Altreno
tretinoin · Lotion · Topical
Uses
1 INDICATIONS AND USAGE 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)
Dosage and administration
Apply a thin layer of ALTRENO to the affected areas once daily. Avoid the eyes, mouth, paranasal creases, and mucous membranes. ALTRENO is for topical use only. Not for ophthalmic, oral, or intravaginal use.
• Apply a thin layer of ALTRENO to affected areas once daily. Avoid eyes, mouth, paranasal creases, and mucous membranes. ( 2 )
• Not for ophthalmic, oral, or intravaginal use. ( 2 )
Dosage forms and strengths
Lotion, 0.05% Each gram of ALTRENO contains 0.5 mg (0.05%) tretinoin in an opaque, pale yellow topical lotion. Lotion, 0.05% ( 3 ) Each gram of ALTRENO contains 0.5 mg (0.05%) tretinoin. ( 3 )
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 ) 5.1 Skin 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. 5.2 Ultraviolet 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. 5.3 Fish 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.
Side effects
• 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. 6.1 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 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%
Use in specific populations
8.1 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. 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. 8.2 Lactation Risk Summary There are no data on the presence of 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 ALTRENO and any potential adverse effects on the breastfed child from ALTRENO.
Pregnancy
8.1 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. 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.
Pediatric use
8.4 Pediatric Use Safety and effectiveness of ALTRENO for the topical treatment of acne vulgaris have been established in pediatric patients age 9 years to less than 17 years based on evidence from two multicenter, randomized, double-blind, parallel-group, vehicle-controlled, 12-week trials and an open-label pharmacokinetic study. A total of 318 pediatric subjects aged 9 to less than 17 years received ALTRENO in the clinical studies [see Clinical Pharmacology (12.3) and Clinical Studies (14) ] . The safety and effectiveness of ALTRENO in pediatric patients below the age of 9 years have not been established.
Geriatric use
8.5 Geriatric Use Clinical trials of ALTRENO did not include any subjects age 65 years and older to determine whether they respond differently from younger subjects.
Description
(tretinoin) lotion is an opaque, pale yellow lotion containing 0.05% tretinoin by weight for topical administration. Chemically, tretinoin is all-trans-retinoic acid, also known as (all-E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid. It is a member of the retinoid class of compounds and a metabolite of vitamin A. Tretinoin has the following chemical structure: Molecular Formula: C 20 H 28 O 2 Molecular Weight: 300.44 Each gram of ALTRENO contains 0.5 mg (0.05%) of tretinoin in an opaque, pale yellow lotion base consisting of benzyl alcohol, butylated hydroxytoluene, carbomer copolymer type B (Pemulen TR-1), carbomer homopolymer type A (Carbopol 981), glycerin, methylparaben, mineral oil, octoxynol-9, purified water, sodium hyaluronate, soluble collagen and trolamine. chemstructure.jpg
Mechanism of action
12.1 Mechanism of Action Tretinoin is a metabolite of vitamin A that binds with high affinity to specific retinoic acid receptors located in both the cytosol and nucleus. Tretinoin activates three members of the retinoic acid (RAR) nuclear receptors (RARα, RARβ, and RARγ) which act to modify gene expression, subsequent protein synthesis, and epithelial cell growth and differentiation. It has not been established whether the clinical effects of tretinoin are mediated through activation of retinoic acid receptors, other mechanisms, or both. Although the exact mode of action of tretinoin in acne treatment is unknown, current evidence suggests that topical tretinoin decreases cohesiveness of follicular epithelial cells with decreased microcomedo formation. Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells causing extrusion of the comedones.
How supplied
(tretinoin) lotion, 0.05% is an opaque, pale yellow topical lotion and available as:
• 45 g tube (NDC 0187-0005-45)
• 20 g tube (NDC 0187-0005-20)
• 50 g pump (NDC 0187-0005-50) Storage and Handling Conditions Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from freezing. Store pump upright.
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information).
• Warn patients of the potential for skin irritation during treatment.
• Advise patients to minimize exposure to sunlight and sunlamps; recommend the use of sunscreen products and protective apparel (e.g., hat) when sun exposure cannot be avoided. Distributed by: Bausch Health US, LLC Bridgewater, NJ 08807 USA Manufactured by: Bausch Health Companies Inc. Laval, Quebec H7L 4A8, Canada ALTRENO is a trademark of Bausch Health Companies Inc. or its affiliates. © 2020 Bausch Health Companies Inc. or its affiliates 9650303
Label text from the FDA structured product label by Bausch Health US, LLC (revised Mar 2, 2020). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Tretinoin in 1 product
Altreno NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0187-0005 | Tretinoin .5 mg/g Lotion | Bausch Health US, LLC | NDA |
Frequently asked questions
What is Altreno used for?
1 INDICATIONS AND USAGE 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)
What are the side effects of Altreno?
• 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. 6.1 Clinical Trials Experience Because clinical trials are conducted under… See the full label for the complete list.
Who makes Altreno?
Altreno is listed by 1 labeler in the FDA NDC directory, including Bausch Health US, LLC.