Twyneo
(benzoyl peroxide / tretinoin)Dosage & Administration
By using PrescriberAI, you agree to the AI Terms of Use.
Twyneo Prescribing Information
TWYNEO is indicated for the topical treatment of acne vulgaris in adults and pediatric patients 9 years of age and older.
- Apply a thin layer of TWYNEO to the affected areas once daily on clean and dry skin. Avoid contact with the eyes, lips, paranasal creases, and mucous membranes.
- Wash hands after application.
- TWYNEO is for topical use only. TWYNEO is not for oral, ophthalmic, or intravaginal use.
Cream, 0.1%/3%: Each gram of TWYNEO contains 1mg (0.1%) of tretinoin and 30 mg (3%) of benzoyl peroxide in a yellow cream in a 30-gram bottle with a pump.
Pregnancy
Risk Summary
Available data from published observational studies of topical tretinoin in pregnant women have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Studies conducted with topical benzoyl peroxide have not demonstrated systemic absorption and maternal use is not expected to result in fetal exposure to benzoyl peroxide. There are no data on TWYNEO use in pregnant women.
There are reports of major birth defects reported with maternal use of topical tretinoin similar to those seen in infants exposed to oral retinoids, but these case reports do not establish a pattern or association with tretinoin-related embryopathy (see Data).
Animal reproductive studies have not been conducted with TWYNEO or benzoyl peroxide. Topical administration of tretinoin to pregnant rats during organogenesis was associated with malformations (craniofacial abnormalities [hydrocephaly], asymmetrical thyroids, variations in ossification, and increased supernumerary ribs) at doses greater than 1 mg tretinoin/kg/day, approximately 5 times the maximum recommended human dose (MRHD) based on body surface area (BSA) comparison and assuming 100% absorption. Oral administration of tretinoin to pregnant cynomolgus monkeys during organogenesis was associated with malformations at 10 mg/kg/day (approximately 100 times the MRHD based on BSA comparison and assuming 100% absorption) (see Data).
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of major birth defects, loss and other adverse outcomes. The background risk in the U.S. general population of major birth defects is 2 to 4% of miscarriage is 15 to 20% of clinically recognized pregnancies.
Data
Human Data
While available studies cannot definitively establish the absence of risk, published data from multiple prospective controlled observational studies on the use of topical tretinoin products during pregnancy have not identified an association with topical tretinoin and major birth defects or miscarriage. The available studies have methodologic limitations, including small sample size and in some cases, lack of physical exam by an expert in birth defects. There are published case reports of infants exposed to topical tretinoin during the first trimester that describe major birth defects similar to those seen in infants exposed to oral retinoids; however, no pattern of malformations has been identified and no causal association has been established in these cases. The significance of these spontaneous reports in terms of risk to the fetus is not known.
Animal Data
For purposes of comparison of the animal exposure to human exposure, the MRHD is defined as 1.5 g of TWYNEO (containing 0.1% tretinoin) applied daily to a 60-kg person (0.03 mg tretinoin/kg body weight).
Topical tretinoin embryofetal development studies have generated equivocal results. There is evidence for malformations (shortened or kinked tail) after topical tretinoin administration in Wistar rats at doses greater than 1 mg/kg/day (approximately 5 times the MHRD based on BSA comparison and assuming 100% absorption). Anomalies (humerus: short 13%, bent 6%, or parietal incompletely ossified 14%) have also been reported when 10 mg/kg/day (approximately 50 times the MRHD based on BSA comparison and assuming 100% absorption) was topically applied to pregnant rats during organogenesis. Increased incidence of domed head and hydrocephaly, typical of retinoid-induced fetal malformations were noted in New Zealand White rabbits administered topical doses greater than 0.2 mg/kg/day (2.2 times the MRHD based on BSA comparison and assuming 100% absorption).
Oral tretinoin induced malformations in rats, mice, hamsters, and nonhuman primates when administered during the period of organogenesis. Fetal malformations were observed when tretinoin was orally administered to pregnant Wistar rats during organogenesis. It was teratogenic and fetotoxic in Wistar rats when given orally or topically in doses greater than 1 mg/kg/day (approximately 5 times the MRHD based on BSA comparison and assuming 100% absorption). In the cynomolgus monkey, fetal malformations were reported when an oral dose of 10 mg/kg/day was administered to pregnant monkeys during organogenesis (approximately 100 times the MRHD based on BSA comparison and assuming 100% absorption). No fetal malformations were observed at an oral dose of 5 mg/kg/day (approximately 50 times the MRHD based on BSA comparison and assuming 100% absorption). Increased skeletal variations were observed at all doses, and a dose-related increase in embryo lethality and abortion was reported in this study. Similar results have also been reported in pigtail macaques. Oral tretinoin has been shown to be fetotoxic in rats when administered at a dose of 2.5 mg/kg/day (13 times the MRHD based on BSA comparison and assuming 100% absorption). Topical tretinoin has been shown to be fetotoxic in rabbits when administered at a dose of 0.5 mg/kg/day (5 times the MRHD based on BSA comparison and assuming 100% absorption).
Lactation
Risk Summary
There are no data on the presence of benzoyl peroxide and tretinoin or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. It is not known whether topical administration of tretinoin could result in sufficient systemic absorption to produce detectable concentrations in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TWYNEO and any potential adverse effects on the breastfed child from TWYNEO or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of TWYNEO for the topical treatment of acne vulgaris have been established in pediatric patients 9 years of age and older based on evidence from two multicenter, randomized, double-blind, parallel-group, vehicle-controlled, 12-week clinical trials and an open-label pharmacokinetic study. A total of 283 pediatric subjects 9 years of age and older received TWYNEO in the clinical studies [see Clinical Pharmacology (12.3) and Clinical Studies (14)].
The safety and effectiveness of TWYNEO in pediatric patients below 9 years of age have not been established.
Geriatric Use
Clinical trials of TWYNEO did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently than younger subjects.
TWYNEO is contraindicated in patients with a history of hypersensitivity reaction to benzoyl peroxide or any components of TWYNEO [see Warnings and Precautions (5.1)].
Hypersensitivity
Hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria, have been reported with the use of benzoyl peroxide products. If a serious hypersensitivity reaction occurs, discontinue TWYNEO immediately and initiate appropriate therapy.
Skin Irritation
Patients using TWYNEO may experience application site dryness, pain, exfoliation, erythema, dermatitis, pruritis, and irritation [see Adverse Reactions (6.1)]. Depending upon the severity of these adverse reactions, instruct patients to use a moisturizer, reduce the frequency of the application of TWYNEO, or discontinue use. Avoid application of TWYNEO to cuts, abrasions, eczematous, or sunburned skin.
Photosensitivity
TWYNEO may increase sensitivity to ultraviolet light. Minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using TWYNEO. Instruct patients to implement sun protection measures (e.g., sunscreen and loose-fitting clothes) when sun exposure cannot be avoided. Discontinue TWYNEO at the first evidence of sunburn.