule Lrule Rrule Toprule">60.75 mg</td><td class="Botrule Lrule Rrule Toprule">Apply 2 pumps of testosterone gel 1.62% to 1 upper arm and shoulder and then apply 1 pump of testosterone gel 1.62% to the opposite upper arm and shoulder.</td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule">4 PUMPS</td><td align="center" class="Botrule Lrule Rrule Toprule">81 mg</td><td class="Botrule Lrule Rrule Toprule">Apply 2 pumps of testosterone gel 1.62% to 1 upper arm and shoulder and then apply 2 pumps of testosterone gel 1.62% to the opposite upper arm and shoulder.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col/>\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Find Your Dose as Prescribed by Your<br/>\n</span><span class=\"Bold\">Healthcare Provider</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Application Method</span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">1 PUMP</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">20.25 mg</td><td class=\"Botrule Lrule Rrule Toprule\">Apply 1 pump of testosterone gel 1.62% to 1 upper arm and shoulder.</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">2 PUMPS</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">40.5 mg</td><td class=\"Botrule Lrule Rrule Toprule\">Apply 1 pump of testosterone gel 1.62% to 1 upper arm and shoulder and then apply 1 pump of testosterone gel 1.62% to the opposite upper arm and shoulder.</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">3 PUMPS</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">60.75 mg</td><td class=\"Botrule Lrule Rrule Toprule\">Apply 2 pumps of testosterone gel 1.62% to 1 upper arm and shoulder and then apply 1 pump of testosterone gel 1.62% to the opposite upper arm and shoulder.</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">4 PUMPS</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">81 mg</td><td class=\"Botrule Lrule Rrule Toprule\">Apply 2 pumps of testosterone gel 1.62% to 1 upper arm and shoulder and then apply 2 pumps of testosterone gel 1.62% to the opposite upper arm and shoulder.</td>\n</tr>\n</tbody>\n</table></div>" }

If you are using testosterone gel 1.62% packets:

{ "type": "p", "children": [], "text": "\nIf you are using testosterone gel 1.62% packets:\n" }

{ "type": "ul", "children": [ "Tear open the packet completely at the dotted line. Squeeze from the bottom of the packet to the top.", "Squeeze all of the testosterone gel 1.62% out of the packet into the palm of your hand. ", "Apply testosterone gel 1.62% to the application site. You may also apply testosterone gel 1.62% directly to the application site.", "Let the application site dry completely before putting on a t-shirt.", "\nTestosterone gel 1.62% is flammable until dry. Let testosterone 1.62% dry before smoking or going near an open flame.", "Avoid showering, swimming or bathing for at least 2 hours after you apply testosterone gel 1.62%. Wash your hands right away with soap and water after applying testosterone 1.62%.\n" ], "text": "" }

<div class="scrollingtable"><table> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Find Your Dose as</span> </p> <p> <span class="Bold">Prescribed by Your</span> </p> <p> <span class="Bold">Healthcare Provider</span> </p> </td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Application Method</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">One 20.25 mg packet</td><td class="Botrule Lrule Rrule Toprule"> 20.25 mg             </td><td class="Botrule Lrule Rrule Toprule"> Apply 1 packet of testosterone gel 1.62% to 1 upper arm and shoulder.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">One 40.5 mg packet</td><td class="Botrule Lrule Rrule Toprule">40.5 mg</td><td class="Botrule Lrule Rrule Toprule">Apply half of the 40.5 mg packet of testosterone gel 1.62% to 1 upper arm and shoulder and then apply the remaining packet contents to the opposite upper arm and shoulder.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> One 40.5 mg packet and one 20.25 mg packet</td><td class="Botrule Lrule Rrule Toprule">60.75 mg</td><td class="Botrule Lrule Rrule Toprule"> Apply one 40.5 mg packet of testosterone gel 1.62% to 1 upper arm and shoulder and then apply one 20.25 mg packet of testosterone gel 1.62% to the opposite upper arm and shoulder.</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Two 40.5 mg packets</td><td class="Botrule Lrule Rrule Toprule">81 mg</td><td class="Botrule Lrule Rrule Toprule">Apply one 40.5 mg packet of testosterone gel 1.62% to 1 upper arm and shoulder and then apply one 40.5 mg packet of testosterone gel 1.62% to the opposite upper arm and shoulder.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col/>\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Find Your Dose as</span>\n</p>\n<p>\n<span class=\"Bold\">Prescribed by Your</span>\n</p>\n<p>\n<span class=\"Bold\">Healthcare Provider</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Application Method</span></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">One 20.25 mg packet</td><td class=\"Botrule Lrule Rrule Toprule\"> 20.25 mg             </td><td class=\"Botrule Lrule Rrule Toprule\"> Apply 1 packet of testosterone gel 1.62% to 1 upper arm and shoulder.</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">One 40.5 mg packet</td><td class=\"Botrule Lrule Rrule Toprule\">40.5 mg</td><td class=\"Botrule Lrule Rrule Toprule\">Apply half of the 40.5 mg packet of testosterone gel 1.62% to 1 upper arm and shoulder and then apply the remaining packet contents to the opposite upper arm and shoulder.</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"> One 40.5 mg packet and one 20.25 mg packet</td><td class=\"Botrule Lrule Rrule Toprule\">60.75 mg</td><td class=\"Botrule Lrule Rrule Toprule\"> Apply one 40.5 mg packet of testosterone gel 1.62% to 1 upper arm and shoulder and then apply one 20.25 mg packet of testosterone gel 1.62% to the opposite upper arm and shoulder.</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\">Two 40.5 mg packets</td><td class=\"Botrule Lrule Rrule Toprule\">81 mg</td><td class=\"Botrule Lrule Rrule Toprule\">Apply one 40.5 mg packet of testosterone gel 1.62% to 1 upper arm and shoulder and then apply one 40.5 mg packet of testosterone gel 1.62% to the opposite upper arm and shoulder.</td>\n</tr>\n</tbody>\n</table></div>" }

How should I store testosterone gel 1.62%?

{ "type": "p", "children": [], "text": "\nHow should I store testosterone gel 1.62%?\n" }

{ "type": "ul", "children": [ "Store testosterone gel 1.62% at 59ºF to 86ºF (15ºC to 30ºC).", "When it is time to throw away the pump or packets, safely throw away used testosterone gel 1.62% in the household trash. Be careful to prevent accidental exposure of children or pets.", "Keep testosterone gel 1.62% away from fire." ], "text": "" }

Keep testosterone gel 1.62% and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep testosterone gel 1.62% and all medicines out of the reach of children. \n" }

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Instructions for Use has been approved by the U.S. Food and Drug Administration." }

Teva Pharmaceuticals USA, Inc.

{ "type": "p", "children": [], "text": "\nTeva Pharmaceuticals USA, Inc.\n" }

North Wales, PA 19454

{ "type": "p", "children": [], "text": "North Wales, PA 19454" }

Rev. A 8/2019

{ "type": "p", "children": [], "text": "Rev. A 8/2019\n\n\n" }

NDC 0591-2924-18

{ "type": "p", "children": [], "text": "NDC 0591-2924-18" }

Testosterone Gel, 1.62% CIII(Alcohol 80% v/v)

{ "type": "p", "children": [], "text": "Testosterone Gel, 1.62% CIII(Alcohol 80% v/v)" }

20.25 mg of testosterone per pump actuation*

{ "type": "p", "children": [], "text": "20.25 mg of testosterone per pump actuation*" }

*Each actuation delivers 1.25 grams of gel

{ "type": "p", "children": [], "text": "*Each actuation delivers 1.25 grams of gel" }

FOR TOPICAL USE ONLY

{ "type": "p", "children": [], "text": "FOR TOPICAL USE ONLY" }

Multi-dose pump capable of dispensing 60 metered pump actuations.

{ "type": "p", "children": [], "text": "Multi-dose pump capable of dispensing 60 metered pump actuations." }

PHARMACIST: Dispense the accompanying Medication Guide to each patient.

{ "type": "p", "children": [], "text": "PHARMACIST: Dispense the accompanying Medication Guide to each patient." }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

Total Contents: 88 grams

{ "type": "p", "children": [], "text": "Total Contents: 88 grams" }

TEVA

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

NDC 0591-2925-30

{ "type": "p", "children": [], "text": "NDC 0591-2925-30" }

Testosterone Gel, 1.62% CIII(Alcohol 80% v/v)

{ "type": "p", "children": [], "text": "Testosterone Gel, 1.62% CIII(Alcohol 80% v/v)" }

Contains 20.25 mg of testosterone, USP in 1.25 grams of gel per unit dose

{ "type": "p", "children": [], "text": "Contains 20.25 mg of testosterone, USP in 1.25 grams of gel per unit dose" }

Clear, colorless gel provides transdermal delivery of testosterone through the skin of the shoulders, and upper arms*Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure.

{ "type": "p", "children": [], "text": "Clear, colorless gel provides transdermal delivery of testosterone through the skin of the shoulders, and upper arms*Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure." }

PHARMACIST: Dispense the enclosed Medication Guide to each patient.

{ "type": "p", "children": [], "text": "PHARMACIST: Dispense the enclosed Medication Guide to each patient.\n" }

*See accompanying package insert.

{ "type": "p", "children": [], "text": "*See accompanying package insert.\n" }

For Topical Use Only

{ "type": "p", "children": [], "text": "For Topical Use Only" }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

30 Unit-dose Packets

{ "type": "p", "children": [], "text": "30 Unit-dose Packets" }

TEVA

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

NDC 0591-2926-30

{ "type": "p", "children": [], "text": "NDC 0591-2926-30" }

Testosterone Gel, 1.62% CIII(Alcohol 80% v/v)

{ "type": "p", "children": [], "text": "Testosterone Gel, 1.62% CIII(Alcohol 80% v/v)" }

Contains 40.5 mg of testosterone, USP in 2.5 grams of gel per unit dose

{ "type": "p", "children": [], "text": "Contains 40.5 mg of testosterone, USP in 2.5 grams of gel per unit dose" }

Clear, colorless gel provides transdermal delivery of testosterone through the skin of the shoulders, and upper arms*Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure.

{ "type": "p", "children": [], "text": "Clear, colorless gel provides transdermal delivery of testosterone through the skin of the shoulders, and upper arms*Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure." }

PHARMACIST: Dispense the enclosed Medication Guide to each patient.

{ "type": "p", "children": [], "text": "PHARMACIST: Dispense the enclosed Medication Guide to each patient.\n" }

*See accompanying package insert.

{ "type": "p", "children": [], "text": "*See accompanying package insert.\n" }

For Topical Use Only

{ "type": "p", "children": [], "text": "For Topical Use Only" }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

30 Unit-dose Packets

{ "type": "p", "children": [], "text": "30 Unit-dose Packets" }

TEVA

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

Testosterone topical solution is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone.

{ "type": "p", "children": [], "text": "\nTestosterone topical solution is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone." }

{ "type": "ul", "children": [ "\nPrimary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (FSH, LH) above the normal range.", "\nHypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations but have gonadotropins in the normal or low range." ], "text": "" }

Limitations of use:

{ "type": "p", "children": [], "text": "\nLimitations of use:\n" }

{ "type": "ul", "children": [ "Safety and efficacy of testosterone topical solution in men with \"age-related hypogonadism\" (also referred to as \"late-onset hypogonadism\") have not been established.", "Safety and efficacy of testosterone topical solution in males <18 years old have not been established [see Use in Specific Populations (8.4)].\n" ], "text": "" }

The recommended starting dose of testosterone topical solution is 60 mg of testosterone (2 pump actuations) applied once daily.

To ensure proper dosing, serum testosterone concentrations should be measured after initiation of therapy to ensure that the desired concentrations (300 ng/dL-1050 ng/dL) are achieved. The testosterone topical solution dose can be adjusted based on the serum testosterone concentration from a single blood draw 2 – 8 hours after applying testosterone topical solution and at least 14 days after starting treatment or following dose adjustment.

If the measured serum testosterone concentration is below 300 ng/dL, the daily testosterone dose may be increased from 60 mg (2 pump actuations) to 90 mg (3 pump actuations) or from 90 mg to 120 mg (4 pump actuations). If the serum testosterone concentration exceeds 1050 ng/dL, the daily testosterone dose should be decreased from 60 mg (2 pump actuations) to 30 mg (1 pump actuation) as instructed by a physician. If the serum testosterone concentration consistently exceeds 1050 ng/dL at the lowest daily dose of 30 mg (1 pump actuation), testosterone topical solution therapy should be discontinued.

The application site and dose of testosterone topical solution are not interchangeable with other topical testosterone products.

Testosterone topical solution is applied to the axilla, preferably at the same time each morning, to clean, dry, intact skin. Do not apply testosterone topical solution to other parts of the body including to the scrotum, penis, abdomen, shoulders or upper arms. After applying the solution, the application site should be allowed to dry completely prior to dressing. Avoid fire, flames or smoking until the solution has dried since alcohol based products, including testosterone topical solution, are flammable.

When deodorants or antiperspirants are used as part of a regular program for personal hygiene, they should not interfere with the efficacy of testosterone topical solution in treating hypogonadism. If patients use an antiperspirant or deodorant (stick or roll-on) then it should be applied alteast 2 minutes prior to the application of testosterone topical solution to avoid contamination of the stick or roll-on product.

Patients should be advised to avoid swimming or washing the application site until two hours following application of testosterone topical solution [see Clinical Pharmacology (12.3)].

To reduce the likelihood of interpersonal transfer of testosterone, the application site should always be washed prior to any skin-to-skin contact regardless of the length of time since application. [See Warnings and Precautions (5.2)].

Testosterone topical solution is available in one presentation (i.e., pump actuated metered – dose pump).                  

Pump Actuated Metered-Dose Pump

Testosterone topical solution is applied to the axilla using an applicator. When using testosterone topical solution for the first time, patients should be instructed to prime the pump by depressing the pump three times, discard any product dispensed directly into a basin, sink, or toilet and then wash the liquid away thoroughly. This priming should be done only prior to the first use of each pump. After priming, patients should completely depress the pump one time (1 pump actuation) to dispense 30 mg of testosterone. Ensure that the liquid is directed into the cup. The cup should be filled with no more than 30 mg (1 pump actuation) of testosterone. Dosing that requires greater than one pump actuation must be applied in increments of 30 mg as is shown in Table 1.

Keeping the applicator upright, patients should place it up into the axilla and wipe steadily down and up into the axilla. If the solution drips or runs, it can be wiped back up with the applicator cup. The solution should not be rubbed into the skin with fingers or hand. The process is then repeated with application of 30 mg of testosterone (1 pump actuation) to the other axilla to achieve a total of 60 mg of testosterone applied. For patients prescribed the 90 mg dose of testosterone, the procedure is the same, but three applications are required. To dose 120 mg of testosterone, four applications are required alternating left and right for each application as shown in Table 1. When repeat application to the same axilla is required, the axilla should be allowed to dry completely before more testosterone topical solution is applied.

After use, the applicator should be rinsed under room temperature, running water and then patted dry with a tissue. The applicator and cap are then replaced on the bottle for storage.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1: Application Technique </span> </caption> <col align="left" valign="middle" width="34%"/> <col align="left" valign="middle" width="33%"/> <col align="left" valign="middle" width="33%"/> <thead> <tr class="First Last"> <th align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Daily Prescribed Dose of Testosterone</span></th><th align="center" class="Botrule Rrule Toprule"><span class="Bold">Number of Pump Actuations</span></th><th align="center" class="Botrule Rrule Toprule"><span class="Bold">Application</span></th> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">30 mg  (once daily)</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">Apply once to one axilla only (left OR right)</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">60 mg (once daily)</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">Apply once to the left axilla and then apply once to the right axilla.</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">90 mg (once daily)</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">Apply once to the left and once to the right axilla, wait for the product to dry, and then apply once again to the left OR right axilla.</p> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">120 mg (once daily)</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">Apply once to the left and once to the right axilla, wait for the product to dry, and then apply once again to the left AND once to the right axilla.</p> </td> </tr> </tbody> </table></div>

Hands should be washed thoroughly with soap and water after testosterone topical solution has been applied [see Warnings and Precautions (5.2)].

Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from testosterone topical solution treated skin:

While interpersonal testosterone transfer can occur with a T-shirt on, it has been shown that transfer can be substantially reduced by wearing a T-shirt and the majority of residual testosterone is removed from the skin surface by washing with soap and water.

Testosterone topical solution is a topical solution available as a metered-dose pump that delivers 30 mg of testosterone per pump.

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Each metered-dose pump is supplied with an applicator.

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{ "type": "ul", "children": [ "Testosterone topical solution is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precaution (5.1)] .", "Testosterone topical solution is contraindicated in women who are, or who may become pregnant, or who are breastfeeding. Testosterone topical solution may cause fetal harm when administered to a pregnant woman. Testosterone topical solution may cause serious adverse reactions in nursing infants. If a pregnant woman is exposed to testosterone topical solution, she should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1,8.3)] ." ], "text": "" }

Cases of secondary exposure to testosterone in children and women have been reported with topical testosterone products applied to the abdomen or upper arms, including cases of secondary exposure resulting in virilization of children. Signs and symptoms have included enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases, these signs and symptoms regressed with removal of the exposure to testosterone. In a few cases, however, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age. The risk of transfer was increased in some of these cases by not adhering to precautions for the appropriate use of the topical testosterone product. Children and women should avoid contact with unwashed or unclothed application sites in men using testosterone topical solution [see Dosage and Administration (2.2), Use in Specific Populations (8.1) and Clinical Pharmacology (12.3)].

Inappropriate changes in genital size or development of pubic hair or libido in children, or changes in body hair distribution, significant increase in acne, or other signs of virilization in adult women should be brought to the attention of a physician and the possibility of secondary exposure to testosterone should also be brought to the attention of a physician. Testosterone therapy should be promptly discontinued at least until the cause of virilization has been identified [see Dosage and Administration (2.2)].

Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating testosterone treatment. It would be appropriate to re-evaluate the hematocrit 3 to 6 months after starting testosterone treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable level. An increase in red blood cell mass may increase the risk of thromboembolic events.

There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as testosterone topical solution. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with testosterone topical solution and initiate appropriate workup and management [see Adverse Reactions (6.2)].

Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use testosterone topical solution.

Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions [see Drug Abuse and Dependence (9)].

If testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range. However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids. Conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events.

Due to lack of controlled studies in women and potential virilizing effects, testosterone topical solution is not indicated for use in women [see Contraindications (4) and Use in Specific Populations (8.1, 8.3)].

At large doses of exogenous androgens, including testosterone, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (FSH) which could possibly lead to adverse effects on semen parameters including sperm count.

Prolonged use of high doses of orally active 17-alpha-alkyl androgens (methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatitis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatitis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate has produced multiple hepatic adenomas. Testosterone topical solution is not known to cause these adverse effects.

Androgens, including testosterone, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal, or hepatic disease [see Adverse Reactions (6)].

Gynecomastia may develop and may persist in patients being treated with androgens, including testosterone, for hypogonadism.

The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, especially those with risk factors such as obesity and chronic lung disease.

Changes in serum lipid profile may require dose adjustment or discontinuation of testosterone therapy.

Androgens, including testosterone, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is recommended in these patients.

Androgens, including testosterone, may decrease concentrations of thyroxin-binding globulins, resulting in decreased total T4 serum concentration and increased resin uptake of T3 and T4. Free thyroid hormone concentration remain unchanged, however there is no clinical evidence of thyroid dysfunction.

Alcohol based products, including testosterone topical solution, are flammable; therefore, patients should be advised to avoid smoking, fire or flame until the testosterone topical solution dose applied has dried.

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

Clinical Trials in Hypogonadal Men

Table 2 shows the treatment emergent adverse reactions that were reported by either >4% of 155 patients in a 120 day, Phase 3 study or by >4% of 71 patients who continued to use testosterone topical solution for up to 180 days. These data reflect the experience primarily with a testosterone dose of 60 mg, which was taken by all patients at the start of the study, and was the maintenance dose for 97 patients. However, the doses used varied from 30 mg to 120 mg.

<div class="scrollingtable"><table width="631"> <caption> <span> Table 2:Adverse Reactions Seen with the Use of Testosterone Topical Solution in either the 120 Day Clinical Trial or in the Extension to 180 Days (&gt;4%) </span> </caption> <col width="241"/> <col width="195"/> <col width="195"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold"> Event</span> <br/> </td><td align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold"> 120 Days</span> <br/> <span class="Bold"> (155 Patients)</span> <br/> </td><td align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold"> 180 Days</span> <br/> <span class="Bold"> (71 Patients)</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Application Site Irritation<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 11 (7%)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 6 (8%)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Application Site Erythema<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 8 (5%)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 5 (7%)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Headache<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 8 (5%)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 4 (6%)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Hematocrit Increased<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 6 (4%)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 5 (7%)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Diarrhea<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 4 (3%)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 3 (4%)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Vomiting<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 4 (3%)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 3 (4%)<br/> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule" valign="top"> PSA Increased<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 2 (1%)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 3 (4%)<br/> </td> </tr> </tbody> </table></div>

Other less common adverse reactions reported by at least 2 patients in the 120 day trial included: application site edema, application site warmth, increased hemoglobin, hypertension, erythema (general), increased blood glucose, acne, nasopharyngitis, anger and anxiety. Other less common adverse reactions reported in fewer than 1% of patients in the 120 day trial included: asthenia, affect lability, folliculitis, increased lacrimation, breast tenderness, increased blood pressure, increased blood testosterone, neoplasm prostate and elevated red blood cell count.

During the 120 day trial one patient discontinued treatment because of affect lability/anger which was considered possibly related to testosterone topical solution administration.

During the 120 day clinical trial there was an increase in mean PSA values of 0.13 ± 0.68 ng/mL from baseline. At the end of the 180 day extension clinical trial, there was an overall increase in mean PSA values of 0.1 ± 0.54 ng/mL.

Following the 120 day study, seventy-one (71) patients entered a two-month extension study with testosterone topical solution. Two patients (3%) had adverse reactions that led to discontinuation of treatment during the period from Day 120 to Day 180. These reactions were: one patient with application site irritation (considered possibly related to testosterone topical solution application) and one patient with dry skin and erythema, but not at the application site (considered not related to testosterone topical solution administration) and application site erythema (considered possibly related to testosterone topical solution administration).

No serious adverse reactions to testosterone topical solution were reported during either the 120 day trial, or the extension to 180 days.

The following adverse reactions have been identified during postapproval use of testosterone topical solution. 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.

Cardiovascular Disorders: myocardial infarction, stroke [see Warnings and Precautions (5.5)].

Vascular Disorders: Venous thromboembolism [see Warnings and Precautions (5.4)].

Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, insulin requirement.

Changes in anticoagulant activity may be seen with androgens. More frequent monitoring of INR and prothrombin time is recommended in patients taking anticoagulants, especially at the initiation and termination of androgen therapy.

The concurrent use of testosterone with ACTH or corticosteroids may result in increased fluid retention and should be monitored cautiously, particularly in patients with cardiac, renal or hepatic disease.

Pregnancy Category X [see Contraindications (4)] - Testosterone topical solution is contraindicated during pregnancy or in women who may become pregnant. Testosterone is teratogenic and may cause fetal harm. Exposure of a female fetus to androgens may result in varying degrees of virilization. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Although it is not known how much testosterone transfers into human milk, testosterone topical solution is contraindicated in nursing women because of the potential for serious adverse reactions in nursing infants. Testosterone and other androgens may adversely affect lactation [see Contraindications (4)].

Safety and efficacy of testosterone topical solution has not been established in males <18 years of age. Improper use may result in acceleration of bone age and premature closure of epiphyses.

There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing testosterone topical solution to determine whether efficacy in those over 65 years of age differs from younger patients. Of the 155 patients enrolled in the pivotal clinical study utilizing testosterone topical solution, 21 were over 65 years of age. Additionally, there were insufficient long-term safety data in these patients utilizing testosterone topical solution to assess a potential incremental risk of cardiovascular disease and prostate cancer.

No formal studies were conducted involving patients with renal impairment.

No formal studies were conducted involving patients with hepatic impairment.

Safety and efficacy of testosterone topical solution in males with BMI >35 kg/m2 has not been established.

Testosterone topical solution contains testosterone, a Schedule III controlled substance in the Controlled Substances Act.

Drug abuse is intentional non-therapeutic use of a drug, even once, for its rewarding psychological and physiological effects. Abuse and misuse of testosterone are seen in male and female adults and adolescents. Testosterone, often in combination with other anabolic androgenic steroids (AAS), and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. There have been reports of misuse by men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice.

Abuse-Related Adverse Reactions

Serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility and aggression.

The following adverse reactions have also been reported in men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility.

The following additional adverse reactions have been reported in women: hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities.

The following adverse reactions have been reported in male and female adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty.

Because these reactions are reported voluntarily from a population of uncertain size and may include abuse of other agents, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Behaviors Associated with Addiction

Continued abuse of testosterone and other anabolic steroids, leading to addiction is characterized by the following behaviors:

Physical dependence is characterized by withdrawal symptoms after abrupt drug discontinuation or a significant dose reduction of a drug. Individuals taking supratherapeutic doses of testosterone may experience withdrawal symptoms lasting for weeks or months which include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido and hypogonadotropic hypogonadism.

Drug dependence in individuals using approved doses of testosterone for approved indications has not been documented.

No cases of overdose with testosterone topical solution have been reported in clinical trials. There is one report of acute overdosage by injection of testosterone enanthate: testosterone concentrations of up to 11,400 ng/dL were implicated in a cerebrovascular accident. Treatment of overdosage would consist of discontinuation of testosterone topical solution together with appropriate symptomatic and supportive care.

{ "type": "p", "children": [], "text": "\nNo cases of overdose with testosterone topical solution have been reported in clinical trials. There is one report of acute overdosage by injection of testosterone enanthate: testosterone concentrations of up to 11,400 ng/dL were implicated in a cerebrovascular accident. Treatment of overdosage would consist of discontinuation of testosterone topical solution together with appropriate symptomatic and supportive care." }

Testosterone topical solution is a clear, colorless, single phase solution containing 30 mg of testosterone in 1.5 mL of testosterone topical solution for topical administration through the axilla. The active pharmacologic ingredient in testosterone topical solution is testosterone. Testosterone USP is a white to practically white crystalline powder chemically described as 17-beta hydroxyandrost-4-en-3-one. The structural formula is:

{ "type": "p", "children": [], "text": "Testosterone topical solution is a clear, colorless, single phase solution containing 30 mg of testosterone in 1.5 mL of testosterone topical solution for topical administration through the axilla. The active pharmacologic ingredient in testosterone topical solution is testosterone. Testosterone USP is a white to practically white crystalline powder chemically described as 17-beta hydroxyandrost-4-en-3-one. The structural formula is:" }

The inactive ingredients are ethanol, isopropyl alcohol, octisalate, and povidone.

{ "type": "p", "children": [], "text": "The inactive ingredients are ethanol, isopropyl alcohol, octisalate, and povidone." }

Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement, vocal cord thickening, alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics.

Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter's Syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).

No specific pharmacodynamic studies were conducted using testosterone topical solution.

Absorption — Testosterone topical solution delivers physiologic circulating testosterone that approximate normal concentration range (i.e., 300 - 1050 ng/dL) seen in healthy men following application to the axilla.

On the skin, the ethanol and isopropyl alcohol evaporate leaving testosterone and octisalate. The skin acts as a reservoir from which testosterone is released into the systemic circulation over time (see Figure 1). In general, steady-state serum concentrations are achieved by approximately 14 days of daily dosing.

Figure 1: Mean (±SD) Serum Testosterone Concentrations on Day 7 in Patients Following Testosterone Topical Solution Once-Daily Application of 30 mg, 60 mg, or 90 mg of Testosterone

When testosterone topical solution treatment is discontinued after achieving steady-state, serum testosterone concentrations returned to their pretreatment concentrations by 7 – 10 days after the last application.

Distribution — Circulating testosterone is primarily bound in the serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is bound to albumin and other proteins.

Metabolism —Testosterone is metabolized to various 17-keto steroids through two different pathways. The major active metabolites of testosterone are estradiol and dihydrotestosterone (DHT).

DHT concentration increased in parallel with testosterone concentration during testosterone topical solution treatment. The mean steady-state DHT/T ratio remained within normal limits and ranged from 0.17 to 0.26 across all doses on Days 15, 60, and 120.

Excretion — There is considerable variation in the half-life of testosterone as reported in the literature, ranging from 10 to 100 minutes. About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; about 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver.

Potential for testosterone transfer: The potential for testosterone transfer from males dosed with testosterone topical solution to healthy females was evaluated in a clinical study conducted with a 2% testosterone formulation. 10 males were treated with 60 mg of testosterone in each axilla (the maximum testosterone dose of 120 mg). At 2 hours after the application of testosterone topical solution to the males, the females rubbed their outer forearms for 15 minutes on the axilla of the males. The males had covered the application area with a T-shirt. Serum concentrations of testosterone were monitored in the female subjects for 72 hours after the transfer procedure. Study results show a 13% and 17% increase in testosterone exposure (AUC[0-24]) and maximum testosterone concentration (Cmax), respectively, compared to baseline in these females. In a prior clinical study conducted with a 1% testosterone formulation under similar study conditions, direct skin-to-skin transfer showed a 131% and 297% increase in testosterone exposure (AUC[0-72]) and maximum testosterone concentration (Cmax), respectively, compared to when men had covered the application area with a T-shirt.

In a clinical study conducted with a 2% testosterone formulation to evaluate the effect of washing on the residual amount of testosterone at the axilla, 10 healthy male subjects received 60 mg of testosterone to each axilla (the maximum testosterone dose of 120 mg). Following 5 minutes of drying time, the left axilla was wiped with alcohol towelettes which were assayed for testosterone content. Subjects were required to shower with soap and water 30 minutes after application. The right axilla was then wiped with alcohol towelettes which were assayed for testosterone content. A mean (SD) of 3.1 (2.8) mg of residual testosterone (i.e., 92.6% reduction compared to when axilla was not washed) was recovered after washing this area with soap and water [see Dosage and Administration (2.2) and Warnings and Precautions (5.2)].

Use of deodorants and anti-perspirants: In a parallel designed clinical study evaluating the effect of deodorants and antiperspirants in healthy premenopausal females dosed with testosterone topical solution, each subject applied either a combined deodorant/antiperspirant spray (6 subjects) or stick (6 subjects) or a deodorant spray (6 subjects) to a single axilla 2 minutes before the application of 30 mg of testosterone to the same axilla. A control group of 6 subjects only applied 30 mg of testosterone to a single axilla. Blood samples were collected for 72 hours from all subjects following testosterone topical solution administration. Although a decrease of up to 33% of testosterone exposure (AUC[0-72]) was observed when antiperspirants or deodorants are used 2 minutes prior to testosterone topical solution application, underarm deodorant or antiperspirant spray or stick products may be used 2 minutes prior to testosterone topical solution application as part of normal, consistent, and daily routine [see Dosage and Administration (2.2), and Patient Counseling Information (17.4)]

Effect of showering/washing: In a parallel designed clinical study to evaluate the effect of washing on the testosterone systemic exposure, two groups of 6 healthy premenopausal female subjects were each dosed with 30 mg of testosterone to a single axilla. The application sites of each group were washed with soap and water 2 hours or 6 hours after the application of testosterone topical solution. A control group of 6 female subjects applied 30 mg of testosterone to a single axilla and did not wash the application site. Blood samples were collected for 72 hours from all subjects following dosing with testosterone topical solution. A decrease of up to 35% of testosterone exposure (AUC[0-72]) was observed when application sites were washed 2 hours and 6 hours after testosterone topical solution application. Patients should be advised to avoid swimming or washing the application site until 2 hours following application of testosterone topical solution [see Dosage and Administration (2.2) and Patient Counseling Information (17.4)].

Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, the implant induced cervical-uterine tumors, which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats. Testosterone was negative in the in vitro Ames and in the in vivo mouse micronucleus assays. The administration of exogenous testosterone has been reported to suppress spermatogenesis in the rat, dog and non-human primates, which was reversible on cessation of the treatment.

Testosterone topical solution was evaluated in a multicenter, open label, 120-day trial that enrolled 155 hypogonadal men at 26 clinical research centers. The median age of subjects was 53 years with a range of 19 – 78 years. Of the 144 subjects whose race was recorded, 122 (84.7%) were Caucasian, 13 (9.0%) were Hispanic, 6 (4.2%) were African Americans, 1 (0.7%) was Asian and 2 (1.4%) had race recorded as "Other".

Patients were instructed to apply testosterone topical solution to unclothed, clean, dry, and unbroken skin. The solution was applied to the axillary area. Patients were not instructed to alter their normal grooming routine, e.g., shave under the arm.

During the initial testosterone topical solution treatment period (Days 1-15) 143 patients were treated with 60 mg of testosterone daily. On Day 45 of the trial, patients were maintained at the same dose, or were titrated up or down, based on their 24 hour average serum testosterone concentration measured on Day 15. On Day 90 of the trial, patients were maintained at the same dose, or were titrated up or down, based on their 24 hour average serum testosterone concentration measured on Day 60.

On day 120, 75% of responding patients finished the study on the starting dose of 60 mg of testosterone, while 2% had been titrated to 30 mg, 17% had been titrated to 90 mg and 6% had been titrated to the 120 mg dose.

On day 60, 84.8% of subjects had total testosterone concentrations in the normal range. Of those who had sufficient data for analysis on day 120, 84.1%, had their average serum testosterone concentration in the normal range of 300 – 1050 ng/dL.

Table 3 summarizes the proportion of subjects having average testosterone concentrations within the normal range on Days 60 and 120.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 3: Proportion of subjects who had an average Serum Total Testosterone in the range 300 to 1050 ng/dL and completed 120 days of treatment (N=138a) </span> </caption> <col align="left" valign="middle" width="34%"/> <col align="left" valign="middle" width="33%"/> <col align="left" valign="middle" width="33%"/> <thead> <tr class="First Last"> <th align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Evaluation Time</span></th><th align="center" class="Botrule Rrule Toprule"><span class="Bold">Statistics</span></th><th align="center" class="Botrule Rrule Toprule"><span class="Bold">Value</span></th> </tr> </thead> <tbody> <tr class="First"> <td align="center" class="Botrule Lrule Rrule"> <p class="First">Baseline Testosterone</p> </td><td align="center" class="Botrule Rrule"> <p class="First">Mean (SD)</p> </td><td align="center" class="Botrule Rrule"> <p class="First">194.6 ng/dL (92.9 ng/dL)</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" rowspan="2"> <p class="First">Day 15</p> </td><td align="center" class="Botrule Rrule"> <p class="First">Normal<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">76.1%<span class="Sup">c</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Rrule"> <p class="First">95% CI</p> </td><td align="center" class="Botrule Rrule"> <p class="First">(69.0%, 83.2%)</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" rowspan="2"> <p class="First">Day 60</p> </td><td align="center" class="Botrule Rrule"> <p class="First">Normal<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">84.8%</p> </td> </tr> <tr> <td align="center" class="Botrule Rrule"> <p class="First">95% CI</p> </td><td align="center" class="Botrule Rrule"> <p class="First">(78.8%, 90.8%)</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" rowspan="2"> <p class="First">Day 120</p> </td><td align="center" class="Botrule Rrule"> <p class="First">Normal<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">84.1%</p> </td> </tr> <tr> <td align="center" class="Botrule Rrule"> <p class="First">95% CI</p> </td><td align="center" class="Botrule Rrule"> <p class="First">(77.9%, 90.2%)</p> </td> </tr> <tr> <td align="left" colspan="3"> <p class="First"> <span class="Sup">a </span>Three patients who withdrew from the study due to adverse reactions are included as treatment failures.</p> </td> </tr> <tr> <td align="left" colspan="3"> <p class="First"> <span class="Sup">b </span>Normal represents the percentage of patients with average testosterone concentration in the range of 300 – 1050 ng/dL.</p> </td> </tr> <tr> <td align="left" colspan="3"> <p class="First"> <span class="Sup">c </span>On Day 15, 72.2% of the 90 subjects in the US study population had an average serum testosterone in the range of 300 ng/dL –    </p> </td> </tr> <tr class="Last"> <td align="left" colspan="3"> <p class="First">1050 ng/dL</p> </td> </tr> </tbody> </table></div>

Of the 135 patients who completed the 120 day treatment, 123 patients did so with no deviation from the protocol. By day 120, average serum testosterone concentration was within normal range for 67% of those who titrated down on the 30 mg dose, 89% of those on the 60 mg dose, 86% of those who titrated up to 90 mg and 70% of those who titrated up to the 120 mg dose. Table 4 below summarizes the testosterone concentration data in the patients who completed 120 days.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 4: Baseline-unadjusted Arithmetic Mean (±SD) Steady-State Serum Testosterone Concentrations on Days 15, 60 and 120 in Patients Who Completed 120 Days of Treatment </span> </caption> <col align="left" valign="middle" width="20%"/> <col align="left" valign="middle" width="16%"/> <col align="left" valign="middle" width="16%"/> <col align="left" valign="middle" width="16%"/> <col align="left" valign="middle" width="16%"/> <col align="left" valign="middle" width="16%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule"> </th><th align="left" class="Botrule Rrule Toprule"><span class="Bold">Dose of Testosterone Topical Solution</span></th><th align="left" class="Botrule Rrule Toprule"> </th><th align="left" class="Botrule Rrule Toprule"> </th><th align="left" class="Botrule Rrule Toprule"> </th><th align="left" class="Botrule Rrule Toprule"> </th> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">30 mg</span> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">60 mg</span> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">90 mg</span> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">120 mg</span> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">Overall</span> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Day 15</span> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">[N=0]</span> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">[N=135]</span> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">[N=0]</span> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">[N=0]</span> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">[N=135]</span> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">C<span class="Sub">avg </span>(ng/dL)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">--</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">456 (±226)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">--</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">--</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">456 (±226)</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">C<span class="Sub">max</span> (ng/dL)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">--</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">744 (±502)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">--</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">--</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">744 (±502)</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Day 60 </span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">[N=1]</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">[N=105]</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">[N=29]</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">[N=0]</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">[N=135]</span> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">C<span class="Sub">avg </span>(ng/dL)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">343 (--)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">523 (±207)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">368 (±138)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">--</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">488 (±204)</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">C<span class="Sub">max</span> (ng/dL)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">491 (--)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">898 (±664)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">646 (±382)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">--</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">840 (±620)</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Day 120 </span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">[N=3]</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">[N=97]</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">[N=25]</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">[N=10]</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">[N=135]</span> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">C<span class="Sub">avg </span>(ng/dL)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">493 (±239)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">506 (±175)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">415 (±165)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">390 (±160)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">480 (±177)</p> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">C<span class="Sub">max</span> (ng/dL)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">779 (±416)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">839 (±436)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">664 (±336)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">658 (±353)</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">792 (±417)</p> </td> </tr> </tbody> </table></div>

Figure 2 summarizes the pharmacokinetic profiles of total testosterone in patients completing 120 days of testosterone topical solution treatment administered as 60 mg of testosterone for the initial 15 days followed by possible titration according to follow-up testosterone measurements.

Figure 2: Mean (± SD) Steady-State Serum Testosterone Concentrations on Day 120 (30, 60, 90 or 120 mg testosterone) in Patients Who Completed 120 Days (N=135) of Testosterone Topical Solution Once-Daily Treatment

Testosterone topical solution is available as a metered-dose pump containing 110 mL of solution. The pump is capable of dispensing 90 mL of solution in 60 metered pump actuations. One actuation delivers 30 mg of testosterone in 1.5 mL of solution. Each metered-dose pump is supplied with an applicator. The bottle and the applicator cup are not made with natural rubber latex.

NDC 69097-363-44

Keep testosterone topical solution out of reach of children.

Store upright at 25°C (77°F). Excursions are permitted to 15°C to 30°C (59°F to 86°F). See USP Controlled Room Temperature.

Used testosterone topical solution bottles and applicators should be discarded in household trash in a manner that prevents accidental exposure of children or pets.

Men with known or suspected prostate or breast cancer should not use testosterone topical solution [see Contraindications (4) and Warnings and Precaution (5.1)].

Cases of secondary exposure to testosterone in children and women have been reported with topical testosterone products applied to the abdomen, shoulders or upper arms, including cases of secondary exposure resulting in virilization of children, with signs and symptoms including enlargement of the penis or clitoris, premature development of pubic hair, increased erections, aggressive behavior and advanced bone age. Inappropriate changes in genital size or premature development of pubic hair or libido in children, or changes in hair distribution, increase in acne, or other signs of testosterone effects in adult women should be brought to the attention of a physician and the possibility of secondary exposure to testosterone topical solution also should be brought to the attention of a physician. Testosterone topical solution should be promptly discontinued at least until the cause of virilization is identified.

Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from testosterone topical solution treated skin:

[See Dosage and Administration (2.2), Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

Patients should be informed that treatment with Androgens may lead to adverse reactions which include:

●   Ensure that the patient understands how to administer the correct dose.

●   The pump should be primed by depressing it 3 times prior to its first use. No priming is needed with subsequent uses of that pump.

●   Testosterone topical solution should NOT be applied to the scrotum, penis, abdomen, shoulders or upper arms.

●   With testosterone doses greater than 60 mg, which require two applications of testosterone topical solution to the same axilla, the product should be allowed to dry after the first application before the second is applied.

●   Testosterone topical solution should be applied once daily at approximately the same time each day. Testosterone topical solution should be applied to clean, dry skin.

●   Patients may use an antiperspirant or deodorant spray before applying testosterone topical solution. If patients use a stick or roll-on antiperspirant or deodorant, then it should be applied alteast 2 minutes prior to application of testosterone topical solution to avoid contamination of the stick or roll-on product.

●   Avoid swimming or washing the application site until two hours following application of testosterone topical solution [see Dosage and Administration (2) and Clinical Pharmacology (12.3)].

●   Avoid splashing in the eyes. In case of contact with eyes, flush thoroughly with water. If irritation persists, seek medical advice.

●   Do not drink testosterone topical solution.

Manufactured by:

Cipla Limited,

Verna Goa, India.

Manufactured for:

Cipla USA, Inc.

10 Independence Boulevard, Suite 300, Warren

New Jersey - 07059

Revised: 02/2020

MEDICATION GUIDE

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

Testosterone (tes-TOS-te-rone) Topical Solution

{ "type": "p", "children": [], "text": "\nTestosterone (tes-TOS-te-rone) Topical Solution\n" }

for topical use CIII

{ "type": "p", "children": [], "text": "\nfor topical use CIII\n" }

What is the most important information I should know about testosterone topical solution?

{ "type": "p", "children": [], "text": "\nWhat is the most important information I should know about testosterone topical solution?\n" }

1. Testosterone topical solution can transfer from your body to others including, children and women. Children and women should avoid contact with the unwashed or not covered (unclothed) areas where testosterone topical solution has been applied to your skin. Early signs and symptoms of puberty have occurred in young children who have come in direct contact with testosterone by touching areas where men have used testosterone topical solution.

{ "type": "p", "children": [], "text": "\n1. Testosterone topical solution can transfer from your body to others including, children and women. Children and women should avoid contact with the unwashed or not covered (unclothed) areas where testosterone topical solution has been applied to your skin. Early signs and symptoms of puberty have occurred in young children who have come in direct contact with testosterone by touching areas where men have used testosterone topical solution." }

Children

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

Signs and symptoms of early puberty in a child when they come in direct contact with testosterone topical solution may include:

{ "type": "p", "children": [], "text": "\nSigns and symptoms of early puberty in a child when they come in direct contact with testosterone topical solution may include:\n" }

Abnormal sexual changes:

{ "type": "p", "children": [], "text": "\nAbnormal sexual changes:\n" }

{ "type": "ul", "children": [ "  enlarged penis or clitoris.", "  early growth of hair near the vagina or around the penis (pubic hair).", "  erections or acting out sexual urges (sex drive)." ], "text": "" }

Behavior problems:

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

{ "type": "ul", "children": [ "  acting aggressively, behaving in an angry or violent way." ], "text": "" }

Women 

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

Signs and symptoms in women when they come in direct contact with testosterone topical solution may include:

{ "type": "p", "children": [], "text": "\nSigns and symptoms in women when they come in direct contact with testosterone topical solution may include:\n" }

{ "type": "ul", "children": [ "  changes in body hair.", "  an abnormal increase in pimples (acne)." ], "text": "" }

Stop using testosterone topical solution and call your healthcare provider right away if you see any signs and symptoms in a child or a woman that may have happened through accidental touching of the area where you have applied testosterone topical solution:

{ "type": "p", "children": [], "text": "\nStop using testosterone topical solution and call your healthcare provider right away if you see any signs and symptoms in a child or a woman that may have happened through accidental touching of the area where you have applied testosterone topical solution:" }

2. To lower the risk of transfer of testosterone topical solution from your body to others, follow these important instructions:

{ "type": "p", "children": [], "text": "\n2. To lower the risk of transfer of testosterone topical solution from your body to others, follow these important instructions:\n" }

{ "type": "ul", "children": [ "Apply testosterone topical solution only to your armpits.", "Wash your hands right away with soap and water after applying testosterone topical solution.", "After the solution has dried, cover the application area with clothing. Keep the area covered until you have washed the application area well or have showered.", "If you expect to have skin-to-skin contact with another person, first wash the application area well with soap and water.", "If a child or woman touches the area where you have applied testosterone topical solution, that area on the child or woman should be washed well with soap and water right away" ], "text": "" }

What is testosterone topical solution?

{ "type": "p", "children": [], "text": "\nWhat is testosterone topical solution?\n" }

{ "type": "ul", "children": [ "Testosterone topical solution is a prescription medicine that contains testosterone. Testosterone topical solution is used to treat adult males who have low or no testosterone due to certain medical conditions.\nYour healthcare provider will test your blood before you start and while you are using testosterone topical solution.\nIt is not known if testosterone topical solution is safe or effective to treat men who have low testosterone due to aging.\nIt is not known if testosterone topical solution is safe and effective in children younger than 18 years old. Improper use of testosterone topical solution may affect bone growth in children.\n\n" ], "text": "" }

{ "type": "ul", "children": [ "  Testosterone topical solution is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your testosterone topical solution in a safe place to protect it. Never give testosterone topical solution to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and it is against the law.", "  Testosterone topical solution is not meant for use in women." ], "text": "" }

Do not use testosterone topical solution if you:

{ "type": "p", "children": [], "text": "\nDo not use testosterone topical solution if you:" }

{ "type": "ul", "children": [ "have breast cancer.", "have or might have prostate cancer.", "are pregnant or may become pregnant or are breastfeeding. Testosterone topical solution may harm your unborn or breastfeeding baby." ], "text": "" }

Women who are pregnant or who may become pregnant should avoid contact with the area of the skin where testosterone topical solution has been applied.

{ "type": "p", "children": [], "text": "Women who are pregnant or who may become pregnant should avoid contact with the area of the skin where testosterone topical solution has been applied." }

Before using testosterone topical solution, tell your healthcare provider about all of your medical conditions, including if you:

{ "type": "p", "children": [], "text": "\nBefore using testosterone topical solution, tell your healthcare provider about all of your medical conditions, including if you:\n" }

{ "type": "ul", "children": [ "have breast cancer.", "have or might have prostate cancer.", "have urinary problems due to an enlarged prostate.", "have heart problems.", "have kidney or liver problems.", "have problems breathing while you sleep (sleep apnea)." ], "text": "" }

Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

{ "type": "p", "children": [], "text": "Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements." }

Using testosterone topical solution with other medicines can affect each other.

{ "type": "p", "children": [], "text": "Using testosterone topical solution with other medicines can affect each other." }

Especially tell your healthcare provider if you take:

{ "type": "p", "children": [], "text": "Especially tell your healthcare provider if you take:" }

{ "type": "ul", "children": [ "insulin", "medicines that decrease blood clotting (blood thinners)", "corticosteroids" ], "text": "" }

How should I use testosterone topical solution?

{ "type": "p", "children": [], "text": "\nHow should I use testosterone topical solution?\n" }

{ "type": "ul", "children": [ "  See the detailed Instructions for Use for information about how to use testosterone topical solution at the end of this Medication Guide.", " Testosterone topical solution comes in a metered-dose pump or twist actuated dispenser. Make sure you have the right pump or dispenser that is prescribed for you.\n", "  It is important that you apply testosterone topical solution exactly as your healthcare provider tells you to.", "  Your healthcare provider may change your testosterone topical solution dose. Do not change your testosterone topical solution dose without talking to your healthcare provider.", "  Apply testosterone topical solution at about the same time each morning. Testosterone topical solution should be applied after showering or bathing." ], "text": "" }

What are the possible side effects of testosterone topical solution?

{ "type": "p", "children": [], "text": "\nWhat are the possible side effects of testosterone topical solution?\n" }

Testosterone topical solution can cause serious side effects including:

{ "type": "p", "children": [], "text": "\nTestosterone topical solution can cause serious side effects including:\n" }

See also "What is the most important information I should know about testosterone topical solution?"

{ "type": "p", "children": [], "text": "See also \"What is the most important information I should know about testosterone topical solution?\"\n" }

{ "type": "ul", "children": [ "\nIf you already have an enlarged prostate, your symptoms can get worse while using testosterone topical solution. This can include:\nincreased urination at night.\ntrouble starting your urine stream.\nhaving to pass urine many times during the day.\nhaving an urge to go to the bathroom right away.\nhaving a urine accident.\nbeing unable to pass urine or weak urine flow.\n\n", "\nPossible increased risk of prostate cancer. Your healthcare provider should check you for prostate cancer or any other prostate problems before you start and while you use testosterone topical solution.", "\nBlood clots in the legs or lungs . Signs and symptoms of a blood clot in your leg can include leg pain, swelling or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain.", "\nPossible increased risk of heart attack or stroke.\n", "\nIn large doses testosterone topical solution may lower your sperm count.\n", "\nSwelling of your ankles, feet, or body, with or without heart failure.\n", "\nEnlarged or painful breasts.\n", "\nHave problems breathing while you sleep (sleep apnea).\n" ], "text": "" }

Call your healthcare provider right away if you have any of the serious side effects listed above.

{ "type": "p", "children": [], "text": "\nCall your healthcare provider right away if you have any of the serious side effects listed above.\n" }

The most common side effects of testosterone topical solution include:

{ "type": "p", "children": [], "text": "\nThe most common side effects of testosterone topical solution include:\n" }

{ "type": "ul", "children": [ "skin redness or irritation where testosterone topical solution is applied", "increased red blood cell count", "headache", "diarrhea", "vomiting", "increase in blood level of Prostate Specific Antigen (a test used to screen for prostate cancer)" ], "text": "" }

Other side effects include more erections than are normal for you or erections that last a long time.

{ "type": "p", "children": [], "text": "\nOther side effects include more erections than are normal for you or erections that last a long time." }

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

{ "type": "p", "children": [], "text": "Tell your healthcare provider if you have any side effect that bothers you or that does not go away." }

These are not all the possible side effects of testosterone topical solution. For more information, ask your healthcare provider or pharmacist.

{ "type": "p", "children": [], "text": "These are not all the possible side effects of testosterone topical solution. For more information, ask your healthcare provider or pharmacist." }

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800‑FDA‑1088.

{ "type": "p", "children": [], "text": "\nCall your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800‑FDA‑1088.\n" }

General information about the safe and effective use of testosterone topical solution

{ "type": "p", "children": [], "text": "\nGeneral information about the safe and effective use of testosterone topical solution\n" }

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use testosterone topical solution for a condition for which it was not prescribed. Do not give testosterone topical solution to other people, even if they have the same symptoms you have. It may harm them.

{ "type": "p", "children": [], "text": "Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use testosterone topical solution for a condition for which it was not prescribed. Do not give testosterone topical solution to other people, even if they have the same symptoms you have. It may harm them." }

You can ask your pharmacist or healthcare provider for information about testosterone topical solution that is written for health professionals.

{ "type": "p", "children": [], "text": "You can ask your pharmacist or healthcare provider for information about testosterone topical solution that is written for health professionals." }

What are the ingredients in testosterone topical solution?

{ "type": "p", "children": [], "text": "\nWhat are the ingredients in testosterone topical solution?\n" }

Active ingredient: testosterone, USP.

{ "type": "p", "children": [], "text": "\nActive ingredient: testosterone, USP." }

Inactive ingredients: ethanol, isopropyl alcohol, octisalate, and povidone.

{ "type": "p", "children": [], "text": "\nInactive ingredients: ethanol, isopropyl alcohol, octisalate, and povidone." }

The bottle and the applicator cup are not made with natural rubber latex.

{ "type": "p", "children": [], "text": "The bottle and the applicator cup are not made with natural rubber latex." }

For more information call 1-866-604-3268.

{ "type": "p", "children": [], "text": "For more information call 1-866-604-3268." }

This Medication Guide has been approved by the U.S. Food and Drug Administration

{ "type": "p", "children": [], "text": "This Medication Guide has been approved by the U.S. Food and Drug Administration" }

Manufactured by:

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

Cipla Limited,

{ "type": "p", "children": [], "text": "Cipla Limited," }

Verna Goa, India.

{ "type": "p", "children": [], "text": "Verna Goa, India." }

Manufactured for:

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

Cipla USA, Inc.

{ "type": "p", "children": [], "text": "Cipla USA, Inc." }

10 Independence Boulevard, Suite 300

{ "type": "p", "children": [], "text": "10 Independence Boulevard, Suite 300" }

Warren, NJ 07059

{ "type": "p", "children": [], "text": "Warren, NJ 07059" }

Revised: 02/2020

{ "type": "p", "children": [], "text": "\nRevised: 02/2020\n" }

Testosterone (tes-TOS-te-rone) Topical solution

{ "type": "p", "children": [], "text": "\nTestosterone (tes-TOS-te-rone) Topical solution\n" }

for topical use CIII

{ "type": "p", "children": [], "text": "\nfor topical use CIII\n" }

Read this Instructions for Use for Testosterone topical solution before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment.

{ "type": "p", "children": [], "text": "Read this Instructions for Use for Testosterone topical solution before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment." }

Applying Testosterone Topical Solution

{ "type": "p", "children": [], "text": "\nApplying Testosterone Topical Solution\n" }

{ "type": "ul", "children": [ "Testosterone topical solution is to be applied to the armpits only. Do not apply testosterone topical solution to any other parts of your body such as your stomach area (abdomen), penis, scrotum, shoulders or upper arms.", "Do not apply testosterone topical solution with your fingers or hands.", "Apply testosterone topical solution at about the same time each morning. Testosterone topical solution should be applied after showering or bathing.", "Avoid swimming or bathing for at least 2 hours after you apply testosterone topical solution.", "You can use an antiperspirant or deodorant before applying testosterone topical solution. If you use antiperspirant or deodorant, then it should be applied at least 2 minutes before you apply testosterone topical solution.", "\nTestosterone topical solution is flammable until dry. Let testosterone topical solution dry before smoking or going near an open flame.\n", "\nAvoid splashing in the eyes. In case of contact with eyes, flush thoroughly with water. If irritation persists, seek medical advice.\n" ], "text": "" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="middle" width="50%"/> <col align="left" valign="middle" width="50%"/> <thead align="center"> <tr class="Last"> <th align="left" class="Lrule Rrule Toprule"><img alt="fig-1-ifu" src="/dailymed/image.cfm?name=fig-1-ifu.jpg&amp;setid=6a46b5de-5d95-4570-91a6-3e4278028c59"/></th><th align="left" class="Botrule Rrule Toprule">Before using a new bottle of testosterone topical solution for the first time, you will need to prime the pump. To prime the testosterone topical solution pump gently push down on the pump 3 times. Do not use any testosterone topical solution that came out while priming. Wash it down the sink to avoid accidental exposure to others. Your testosterone topical solution pump is now ready to use.</th> </tr> </thead> <tbody> <tr class="First Last"> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Figure 1</span> </p> </td><td align="left" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Use testosterone topical solution exactly as your healthcare provider tells you to use it. </span>Your healthcare provider will tell you the dose of testosterone topical solution that is right for you. Apply your dose correctly by following the application instructions in the table below.</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"middle\" width=\"50%\"/>\n<col align=\"left\" valign=\"middle\" width=\"50%\"/>\n<thead align=\"center\">\n<tr class=\"Last\">\n<th align=\"left\" class=\"Lrule Rrule Toprule\"><img alt=\"fig-1-ifu\" src=\"/dailymed/image.cfm?name=fig-1-ifu.jpg&amp;setid=6a46b5de-5d95-4570-91a6-3e4278028c59\"/></th><th align=\"left\" class=\"Botrule Rrule Toprule\">Before using a new bottle of testosterone topical solution for the first time, you will need to prime the pump. To prime the testosterone topical solution pump gently push down on the pump 3 times. Do not use any testosterone topical solution that came out while priming. Wash it down the sink to avoid accidental exposure to others. Your testosterone topical solution pump is now ready to use.</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"First Last\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Figure 1</span>\n</p>\n</td><td align=\"left\" class=\"Botrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Use testosterone topical solution exactly as your healthcare provider tells you to use it. </span>Your healthcare provider will tell you the dose of testosterone topical solution that is right for you. Apply your dose correctly by following the application instructions in the table below.</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="middle" width="50%"/> <col align="left" valign="middle" width="50%"/> <thead align="center"> <tr class="Last"> <th align="left" class="Botrule Lrule Rrule Toprule"><span class="Bold">Find Your Dose as Prescribed by Your Healthcare Provider</span></th><th align="left" class="Botrule Rrule Toprule"><span class="Bold">Each application equals 1 press (depression) of the pump.</span></th> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule"> <p class="First">30 mg</p> </td><td align="left" class="Botrule Rrule"> <p class="First">Apply 1 application one time, to one armpit only (left <span class="Bold">or </span>right).</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> <p class="First">60 mg</p> </td><td align="left" class="Botrule Rrule"> <p class="First">Apply 2 applications: one to the left armpit and then one to the right armpit.</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> <p class="First">90 mg</p> </td><td align="left" class="Botrule Rrule"> <p class="First">Apply 3 applications: one to the left and one to the right armpit, wait for the product to dry, and then apply again one to the left <span class="Bold">or </span>right armpit.</p> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule"> <p class="First">120 mg</p> </td><td align="left" class="Botrule Rrule"> <p class="First">Apply 4 applications: one to the left and one to the right armpit, wait for the product to dry, and then apply again one to the left <span class="Bold">and </span>one to the right armpit.</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"middle\" width=\"50%\"/>\n<col align=\"left\" valign=\"middle\" width=\"50%\"/>\n<thead align=\"center\">\n<tr class=\"Last\">\n<th align=\"left\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Find Your Dose as Prescribed by Your Healthcare Provider</span></th><th align=\"left\" class=\"Botrule Rrule Toprule\"><span class=\"Bold\">Each application equals 1 press (depression) of the pump.</span></th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"First\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">\n<p class=\"First\">30 mg</p>\n</td><td align=\"left\" class=\"Botrule Rrule\">\n<p class=\"First\">Apply 1 application one time, to one armpit only (left <span class=\"Bold\">or </span>right).</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">\n<p class=\"First\">60 mg</p>\n</td><td align=\"left\" class=\"Botrule Rrule\">\n<p class=\"First\">Apply 2 applications: one to the left armpit and then one to the right armpit.</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">\n<p class=\"First\">90 mg</p>\n</td><td align=\"left\" class=\"Botrule Rrule\">\n<p class=\"First\">Apply 3 applications: one to the left and one to the right armpit, wait for the product to dry, and then apply again one to the left <span class=\"Bold\">or </span>right armpit.</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">\n<p class=\"First\">120 mg</p>\n</td><td align=\"left\" class=\"Botrule Rrule\">\n<p class=\"First\">Apply 4 applications: one to the left and one to the right armpit, wait for the product to dry, and then apply again one to the left <span class=\"Bold\">and </span>one to the right armpit.</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

{ "type": "ul", "children": [ "  Before applying testosterone topical solution, make sure that your armpit is clean, dry and that there is no broken skin." ], "text": "" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="middle" width="50%"/> <col align="left" valign="middle" width="50%"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"><img alt="fig-2-ifu" src="/dailymed/image.cfm?name=fig-2-ifu.jpg&amp;setid=6a46b5de-5d95-4570-91a6-3e4278028c59"/><p class="First"> </p> <p> <span class="Bold">Figure 2</span> </p> </td><td align="justify" class="Botrule Rrule Toprule"> <p class="First">Remove the cap and the applicator cup from the pump. Then, position the nozzle over the applicator cup and gently press down on (depress) the pump (<span class="Bold Italics">see </span><span class="Bold">Figure 2</span>).</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"middle\" width=\"50%\"/>\n<col align=\"left\" valign=\"middle\" width=\"50%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\"><img alt=\"fig-2-ifu\" src=\"/dailymed/image.cfm?name=fig-2-ifu.jpg&amp;setid=6a46b5de-5d95-4570-91a6-3e4278028c59\"/><p class=\"First\"> </p>\n<p>\n<span class=\"Bold\">Figure 2</span>\n</p>\n</td><td align=\"justify\" class=\"Botrule Rrule Toprule\">\n<p class=\"First\">Remove the cap and the applicator cup from the pump. Then, position the nozzle over the applicator cup and gently press down on (depress) the pump (<span class=\"Bold Italics\">see </span><span class=\"Bold\">Figure 2</span>).</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="middle" width="50%"/> <col align="left" valign="middle" width="50%"/> <thead align="center"> <tr class="Last"> <th align="left" class="Lrule Rrule Toprule"><img alt="fig-3-ifu" src="/dailymed/image.cfm?name=fig-3-ifu.jpg&amp;setid=6a46b5de-5d95-4570-91a6-3e4278028c59"/></th><th align="left" class="Botrule Rrule Toprule">To apply the testosterone topical solution, keep the applicator upright, place it up into the armpit application site and wipe steadily down and up (<span class="Bold Italics">see </span><span class="Bold">Figure 3</span>).</th> </tr> </thead> <tbody> <tr class="First Last"> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Figure 3</span> </p> </td><td align="left" class="Botrule Rrule Toprule" valign="top"> <p class="First">If testosterone topical solution drips or runs, wipe it back up with the applicator cup. Do not rub in the solution with your fingers or hand after it has been applied.</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"middle\" width=\"50%\"/>\n<col align=\"left\" valign=\"middle\" width=\"50%\"/>\n<thead align=\"center\">\n<tr class=\"Last\">\n<th align=\"left\" class=\"Lrule Rrule Toprule\"><img alt=\"fig-3-ifu\" src=\"/dailymed/image.cfm?name=fig-3-ifu.jpg&amp;setid=6a46b5de-5d95-4570-91a6-3e4278028c59\"/></th><th align=\"left\" class=\"Botrule Rrule Toprule\">To apply the testosterone topical solution, keep the applicator upright, place it up into the armpit application site and wipe steadily down and up (<span class=\"Bold Italics\">see </span><span class=\"Bold\">Figure 3</span>).</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"First Last\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Figure 3</span>\n</p>\n</td><td align=\"left\" class=\"Botrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">If testosterone topical solution drips or runs, wipe it back up with the applicator cup. Do not rub in the solution with your fingers or hand after it has been applied.</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

{ "type": "ul", "children": [ "Let the application site dry completely for 3 minutes before putting on a shirt.", "After you have finished applying testosterone topical solution, rinse the applicator cup with room temperature running water, and then pat it dry with a tissue. Carefully replace the applicator cup and cap back onto the bottle and make sure you store the bottle safely.", "Clean up any spilled solution from surfaces such as the sink or floor to make sure others do not come into contact with it.", "\nWash your hands with soap and water right away.\n" ], "text": "" }

How should I store testosterone topical solution?

{ "type": "p", "children": [], "text": "\nHow should I store testosterone topical solution?\n" }

{ "type": "ul", "children": [ "Store testosterone topical solution upright at room temperature between 15°C to 30°C (59°F to 86°F)" ], "text": "" }

{ "type": "ul", "children": [ "When it is time to throw away the bottle, safely throw away all parts of the testosterone topical solution dispenser including the bottle applicator cup and cap into the household trash. ", "Be careful to prevent accidental exposure of children or pets.", "Keep testosterone topical solution away from fire." ], "text": "" }

Keep testosterone topical solution and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep testosterone topical solution and all medicines out of the reach of children.\n" }

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Instructions for Use has been approved by the U.S. Food and Drug Administration. " }

Revised: 02/2020

{ "type": "p", "children": [], "text": "Revised: 02/2020" }

NDC 69097-363-44

{ "type": "p", "children": [], "text": "NDC 69097-363-44 " }

Rx ONLY

{ "type": "p", "children": [], "text": "Rx ONLY" }

Testosterone

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

Topical Solution

{ "type": "p", "children": [], "text": "Topical Solution" }

CIII

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

30 mg of testosterone

{ "type": "p", "children": [], "text": "30 mg of testosterone" }

per pump actuation*

{ "type": "p", "children": [], "text": "per pump actuation*" }

*Each actuation delivers 1.5 mL of solution

{ "type": "p", "children": [], "text": "*Each actuation delivers 1.5 mL of solution" }

Total contents:

{ "type": "p", "children": [], "text": "Total contents:" }

110 mL to deliver 90 mL

{ "type": "p", "children": [], "text": "110 mL to deliver 90 mL" }

NDC 69097-363-44

{ "type": "p", "children": [], "text": "NDC 69097-363-44 " }

Rx ONLY

{ "type": "p", "children": [], "text": "Rx ONLY" }

Testosterone

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

Topical Solution

{ "type": "p", "children": [], "text": "Topical Solution" }

CIII  

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

30 mg of testosterone

{ "type": "p", "children": [], "text": "30 mg of testosterone" }

per pump actuation*

{ "type": "p", "children": [], "text": "per pump actuation*" }

*Each actuation delivers 1.5 mL of solution

{ "type": "p", "children": [], "text": "*Each actuation delivers 1.5 mL of solution" }

Total contents:

{ "type": "p", "children": [], "text": "Total contents:" }

110 mL to deliver 90 mL

{ "type": "p", "children": [], "text": "110 mL to deliver 90 mL" }