Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 23 March 2017

Indication(s)

1 INDICATIONS AND USAGE Tretinoin gel, USP is indicated for topical treatment of acne vulgaris. Tretinoin gel, USP is a retinoid indicated for topical treatment of acne vulgaris (1)

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Advisory information

contraindications
4 CONTRAINDICATIONS None. None (4)
Adverse reactions
6 ADVERSE REACTIONS The most common adverse reactions (incidence ≥ 5%) with tretinoin gel, USP are dry skin, peeling/scaling/flaking skin, skin burning sensation, and erythema. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Spear Dermatology Products at 1-866-SPEAR-RX (773-2279) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under prescribed 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. In two randomized, controlled trials, 674 subjects received treatment for up to 12 weeks with tretinoin gel, USP [see Clinical Trials (14)]. In these studies, 50% of the subjects who were treated with tretinoin gel, USP reported one or more adverse reactions; 30% of the subjects reported treatment-related adverse reactions. In the vehicle group, 29% of the 487 randomized subjects reported at least one adverse reaction; 5% of the subjects reported events that were treatment-related. There were no serious, treatment-related adverse reactions reported by subjects in any of the treatment groups. Selected adverse reactions that occurred in at least 1% of subjects in the two studies combined are shown in Table 1 (below). Most skin-related adverse reactions first appear during the first two weeks of treatment with tretinoin gel, USP, and the incidence rate for skin-related reactions peaks around the second and third week of treatment. In some subjects the skin-related adverse reactions persists throughout the treatment period. Table 1. Number of Subjects with Selected Adverse Reactions (Occurring in At Least 1% of Subjects) Event Tretinoin Gel, USP (n = 674) Vehicle Gel (n = 487) Dry Skin 109 (16%) 8 (2%) Peeling/Scaling/Flaking Skin 78 (12%) 7 (1%) Skin Burning Sensation 53 (8%) 8 (2%) Erythema 47 (7%) 1 (<1%) Pruritus 11 (2%) 3 (1%) Pain of Skin 7 (1%) 0 (0%) Sunburn 7 (1%) 3 (1%) 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of tretinoin gel, USP. 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. Temporary hyper- or hypopigmentation has been reported with repeated application of tretinoin.

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION For topical use only. Not for ophthalmic, oral, or intravaginal use. Tretinoin gel, USP should be applied once daily, before bedtime, to the skin where acne lesions appear, using a thin layer to cover the entire affected area. Tretinoin gel, USP should be kept away from the eyes, the mouth, paranasal creases, and mucous membranes. Application of excessive amounts of gel will not provide incremental efficacy. Patients treated with tretinoin gel, USP may use cosmetics, but the areas to be treated should be cleansed thoroughly before the medication is applied. When treating with tretinoin gel, USP, caution should be exercised with the use of concomitant topical over-the-counter preparations, topical medications, medicated or abrasive soaps and cleansers, products that have strong drying effect, and products with high concentrations of alcohol, astringents, spices, or lime. Particular caution should be exercised with acne preparations containing benzoyl peroxide, sulfur, resorcinol, or salicylic acid. Allow the effects of such preparations to subside before use of tretinoin gel, USP has begun. Apply a thin layer of tretinoin gel, USP once daily, before bedtime, to skin where lesions occur. Keep away from eyes, mouth, nasal creases, and mucous membranes (2) Tretinoin gel, USP is not for oral, ophthalmic, or intravaginal use (2).
Use in special populations
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C. There are no well-controlled studies in pregnant women treated with tretinoin gel, USP. Tretinoin gel, USP should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Tretinoin gel, USP at doses of 0.1, 0.3 and 1 g/kg/day was tested for maternal and developmental toxicity in pregnant Sprague-Dawley rats by dermal application. The dose of 1 g/kg/day was approximately 4 times the clinical dose assuming 100% absorption and based on body surface area comparison. Possible tretinoin-associated teratogenic effects (craniofacial abnormalities (hydrocephaly), asymmetrical thyroids, variations in ossification, and increased supernumerary ribs) were noted in the fetuses of tretinoin gel, USP treated animals. These findings were not observed in control animals. Other maternal and reproductive parameters in the tretinoin gel, USP treated animals were not different from control. For purposes of comparison of the animal exposure to human exposure, the clinical dose is defined as 2 g of tretinoin gel, USP applied daily to a 50 kg person. Oral tretinoin has been shown to be teratogenic in rats, mice, rabbits, hamsters and nonhuman primates. Tretinoin was teratogenic in Wistar rats when given orally in doses greater than 1 mg/kg/day (approximately 8 times the clinical dose based on body surface area comparison). In the cynomolgus monkey, fetal malformations were reported for doses of 10 mg/kg/day, but none were observed at 5 mg/kg/day (approximately 80 times the clinical dose based on body surface area comparison), although increased skeletal variations were observed at all doses. Dose-related increases in embryolethality and abortion also were reported. Similar results have also been reported in pigtail macaques. Topical tretinoin in a different formulation has generated equivocal results in animal teratogenicity tests. There is evidence for teratogenicity (shortened or kinked tail) of topical tretinoin in Wistar rats at doses greater than 1 mg/kg/day (approximately 8 times the clinical dose assuming 100% absorption and based on body surface area comparison). Anomalies (humerus: short 13%, bent 6%, os parietal incompletely ossified 14%) have also been reported when 10 mg/kg/day (approximately 160 times the clinical dose assuming 100% absorption and based on body surface area comparison) was topically applied. Supernumerary ribs have been a consistent finding in rats when dams were treated topically or orally with retinoids. With widespread use of any drug, a small number of birth defect reports associated temporally with the administration of the drug would be expected by chance alone. Cases of temporally associated congenital malformations have been reported with use of other topical tretinoin products. The significance of these spontaneous reports in terms of risk to the fetus is not known. Nonteratogenic effects on fetuses: Oral tretinoin has been shown to be fetotoxic in rats when administered in doses 20 times the clinical dose based on a body surface area comparison. Topical tretinoin has been shown to be fetotoxic in rabbits when administered in doses 8 times the clinical dose based on a body surface area comparison. 8.3 Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when tretinoin gel, USP is administered to a nursing woman. 8.4 Pediatric Use Safety and effectiveness in children below the age of 10 have not been established. A total of 381 pediatric subjects (aged 10 to 16 years), treated with tretinoin gel, USP were enrolled into the two clinical studies. Across these two studies, comparable safety and efficacy were observed between pediatric and adult subjects. 8.5 Geriatric Use Safety and effectiveness in a geriatric population have not been established. Clinical studies of tretinoin gel, USP did not include any subjects over age 65 to determine whether they respond differently from younger subjects.
Pregnancy and lactation
8.3 Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when tretinoin gel, USP is administered to a nursing woman.

More information

Category Value
Authorisation number ANDA207955
Agency product number 5688UTC01R
Orphan designation No
Product NDC 66530-262
Date Last Revised 18-10-2016
Type HUMAN PRESCRIPTION DRUG
RXCUI 245723
Storage and handling Storage and Handling: Store at controlled room temperature 20° - 25°C (68° - 77°F) with excursions permitted between 15°-30°C (59°-86°F). Protect from freezing. Keep out of reach of children.
Marketing authorisation holder Spear Dermatology Products