Save up to 80% by drug discount in your pharmacy with "Pharmacy Near Me - National Drug Discount Card"
You can scan QR Code(just open camera on your phone/scan by application) from the image on prescription drug discount card to save it to your mobile phone. Or just click on image if you're on mobile phone.
| Product NDC Code | 0299-3822 | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Drug Name | Oracea |
||||||||||||||
| Type | Brand | ||||||||||||||
| Pharm Class | Tetracycline-class Drug [EPC], Tetracyclines [CS] |
||||||||||||||
| Active Ingredients |
|
||||||||||||||
| Route | ORAL | ||||||||||||||
| Dosage Form | CAPSULE | ||||||||||||||
| RxCUI drug identifier | 901399, 901401 |
||||||||||||||
| Application Number | NDA050805 | ||||||||||||||
| Labeler Name | Galderma Laboratories, L.P. | ||||||||||||||
| Packages |
|
||||||||||||||
| Check if available Online | Get Medication Prices online with Discount |
Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.6 ADVERSE REACTIONS Some of the most common adverse reactions (incidence >2% and more common than with placebo) are nasopharyngitis, sinusitis, diarrhea, hypertension and aspartate aminotransferase increase. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Galderma Laboratories, L.P. at 1-866-735-4137 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience 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: Table 1. Incidence (%) of Selected Adverse Reactions in Clinical Trials of ORACEA (n=269) v.s. Placebo (n=268) ORACEA Placebo Nasopharyngitis 13 (5) 9 (3) Pharyngolaryngeal Pain 3 (1) 2 (1) Sinusitis 7 (3) 2 (1) Nasal Congestion 4 (2) 2 (1) Fungal Infection 5 (2) 1 (0) Influenza 5 (2) 3 (1) Diarrhea 12 (5) 7 (3) Abdominal Pain Upper 5 (2) 1 (0) Abdominal Distention 3 (1) 1 (0) Abdominal Pain 3 (1) 1 (0) Stomach Discomfort 3 (1) 2 (1) Dry Mouth 3 (1) 0 (0) Hypertension 8 (3) 2 (1) Blood Pressure Increase 4 (2) 1 (0) Aspartate Aminotransferase Increase 6 (2) 2 (1) Blood Lactate Dehydrogenase Increase 4 (2) 1 (0) Blood Glucose Increase 3 (1) 0 (0) Anxiety 4 (2) 0 (0) Pain 4 (2) 1 (0) Back Pain 3 (1) 0 (0) Sinus Headache 3 (1) 0 (0) Note: Percentages based on total number of study participants in each treatment group. 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. 6.2 Postmarketing Experience 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.
| ORACEA | Placebo | |
| Nasopharyngitis | 13 (5) | 9 (3) |
| Pharyngolaryngeal Pain | 3 (1) | 2 (1) |
| Sinusitis | 7 (3) | 2 (1) |
| Nasal Congestion | 4 (2) | 2 (1) |
| Fungal Infection | 5 (2) | 1 (0) |
| Influenza | 5 (2) | 3 (1) |
| Diarrhea | 12 (5) | 7 (3) |
| Abdominal Pain Upper | 5 (2) | 1 (0) |
| Abdominal Distention | 3 (1) | 1 (0) |
| Abdominal Pain | 3 (1) | 1 (0) |
| Stomach Discomfort | 3 (1) | 2 (1) |
| Dry Mouth | 3 (1) | 0 (0) |
| Hypertension | 8 (3) | 2 (1) |
| Blood Pressure Increase | 4 (2) | 1 (0) |
| Aspartate Aminotransferase Increase | 6 (2) | 2 (1) |
| Blood Lactate Dehydrogenase Increase | 4 (2) | 1 (0) |
| Blood Glucose Increase | 3 (1) | 0 (0) |
| Anxiety | 4 (2) | 0 (0) |
| Pain | 4 (2) | 1 (0) |
| Back Pain | 3 (1) | 0 (0) |
| Sinus Headache | 3 (1) | 0 (0) |
| Note: Percentages based on total number of study participants in each treatment group. | ||
ORACEA Drug Interactions
Information about and practical guidance on preventing clinically significant drug/drug and drug/food interactions that may occur in people taking the drug.7 DRUG INTERACTIONS Patients on anticoagulant therapy may require downward adjustment of their anticoagulant dosage. ( 7.1 ) Some bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracycline-class drugs in conjunction with penicillin. ( 7.2 ) The concurrent use of tetracycline and methoxyflurane has been reported to result in fatal renal toxicity. ( 7.3 ) 7.1 Anticoagulants Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage. 7.2 Penicillin Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracycline-class drugs in conjunction with penicillin. 7.3 Methoxyflurane The concurrent use of tetracycline and methoxyflurane has been reported to result in fatal renal toxicity. 7.4 Antacids and Iron Preparations Absorption of tetracyclines is impaired by bismuth subsalicylate, proton pump inhibitors, antacids containing aluminum, calcium or magnesium and iron-containing preparations. 7.5 Oral Retinoids 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. 7.6 Barbiturates and Anti-epileptics Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline. 7.7 Drug/Laboratory Test Interactions False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of ORACEA in the treatment of inflammatory lesions of rosacea is unknown. 12.3 Pharmacokinetics ORACEA capsules are not bioequivalent to other doxycycline products. The pharmacokinetics of doxycycline following oral administration of ORACEA 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. Table 2. Pharmcokinetic Parameters [Mean (± SD)] for ORACEA N C max Mean (ng/mL) T max Median (hr) AU 0-∞ (ng●hr/mL) t ½ (hr) Single Dose 40 mg capsules 30 510 ± 220.7 3.00 (1.0 - 4.1) 9227 ± 3212.8 21.2 ± 7.6 Steady-State Day 7 40 mg capsules 31 600 ± 194.2 2.00 (1.0 - 4.0) 7543 ± 2443.9 23.2 ± 6.2 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 (C max 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 C max 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) ]. 12.4 Microbiology 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.
| N | C max | T max | AU 0-∞ | t ½ | |
| Single Dose 40 mg capsules | 30 | 510 ± 220.7 | 3.00 (1.0 - 4.1) | 9227 ± 3212.8 | 21.2 ± 7.6 |
| Steady-State | 31 | 600 ± 194.2 | 2.00 (1.0 - 4.0) | 7543 ± 2443.9 | 23.2 ± 6.2 |
Mechanism of action
Information about the established mechanism(s) of the drugÕs action in humans at various levels (for example receptor, membrane, tissue, organ, whole body). If the mechanism of action is not known, this field contains a statement about the lack of information.12.1 Mechanism of Action The mechanism of action of ORACEA in the treatment of inflammatory lesions of rosacea is unknown.
Pharmacokinetics
Information about the clinically significant pharmacokinetics of a drug or active metabolites, for instance pertinent absorption, distribution, metabolism, and excretion parameters.12.3 Pharmacokinetics ORACEA capsules are not bioequivalent to other doxycycline products. The pharmacokinetics of doxycycline following oral administration of ORACEA 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. Table 2. Pharmcokinetic Parameters [Mean (± SD)] for ORACEA N C max Mean (ng/mL) T max Median (hr) AU 0-∞ (ng●hr/mL) t ½ (hr) Single Dose 40 mg capsules 30 510 ± 220.7 3.00 (1.0 - 4.1) 9227 ± 3212.8 21.2 ± 7.6 Steady-State Day 7 40 mg capsules 31 600 ± 194.2 2.00 (1.0 - 4.0) 7543 ± 2443.9 23.2 ± 6.2 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 (C max 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 C max 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) ].
| N | C max | T max | AU 0-∞ | t ½ | |
| Single Dose 40 mg capsules | 30 | 510 ± 220.7 | 3.00 (1.0 - 4.1) | 9227 ± 3212.8 | 21.2 ± 7.6 |
| Steady-State | 31 | 600 ± 194.2 | 2.00 (1.0 - 4.0) | 7543 ± 2443.9 | 23.2 ± 6.2 |
Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.4 CONTRAINDICATIONS This drug is contraindicated in persons who have shown hypersensitivity to doxycycline or any of the other tetracyclines. ORACEA is contraindicated in persons who have shown hypersensitivity to doxycycline or other tetracyclines. ( 4 )
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.11 DESCRIPTION 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 (C 22 H 24 N 2 O 8 ). The structural formula of doxycycline, USP is: with an empirical formula of C 22 H 24 N 2 O 8 •H 2 O 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: hard gelatin capsule, hypromellose, methacrylic acid copolymer, Opadry beige, sugar spheres, talc, and triethyl citrate. oracea-chem-struct
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.2 DOSAGE AND ADMINISTRATION 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. ( 2.1 ) Exceeding the recommended dosage may result in an increased incidence of side effects including the development of resistant microorganisms. ( 2.2 , 5.9 ) 2.1 General Dosing Information 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) ]. 2.2 Important Considerations for Dosing Regimen 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.
Dosage forms and strengths
Information about all available dosage forms and strengths for the drug product to which the labeling applies. This field may contain descriptions of product appearance.3 DOSAGE FORMS AND STRENGTHS 40 mg beige opaque capsule imprinted with “GLD 40” 40 mg capsule. ( 3 )
Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.1 INDICATIONS AND USAGE • ORACEA is a tetracycline-class drug indicated for the treatment of only inflammatory lesions (papules and pustules) of rosacea in adult patients. ( 1. 1) Limitations of Use 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. ( 1.2 ) ORACEA has not been evaluated for the treatment of the erythematous, telangiectatic, or ocular components of rosacea. ( 1.2 ) 1.1 Indication 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. 1.2 Limitations of Use 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.
Spl product data elements
Usually a list of ingredients in a drug product.ORACEA DOXYCYCLINE HYPROMELLOSE, UNSPECIFIED METHACRYLIC ACID AND ETHYL ACRYLATE COPOLYMER FERRIC OXIDE RED FERRIC OXIDE YELLOW POLYETHYLENE GLYCOL, UNSPECIFIED POLYSORBATE 80 TITANIUM DIOXIDE SUCROSE TALC ACETYL TRIETHYLHEXYL CITRATE DOXYCYCLINE DOXYCYCLINE ANHYDROUS GLD;40 beige
Carcinogenesis and mutagenesis and impairment of fertility
Information about carcinogenic, mutagenic, or fertility impairment potential revealed by studies in animals. Information from human data about such potential is part of the warnings field.13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 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.
Nonclinical toxicology
Information about toxicology in non-human subjects.13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 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.
Microbiology
Microbiology12.4 Microbiology 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.
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.PACKAGE LABEL NDC 0299-3822-30 ORACEA ® (doxycycine, USP) capsules 40 mg * * 30 mg IMMEDIATE RELEASE & 10 mg DELAYED RELEASE BEADS 30 CAPSULES RX ONLY GALDERMA Marketed by: Galderma Laboratories, L.P. Dallas, TX 75201 USA All trademarks are the property of their respective owners. oracea.com P56801-1 30-capsule-label
ORACEA: Information for patients
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (Patient Information) Patients taking ORACEA Capsules 40 mg should receive the following information and instructions: 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.
Spl patient package insert
Information necessary for patients to use the drug safely and effectively.PATIENT INFORMATION ORACEA (Or-RAY-sha) (doxycycline) capsules 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: 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. 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. What should I tell my doctor before taking ORACEA? Before you take ORACEA tell your doctor if you: 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. 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: 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. 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. How should I take ORACEA? 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. 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. What are the possible side effects of ORACEA? ORACEA may cause serious side effects, including: Harm to an unborn baby. See “ What should I tell my doctor before taking ORACEA? ” P ermanent 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?” Intestine infection (pseudomembranous colitis). Pseudomembranous colitis can happen with most antibiotics, including ORACEA. Call your doctor right away if you get diarrhea or bloody stools. I mmune 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. Discoloration (hyperpigmentation). ORACEA can cause darkening of your skin, scars, teeth, gums, nails, and whites of your eyes. Benign 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 The most common side effects of ORACEA include: 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 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 How should I store ORACEA? 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. Keep ORACEA and all medicine out of the reach of children. 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. What are the ingredients in ORACEA? Active ingredient: doxycycline Inactive ingredients: hard gelatin capsule, hypromellose, methacrylic acid copolymer, Opadry beige, sugar spheres, talc, and triethyl citrate. Marketed by: Galderma Laboratories, L.P. Dallas, Texas 75201 USA All trademarks are the property of their respective owners. P52631-3 This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: September 2022
Clinical studies
This field may contain references to clinical studies in place of detailed discussion in other sections of the labeling.6.1 Clinical Trials Experience 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: Table 1. Incidence (%) of Selected Adverse Reactions in Clinical Trials of ORACEA (n=269) v.s. Placebo (n=268) ORACEA Placebo Nasopharyngitis 13 (5) 9 (3) Pharyngolaryngeal Pain 3 (1) 2 (1) Sinusitis 7 (3) 2 (1) Nasal Congestion 4 (2) 2 (1) Fungal Infection 5 (2) 1 (0) Influenza 5 (2) 3 (1) Diarrhea 12 (5) 7 (3) Abdominal Pain Upper 5 (2) 1 (0) Abdominal Distention 3 (1) 1 (0) Abdominal Pain 3 (1) 1 (0) Stomach Discomfort 3 (1) 2 (1) Dry Mouth 3 (1) 0 (0) Hypertension 8 (3) 2 (1) Blood Pressure Increase 4 (2) 1 (0) Aspartate Aminotransferase Increase 6 (2) 2 (1) Blood Lactate Dehydrogenase Increase 4 (2) 1 (0) Blood Glucose Increase 3 (1) 0 (0) Anxiety 4 (2) 0 (0) Pain 4 (2) 1 (0) Back Pain 3 (1) 0 (0) Sinus Headache 3 (1) 0 (0) Note: Percentages based on total number of study participants in each treatment group. 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.
14 CLINICAL STUDIES 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. Table 3: Clinical Results of ORACEA versus Placebo Study 1 Study 2 ORACEA Placebo ORACEA Placebo 40 mg N=127 N=124 40 mg N=142 N=144 Mean Change in Lesion Count from Baseline - 11.8 - 5.9 - 9.5 - 4.3 No. (%) of Subjects Clear or Almost Clear in the IGA Investigator's Global Assessment 39 (30.7%) 24 (19.4%) 21 (14.8%) 9 (6.3%) Subjects treated with ORACEA did not demonstrate significant improvement in erythema when compared to those treated with placebo.
| ORACEA | Placebo | |
| Nasopharyngitis | 13 (5) | 9 (3) |
| Pharyngolaryngeal Pain | 3 (1) | 2 (1) |
| Sinusitis | 7 (3) | 2 (1) |
| Nasal Congestion | 4 (2) | 2 (1) |
| Fungal Infection | 5 (2) | 1 (0) |
| Influenza | 5 (2) | 3 (1) |
| Diarrhea | 12 (5) | 7 (3) |
| Abdominal Pain Upper | 5 (2) | 1 (0) |
| Abdominal Distention | 3 (1) | 1 (0) |
| Abdominal Pain | 3 (1) | 1 (0) |
| Stomach Discomfort | 3 (1) | 2 (1) |
| Dry Mouth | 3 (1) | 0 (0) |
| Hypertension | 8 (3) | 2 (1) |
| Blood Pressure Increase | 4 (2) | 1 (0) |
| Aspartate Aminotransferase Increase | 6 (2) | 2 (1) |
| Blood Lactate Dehydrogenase Increase | 4 (2) | 1 (0) |
| Blood Glucose Increase | 3 (1) | 0 (0) |
| Anxiety | 4 (2) | 0 (0) |
| Pain | 4 (2) | 1 (0) |
| Back Pain | 3 (1) | 0 (0) |
| Sinus Headache | 3 (1) | 0 (0) |
| Note: Percentages based on total number of study participants in each treatment group. | ||
| Study 1 | Study 2 | |||
| ORACEA | Placebo | ORACEA | Placebo | |
| 40 mg N=127 | N=124 | 40 mg N=142 | N=144 | |
| Mean Change in Lesion Count from Baseline | - 11.8 | - 5.9 | - 9.5 | - 4.3 |
| No. (%) of Subjects Clear or Almost Clear in the IGA | 39 (30.7%) | 24 (19.4%) | 21 (14.8%) | 9 (6.3%) |
Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.8.5 Geriatric Use 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.
Labor and delivery
Information about the drug’s use during labor or delivery, whether or not the use is stated in the indications section of the labeling, including the effect of the drug on the mother and fetus, on the duration of labor or delivery, on the possibility of delivery-related interventions, and the effect of the drug on the later growth, development, and functional maturation of the child.8.2 Lactation 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.
Pediatric use
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.8.4 Pediatric Use 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.
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)8.1 Pregnancy 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.
Use in specific populations
Information about use of the drug by patients in specific populations, including pregnant women and nursing mothers, pediatric patients, and geriatric patients.8 USE IN SPECIFIC POPULATIONS Lactation: Breastfeeding is not recommended ( 8.2 ) 8.1 Pregnancy 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. 8.2 Lactation 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. 8.4 Pediatric Use 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. 8.5 Geriatric Use 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.
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.16 HOW SUPPLIED/STORAGE AND HANDLING 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). Storage: 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.
Disclaimer: Do not rely on openFDA or Phanrmacy Near Me to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. Source: OpenFDA, Healthporta Drugs API