ALTRENO ® (tretinoin) lotion, 0.05% is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older. ALTRENO is a retinoid indicated for the topical treatment of acne vulgaris in patients 9 years of age and older. (1)
Contraindications
None. None. ( 4 )
Warnings and precautions
Skin Irritation: Dryness, pain, erythema, irritation and exfoliation may occur with use of ALTRENO. ( 5.1 )
Ultraviolet Light and Environmental Exposure: Minimize exposure to sunlight and sunlamps. Use sunscreen and protective clothing when sun exposure cannot be avoided. ( 5.2 )
Fish Allergies: Use ALTRENO with caution if allergic to fish due to potential for allergenicity to fish protein. Advise patients to contact their healthcare provider if they develop pruritus or urticaria. ( 5.3 )
5.1Skin Irritation
Patients using ALTRENO may experience application site dryness, pain, erythema, irritation, and exfoliation. Depending upon the severity of these adverse reactions, instruct patients to use a moisturizer, reduce the frequency of the application of ALTRENO, or discontinue use. Avoid application of ALTRENO to eczematous or sunburned skin.
5.2Ultraviolet Light and Environmental Exposure
Minimize unprotected exposure to ultraviolet light including sunlight and sunlamps during the use of ALTRENO. Warn patients who normally experience high levels of sun exposure and those with inherent sensitivity to sun to exercise caution. Use sunscreen products and protective clothing over treated areas when sun exposure cannot be avoided.
5.3Fish Allergies
ALTRENO contains soluble fish proteins. Use with caution in patients with known sensitivity or allergy to fish. Advise patients to contact their healthcare provider if they develop pruritus or urticaria.
Pregnancy and breastfeeding
At a glance
Brand name
Altreno
Active substance
tretinoin
Drug class
Retinoids for topical use in acne, Retinoids for cancer treatment
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. There are no data on ALTRENO use in pregnant women. The systemic levels following topical administration are lower than with administration of oral tretinoin; however, absorption of this product may result in fetal exposure.
There are reports of major birth defects 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 reproduction studies have not been conducted with ALTRENO. Topical administration of tretinoin in a different formulation to pregnant rats during organogenesis was associated with malformations (craniofacial abnormalities [hydrocephaly], asymmetrical thyroids, variations in ossification, and increased supernumerary ribs) at doses up to 0.5 mg tretinoin/kg/day, approximately 2 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 estimated 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% and 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 Tretinoin in a 0.05% gel formulation was topically administered to pregnant rats during organogenesis at doses of 0.1, 0.3 and 1 g/kg/day (0.05, 0.15, 0.5 mg tretinoin/kg/day). Possible tretinoin malformations (craniofacial abnormalities [hydrocephaly], asymmetrical thyroids, variations in ossification, and increased supernumerary ribs) were observed at maternal doses of 0.5 mg tretinoin/kg/day (approximately 2 times the MRHD based on BSA comparison and assuming 100% absorption).
These findings were not observed in control animals. Other maternal and reproductive parameters in tretinoin-treated animals were not different from control. For purposes of comparison of the animal exposure to human exposure, the MRHD is defined as 4 g of ALTRENO applied daily to a 60 kg person. Other topical tretinoin embryofetal development studies have generated equivocal results. There is evidence for malformations (shortened or kinked tail) after topical administration of tretinoin to pregnant Wistar rats during organogenesis at doses greater than 1 mg/kg/day (approximately 5 times the MRHD based on BSA comparison and assuming 100% absorption).
Anomalies (humerus: short 13%, bent 6%, os 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. Supernumerary ribs have been a consistent finding in rat fetuses when pregnant rats were treated topically or orally with retinoids. Oral administration of tretinoin during organogenesis has been shown to induce malformations in rats, mice, rabbits, hamsters, and nonhuman primates.
Fetal malformations were observed when tretinoin was orally administered to pregnant Wistar rats during organogenesis at doses greater than 1 mg/kg/day (approximately 5 times the MRHD based on BSA comparison). 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).
No fetal malformations were observed at an oral dose of 5 mg/kg/day (approximately 50 times the MRHD based on BSA comparison). Increased skeletal variations were observed at all doses in this study and dose-related increases in embryo lethality and abortion were 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 doses 10 times the MRHD based on BSA comparison.
Topical tretinoin has been shown to be fetotoxic in rabbits when administered at doses 4 times the MRHD based on BSA comparison.
Adverse reactions
The most common adverse reactions occurring in ≥1% of subjects and greater than vehicle were dryness, pain, erythema, irritation and exfoliation (all at the application site). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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 clinical practice. In 2 randomized, double-blind, vehicle-controlled trials, subjects age 9 years and older applied ALTRENO or vehicle once daily for 12 weeks. The majority of subjects were White (74%) and female (55%).
Approximately 47% were Hispanic/Latino and 45% were younger than 18 years of age. Adverse reactions reported by ≥1% of subjects treated with ALTRENO and more frequently than vehicle are summarized in Table 1. Table 1: Adverse Reactions Reported by ≥1% of Subjects Treated with ALTRENO and More Frequently than Vehicle Adverse Reactions n (%) ALTRENO N=767 Vehicle N=783 Application site dryness 29 (4) 1 (<1) Application site pain Application site pain defined as application site stinging, burning or pain. 25 (3) 3 (<1) Application site erythema 12 (2) 1 (<1) Application site irritation 7 (1) 1 (<1) Application site exfoliation 6 (1) 3 (<1) Skin irritation was evaluated by active assessment of erythema, scaling, hypopigmentation, hyperpigmentation, itching, burning and stinging.
The percentage of subjects who were assessed to have these signs and symptoms at any post baseline visit are summarized in Table 2. Table 2: Application Site Tolerability Reactions at Any Post Baseline Visit ALTRENO N=760 Mild/Mod/Severe Vehicle N=782 Mild/Mod/Severe Erythema 51% 44% Scaling 49% 30% Hypopigmentation 12% 10% Hyperpigmentation 35% 35% Itching 35% 28% Burning 30% 14% Stinging 21% 8%
Composition
Active ingredients
TRETINOIN 0.05%
Official product information
Drugs@FDA lists the approved labels, letters and reviews for application NDA209353.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
