ORACEA is indicated for the treatment of only inflammatory lesions (papules and pustules) of rosacea in adult patients. No meaningful effect was demonstrated for generalized erythema (redness) of rosacea.

This formulation of doxycycline has not been evaluated in the treatment or prevention of infections. Do not use ORACEA for treating bacterial infections, providing antibacterial prophylaxis, or reducing the numbers or eliminating microorganisms associated with any bacterial disease. To reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of other antibacterial drugs, ORACEA should be used only as indicated.

ORACEA has not been evaluated for the treatment of the erythematous, telangiectatic, or ocular components of rosacea.

Take one ORACEA capsule (40 mg) once daily in the morning on an empty stomach, preferably at least one hour prior to or two hours after meals. Administration of adequate amounts of fluid along with the capsules is recommended to wash down the capsule to reduce the risk of esophageal irritation and ulceration [see Adverse Reactions (6)].

The dosage of ORACEA differs from that of doxycycline used to treat infections. Exceeding the recommended dosage may result in an increased incidence of side effects including the development of resistant organisms.

40 mg beige opaque capsule imprinted with “GLD 40”

{ "type": "p", "children": [], "text": "40 mg beige opaque capsule imprinted with “GLD 40”" }

​This drug is contraindicated in persons who have shown hypersensitivity to doxycycline or any of the other tetracyclines.

{ "type": "p", "children": [], "text": "​This drug is contraindicated in persons who have shown hypersensitivity to doxycycline or any of the other tetracyclines." }

Doxycycline, like other tetracycline-class drugs, may cause inhibition of bone growth when administered during the second and third trimesters of pregnancy, infancy, and childhood. All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in premature human infants given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued. If doxycycline is used during the second or third trimester of pregnancy, advise the patient of the potential risk to the fetus [see Use in Specific Populations (8.1)].

The use of tetracycline class drugs orally during tooth development (last half of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of the drug but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Use of tetracycline drugs is not recommended during tooth development [see Use in Specific Populations (8.1)].

Clostridium difficile associated diarrhea (CDAD) has been reported with nearly all antibacterial agents, including doxycycline, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate management should be instituted as clinically indicated.

The anti-anabolic action of the tetracyclines may cause an increase in BUN. While this is not a problem in those with normal renal function, in patients with significantly impaired function, higher serum levels of tetracycline-class antibiotics may lead to azotemia, hyperphosphatemia, and acidosis. If renal impairment exists, even usual oral or parenteral doses may lead to excessive systemic accumulations of the drug and possible liver toxicity. Under such conditions, lower than usual total doses are indicated, and if therapy is prolonged, serum level determinations of the drug may be advisable.

Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Although this was not observed during the duration of the clinical studies with ORACEA, patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using ORACEA. If patients need to be outdoors while using ORACEA, they should wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician.

Tetracyclines have been associated with the development of autoimmune syndromes. Symptoms may be manifested by fever, rash, arthralgia, and malaise. In symptomatic patients, liver function tests, ANA, CBC, and other appropriate tests should be performed to evaluate the patients. Use of all tetracycline-class drugs should be discontinued immediately.

Tetracycline-class drugs are known to cause hyperpigmentation. Tetracycline therapy may induce hyperpigmentation in many organs, including nails, bone, skin, eyes, thyroid, visceral tissue, oral cavity (teeth, mucosa, alveolar bone), sclerae and heart valves. Skin and oral pigmentation has been reported to occur independently of time or amount of drug administration, whereas other pigmentation has been reported to occur upon prolonged administration. Skin pigmentation includes diffuse pigmentation as well as over sites of scars or injury.

Pseudotumor cerebri (benign intracranial hypertension) in adults has been associated with the use of tetracyclines. The usual clinical manifestations are headache and blurred vision. Bulging fontanels have been associated with the use of tetracyclines in infants. While both of these conditions and related symptoms usually resolve after discontinuation of the tetracycline, the possibility for permanent sequelae exists. Patients should be questioned for visual disturbances prior to initiation of treatment with tetracyclines and should be routinely checked for papiledema while on treatment.

Bacterial resistance to tetracyclines may develop in patients using ORACEA. Because of the potential for drug-resistant bacteria to develop during the use of ORACEA, it should only be used as indicated.

As with other antibiotic preparations, use of ORACEA may result in overgrowth of non-susceptible microorganisms, including fungi. If superinfection occurs, ORACEA should be discontinued and appropriate therapy instituted. Although not observed in clinical trials with ORACEA, the use of tetracyclines may increase the incidence of vaginal candidiasis. ORACEA should be used with caution in patients with a history of or predisposition to Candida overgrowth.

Periodic laboratory evaluations of organ systems, including hematopoietic, renal and hepatic studies should be performed. Appropriate tests for autoimmune syndromes should be performed as indicated.

Fixed drug eruptions have occurred with doxycycline and have been associated with worsening severity upon subsequent administrations, including generalized bullous fixed drug eruption [see Adverse Reactions (6.2)].  If severe reactions occur, discontinue ORACEA immediately and initiate appropriate therapy.

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.

Adverse Reactions in Clinical Trials of ORACEA: In controlled clinical trials of adult subjects with mild to moderate rosacea, 537 subjects received ORACEA or placebo over a 16-week period. The following table summarizes selected adverse reactions that occurred in the clinical trials at a rate of ≥1% for the active arm:

<div class="scrollingtable"><table border="1" cellpadding="4" cellspacing="0" width="50%"> <caption> <span>Table 1.  Incidence (%) of Selected Adverse Reactions in Clinical Trials of ORACEA (n=269) v.s. Placebo (n=268)</span> </caption> <colgroup> <col/> <col/> <col/> </colgroup> <tbody class="Headless"> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule">ORACEA</td><td align="center" class="Botrule Lrule Rrule Toprule">Placebo</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Nasopharyngitis</td><td align="center" class="Botrule Lrule Rrule Toprule">13 (5)</td><td align="center" class="Botrule Lrule Rrule Toprule">9 (3)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Pharyngolaryngeal Pain</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule">2 (1)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Sinusitis</td><td align="center" class="Botrule Lrule Rrule Toprule">7 (3)</td><td align="center" class="Botrule Lrule Rrule Toprule">2 (1)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Nasal Congestion</td><td align="center" class="Botrule Lrule Rrule Toprule">4 (2)</td><td align="center" class="Botrule Lrule Rrule Toprule">2 (1)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Fungal Infection</td><td align="center" class="Botrule Lrule Rrule Toprule">5 (2)</td><td align="center" class="Botrule Lrule Rrule Toprule">1 (0)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Influenza</td><td align="center" class="Botrule Lrule Rrule Toprule">5 (2)</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (1)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Diarrhea</td><td align="center" class="Botrule Lrule Rrule Toprule">12 (5)</td><td align="center" class="Botrule Lrule Rrule Toprule">7 (3)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Abdominal Pain Upper</td><td align="center" class="Botrule Lrule Rrule Toprule">5 (2)</td><td align="center" class="Botrule Lrule Rrule Toprule">1 (0)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Abdominal Distention</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule">1 (0)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Abdominal Pain</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule">1 (0)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Stomach Discomfort</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule">2 (1)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Dry Mouth</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule">0 (0)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Hypertension</td><td align="center" class="Botrule Lrule Rrule Toprule">8 (3)</td><td align="center" class="Botrule Lrule Rrule Toprule">2 (1)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Blood Pressure Increase</td><td align="center" class="Botrule Lrule Rrule Toprule">4 (2)</td><td align="center" class="Botrule Lrule Rrule Toprule">1 (0)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Aspartate Aminotransferase Increase</td><td align="center" class="Botrule Lrule Rrule Toprule">6 (2)</td><td align="center" class="Botrule Lrule Rrule Toprule">2 (1)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Blood Lactate Dehydrogenase Increase</td><td align="center" class="Botrule Lrule Rrule Toprule">4 (2)</td><td align="center" class="Botrule Lrule Rrule Toprule">1 (0)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Blood Glucose Increase</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule">0 (0)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Anxiety</td><td align="center" class="Botrule Lrule Rrule Toprule">4 (2)</td><td align="center" class="Botrule Lrule Rrule Toprule">0 (0)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Pain</td><td align="center" class="Botrule Lrule Rrule Toprule">4 (2)</td><td align="center" class="Botrule Lrule Rrule Toprule">1 (0)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Back Pain</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule">0 (0)</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule">Sinus Headache</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule">0 (0)</td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="3">Note: Percentages based on total number of study participants in each treatment group.</td> </tr> </tbody> </table></div>

Adverse Reactions for Tetracyclines: The following adverse reactions have been observed in patients receiving tetracyclines at higher, antimicrobial doses:

Gastrointestinal: anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, and inflammatory lesions (with vaginal candidiasis) in the anogenital region. Hepatotoxicity, Esophagitis and esophageal ulcerations have been reported in patients receiving the capsule forms of the drugs in the tetracycline-class. Most of the patients experiencing esophagitis and/or esophageal ulceration took their medication immediately before lying down [see Dosage and Administration (2)]. Renal toxicity: Rise in BUN has been reported and is apparently dose-related [see Warnings and Precautions (5.4)]. Skin: maculopapular and erythematous rashes. Exfoliative dermatitis. Photosensitivity is discussed above [see Warnings and Precautions (5.5)]. Hypersensitivity reactions: urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, and exacerbation of systemic lupus erythematosus. Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia.

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. The following adverse reactions have been identified during post approval use of ORACEA. Nervous system: Pseudotumor cerebri (benign intracranial hypertension), headache. Skin: fixed drug eruption Psychiatric: depression, anxiety, suicidal ideation, insomnia, abnormal dreams, hallucination

Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.

Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracycline-class drugs in conjunction with penicillin.

The concurrent use of tetracycline and methoxyflurane has been reported to result in fatal renal toxicity.

Absorption of tetracyclines is impaired by bismuth subsalicylate, proton pump inhibitors, antacids containing aluminum, calcium or magnesium and iron-containing preparations.

There have been reports of pseudotumor cerebri (benign intracranial hypertension) associated with the concomitant use of isotretinoin and tetracyclines. Since both oral retinoids, including isotretinoin and acitretin, and the tetracyclines, primarily minocycline, can cause increased intracranial pressure, the concurrent use of an oral retinoid and a tetracycline should be avoided.

Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline.

False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.

Risk Summary Doxycycline may cause reversible inhibition of bone growth and permanent discoloration of deciduous teeth when administered during the second and third trimesters of pregnancy [see Warnings and Precautions (5.1 and 5.2)]. Available data from published studies have not shown a difference in major birth defect risk with doxycycline exposure in the first trimester of pregnancy compared to unexposed pregnancies. Avoid use of ORECEA during the second and third trimester of pregnancy. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Data Human Data Published studies, including epidemiological and observational studies, with use of doxycycline during the first trimester of pregnancy have not identified drug-related increases in major birth defects. The use of tetracycline during tooth development (second and third trimester of pregnancy) may cause permanent discoloration of deciduous teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of the drug but has been observed following repeated short- term courses. Animal Data Results from animal studies indicate that doxycycline crosses the placenta and is found in fetal tissues.

Risk Summary Based on available published data, doxycycline is likely to be present in human breast milk but the specific concentration in breastmilk is not clear. There is no information on the effects of doxycycline on the breastfed infant or the effects on milk production. Because there are other antibacterial drug options available to treat rosacea in lactating women and because of the potential for serious adverse reactions, including tooth discoloration and inhibition of bone growth, advise patients that breastfeeding is not recommended during treatment with ORACEA and for 5 days after the last dose.

ORACEA should not be used in infants and children less than 8 years of age [see Warnings and Precautions (5.1)]. ORACEA has not been studied in children of any age with regard to safety or efficacy, therefore use in children is not recommended.

Clinical studies of ORACEA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.

ORACEA (doxycycline, USP) Capsules 40 mg are hard gelatin capsule shells filled with two types of doxycycline beads (30 mg immediate release and 10 mg delayed release) that together provide a dose of 40 mg of anhydrous doxycycline (C22H24N2O8).

{ "type": "p", "children": [], "text": "ORACEA (doxycycline, USP) Capsules 40 mg are hard gelatin capsule shells filled with two types of doxycycline beads (30 mg immediate release and 10 mg delayed release) that together provide a dose of 40 mg of anhydrous doxycycline (C22H24N2O8)." }

The structural formula of doxycycline, USP is:

{ "type": "p", "children": [], "text": "The structural formula of doxycycline, USP is:" }

with an empirical formula of C22H24N2O8•H2O and a molecular weight of 462.46. The chemical designation for doxycycline is 2-Naphthacenecar-boxamide,4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-, [4S-(4α, 4aα, 5α, 5aα, 6α,12aα)]-, monohydrate. It is very slightly soluble in water.

{ "type": "p", "children": [], "text": "with an empirical formula of C22H24N2O8•H2O and a molecular weight of 462.46. The chemical designation for doxycycline is 2-Naphthacenecar-boxamide,4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-, [4S-(4α, 4aα, 5α, 5aα, 6α,12aα)]-, monohydrate. It is very slightly soluble in water." }

Inert ingredients in the formulation are: hypromellose, iron oxide red, iron oxide yellow, methacrylic acid copolymer, polyethylene glycol, Polysorbate 80, sugar spheres, talc, titanium dioxide, and triethyl citrate.

{ "type": "p", "children": [], "text": "Inert ingredients in the formulation are: hypromellose, iron oxide red, iron oxide yellow, methacrylic acid copolymer, polyethylene glycol, Polysorbate 80, sugar spheres, talc, titanium dioxide, and triethyl citrate." }

The mechanism of action of ORACEA in the treatment of inflammatory lesions of rosacea is unknown.

ORACEA capsules are not bioequivalent to other doxycycline products. The pharmacokinetics of doxycycline following oral administration ofORACEA was investigated in 2 volunteer studies involving 61 adults. Pharmacokinetic parameters for ORACEA following single oral doses and at steady-state in healthy subjects are presented in Table 2.

<div class="scrollingtable"><table border="1" cellpadding="4" cellspacing="0"> <caption> <span>Table 2.  Pharmcokinetic Parameters [Mean (± SD)] for ORACEA</span> </caption> <colgroup> <col/> <col/> <col/> <col/> <col/> <col/> </colgroup> <tfoot> <tr> <td align="left" colspan="6"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Mean</dd> <dt> <a href="#footnote-reference-2" name="footnote-2">†</a> </dt> <dd>Median</dd> <dt> <a href="#footnote-reference-3" name="footnote-3">‡</a> </dt> <dd>Day 7</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule">N</td><td align="center" class="Botrule Lrule Rrule Toprule">C<span class="Sub">max </span><a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a> <br/> <span class="Sub">(ng/mL)</span></td><td align="center" class="Botrule Lrule Rrule Toprule">T<span class="Sub">max   </span><a class="Sup" href="#footnote-2" name="footnote-reference-2">†</a> (hr)</td><td align="center" class="Botrule Lrule Rrule Toprule">AU<span class="Sub">0-∞</span>  <a class="Sup" href="#footnote-1">*</a> <br/>(ng●hr/mL)</td><td align="center" class="Botrule Lrule Rrule Toprule">t<span class="Sub">½  </span> <a class="Sup" href="#footnote-1">*</a> (hr)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Single Dose<br/>40 mg<br/>capsules</td><td align="center" class="Botrule Lrule Rrule Toprule">30</td><td align="center" class="Botrule Lrule Rrule Toprule">510 ± 220.7</td><td align="center" class="Botrule Lrule Rrule Toprule">3.00<br/>(1.0 - 4.1)</td><td align="center" class="Botrule Lrule Rrule Toprule">9227 ±<br/>3212.8</td><td align="center" class="Botrule Lrule Rrule Toprule">21.2 ± 7.6</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Steady-State <a class="Sup" href="#footnote-3" name="footnote-reference-3">‡</a> <br/>40 mg capsules</td><td align="center" class="Botrule Lrule Rrule Toprule">31</td><td align="center" class="Botrule Lrule Rrule Toprule">600 ± 194.2 </td><td align="center" class="Botrule Lrule Rrule Toprule">2.00<br/>(1.0 - 4.0)</td><td align="center" class="Botrule Lrule Rrule Toprule">7543 ± <br/>2443.9</td><td align="center" class="Botrule Lrule Rrule Toprule">23.2 ± 6.2</td> </tr> </tbody> </table></div>

Absorption: In a single-dose food-effect study involving administration of ORACEA to healthy volunteers, concomitant administration with a 1000 calorie, high-fat, high-protein meal that included dairy products, resulted in a decrease in the rate and extent of absorption (Cmax and AUC) by about 45% and 22%, respectively, compared to dosing under fasted conditions. This decrease in systemic exposure can be clinically significant, and therefore if ORACEA is taken close to meal times, it is recommended that it be taken at least one hour prior to or two hours after meals.

Distribution: Doxycycline is greater than 90% bound to plasma proteins.

Metabolism: Major metabolites of doxycycline have not been identified. However, enzyme inducers such as barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline.

Excretion: Doxycycline is excreted in the urine and feces as unchanged drug. It is reported that between 29% and 55.4% of an administered dose can be accounted for in the urine by 72 hours. Terminal half-life averaged 21.2 hours in subjects receiving a single dose of ORACEA.

Special Populations

Geriatric: Doxycycline pharmacokinetics have not been evaluated in geriatric patients.

Pediatric: Doxycycline pharmacokinetics have not been evaluated in pediatric patients [see Warnings and Precautions (5.1)]

Gender: The pharmacokinetics of ORACEA were compared in 16 male and 14 female subjects under fed and fasted conditions. While female subjects had a higher Cmax and AUC than male subjects, these differences were thought to be due to differences in body weight/lean body mass.

Race: Differences in doxycycline pharmacokinetics among racial groups have not been evaluated.

Renal Insufficiency: Studies have shown no significant difference in serum half-life of doxycycline in patients with normal and severely impaired renal function. Hemodialysis does not alter the serum half-life of doxycycline.

Hepatic Insufficiency: Doxycycline pharmacokinetics have not been evaluated in patients with hepatic insufficiency.

Gastric Insufficiency:In a study in healthy volunteers (N=24) the bioavailability of doxycycline is reported to be reduced at high pH. This reduced bioavailability may be clinically significant in patients with gastrectomy, gastric bypass surgery or who are otherwise deemed achlorhydric.

Drug Interactions: [see Drug Interactions (7)].

Doxycycline is a member of the tetracycline-class of drugs. The plasma concentrations of doxycycline achieved with ORACEA during administration [see Clinical Pharmacology (12.3) and Dosage and Administration (2.2)] are less than the concentration required to treat bacterial diseases. ORACEA should not be used for treating bacterial infections, providing antibacterial prophylaxis, or reducing the numbers or eliminating microorganisms associated with any bacterial disease [see Indications and Usage (1.2)].  In vivo microbiological studies utilizing a similar drug exposure for up to 18 months demonstrated no detectable long term effects on bacterial flora of the oral cavity, skin, intestinal tract and vagina.

Doxycycline was assessed for potential to induce carcinogenesis in a study in which the compound was administered to Sprague-Dawley rats by gavage at dosages of 20, 75, and 200 mg/kg/day for two years. An increased incidence of uterine polyps was observed in female rats that received 200 mg/kg/day, a dosage that resulted in a systemic exposure to doxycycline approximately 12.2 times that observed in female humans who use ORACEA [exposure comparison based upon area under the curve (AUC) values]. No impact upon tumor incidence was observed in male rats up to at 200 mg/kg/day, or in females at the lower dosages studied.

Doxycyline was assessed for potential to induce carcinogenesis in CD-1 mice by gavage at dosages 20, 75, and 150 mg/kg/day in males and at dosages of 20, 100, and 300 mg/kg/day in females. No impact upon tumor incidence was observed in male and female mice at systemic exposures approximately 4.2 and 8.3 times that observed in humans, respectively.

Doxycycline demonstrated no potential to cause genetic toxicity in an in vitro point mutation study with mammalian cells (CHO/HGPRT forward mutation assay) or in an in vivo micronucleus assay conducted in CD-1 mice. However, data from an in vitro mammalian chromosomal aberration assay conducted with CHO cells suggest that doxycycline is a weak clastogen. Oral administration of doxycycline to male and female Sprague-Dawley rats adversely affected fertility and reproductive performance, as evidenced by increased time for mating to occur, reduced sperm motility, velocity, and concentration, abnormal sperm morphology, and increased pre-and post-implantation losses. Doxycycline induced reproductive toxicity at all dosages that were examined in this study, as even the lowest dosage tested (50 mg/kg/day) induced a statistically significant reduction in sperm velocity. Note that 50 mg/kg/day is approximately 3.6 times the amount of doxycycline contained in the recommended daily dose of ORACEA when compared on the basis of AUC estimates. Although doxycycline impairs the fertility of rats when administered at sufficient dosage, the effect of ORACEA on human fertility is unknown.

The safety and efficacy of ORACEA in the treatment of only inflammatory lesions (papules and pustules) of rosacea was evaluated in two randomized, placebo-controlled, multi-centered, double-blind, 16-week Phase 3 trials involving 537 subjects (total of 269 subjects on ORACEA from the two trials) with rosacea (10 to 40 papules and pustules and two or fewer nodules). Mean baseline lesion counts were 20 and 21 for ORACEA and placebo subject groups respectively. Pregnant and nursing women, subjects <18 years of age, and subjects with ocular rosacea and/or blepharitis/meibomianitis who require ophthalmologic treatment were excluded from trials.

{ "type": "p", "children": [], "text": "The safety and efficacy of ORACEA in the treatment of only inflammatory lesions (papules and pustules) of rosacea was evaluated in two randomized, placebo-controlled, multi-centered, double-blind, 16-week Phase 3 trials involving 537 subjects (total of 269 subjects on ORACEA from the two trials) with rosacea (10 to 40 papules and pustules and two or fewer nodules). Mean baseline lesion counts were 20 and 21 for ORACEA and placebo subject groups respectively. Pregnant and nursing women, subjects <18 years of age, and subjects with ocular rosacea and/or blepharitis/meibomianitis who require ophthalmologic treatment were excluded from trials." }

At Week 16, subjects in the ORACEA group were evaluated using co-primary endpoints of mean reduction in lesion counts and a dichotomized static Investigator’s Global Assessment of Clear or Almost Clear (defined as 1 to 2 small papules or pustules) when compared to the placebo group in both Phase 3 trials.

{ "type": "p", "children": [], "text": "At Week 16, subjects in the ORACEA group were evaluated using co-primary endpoints of mean reduction in lesion counts and a dichotomized static Investigator’s Global Assessment of Clear or Almost Clear (defined as 1 to 2 small papules or pustules) when compared to the placebo group in both Phase 3 trials." }

<div class="scrollingtable"><table border="1" cellpadding="4" cellspacing="0"> <caption> <span>Table 3: Clinical Results of ORACEA versus Placebo</span> </caption> <colgroup> <col/> <col width="15%"/> <col width="15%"/> <col width="15%"/> <col width="15%"/> </colgroup> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-4" name="footnote-4">*</a> </dt> <dd>Investigator's Global Assessment</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless HeadlessHeadlessHeadless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2">Study 1</td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2">Study 2</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule">ORACEA</td><td align="center" class="Botrule Lrule Rrule Toprule">Placebo</td><td align="center" class="Botrule Lrule Rrule Toprule">ORACEA</td><td align="center" class="Botrule Lrule Rrule Toprule">Placebo</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule">40 mg<br/>N=127</td><td align="center" class="Botrule Lrule Rrule Toprule">N=124</td><td align="center" class="Botrule Lrule Rrule Toprule">40 mg<br/>N=142</td><td align="center" class="Botrule Lrule Rrule Toprule">N=144</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Mean Change in Lesion Count from Baseline</td><td align="center" class="Botrule Lrule Rrule Toprule">- 11.8</td><td align="center" class="Botrule Lrule Rrule Toprule">- 5.9</td><td align="center" class="Botrule Lrule Rrule Toprule">- 9.5</td><td align="center" class="Botrule Lrule Rrule Toprule">- 4.3</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">No. (%) of Subjects Clear or Almost Clear in the IGA <a class="Sup" href="#footnote-4" name="footnote-reference-4">*</a></td><td align="center" class="Botrule Lrule Rrule Toprule">39 (30.7%)</td><td align="center" class="Botrule Lrule Rrule Toprule">24 (19.4%)</td><td align="center" class="Botrule Lrule Rrule Toprule">21 (14.8%)</td><td align="center" class="Botrule Lrule Rrule Toprule">9 (6.3%)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"4\" cellspacing=\"0\">\n<caption>\n<span>Table 3: Clinical Results of ORACEA versus Placebo</span>\n</caption>\n<colgroup>\n<col/>\n<col width=\"15%\"/>\n<col width=\"15%\"/>\n<col width=\"15%\"/>\n<col width=\"15%\"/>\n</colgroup>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"5\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-4\" name=\"footnote-4\">*</a>\n</dt>\n<dd>Investigator's Global Assessment</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless HeadlessHeadlessHeadless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\"></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">Study 1</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">Study 2</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">ORACEA</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">Placebo</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">ORACEA</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">Placebo</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">40 mg<br/>N=127</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">N=124</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">40 mg<br/>N=142</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">N=144</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">Mean Change in Lesion Count from Baseline</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">- 11.8</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">- 5.9</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">- 9.5</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">- 4.3</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\">No. (%) of Subjects Clear or Almost Clear in the IGA <a class=\"Sup\" href=\"#footnote-4\" name=\"footnote-reference-4\">*</a></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">39 (30.7%)</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">24 (19.4%)</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">21 (14.8%)</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">9 (6.3%)</td>\n</tr>\n</tbody>\n</table></div>" }

Subjects treated with ORACEA did not demonstrate significant improvement in erythema when compared to those treated with placebo.

{ "type": "p", "children": [], "text": "Subjects treated with ORACEA did not demonstrate significant improvement in erythema when compared to those treated with placebo." }

ORACEA (beige opaque capsule imprinted with “GLD 40”) containing doxycycline, USP in an amount equivalent to 40 mg of anhydrous doxycycline.

{ "type": "p", "children": [], "text": "ORACEA (beige opaque capsule imprinted with “GLD 40”) containing doxycycline, USP in an amount equivalent to 40 mg of anhydrous doxycycline." }

Bottle of 30 (NDC 0299-3822-30).

{ "type": "p", "children": [], "text": "Bottle of 30 (NDC 0299-3822-30)." }

Storage:

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

All products are to be stored at controlled room temperatures of 59°F - 86°F (15°C - 30°C) and dispensed in tight, light-resistant containers (USP).

{ "type": "p", "children": [], "text": "All products are to be stored at controlled room temperatures of 59°F - 86°F (15°C - 30°C) and dispensed in tight, light-resistant containers (USP)." }

Keep out of reach of children.

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

See FDA-approved patient labeling (Patient Information)

{ "type": "p", "children": [], "text": "See FDA-approved patient labeling (Patient Information)" }

Patients taking ORACEA Capsules 40 mg should receive the following information and instructions:

{ "type": "p", "children": [], "text": "Patients taking ORACEA Capsules 40 mg should receive the following information and instructions:" }

{ "type": "ul", "children": [ "Advise pregnant women that doxycycline, like other tetracycline-class drugs, may cause permanent discoloration of deciduous teeth and reversible inhibition of bone growth when administered during the second and third trimesters of pregnancy [see Warnings and Precautions (5.1 and 5.2) and Use in Specific Populations (8.1)]. ", "Advise women not to breastfeed during treatment with ORACEA and for 5 days after the last dose [see Use in Specific Populations (8.2)]. ", "Advise patients that use of tetracycline class drugs orally during tooth development (infancy and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). ", "Advise patients that use of doxycycline, like other tetracycline-class drugs, may cause inhibition of bone growth when administered during infancy and childhood. ", "Advise patients that pseudomembranous colitis can occur with doxycycline therapy. If patients develop watery or bloody stools, they should seek medical attention. ", "Advise patients that pseudotumor cerebri can occur with doxycycline therapy. If patients experience headache or blurred vision they should seek medical attention. ", "Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines, including doxycycline. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using doxycycline. If patients need to be outdoors while using doxycycline, they should wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician. Treatment should be discontinued at the first evidence of sunburn.", "Autoimmune syndromes, including drug-induced lupus-like syndrome, autoimmune hepatitis, vasculitis and serum sickness have been observed with tetracycline-class drugs, including doxycycline. Symptoms may be manifested by arthralgia, fever, rash and malaise. Patients who experience such symptoms should be cautioned to stop the drug immediately and seek medical help. ", "Counsel patients about discoloration of skin, scars, teeth or gums that can arise from doxycycline therapy. ", "Advise patients to take ORACEA exactly as directed. Increasing doses beyond 40 mg every morning may increase the likelihood that bacteria will develop resistance and will not be treatable by other antibacterial drugs in the future." ], "text": "" }

ORACEA (Or-RAY-sha) (doxycycline) capsules

{ "type": "p", "children": [], "text": "\nORACEA (Or-RAY-sha)\n\n(doxycycline) capsules\n" }

Read this Patient Information before you start taking ORACEA and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or treatment.

{ "type": "p", "children": [], "text": "Read this Patient Information before you start taking ORACEA and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or treatment. " }

What is ORACEA? ORACEA is a tetracycline-class medicine. ORACEA is a prescription medicine used in adults to treat only pimples or bumps (papules and pustules) caused by a condition called rosacea. ORACEA does not lessen redness caused by rosacea. ORACEA should not be used for the treatment or prevention of infections.It is not known if ORACEA is:

{ "type": "p", "children": [], "text": "\nWhat is ORACEA?\nORACEA is a tetracycline-class medicine. ORACEA is a prescription medicine used in adults to treat only pimples or bumps (papules and pustules) caused by a condition called rosacea. ORACEA does not lessen redness caused by rosacea. ORACEA should not be used for the treatment or prevention of infections.It is not known if ORACEA is:\n" }

{ "type": "ul", "children": [ "effective for use for longer than 16 weeks. ", "safe for use longer than 9 months. ", "safe and effective in children. ORACEA should not be used in infants and children less than 8 years of age because it may cause stained teeth in infants and children." ], "text": "" }

Who should not take ORACEA? Do not take ORACEA if you are allergic to doxycycline or other medicines in the tetracycline-class. Ask your doctor or pharmacist for a list of these medicines if you are not sure.

{ "type": "p", "children": [], "text": "\nWho should not take ORACEA?\nDo not take ORACEA if you are allergic to doxycycline or other medicines in the tetracycline-class. Ask your doctor or pharmacist for a list of these medicines if you are not sure." }

What should I tell my doctor before taking ORACEA? Before you take ORACEA tell your doctor if you:

{ "type": "p", "children": [], "text": "\nWhat should I tell my doctor before taking ORACEA?\nBefore you take ORACEA tell your doctor if you:" }

{ "type": "ul", "children": [ "have kidney problems.", "have liver problems.", "have diarrhea or watery stools. ", "have vision problems. ", "have had surgery on your stomach (gastric surgery). ", "have or had a yeast or fungal infection in your mouth or vagina. ", "have any other medical condition. • are pregnant or plan to become pregnant. ORACEA may harm your unborn baby. Taking ORACEA while you are pregnant may cause serious side effects on the growth of bone and teeth of your baby. Stop taking ORACEA and call your doctor right away if you become pregnant while taking ORACEA. ", "are breastfeeding or plan to breastfeed. ORACEA can pass into your breast milk and may harm your baby. Talk to your doctor about the best way to feed your baby if you take ORACEA. You and your doctor should decide if you will take ORACEA or breastfeed. You should not do both." ], "text": "" }

Tell your doctor about all of the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. ORACEA and other medicines can affect each other causing serious side effects. Especially tell your doctor if you take:

{ "type": "p", "children": [], "text": "Tell your doctor about all of the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. ORACEA and other medicines can affect each other causing serious side effects. \n\nEspecially tell your doctor if you take:\n" }

{ "type": "ul", "children": [ "a blood thinner medicine. ", "a penicillin (antibacterial medicine). ", "proton pump inhibitors or antacids that contain aluminum, calcium, or magnesium. ", "products containing iron or bismuth subsalicylate. ", "a medicine taken by mouth that contains isotretinoin or acitretin. ", "a medicine to treat seizures, such as carbamazepineor or phenytoin." ], "text": "" }

Ask your doctor or pharmacist for a full list of these medicines, if you are not sure. Know the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine.

{ "type": "p", "children": [], "text": "Ask your doctor or pharmacist for a full list of these medicines, if you are not sure. \nKnow the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine." }

How should I take ORACEA?

{ "type": "p", "children": [], "text": "\nHow should I take ORACEA?\n\n" }

{ "type": "ul", "children": [ "Take ORACEA exactly as prescribed by your doctor. Taking more than your prescribed dose may increase your chance of side effects, including the chance that bacteria will become resistant to ORACEA. ", "Take ORACEA 1 time a day in the morning on an empty stomach. ", "You should take ORACEA at least one hour before or two hours after a meal. ", "Take ORACEA with enough fluid to completely swallow the capsule and to lower your risk of getting irritation or ulcer in your esophagus. Your esophagus is the tube that connects your mouth to your stomach. ", "If you took too much ORACEA call your doctor right away. ", "Your doctor may do blood tests during treatment with ORACEA to check for side effects." ], "text": "" }

What should I avoid while taking ORACEA? Avoid sunlight or artificial sunlight, such as a tanning booth or sunlamp. You could get severe sunburn. Use sunscreen and wear clothes that cover your skin while out in sunlight.

{ "type": "p", "children": [], "text": "\nWhat should I avoid while taking ORACEA?\nAvoid sunlight or artificial sunlight, such as a tanning booth or sunlamp. You could get severe sunburn. Use sunscreen and wear clothes that cover your skin while out in sunlight. " }

What are the possible side effects of ORACEA? ORACEA may cause serious side effects, including:

{ "type": "p", "children": [], "text": "\nWhat are the possible side effects of ORACEA?\nORACEA may cause serious side effects, including:\n" }

{ "type": "ul", "children": [ "\nHarm to an unborn baby. See “What should I tell my doctor before taking ORACEA?” ", "Permanent teeth discoloration. ORACEA may permanently turn a baby or child's teeth yellow-grey-brown during tooth development. ORACEA should not be used during tooth development. Tooth development happens in the last half of pregnancy, and from birth to 8 years of age. See “What should I tell my doctor before taking ORACEA?” ", "\nIntestine infection (pseudomembranous colitis). Pseudomembranous colitis can happen with most antibiotics, including ORACEA. Call your doctor right away if you get diarrhea or bloody stools. ", "Immune system reactions including a lupus-like syndrome, hepatitis,and inflammation of blood or lymph vessels (vasculitis). Stop taking ORACEA and tell your doctor right away if you get joint pain, fever, rash, or body weakness. ", "\nDiscoloration (hyperpigmentation). ORACEA can cause darkening of your skin, scars, teeth, gums, nails, and whites of your eyes. ", "\nBenign intracranial hypertension, also called pseudotumor cerebri. This is a condition where there is high pressure in the fluid around the brain. This swelling may lead to vision changes and permanent vision loss. Stop taking ORACEA and tell your doctor right away if you have blurred vision, vision loss, or unusual headaches" ], "text": "" }

The most common side effects of ORACEA include:

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

{ "type": "ul", "children": [ "soreness in the nose and throat", "sinus infection ", "fungus infection ", "flu-like symptoms ", "diarrhea ", "stomach (abdominal) bloating or pain ", "high blood pressure (hypertension) ", "change in certain blood tests" ], "text": "" }

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of ORACEA. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.  You may also report side effects to Galderma Laboratories, L.P. at 1-866-735-4137

{ "type": "p", "children": [], "text": "Tell your doctor if you have any side effect that bothers you or that does not go away. \nThese are not all the possible side effects of ORACEA. For more information, ask your doctor or pharmacist. \nCall your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.  You may also report side effects to Galderma Laboratories, L.P. at 1-866-735-4137" }

How should I store ORACEA?

{ "type": "p", "children": [], "text": "\nHow should I store ORACEA?\n\n" }

{ "type": "ul", "children": [ "Store ORACEA at room temperature between 59°F to 86°F (15°C to 30°C). ", "Keep ORACEA in a tightly closed container. ", "Keep ORACEA inside container and out of light." ], "text": "" }

Keep ORACEA and all medicine out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep ORACEA and all medicine out of the reach of children.\n" }

General information about ORACEA Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not take ORACEA for a condition for which it was not prescribed. Do not give ORACEA to other people, even if they have the same symptoms you have. It may harm them. This Patient Information leaflet summarizes the most important information about ORACEA. If you would like more information, talk with your doctor. You can also ask your doctor or pharmacist for information that is written for health professionals.

{ "type": "p", "children": [], "text": "\nGeneral information about ORACEA\nMedicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not take ORACEA for a condition for which it was not prescribed. Do not give ORACEA to other people, even if they have the same symptoms you have. It may harm them.\nThis Patient Information leaflet summarizes the most important information about ORACEA. If you would like more information, talk with your doctor. You can also ask your doctor or pharmacist for information that is written for health professionals.\n" }

What are the ingredients in ORACEA? Active ingredient: doxycyclineInactive ingredients: hypromellose, iron oxide red, iron oxide yellow, methacrylic acid copolymer, polyethylene glycol, Polysorbate 80, sugar spheres, talc, titanium dioxide, and triethyl citrate.

{ "type": "p", "children": [], "text": "\nWhat are the ingredients in ORACEA?\nActive ingredient: doxycyclineInactive ingredients: hypromellose, iron oxide red, iron oxide yellow, methacrylic acid copolymer, polyethylene glycol, Polysorbate 80, sugar spheres, talc, titanium dioxide, and triethyl citrate. \n" }

Marketed by:Galderma Laboratories, L.P.Dallas, Texas 75201 USA All trademarks are the property of their respective owners.P55304-2

{ "type": "p", "children": [], "text": "Marketed by:Galderma Laboratories, L.P.Dallas, Texas 75201 USA\nAll trademarks are the property of their respective owners.P55304-2" }

This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: April 2025

{ "type": "p", "children": [], "text": "This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: April 2025" }

NDC 0299-3822-30

{ "type": "p", "children": [], "text": "\nNDC 0299-3822-30" }

ORACEA®

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

(doxycycine, USP)capsules

{ "type": "p", "children": [], "text": "\n (doxycycine, USP)capsules \n" }

40 mg*

{ "type": "p", "children": [], "text": "\n40 mg*\n" }

*30 mg IMMEDIATE RELEASE &10 mg DELAYED RELEASE BEADS

{ "type": "p", "children": [], "text": "\n*30 mg IMMEDIATE RELEASE &10 mg DELAYED RELEASE BEADS" }

30 CAPSULES

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

RX ONLY

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

GALDERMA

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

Marketed by:Galderma Laboratories, L.P.Dallas, TX 75201 USA All trademarks are the property of their respective owners.oracea.comP56801-1

{ "type": "p", "children": [], "text": "Marketed by:Galderma Laboratories, L.P.Dallas, TX 75201 USA\nAll trademarks are the property of their respective owners.oracea.comP56801-1" }

Doxycycline hyclate tablets are indicated for treatment of Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox, and tick fevers caused by Rickettsiae.

Doxycycline hyclate tablets are indicated for treatment of the following sexually transmitted infections:

Doxycycline hyclate tablets are indicated for treatment of the following respiratory tract infections:

Doxycycline hyclate tablets are indicated for treatment of the following specific bacterial infections:

Doxycycline hyclate tablets are indicated for treatment of the following ophthalmic infections:

Doxycycline hyclate tablets are indicated for the treatment of Anthrax due to Bacillus anthracis, including inhalational anthrax (post-exposure); to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis.

Doxycycline hyclate tablets are indicated as an alternative treatment for the following selected infections when penicillin is contraindicated:

In acute intestinal amebiasis, doxycycline hyclate tablets may be a useful adjunct to amebicides.

In severe acne, doxycycline hyclate tablets may be useful adjunctive therapy.

Doxycycline hyclate tablets are indicated for the prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (less than 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains [see Dosage and Administration (2.4) and Patient Counseling Information (17)].

To reduce the development of drug-resistant bacteria and maintain the effectiveness of doxycycline hyclate tablets and other antibacterial drugs, doxycycline hyclate tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

For adults, the recommended dose of doxycycline hyclate tablets is 100 mg daily.

For pediatric patients 8 years of age and older, the recommended dosage of doxycycline hyclate tablets is 2 mg per kg of body weight administered once daily. Pediatric patients weighing 45 kg or more should receive the adult dose.

Prophylaxis should begin 1 or 2 days before travel to the malarious area. Prophylaxis should be continued daily during travel in the malarious area and for 4 weeks after the traveler leaves the malarious area.

For adults, the recommended dosage is 100 mg, of doxycycline hyclate tablets, by mouth, twice-a-day for 60 days.

For pediatric patients weighing less than 45 kg, the recommended dosage of doxycycline hyclate tablets is 2.2 mg per kg of body weight, by mouth, twice-a-day for 60 days. Pediatric patients weighing 45 kg or more should receive the adult dose.

Doxycycline hyclate tablets, USP:

{ "type": "p", "children": [], "text": "\nDoxycycline hyclate tablets, USP:\n" }

Doxycycline hyclate tablets USP, 75 mg are light-teal colored, round shaped, biconvex film-coated tablets, debossed with “A3” on one side and plain on the other side (each tablet contains 75 mg doxycycline as 86.6 mg doxycycline hyclate).

{ "type": "p", "children": [], "text": "Doxycycline hyclate tablets USP, 75 mg are light-teal colored, round shaped, biconvex film-coated tablets, debossed with “A3” on one side and plain on the other side (each tablet contains 75 mg doxycycline as 86.6 mg doxycycline hyclate)." }

Doxycycline hyclate tablets USP, 150 mg are mossy-green colored, oval shaped, biconvex film-coated tablets, each side of the functionally scored tablet has two parallel score lines for splitting into 3 equal portions, debossed with “A | 2 | 1” on one side and no debossing on the other side (each tablet contains 150 mg doxycycline as 173.2 mg doxycycline hyclate).

{ "type": "p", "children": [], "text": "Doxycycline hyclate tablets USP, 150 mg are mossy-green colored, oval shaped, biconvex film-coated tablets, each side of the functionally scored tablet has two parallel score lines for splitting into 3 equal portions, debossed with “A | 2 | 1” on one side and no debossing on the other side (each tablet contains 150 mg doxycycline as 173.2 mg doxycycline hyclate)." }

Doxycycline hyclate is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.

{ "type": "p", "children": [], "text": "Doxycycline hyclate is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines." }

The use of doxycycline hyclate during tooth development (last half of pregnancy, infancy and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of the drugs of the tetracycline class, but it has been observed following repeated short-term courses. Enamel hypoplasia has also been reported with drugs of the tetracycline class. Advise the patient of the potential risk to the fetus if doxycycline hyclate is used during pregnancy [see Use in Specific Populations (8.1, 8.4)].

Use doxycycline hyclate in pediatric patients 8 years of age or less only when the potential benefits are expected to outweigh the risks in severe or life-threatening conditions (e.g., anthrax, Rocky Mountain spotted fever), particularly when there are no alternative therapies.

The use of doxycycline hyclate during the second and third trimester of pregnancy, infancy and childhood up to the age of 8 years may cause reversible inhibition of bone growth. All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in premature infants given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued. Advise the patient of the potential risk to the fetus if doxycycline hyclate is used during pregnancy [see Use in Specific Populations (8.1, 8.4)].

Clostridioides difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including doxycycline hyclate, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients apt to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracycline drugs, and treatment should be discontinued at the first evidence of skin erythema.

Severe skin reactions, such as exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in patients receiving doxycycline. Fixed drug eruptions have occurred with doxycycline and have been associated with worsening severity upon subsequent administrations, including generalized bullous fixed drug eruption [see Adverse Reactions (6)]. If severe skin reactions occur, discontinue doxycycline immediately and institute appropriate therapy.

Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines including doxycycline hyclate. Clinical manifestations of IH include headache, blurred vision, diplopia, and vision loss; papilledema can be found on fundoscopy. Women of childbearing age who are overweight or have a history of IH are at greater risk for developing tetracycline associated IH. Concomitant use of isotretinoin and doxycycline hyclate should be avoided because isotretinoin is also known to cause pseudotumor cerebri.

Although IH typically resolves after discontinuation of treatment, the possibility for permanent visual loss exists. If visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted. Since intracranial pressure can remain elevated for weeks after drug cessation patients should be monitored until they stabilize.

The antianabolic action of the tetracyclines may cause an increase in BUN. Studies to date indicate that this does not occur with the use of doxycycline in patients with impaired renal function.

Doxycycline offers substantial but not complete suppression of the asexual blood stages of Plasmodium strains.

Doxycycline does not suppress P. falciparum’s sexual blood stage gametocytes. Subjects completing this prophylactic regimen may still transmit the infection to mosquitoes outside endemic areas.

Prescribing doxycycline hyclate in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Doxycycline hyclate may result in overgrowth of non-susceptible organisms, including fungi. If such infections occur, discontinue use and institute appropriate therapy.

In long-term therapy, periodic laboratory evaluation of organ systems, including hematopoietic, renal and hepatic studies should be performed.

The following adverse reactions have been identified during clinical trials or post-approval use of tetracycline-class drugs, including doxycycline. 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.

{ "type": "p", "children": [], "text": "The following adverse reactions have been identified during clinical trials or post-approval use of tetracycline-class drugs, including doxycycline. 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." }

Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, and inflammatory lesions (with monilial overgrowth) in the anogenital region, and pancreatitis. Hepatotoxicity has been reported. These reactions have been caused by both the oral and parenteral administration of tetracyclines. Superficial discoloration of the adult permanent dentition, reversible upon drug discontinuation and professional dental cleaning has been reported. Permanent tooth discoloration and enamel hypoplasia may occur with drugs of the tetracycline class when used during tooth development [see Warnings and Precautions (5.1)]. Instances of esophagitis and esophageal ulcerations have been reported in patients receiving tablet form of drugs in the tetracycline-class. Most of these patients took medications immediately before going to bed [see Dosage and Administration (2.1)].

{ "type": "p", "children": [], "text": "\nGastrointestinal: Anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, and inflammatory lesions (with monilial overgrowth) in the anogenital region, and pancreatitis. Hepatotoxicity has been reported. These reactions have been caused by both the oral and parenteral administration of tetracyclines. Superficial discoloration of the adult permanent dentition, reversible upon drug discontinuation and professional dental cleaning has been reported. Permanent tooth discoloration and enamel hypoplasia may occur with drugs of the tetracycline class when used during tooth development [see Warnings and Precautions (5.1)]. Instances of esophagitis and esophageal ulcerations have been reported in patients receiving tablet form of drugs in the tetracycline-class. Most of these patients took medications immediately before going to bed [see Dosage and Administration (2.1)].\n" }

Skin: Maculopapular and erythematous rashes, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme and fixed drug eruption have been reported. Photosensitivity has been reported [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "\nSkin: Maculopapular and erythematous rashes, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme and fixed drug eruption have been reported. Photosensitivity has been reported [see Warnings and Precautions (5.4)].\n" }

Renal: Rise in BUN has been reported and is apparently dose-related [see Warnings and Precautions (5.7)].

{ "type": "p", "children": [], "text": "\nRenal: Rise in BUN has been reported and is apparently dose-related [see Warnings and Precautions (5.7)].\n" }

Hypersensitivity reactions: Urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, and exacerbation of systemic lupus erythematosus, and drug reaction with eosinophilia and systemic symptoms (DRESS).

{ "type": "p", "children": [], "text": "\nHypersensitivity reactions: Urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, and exacerbation of systemic lupus erythematosus, and drug reaction with eosinophilia and systemic symptoms (DRESS)." }

Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported.

{ "type": "p", "children": [], "text": "\nBlood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported." }

Intracranial Hypertension: Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines [see Warnings and Precautions (5.6)].

{ "type": "p", "children": [], "text": "\nIntracranial Hypertension: Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines [see Warnings and Precautions (5.6)].\n" }

Thyroid Gland Changes: When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of thyroid glands. No abnormalities of thyroid function are known to occur.

{ "type": "p", "children": [], "text": "\nThyroid Gland Changes: When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of thyroid glands. No abnormalities of thyroid function are known to occur." }

Psychiatric: Depression, anxiety, suicidal ideation, insomnia, abnormal dreams, hallucination

{ "type": "p", "children": [], "text": "\nPsychiatric: Depression, anxiety, suicidal ideation, insomnia, abnormal dreams, hallucination" }

Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.

Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracyclines, including doxycycline hyclate in conjunction with penicillin.

Absorption of tetracyclines, including doxycycline hyclate is impaired by antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate, and iron-containing preparations.

Concurrent use of tetracyclines, including doxycycline hyclate may render oral contraceptives less effective.

Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline.

False elevations of urinary catecholamines may occur due to interference with the fluorescence test.

Risk Summary

Doxycycline hyclate, like other tetracycline-class antibacterial drugs, may cause discoloration deciduous teeth, and reversible inhibition of bone growth when administered during the second and third trimester of pregnancy [see Warnings and Precautions (5.1) and (5.2)]. Available data from published studies over decades have not shown a difference in major birth defect risk compared to unexposed pregnancies with doxycycline exposure in the first trimester of pregnancy (see Data). There are no available data on the risk of miscarriage following exposure to doxycycline in pregnancy. Advise the patient of the potential risk to the fetus if doxycycline hyclate is used during pregnancy.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Human Data

A retrospective cohort study of 1,690 pregnant patients who received doxycycline prescriptions in the first trimester of pregnancy compared to an unexposed pregnant cohort showed no difference in the major malformation rate. There is no information on the dose or duration of treatment, or if the patients actually ingested the doxycycline that was prescribed.

Other published studies on exposure to doxycycline in the first trimester of pregnancy have small sample sizes; however, these studies have not shown an increased risk of major malformations.

The use of tetracyclines during tooth development (second and third trimester of pregnancy) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of the drug but has been observed following repeated short-term courses [see Warnings and Precautions (5.1, 5.2)].

Animal Data

Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can have toxic effects on the developing fetus (often related to retardation of skeletal development). Evidence of embryotoxicity also has been noted in animals treated early in pregnancy.

Risk Summary

Based on available published data, doxycycline is present in human milk. There are no data that inform the levels of doxycycline in breast milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions, including tooth discoloration and inhibition of bone growth, advise patients that breastfeeding is not recommended during treatment with doxycycline hyclate and for 5 days after the last dose.

Infertility

Based on findings from a fertility study in animals, doxycycline may impair female and male fertility. The reversibility of this finding is unclear [see Nonclinical Toxicology (13.1)].

Because of the effects of drugs of the tetracycline-class on tooth development and growth, use doxycycline hyclate in pediatric patients 8 years of age or less only when the potential benefits are expected to outweigh the risks in severe or life-threatening conditions (e.g., anthrax, Rocky Mountain spotted fever), particularly when there are no alternative therapies [see Warnings and Precautions (5.1, 1.1) and Dosage and Administration (2.1, 2.5)].

Clinical studies of doxycycline hyclate tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Doxycycline hyclate tablets each contains less than 1 mg of sodium.

In case of overdosage, discontinue medication, treat symptomatically and institute supportive measures. Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdosage.

{ "type": "p", "children": [], "text": "In case of overdosage, discontinue medication, treat symptomatically and institute supportive measures. Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdosage." }

Doxycycline hyclate tablets, USP contain doxycycline hyclate, USP a tetracycline class drug synthetically derived from oxytetracycline, in an immediate release formulation for oral administration.

{ "type": "p", "children": [], "text": "Doxycycline hyclate tablets, USP contain doxycycline hyclate, USP a tetracycline class drug synthetically derived from oxytetracycline, in an immediate release formulation for oral administration." }

The molecular formula of doxycycline hyclate is (C22H24N2O8 • HCl)2• C2H6O•H2O and the molecular weight of doxycycline hyclate is 1025.87. The chemical name for doxycycline hyclate is:

{ "type": "p", "children": [], "text": "The molecular formula of doxycycline hyclate is (C22H24N2O8 • HCl)2• C2H6O•H2O and the molecular weight of doxycycline hyclate is 1025.87. The chemical name for doxycycline hyclate is:" }

4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide monohydrochloride, compound with ethyl alcohol (2:1), monohydrate.

{ "type": "p", "children": [], "text": "4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide monohydrochloride, compound with ethyl alcohol (2:1), monohydrate." }

The structural formula for doxycycline hyclate is:

{ "type": "p", "children": [], "text": "The structural formula for doxycycline hyclate is:" }

Figure 1: Structure of Doxycycline Hyclate

{ "type": "p", "children": [], "text": "\nFigure 1: Structure of Doxycycline Hyclate\n" }

Doxycycline hyclate, USP is a yellow crystalline powder soluble in water and in solutions of alkali hydroxides and carbonates.

{ "type": "p", "children": [], "text": "Doxycycline hyclate, USP is a yellow crystalline powder soluble in water and in solutions of alkali hydroxides and carbonates." }

Doxycycline hyclate tablets, USP: Doxycycline hyclate tablets, USP is available as 75 mg and 150 mg tablets. Each 75 mg tablet contains 86.6 mg of doxycycline hyclate, USP equivalent to 75 mg of doxycycline, USP. Each 150 mg tablet contains 173.2 mg of doxycycline hyclate, USP equivalent to 150 mg of doxycycline, USP.

{ "type": "p", "children": [], "text": "\nDoxycycline hyclate tablets, USP:\nDoxycycline hyclate tablets, USP is available as 75 mg and 150 mg tablets. Each 75 mg tablet contains 86.6 mg of doxycycline hyclate, USP equivalent to 75 mg of doxycycline, USP. Each 150 mg tablet contains 173.2 mg of doxycycline hyclate, USP equivalent to 150 mg of doxycycline, USP." }

Inactive ingredients in the tablet formulation are: croscarmellose sodium, magnesium stearate, microcrystalline cellulose and sodium lauryl sulfate. Film-coating contains: polyvinyl alcohol, polyethylene glycol, talc, titanium dioxide, FD&C Blue #1 aluminum lake (75 mg Tablet), FD&C Yellow #6 aluminum lake (75 mg Tablet), FD&C Blue #2 (150 mg Tablet) and iron oxide yellow (150 mg Tablet). Doxycycline hyclate tablets, 75 mg contain 0.13 mg (0.0056 mEq) of sodium. Doxycycline hyclate tablets, 150 mg contain 0.26 mg (0.0113 mEq) of sodium.

{ "type": "p", "children": [], "text": "Inactive ingredients in the tablet formulation are: croscarmellose sodium, magnesium stearate, microcrystalline cellulose and sodium lauryl sulfate. Film-coating contains: polyvinyl alcohol, polyethylene glycol, talc, titanium dioxide, FD&C Blue #1 aluminum lake (75 mg Tablet), FD&C Yellow #6 aluminum lake (75 mg Tablet), FD&C Blue #2 (150 mg Tablet) and iron oxide yellow (150 mg Tablet). Doxycycline hyclate tablets, 75 mg contain 0.13 mg (0.0056 mEq) of sodium. Doxycycline hyclate tablets, 150 mg contain 0.26 mg (0.0113 mEq) of sodium." }

Doxycycline is a tetracycline-class antimicrobial drug [see Microbiology (12.4)].

Absorption

Doxycycline hyclate tablets: Following administration of a single 300 mg dose to adult volunteers, average peak plasma doxycycline levels were 3 mcg per mL at 3 hours, decreasing to 1.18 mcg per mL at 24 hours. The mean Cmax and AUC0-∞ of doxycycline are 24% and 15% lower, respectively, following single dose administration of doxycycline hyclate, 150 mg tablets with a high fat meal (including milk) compared to fasted conditions. The clinical significance of these decreases is unknown.

Excretion

Tetracyclines are concentrated in bile by the liver and excreted in the urine and feces at high

concentrations and in a biologically active form.

Excretion of doxycycline by the kidney is about 40% per 72 hours in individuals with a creatinine clearance of about 75 mL per minute. This percentage may fall as low as 1% per 72 hours to 5% per 72 hours in individuals with a creatinine clearance below 10 mL per minute. Studies have shown no significant difference in the serum half-life of doxycycline (range 18 to 22 hours) in individuals with normal and severely impaired renal function. Hemodialysis does not alter the serum half-life.

Pediatric Patients

Population pharmacokinetic analysis of sparse concentration-time data of doxycycline following standard of care intravenous and oral dosing in 44 children (2 to 18 years of age) showed that allometrically-scaled clearance of doxycycline in children ≥ 2 to ≤ 8 years of age (median [range] 3.58 [2.27 to 10.82] L/h/70 kg, N = 11) did not differ significantly from children > 8 to 18 years of age (3.27 [1.11 to 8.12] L/h/70 kg, N = 33).

For pediatric patients weighing ≤ 45 kg, body weight normalized doxycycline CL in those ≥ 2 to ≤ 8 years of age (median [range] 0.071 [0.041 to 0.202] L/kg/h, N = 10) did not differ significantly from those > 8 to 18 years of age (0.081 [0.035 to 0.126] L/kg/h, N = 8). In pediatric patients weighing > 45 kg no clinically significant differences in body weight normalized doxycycline CL were observed between those ≥ 2 to ≤ 8 years (0.050 L/kg/h, N = 1) and those > 8 years of age (0.044 [0.014 to 0.121] L/kg/h, N = 25). No clinically significant difference in CL differences between oral and IV were observed in the small cohort of pediatric patients who received the oral (N = 19) or IV (N = 21) formulation alone.

Mechanism of Action

Doxycycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit. Doxycycline has bacteriostatic activity against a broad range of Gram-positive and Gram-negative bacteria.

Resistance

Cross resistance with other tetracyclines is common.

Antimicrobial Activity

Doxycycline has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [see Indications and Usage (1)].

Gram-negative bacteria

Acinetobacter species

Bartonella bacilliformis

Brucella species

Campylobacter fetus

Enterobacter aerogenes

Escherichia coli

Francisella tularensis

Haemophilus ducreyi

Haemophilus influenzae

Klebsiella granulomatis

Klebsiella species

Neisseria gonorrhoeae

Shigella species

Vibrio cholerae

Yersinia pestis

Gram-positive bacteria

Bacillus anthracis

Listeria monocytogenes

Streptococcus pneumoniae

Anaerobic bacteria

Clostridium species

Fusobacterium fusiforme

Propionibacterium acnes

Other bacteria

Nocardiae and other aerobic Actinomyces species

Borrelia recurrentis

Chlamydophila psittaci

Chlamydia trachomatis

Mycoplasma pneumoniae

Rickettsiae species

Treponema pallidum

Treponema pallidum subspecies pertenue

Ureaplasma urealyticum

Parasites

Balantidium coli

Entamoeba species

Plasmodium falciparum*

*Doxycycline has been found to be active against the asexual erythrocytic forms of Plasmodium falciparum, but not against the gametocytes of P. falciparum. The precise mechanism of action of the drug is not known.

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria, and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

Long-term studies in animals to evaluate carcinogenic potential of doxycycline hyclate have not been conducted.

However, a 2 year carcinogenicity study with doxycycline administered daily by oral gavage to adult rats (20, 75, 200 mg/kg/day) demonstrated an increase in uterine polyps in female rats at 200 mg/kg/day (10 times the maximum recommended daily adult dose of doxycycline hyclate based on body surface area comparison) with no change in tumor incidence in male rats at the same dose. A 2-year carcinogenicity study with doxycycline administered daily by oral gavage to adult male (maximum dose 150 mg/kg/day) and female (maximum dose 300 mg/kg/day) mice showed no changes in tumor incidence, at approximately 4 and 7 times the maximum recommended daily adult dose of doxycycline hyclate, based on a body surface area comparison, respectively.

Mutagenesis and fertility studies have not been conducted with doxycycline hyclate. Mutagenesis studies with doxycycline demonstrated no potential to cause genetic toxicity in an in vitro point mutation study with mammalian cells or in an in vivo micronucleus assay in CD-1 mice. However, data from an in vitro mammalian chromosomal aberration assay conducted in CHO cells suggest that doxycycline is a weak clastogen. Oral administration of doxycycline to Sprague-Dawley rats showed adverse effects on fertility and reproduction including increased time for mating, reduced sperm motility, velocity and concentration as well as increased pre and post implantation loss. Reduced sperm velocity was seen at the lowest dosage tested, 50 mg/kg/day which is 2.5 times the maximum recommended daily adult dose of doxycycline hyclate. Although doxycycline impairs the fertility of rats when administered at sufficient dosages, the effect of doxycycline hyclate on human fertility is unknown.

Hyperpigmentation of the thyroid has been produced by members of the tetracycline-class in the following species: in rats by oxytetracycline, doxycycline, tetracycline PO4, and methacycline; in minipigs by doxycycline, minocycline, tetracycline PO4, and methacycline; in dogs by doxycycline and minocycline; in monkeys by minocycline.

Minocycline, tetracycline PO4, methacycline, doxycycline, tetracycline base, oxytetracycline HCl, and tetracycline HCl, were goitrogenic in rats fed a low iodine diet. This goitrogenic effect was accompanied by high radioactive iodine uptake. Administration of minocycline also produced a large goiter with high radioiodine uptake in rats fed a relatively high iodine diet.

Treatment of various animal species with this class of drugs has also resulted in the induction of thyroid hyperplasia in the following: in rats and dogs (minocycline); in chickens (chlortetracycline); and in rats and mice (oxytetracycline). Adrenal gland hyperplasia has been observed in goats and rats treated with oxytetracycline.

Results of animal studies indicate that tetracyclines cross the placenta and are found in fetal tissues.

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

How Supplied

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

Doxycycline hyclate tablets USP, 75 mg are supplied as light-teal colored, round shaped, biconvex film-coated tablets, debossed with “A3” on one side and plain on the other side. Each 75 mg tablet contains 86.6 mg of doxycycline hyclate, USP equivalent to 75 mg of doxycycline, USP.

{ "type": "p", "children": [], "text": "Doxycycline hyclate tablets USP, 75 mg are supplied as light-teal colored, round shaped, biconvex film-coated tablets, debossed with “A3” on one side and plain on the other side. Each 75 mg tablet contains 86.6 mg of doxycycline hyclate, USP equivalent to 75 mg of doxycycline, USP." }

They are available as follows:

{ "type": "p", "children": [], "text": "They are available as follows:" }

Bottles of 60:                   NDC 69238-1500-6

{ "type": "p", "children": [], "text": "Bottles of 60:                   NDC 69238-1500-6" }

Doxycycline hyclate tablets USP, 150 mg are supplied as mossy-green colored, oval shaped, biconvex film-coated tablets, each side of the functionally scored tablet has two parallel score lines for splitting into 3 equal portions, debossed with “A | 2 | 1” on one side and no debossing on the other side. Each 150 mg tablet contains 173.2 mg of doxycycline hyclate, USP equivalent to 150 mg of doxycycline, USP.

{ "type": "p", "children": [], "text": "Doxycycline hyclate tablets USP, 150 mg are supplied as mossy-green colored, oval shaped, biconvex film-coated tablets, each side of the functionally scored tablet has two parallel score lines for splitting into 3 equal portions, debossed with “A | 2 | 1” on one side and no debossing on the other side. Each 150 mg tablet contains 173.2 mg of doxycycline hyclate, USP equivalent to 150 mg of doxycycline, USP." }

They are available as follows:

{ "type": "p", "children": [], "text": "They are available as follows:" }

Bottles of 60:                  NDC 69238-1501-6

{ "type": "p", "children": [], "text": "Bottles of 60:                  NDC 69238-1501-6" }

Storage

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

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

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

Protect from light and moisture. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

{ "type": "p", "children": [], "text": "Protect from light and moisture. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. " }

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

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

Important Administration and Safety Information for Patients and Caregivers

{ "type": "p", "children": [], "text": "\nImportant Administration and Safety Information for Patients and Caregivers\n" }

Advise patients taking doxycycline hyclate for malaria prophylaxis:

{ "type": "p", "children": [], "text": "Advise patients taking doxycycline hyclate for malaria prophylaxis:" }

{ "type": "ul", "children": [ "that no present-day antimalarial agent, including doxycycline, guarantees protection against malaria.", "to avoid being bitten by mosquitoes by using personal protective measures that help avoid contact with mosquitoes, especially from dusk to dawn (for example, staying in well-screened areas, using mosquito nets, covering the body with clothing, and using an effective insect repellent).", "that doxycycline prophylaxis:\n -     should begin 1 day to 2 days before travel to the malarious area, \n-     should be continued daily while in the malarious area and after leaving the malarious area, \n-     should be continued for 4 further weeks to avoid development of malaria after returning from an endemic area, \n-     should not exceed 4 months. \nAdvise all patients taking doxycycline hyclate: \n", "that doxycycline hyclate tablets (150 mg) can be broken into two-thirds or one-third at the scored lines to provide 100 mg or 50 mg strength doses, respectively.\n\n", "to avoid excessive sunlight or artificial ultraviolet light while receiving doxycycline and to discontinue therapy if phototoxicity (for example, skin eruptions, etc.) occurs. Sunscreen or sunblock should be considered [see Warnings and Precautions (5.4)].\n", "to drink fluids liberally along with doxycycline hyclate to reduce the risk of esophageal irritation and ulceration [see Adverse Reactions (6)].", "that the absorption of tetracyclines is reduced when taken with foods, especially those that contain calcium [see Drug Interactions (7.3)]. However, the absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk [see Clinical Pharmacology (12.3)].", "that if gastric irritation occurs, doxycycline hyclate may be given with food or milk [see Clinical Pharmacology (12.3)].\n", "that the absorption of tetracyclines is reduced when taken with antacids containing aluminum, calcium or magnesium, bismuth subsalicylate, and iron-containing preparations [see Drug Interactions (7.3)].\n", "that the use of doxycycline might increase the incidence of vaginal candidiasis." ], "text": "" }

Tooth Discoloration and Inhibition of Bone Growth

{ "type": "p", "children": [], "text": "\nTooth Discoloration and Inhibition of Bone Growth\n" }

Advise patients that doxycycline hyclate, like other tetracycline-class drugs, may cause permanent tooth discoloration of deciduous teeth and reversible inhibition of bone growth when administered during pregnancy. Tell your healthcare provider right away if you become pregnant during treatment [see Warnings and Precautions (5.1, 5.2) and Use in Specific Populations (8.1, 8.4)].

{ "type": "p", "children": [], "text": "Advise patients that doxycycline hyclate, like other tetracycline-class drugs, may cause permanent tooth discoloration of deciduous teeth and reversible inhibition of bone growth when administered during pregnancy. Tell your healthcare provider right away if you become pregnant during treatment [see Warnings and Precautions (5.1, 5.2) and Use in Specific Populations (8.1, 8.4)]." }

Lactation

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

Advise women not to breastfeed during treatment with doxycycline hyclate and for 5 days after the last dose [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "Advise women not to breastfeed during treatment with doxycycline hyclate and for 5 days after the last dose [see Use in Specific Populations (8.2)]." }

Diarrhea

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

Advise patients that diarrhea is a common problem caused by antibacterial drugs which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterial drugs, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of antibacterial. If this occurs, patients should contact their physician as soon as possible.

{ "type": "p", "children": [], "text": "Advise patients that diarrhea is a common problem caused by antibacterial drugs which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterial drugs, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of antibacterial. If this occurs, patients should contact their physician as soon as possible." }

Development of Resistance

{ "type": "p", "children": [], "text": "\nDevelopment of Resistance\n" }

Counsel patients that antibacterial drugs including doxycycline hyclate should only be used to treat bacterial infections. They do not treat viral infections (for example, the common cold). When doxycycline hyclate are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by doxycycline hyclate or other antibacterial drugs in the future.

{ "type": "p", "children": [], "text": "Counsel patients that antibacterial drugs including doxycycline hyclate should only be used to treat bacterial infections. They do not treat viral infections (for example, the common cold). When doxycycline hyclate are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by doxycycline hyclate or other antibacterial drugs in the future." }

Manufactured by: Amneal Pharmaceutical Pvt. Ltd. Oral Solid Dosage Unit Ahmedabad 382213, INDIA

{ "type": "p", "children": [], "text": "Manufactured by:\n\nAmneal Pharmaceutical Pvt. Ltd.\nOral Solid Dosage Unit\n\nAhmedabad 382213, INDIA " }

Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807

{ "type": "p", "children": [], "text": "Distributed by:\n\nAmneal Pharmaceuticals LLC\n\nBridgewater, NJ 08807" }

Rev. 04-2025-04

{ "type": "p", "children": [], "text": "Rev. 04-2025-04" }

Instructions for Use Doxycycline Hyclate (dox” i sye’ kleen hye’ klate) Tablets, USP for oral use

{ "type": "p", "children": [], "text": "\nInstructions for Use\nDoxycycline Hyclate (dox” i sye’ kleen hye’ klate) Tablets, USP\nfor oral use\n" }

Read this Instructions for Use before you start using doxycycline hyclate tablets and each time you get a refill. There may be new information. This information 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 before you start using doxycycline hyclate tablets and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment." }

Note:

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

{ "type": "ul", "children": [ "Your healthcare provider may need to change your dose of doxycycline hyclate tablets during treatment as needed.", "Doxycycline hyclate tablets can be taken whole or broken at scored lines.", "Doxycycline hyclate tablets are marked with scored lines and may be broken at these scored lines to provide the following doses:" ], "text": "" }

150 mg treatment (take the entire whole tablet)

{ "type": "p", "children": [], "text": "\n150 mg treatment (take the entire whole tablet)\n" }

100 mg treatment (take two-thirds of the tablet)

{ "type": "p", "children": [], "text": "\n100 mg treatment (take two-thirds of the tablet)\n" }

50 mg treatment (take one-third of the tablet)

{ "type": "p", "children": [], "text": "\n50 mg treatment (take one-third of the tablet)\n" }

How to break your doxycycline hyclate tablet:

{ "type": "p", "children": [], "text": "\nHow to break your doxycycline hyclate tablet:\n" }

{ "type": "ul", "children": [ "Hold the tablet between your thumb and index finger close to the scored line for your dose of doxycycline hyclate tablet as shown above.", "Apply enough pressure to break the tablet at the scored line.", "\nDo not break the doxycycline hyclate tablet in any other way." ], "text": "" }

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. " }

Rx only

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

Manufactured by: Amneal Pharmaceuticals Pvt. Ltd. Oral Solid Dosage Unit Ahmedabad 382213, INDIA

{ "type": "p", "children": [], "text": "Manufactured by:\n\nAmneal Pharmaceuticals Pvt. Ltd.\nOral Solid Dosage Unit\n\nAhmedabad 382213, INDIA " }

Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807

{ "type": "p", "children": [], "text": "Distributed by:\n\nAmneal Pharmaceuticals LLC\n\nBridgewater, NJ 08807" }

Rev. 04-2025-03

{ "type": "p", "children": [], "text": "Rev. 04-2025-03" }

NDC 69238-1500-6

{ "type": "p", "children": [], "text": "\nNDC 69238-1500-6\n" }

Doxycycline Hyclate Tablets USP, 75 mg

{ "type": "p", "children": [], "text": "\nDoxycycline Hyclate Tablets USP, 75 mg\n" }

Rx only

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

60 Tablets

{ "type": "p", "children": [], "text": "\n60 Tablets \n" }

Amneal Pharmaceuticals LLC

{ "type": "p", "children": [], "text": "\nAmneal Pharmaceuticals LLC\n" }

NDC 69238-1501-6

{ "type": "p", "children": [], "text": "\nNDC 69238-1501-6\n" }

Doxycycline Hyclate Tablets USP, 150 mg

{ "type": "p", "children": [], "text": "\nDoxycycline Hyclate Tablets USP, 150 mg\n" }

Rx only

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

60 Tablets

{ "type": "p", "children": [], "text": "\n60 Tablets \n" }

Amneal Pharmaceuticals LLC

{ "type": "p", "children": [], "text": "\nAmneal Pharmaceuticals LLC\n" }