TRETINOIN .8 mg/g Gel — NDC 21922-043-40 (Billing 21922-0043-40)
This is a package of TRETINOIN .8 mg/g Gel from Encube Ethicals, Inc., marketed since Aug 2023 and currently FDA-listed; retail pharmacies pay about $11.46 per g (NADAC). It is this product's only package size.
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 072395
- GCN: 36604
- GPI-14 (Medi-Span): 90050030204020
- HICL (First Databank): 032888
- AHFS class code: 10:00.00.00
- RxCUI (RxNorm): 1488045
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Retinoid class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
Tretinoin is used to treat acne. Tretinoin is also used to reduce fine wrinkles. Tretinoin is in a class of medications called retinoids. It works by increasing production of new skin cells and unclogging pores.
Read the full MedlinePlus article ↗- It depends on the form. Creams, gels and lotions treat acne, and Renova eases fine facial wrinkles. The capsules treat a blood cancer called acute promyelocytic leukemia.
- Wash the area, pat dry, and apply a thin layer once daily, usually in the evening. Keep it away from your eyes, mouth, nose creases and mucous membranes. More does not work faster...
- Mild warmth or stinging, redness and peeling are common. If it becomes severe, call your prescriber, who may have you use less or pause. Acne can seem to flare early on, which is n...
- What side effects should I expect on the skin?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Tretinoin — tap one for details:
Tretinoin may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per g | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $11.465 | $573.23 / 50 g |
| Medicaid paysCMS SDUD · 12 mo | $10.79 | $539.53 / 50 g |
| Medicare drug plans payPart D · Q2 2026 | $11.69 | $584.60 / 50 g |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q1 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 21922-0043-40 You're viewing this Main listing | 1 BOTTLE, PUMP in 1 CARTON / 50 g in 1 BOTTLE, PUMP | 2023-08-24 | — | Active |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Tretinoin .8 mg/gthis 21922-0043-40 | Encube | 1 bottle | $11.465 | AB | Availability likely | — |
| Tretinoin (Microsphere) .8 mg/g 68308-0777-50 | Mayne | 1 bottle | $11.465 | AB | Availability likely | — |
| Retin-A MICRO .8 mg/g 00187-5148-02 | Bausch | 24 tubes | — | — | FDA listed | — |
| Tretinoin .8 mg/g 68682-0515-95 | Oceanside | 1 bottle | — | — | FDA listed | — |
| Tretinoin .8 mg/g 69238-2323-01 | Amneal | 1 bottle | — | AB | FDA listed | — |
| Tretinoin .8 mg/g 72162-2303-02 | Bryant | 1 bottle | — | AB | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Sep 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
- FDA Orange Book · refreshed Sep 3, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII LKG8494WBH
Benzyl alcohol is a clear liquid used as a preservative and solvent in medicines. It helps prevent bacterial and fungal growth and dissolves other ingredients to create uniform liquid formulations.
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UNII 1P9D0Z171K
BHT is a synthetic antioxidant that prevents fats and oils in medicines from breaking down and becoming rancid. It helps keep the product stable and effective during storage.
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UNII HHT01ZNK31
Carbomer Homopolymer Type B is a synthetic polymer made from acrylic acid. It absorbs water and forms a gel, so it's used in medicines as a thickener, suspending agent, and to help create a smooth texture in creams, gels, and lotions.
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UNII NMQ347994Z
Cyclomethicone is a silicone-based fluid that acts as a lubricant and solvent in medicines. It helps products flow smoothly, reduces friction between particles, and aids in even distribution of active ingredients.
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UNII 7FLD91C86K
Edetate disodium is a chemical compound that binds and removes certain metal ions. In medicines, it acts as a preservative and stabilizer by preventing metals like calcium from interfering with the product's shelf life and consistency.
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UNII PDC6A3C0OX
Glycerin is a clear, thick liquid derived from plant oils or fats. It acts as a humectant to retain moisture, a sweetener, and a solvent in medications.
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UNII 0057334FAB
A synthetic compound derived from glucose that combines water-repelling and water-attracting properties. It works as an emulsifier to help blend oil and water-based ingredients, and may also function as a thickener in creams and lotions.
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UNII 6DC9Q167V3
Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
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UNII X045WJ989B
Sorbic acid is a preservative derived from berries that prevents mold, yeast, and bacterial growth in medicines. It keeps the product stable and safe during storage.
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UNII 9O3K93S3TK
Trolamine is an alkaline compound used as a pH buffer and emulsifier in medicines. It helps neutralize acids, stabilize formulations, and enable mixing of oil and water-based ingredients.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
11 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 1, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
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Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Tretinoin gel (microsphere) is indicated for the topical treatment of acne vulgaris in adults and pediatric patients 12 years of age and older. Tretinoin gel (microsphere) is a retinoid indicated for the topical treatment of acne vulgaris in adults and pediatric patients 12 years of age and older. (1)
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION For topical use only. Not for oral, ophthalmic, or intravaginal use. Prior to tretinoin gel (microsphere) use, thoroughly cleanse area(s) with a mild, non-medicated cleanser then pat the skin dry.
When applying tretinoin gel (microsphere), keep away from the eyes, the mouth, paranasal creases of the nose, and mucous membranes. Apply a thin layer of tretinoin gel (microsphere) (0.06%, or 0.08%) to skin where acne lesions appear (cover the entire affected area), once daily in the evening. Do not apply more than a thin layer [see Warning and Precautions ( 5.1 )].
Improvements in acne lesions may be noticed after two weeks of tretinoin gel (microsphere) therapy, but more than seven weeks of therapy may be needed for sustained benefit. If tretinoin gel (microsphere) was temporarily discontinued due to local adverse reactions, tretinoin gel (microsphere) therapy may be resumed upon resolution of local adverse reactions. For topical use only.
Not for oral, ophthalmic, or intravaginal use. ( 2 ) Keep away from eyes, mouth, paranasal creases of the nose, and mucous membranes. ( 2 ) Apply a thin layer of tretinoin gel (microsphere) to skin where acne lesions appear (cover the entire affected area) (0.06%, or 0.08%) once daily in the evening ( 2 ).
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Gel (white to very pale yellow and opaque): 0.06% (0.6 mg of tretinoin per gram) 0.08% (0.8 mg of tretinoin per gram) Gel: 0.06%, and 0.08%, (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. (4)
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Local Skin Irritation : Tretinoin gel (microsphere) can cause local skin irritation, including excessive dryness, redness, swelling, peeling, itching, blistering, burning, or stinging ( 5.1 ) Avoid use on eczematous skin or during weather extremes, such as severe wind or cold. To reduce the risk of local skin irritation, wash the treated skin gently, using a mild, non-medicated soap, avoid washing the treated skin too often or scrubbing it hard when washing, and apply a topical moisturizer.
If severe local skin irritation occurs, discontinue use temporarily or permanently. Initial Worsening of Inflammatory Acne Vulgaris : During the early weeks of tretinoin gel (microsphere) treatment, an apparent exacerbation of inflammatory lesions may occur. If tretinoin gel (microsphere) is tolerated, this should not be considered a reason to discontinue therapy.
( 5.2 ) Photosensitivity : Tretinoin gel (microsphere) can cause photosensitivity. Advise patients to avoid or minimize unnecessary exposure to UV light, including sunlight and sunlamps. Advise patients to use sunscreen (SPF ≥15) and sun-protective clothing if UV light exposure cannot be avoided.
Avoid use on sunburn skin. ( 5.3 )
5.1Local Irritation Tretinoin gel (microsphere) can cause local skin irritation, including excessive dryness, redness, swelling, peeling, itching, blistering, burning, or stinging [see Adverse Reactions ( 6.1 )] . Use of tretinoin gel (microsphere) in greater than the recommended dosage (more frequent than once daily application or excessive application) will not result in more rapid or improved acne results and may result in marked redness, peeling, or discomfort. Tretinoin has been reported to cause severe local skin irritation on eczematous skin.
Weather extremes, such as severe wind or cold, may increase the risk of skin irritation in patients using tretinoin gel (microsphere). To reduce the risk of local skin irritation, instruct tretinoin gel (microsphere) - treated patients to: Avoid use of tretinoin gel (microsphere) in areas affected by eczema. Minimize or avoid use of tretinoin gel (microsphere) with weather extremes.
Wash the treated skin gently, using a mild, non-medicated soap, pat it dry, and avoid washing the treated skin too often or scrubbing it hard when washing. Tretinoin gel (microsphere) is not recommended with concomitant use of medicated or abrasive soaps and cleansers, products that have a strong drying effect, products with high concentrations of alcohol, astringents, spices, or lime peels. Apply a topical moisturizer.
Advise patients that concomitant use of topical over the counter (OTC) acne products containing benzoyl peroxide, sulfur, resorcinol, or salicylic acid with tretinoin gel (microsphere) may increase the risk for local skin irritation including dryness, erythema, and peeling. Consider withholding the use of topical OTC acne products if signs of skin irritation develop. Advise patients to allow the skin irritation effects of the topical OTC acne products to subside before initiation of tretinoin gel (microsphere) treatment .
If severe local skin irritation occurs, discontinue tretinoin gel (microsphere) use temporarily or permanently. Efficacy of tretinoin gel (microsphere) at reduced frequencies of application has not been established.
5.2Initial Worsening of Inflammatory Acne Vulgaris During the early weeks of tretinoin gel (microsphere) treatment, an apparent exacerbation of inflammatory acne vulgaris lesions may occur. If tretinoin gel (microsphere) is tolerated, initial worsening of inflammatory acne vulgaris lesions should not be considered a reason to discontinue therapy.
5.3Photosensitivity Tretinoin gel (microsphere) can cause photosensitivity. Advise patients to avoid or minimize unnecessary exposure to ultraviolet (UV) light, including sunlight and sunlamps, while using tretinoin gel (microsphere). Advise patients with sunburn to not use tretinoin gel (microsphere) until the su… [Excerpted — this section continues on DailyMed.]
⚠️ Warnings ▾
5.3Photosensitivity Tretinoin gel (microsphere) can cause photosensitivity. Advise patients to avoid or minimize unnecessary exposure to ultraviolet (UV) light, including sunlight and sunlamps, while using tretinoin gel (microsphere). Advise patients with sunburn to not use tretinoin gel (microsphere) until the sunburn fully recovers.
Advise patients, especially those who may be required to have extended periods of UV light exposure (e.g., due to occupation or sports), those with inherent sensitivity to the sun, or those using drugs that cause photosensitivity, to use sun protection daily in the form of sunscreen (sun protection factor [SPF] ≥ 15) and sun- protective clothing, when UV exposure cannot be avoided, even on days when it is not sunny or inside activities are expected.
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Most common adverse reactions were skin irritation, skin burning, erythema, peeling, dryness, itching, and dermatitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Encube Ethicals Private Limited at 1-833-285-4151 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 practice. Tretinoin gel (microsphere), 0.1% The safety of tretinoin gel (microsphere), 0.1% for the treatment of acne vulgaris was evaluated in two multicenter, double-blind, randomized, vehicle-controlled clinical trials (Studies 1 and 2).
A total of 347 subjects with acne vulgaris were treated in Studies 1 and 2 in which 172 subjects received tretinoin gel (microsphere), 0.1% and 175 subjects received vehicle, applied topically once daily in the evening, for 12 weeks. Mean age was 19 years (range 11-40) and 55% were female [see Clinical Studies (14.1) ]. Tretinoin gel (microsphere) is not approved for use in pediatric patients younger than 12 years of age [see Indications and Usage (1) ].
In Studies 1 and 2, subjects treated with tretinoin gel (microsphere), 0.1% had increased cutaneous irritation scores for erythema, peeling, dryness, burning/stinging, or itching that peaked during the initial two weeks of therapy and decreased thereafter, compared to those treated with vehicle [see Warnings and Precautions (5.1) ]. During the 12-week treatment period, no more than 3% of tretinoin gel (microsphere), 0.1%-treated subjects had cutaneous irritation scores indicative of severe cutaneous irritation and 6% (14/224) of tretinoin gel (microsphere) 0.1%-treated subjects discontinued treatment due to cutaneous irritation.
Of these 14 subjects, four had severe cutaneous irritation after 3 to 5 days of treatment, with blistering in one subject. Tretinoin gel (microsphere), 0.04% The safety of tretinoin gel (microsphere), 0.04% for the treatment of acne vulgaris was evaluated in two multicenter, double-blind, randomized, vehicle-controlled clinical trials (Studies 3 and 4). A total of 451 subjects with acne vulgaris were treated in Studies 3 and 4 in which 225 subjects received tretinoin gel (microsphere), 0.04% and 226 subjects received vehicle, applied once daily in the evening, for 12 weeks.
Mean age was 19 years (range 11-49) and 57% were female [see Clinical Studies (14.2) ]. Tretinoin gel (microsphere) is not approved for use in pediatric patients younger than 12 years of age [see Indications and Usage (1) ]. In Studies 3 and 4, subjects treated with tretinoin gel (microsphere), 0.04% had increased cutaneous irritation scores for erythema, peeling, dryness, burning/stinging, or itching that peaked during the initial two weeks of therapy and decreased thereafter, compared to those treated with vehicle [see Warnings and Precautions (5.1) ].
Approximately half of the 225 subjects in the tretinoin gel (microsphere), 0.04%-treated group had cutaneous irritation at Week 2. Of the subjects who experienced cutaneous irritation, most had signs or symptoms that were mild in severity (severity was ranked on a 4-point ordinal scale: 0=none, 1=mild, 2=moderate, and 3=severe). Less than 10% of tretinoin gel (microsphere), 0.04%-treated subjects experienced moderate cutaneous irritation, and none had severe cutaneous irritation at Week 2.
In Studies 3 and 4, during the 12-week treatment period, the majority of tretinoin gel (microsphere), 0.04%-treated subjects experienced cutaneous irritation (mild, moderate, or severe), of which, 1% (2/225) of subjects had cutaneous irritation scores indicative of a severe irritation and 1.3% (3/225) of subjects discontinued treatment due to cutaneous irritation, which included dryness in one subject and peeling and urticaria in another. Tret… [Excerpted — this section continues on DailyMed.]
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary Available data from published prospective observational studies and retrospective cohort studies over decades of use of topical tretinoin in pregnant women have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) . In animal reproduction studies with pregnant rats, alterations in the vertebrae and ribs of offspring were observed with daily topical dosing of 0.1% tretinoin gel (microsphere) during organogenesis at 5 to 10 times the maximum recommended human dose (MRHD).
In animal reproduction studies with pregnant rabbits, fetal malformations, such as domed head and hydrocephaly, were observed in the offspring with daily topical dosing of 0.1% tretinoin gel (microsphere) during organogenesis at 10 to 19 times the MRHD [ see Data ]. 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 US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4%, and 15% to 20%, respectively. Data Human Data: Published data from prospective observational studies and retrospective cohort 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 potential misclassification of exposure, small sample size and in some cases, lack of physical exam by an expert in birth defects.
Animal Data: For purposes of comparison of the animal exposure to systemic human exposure, the MRHD applied topically is defined as 1 gram of tretinoin gel (microsphere), 0.1%, applied daily to a 60 kg person (0.017 mg tretinoin/kg body weight). Pregnant rats were treated with 0.1% tretinoin gel (microsphere) at daily dermal doses of 0.2, 0.5, and 1 mg/kg/day tretinoin on gestation days 6-15. Alterations were seen in the vertebrae and ribs of the affected offsprings at 0.5 mg/kg/day tretinoin, 5 to 10 times the MRHD based on body surface area (BSA) comparison.
Pregnant rabbits were treated with 0.1% tretinoin gel (microsphere) at daily dermal doses of 0.2, 0.5, and 1 mg/kg/day tretinoin on gestation days 7-19. Doses were administered topically for 24 hours a day while wearing Elizabethan collars to prevent ingestion of the drug. Increased incidences of certain alterations, including domed head and hydrocephaly, typical of retinoid-induced fetal malformations in this species were observed at doses of 0.5 and 1 mg/kg/day.
Similar malformations were not observed in the offspring at 0.2 mg/kg/day, 4 times the MRHD based on BSA comparison. In a second rabbit study, pregnant rabbits were treated with 0.1% tretinoin gel (microsphere) at daily dermal doses of 0.5 or 1 mg/kg/day tretinoin on gestation days 7-19. Doses were administered topically for six hours per day while pregnant rabbits were restrained in stocks to prevent ingestion.
The offspring of pregnant rabbits exposed to 0.5 or 1 mg/kg/day tretinoin did not show any malformations at doses up to 19 times (1.0 mg/kg/day) the MRHD based on BSA comparison, but fetal resorptions were increased at 0.5 mg/kg (10 times the MRHD based on BSA comparison). Malformations (shortened or kinked tail) were observed in the offspring of pregnant rats treated with topical tretinoin at doses greater than 1 mg/kg/day during the period of organogenesis (10 times the MRHD based on BSA comparison). Anomalies (humerus: short 13%, bent 6%, os parietal incompletely ossified 14%) have also been reported in offspring when 10 mg/kg/day was topically applied to pregnant rats during the period of organogenesis.
Supernumerary ribs have been a consistent finding in newborn rats when dams were treated topically or orally with retinoids. Oral administ… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Available data from published prospective observational studies and retrospective cohort studies over decades of use of topical tretinoin in pregnant women have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) . In animal reproduction studies with pregnant rats, alterations in the vertebrae and ribs of offspring were observed with daily topical dosing of 0.1% tretinoin gel (microsphere) during organogenesis at 5 to 10 times the maximum recommended human dose (MRHD).
In animal reproduction studies with pregnant rabbits, fetal malformations, such as domed head and hydrocephaly, were observed in the offspring with daily topical dosing of 0.1% tretinoin gel (microsphere) during organogenesis at 10 to 19 times the MRHD [ see Data ]. 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 US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4%, and 15% to 20%, respectively. Data Human Data: Published data from prospective observational studies and retrospective cohort 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 potential misclassification of exposure, small sample size and in some cases, lack of physical exam by an expert in birth defects.
Animal Data: For purposes of comparison of the animal exposure to systemic human exposure, the MRHD applied topically is defined as 1 gram of tretinoin gel (microsphere), 0.1%, applied daily to a 60 kg person (0.017 mg tretinoin/kg body weight). Pregnant rats were treated with 0.1% tretinoin gel (microsphere) at daily dermal doses of 0.2, 0.5, and 1 mg/kg/day tretinoin on gestation days 6-15. Alterations were seen in the vertebrae and ribs of the affected offsprings at 0.5 mg/kg/day tretinoin, 5 to 10 times the MRHD based on body surface area (BSA) comparison.
Pregnant rabbits were treated with 0.1% tretinoin gel (microsphere) at daily dermal doses of 0.2, 0.5, and 1 mg/kg/day tretinoin on gestation days 7-19. Doses were administered topically for 24 hours a day while wearing Elizabethan collars to prevent ingestion of the drug. Increased incidences of certain alterations, including domed head and hydrocephaly, typical of retinoid-induced fetal malformations in this species were observed at doses of 0.5 and 1 mg/kg/day.
Similar malformations were not observed in the offspring at 0.2 mg/kg/day, 4 times the MRHD based on BSA comparison. In a second rabbit study, pregnant rabbits were treated with 0.1% tretinoin gel (microsphere) at daily dermal doses of 0.5 or 1 mg/kg/day tretinoin on gestation days 7-19. Doses were administered topically for six hours per day while pregnant rabbits were restrained in stocks to prevent ingestion.
The offspring of pregnant rabbits exposed to 0.5 or 1 mg/kg/day tretinoin did not show any malformations at doses up to 19 times (1.0 mg/kg/day) the MRHD based on BSA comparison, but fetal resorptions were increased at 0.5 mg/kg (10 times the MRHD based on BSA comparison). Malformations (shortened or kinked tail) were observed in the offspring of pregnant rats treated with topical tretinoin at doses greater than 1 mg/kg/day during the period of organogenesis (10 times the MRHD based on BSA comparison). Anomalies (humerus: short 13%, bent 6%, os parietal incompletely ossified 14%) have also been reported in offspring when 10 mg/kg/day was topically applied to pregnant rats during the period of organogenesis.
Supernumerary ribs have been a consistent finding in newborn rats when dams were treated topically or orally with retinoids. Oral administration of tretinoin during org… [Excerpted — this section continues on DailyMed.]
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of tretinoin gel (microsphere) for topical application for the treatment of acne vulgaris have been established in pediatric patients aged 12 years and older [see Clinical Studies (14) ] . The safety and effectiveness of tretinoin gel (microsphere) have not been established in pediatric patients younger than 12 years of age.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical trials of tretinoin gel (microsphere) did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger adult subjects. Acne vulgaris is largely a disease of pediatric and young adult patients. Clinical studies of tretinoin gel (microsphere) did not include patients 65 years of age and older.
🆘 Overdosage ▾
10 OVERDOSAGE Oral ingestion of large amounts of tretinoin gel (microsphere) may lead to the same adverse reactions as those associated with excessive oral intake of Vitamin A. Consider contacting the Poison Help Line (1-800-222-1222) or a medical toxicologist for overdose recommendations.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Although tretinoin activates three members of the retinoic acid (RAR) nuclear receptors (RARα, RARβ, and RARγ) which may 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 and/or other mechanisms. The exact mechanism of action of topical tretinoin for treatment of acne vulgaris is unknown. Current evidence suggests that topical tretinoin decreases cohesiveness of follicular epithelial cells with decreased microcomedone formation.
Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells causing extrusion of the comedones.
12.2Pharmacodynamics The pharmacodynamics of tretinoin gel (microsphere) is unknown.
12.3Pharmacokinetics Absorption Tretinoin is a metabolite of Vitamin A. Percutaneous absorption, as determined by the cumulative excretion of radiolabeled drug into urine and feces, was assessed in 44 healthy males and females after single and repeated daily tretinoin applications up to 28 days of 500 mg of a 0.1% tretinoin gel product. In this assessment, estimates of in vivo bioavailability, mean (SD) were 0.82 (0.11)% and 1.41 (0.54)%, for single and multiple daily topical applications, respectively.
The plasma concentrations of tretinoin and its metabolites, 13- cis - retinoic acid, all- trans -4-oxo-retinoic acid, and 13- cis -4-oxo-retinoic acid, generally ranged from 1 to 3 ng/mL and were essentially unaltered after either single or multiple daily applications of tretinoin gel (microsphere), 0.1%, relative to baseline levels. Clinical pharmacokinetic studies have not been performed with tretinoin gel (microsphere), 0.08%, 0.06% and 0.04%.
🧬 Mechanism of Action ▾
12.1Mechanism of Action Although tretinoin activates three members of the retinoic acid (RAR) nuclear receptors (RARα, RARβ, and RARγ) which may 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 and/or other mechanisms. The exact mechanism of action of topical tretinoin for treatment of acne vulgaris is unknown. Current evidence suggests that topical tretinoin decreases cohesiveness of follicular epithelial cells with decreased microcomedone formation.
Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells causing extrusion of the comedones.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Tretinoin gel (microsphere) is opaque and white to very pale yellow in color and is supplied as follows: Strength Amount of Tretinoin in One Gram of Gel Quantity/Package Type NDC 0.06% 0.6 mg 50 gram pump 21922-042-40 0.08% 0.8 mg 50 gram pump 21922-043-40 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Store pump upright.
📋 Description ▾
11 DESCRIPTION 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. Tretinoin is a retinoid and a metabolite of naturally occurring Vitamin A. Tretinoin has a molecular weight of 300.44, a molecular formula of C20H28O2 and the following chemical structure Tretinoin gel (microsphere) is for topical use.
Each gram of tretinoin gel (microsphere): 0.06%, contains 0.6 mg of tretinoin 0.08%, contains 0.8 mg of tretinoin The formulation uses acrylate copolymer microsphere system to enable inclusion of the active ingredient, tretinoin, in an aqueous gel. Other components consist of benzyl alcohol, butylated hydroxytoluene, carbomer 974P, cyclomethicone and dimethicone copolyol, disodium EDTA, glycerin, PPG-20 methyl glucose ether distearate, propylene glycol, propylene glycol dicaprylate/dicaprate, purified water, sorbic acid, and trolamine. str.jpg
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Administration Instruct the patient to [see Dosage and Administration (2) ] : Thoroughly cleanse treatment area(s) with a mild, non-medicated cleanser then pat the skin dry prior to application of tretinoin gel (microsphere). Avoid contact with eyes, mouth, paranal creases of nose, and mucous membranes when applying tretinoin gel (microsphere).
Apply a thin layer of tretinoin gel (microsphere) to cover the affected area(s). Local Skin Irritation: Advise the patient that use of tretinoin gel (microsphere) greater than the recommended dosage will not result in more rapid of improved acne results and may result in marked redness, peeling or discomfort [see Warnings and Precautions (5.1) ]. To reduce the risk of local skin irritation, advise the patient to: Minimize or avoid use of tretinoin gel (microsphere) during weather extremes, such as severe wind or cold.
Wash the treated skin gently, using a mild, non-medicated soap, and pat it dry, and avoid washing the treated skin too often or scrubbing it hard when washing. Not use medicated or abrasive soaps and cleansers, products that have a strong drying effect, products with high concentrations of alcohol, astringents, spices, and lime peels while using tretinoin gel (microsphere). Apply a topical moisturizer when using tretinoin gel (microsphere).
Advise the patient that concomitant use of topical OTC acne products containing benzoyl peroxide, sulfur, resorcinol, or salicylic acid with tretinoin gel (microsphere) may increase the risk of local skin irritation. Advise the patient to withhold the use of topical OTC acne products if signs of skin irritation develop. Advise the patient to allow the skin irritation effects of the topical OTC acne products to subside before initiation of tretinoin gel (microsphere) [see Warning and Precautions (5.1) ].
Photosensitivity Advise the patient to avoid or minimize unnecessary exposure to ultraviolet (UV) light, including sunlight and sunlamps, while using tretinoin gel (microsphere). Advise the patient to not use tretinoin gel (microsphere) on sunburn skin. Advise the patient to use sun protection in the form of sunscreen (SPF ≥15) and sun-protective clothing if UV exposure cannot be avoided [see Warnings and Precautions (5.3) ].
Lactation Advise the female patient to use tretinoin gel (microsphere) on the smallest area of skin with acne vulgaris and for the shortest duration possible while breastfeeding. To avoid direct infant exposure, instruct the patient who is breastfeeding not to apply tretinoin gel (microsphere) directly to the nipple and areola [see Use in Specific Populations (8.2) ] . Made in Italy, formulated in India.
Manufactured by: Encube Ethicals Pvt. Ltd. Plot No.
C-1, Madkaim Industrial Estate, Madkaim, Post: Mardol, Ponda, Goa - 403 404, India. Distributed by: Encube Ethicals, Inc. 200 Meredith Drive, Suite 202, Durham, NC 27713 USA Revised: 10/2025
🍼 Nursing Mothers ▾
8.2Lactation 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 quantities in human milk (see Clinical Considerations) . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tretinoin gel (microsphere) and any potential adverse effects on the breastfed infant from the tretinoin gel (microsphere) or from the underlying maternal condition.
Clinical Considerations To minimize potential exposure to the infant via human milk, during breastfeeding, use tretinoin gel (microsphere) on the smallest area of skin with acne and for the shortest duration possible. Advise breastfeeding women not to apply tretinoin gel (microsphere) directly to the nipple and areola to avoid direct infant exposure.
🧬 Pharmacokinetics ▾
12.2Pharmacodynamics The pharmacodynamics of tretinoin gel (microsphere) is unknown.
🧬 Pharmacodynamics ▾
12.3Pharmacokinetics Absorption Tretinoin is a metabolite of Vitamin A. Percutaneous absorption, as determined by the cumulative excretion of radiolabeled drug into urine and feces, was assessed in 44 healthy males and females after single and repeated daily tretinoin applications up to 28 days of 500 mg of a 0.1% tretinoin gel product. In this assessment, estimates of in vivo bioavailability, mean (SD) were 0.82 (0.11)% and 1.41 (0.54)%, for single and multiple daily topical applications, respectively.
The plasma concentrations of tretinoin and its metabolites, 13- cis - retinoic acid, all- trans -4-oxo-retinoic acid, and 13- cis -4-oxo-retinoic acid, generally ranged from 1 to 3 ng/mL and were essentially unaltered after either single or multiple daily applications of tretinoin gel (microsphere), 0.1%, relative to baseline levels. Clinical pharmacokinetic studies have not been performed with tretinoin gel (microsphere), 0.08%, 0.06% and 0.04%.
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Clinical Studies of tretinoin gel (microsphere), 0.1% The efficacy of tretinoin gel (microsphere), 0.1% was evaluated in two double-blind, randomized, vehicle-controlled trials in adult and pediatric subjects 11 years of age and older with acne vulgaris (Studies 1 and 2). Tretinoin gel (microsphere) is not approved for use in pediatric patients younger than 12 years of age [see Indications and Usage (1) ]. Tretinoin gel (microsphere), 0.1%, applied topically once daily in the evening, was superior to vehicle gel, applied topically once daily, in reducing the acne lesion counts.
The mean reduction in lesion counts from baseline after treatment for 12 weeks are shown in Table 1: Table 1: Mean Percent Reduction in Lesion Counts in Subjects with Acne Vulgaris at Week 12 in Studies 1 and 2 Study 1 Study 2 Tretinoin gel (microsphere),0.1% (n=72) Vehicle Gel (n=71) Tretinoin gel (microsphere), 0.1% (n=72) Vehicle Gel (n=67) Non-inflammatory lesion counts 49% 22% 32% 3% Inflammatory lesion counts 37% 18% 29% 24% Total lesion counts 45% 23% 32% 16% Efficacy was also assessed by the investigator’s global evaluation, which included categories of “excellent”, “good”, “fair”, “no change”, and “poor”.
Tretinoin gel (microsphere), 0.1%, was significantly superior (p<0.001) to the vehicle in the investigator's global evaluation of the clinical response: In Study #1, 35% of tretinoin gel (microsphere), 0.1% - treated subjects achieved an “excellent” result, as compared to 11% of vehicle-treated subjects. In Study #2, 28% of tretinoin gel (microsphere), 0.1% - treated subjects achieved an “excellent” result, as compared to 9% of vehicle-treated subjects.
14.2Clinical Studies with tretinoin gel (microsphere), 0.04% In two vehicle-controlled clinical trials in adult and pediatric subjects 11 years of age and older with acne vulgaris (Studies 3 and 4). Tretinoin gel (microsphere) is not approved for use in pediatric patients younger than 12 years of age [see Indications and Usage (1) ]. Tretinoin gel (microsphere), 0.04%, applied topically once daily in the evening, was more effective (p<0.05) than vehicle gel, applied topically once daily, in reducing the acne lesion counts.
The mean reduction in lesion counts from baseline after treatment for 12 weeks are shown in Table 2: Table 2: Mean Percent Reduction in Lesion Counts in Subjects with Acne Vulgaris at Week 12 in Studies 3 and 4 Study 3 Study 4 Tretinoin gel (microsphere) 0.04% (n=108) Vehicle Gel (n=111) Tretinoin gel (microsphere) 0.04% (n=110) Vehicle Gel (n=103) Non-inflammatory lesion counts 37% -2%* 29% 14% Inflammatory lesion counts 44% 13% 41% 30% Total lesion counts 40% 8% 35% 20% * -2% represents a mean percent increase of 2% Efficacy was also assessed by the investigator’s global evaluation, which included categories of “excellent”, “good”, “fair”, “no change”, and “poor”.
Tretinoin gel (microsphere) 0.04% was superior (p<0.05) to the vehicle in the investigator's global evaluation of the clinical response: In Study #3, 14% of tretinoin gel (microsphere) 0.04%-treated subjects achieved an “excellent” result, as compared to 5% of vehicle-treated subjects. In Study #4, 19% of tretinoin gel (microsphere) 0.04%-treated subjects achieved an “excellent” result, as compared to 9% of vehicle-treated subjects.
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Dermal carcinogenicity testing has not been performed with tretinoin gel (microsphere), 0.04%, 0.06%, 0.08%, or 0.1%. In a 91-week dermal study in which CD-1 mice were administered 0.017% and 0.035% formulations of tretinoin, cutaneous squamous cell carcinomas and papillomas in the treatment area were observed in some female mice. These concentrations are near the tretinoin concentration of the 0.04% and 0.1% clinical formulations.
A dose-dependent incidence of liver tumors in male mice was observed at those same doses. The maximum systemic doses associated with the administered 0.017% and 0.035% formulations are 0.5 and 1 mg/kg/day tretinoin, respectively. These doses are two and four times the MRHD based on BSA comparison.
The biological significance of these findings is not clear because they occurred at doses that exceeded the dermal maximally tolerated dose of tretinoin and because they were within the background natural occurrence rate for these tumors in this strain of mice. There was no evidence of carcinogenic potential when 0.025 mg/kg/day of tretinoin was administered topically to mice (0.1 times the MRHD based on BSA comparison). Studies in hairless albino mice suggest that concurrent exposure to tretinoin may enhance the tumorigenic potential of carcinogenic doses of UVB and UVA light from a solar simulator.
This effect has been confirmed in a later study in pigmented mice, and dark pigmentation did not overcome the enhancement of photo carcinogenesis by 0.05% tretinoin. Although the significance of these studies to humans is not clear, patients should minimize exposure to sunlight or artificial ultraviolet irradiation sources [ see Warnings and Precautions (5.3) ]. The genotoxic potential of tretinoin was evaluated in the Ames assay and an in vivo mouse micronucleus assay.
Both tests were negative. The components of the microspheres have shown potential for genetic toxicity and fetal malformation. EGDMA, a component of the excipient acrylates copolymer, was positive for induction of structural chromosomal aberrations in an in vitro chromosomal aberration assay in mammalian cells in the absence of metabolic activation, and negative for genetic toxicity in the Ames assay, and an in vivo mouse micronucleus assay.
In fertility studies in rats with oral tretinoin, the no-observable effect level was 2 mg/kg/day (19 times the MRHD based on BSA comparison).
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Dermal carcinogenicity testing has not been performed with tretinoin gel (microsphere), 0.04%, 0.06%, 0.08%, or 0.1%. In a 91-week dermal study in which CD-1 mice were administered 0.017% and 0.035% formulations of tretinoin, cutaneous squamous cell carcinomas and papillomas in the treatment area were observed in some female mice. These concentrations are near the tretinoin concentration of the 0.04% and 0.1% clinical formulations.
A dose-dependent incidence of liver tumors in male mice was observed at those same doses. The maximum systemic doses associated with the administered 0.017% and 0.035% formulations are 0.5 and 1 mg/kg/day tretinoin, respectively. These doses are two and four times the MRHD based on BSA comparison.
The biological significance of these findings is not clear because they occurred at doses that exceeded the dermal maximally tolerated dose of tretinoin and because they were within the background natural occurrence rate for these tumors in this strain of mice. There was no evidence of carcinogenic potential when 0.025 mg/kg/day of tretinoin was administered topically to mice (0.1 times the MRHD based on BSA comparison). Studies in hairless albino mice suggest that concurrent exposure to tretinoin may enhance the tumorigenic potential of carcinogenic doses of UVB and UVA light from a solar simulator.
This effect has been confirmed in a later study in pigmented mice, and dark pigmentation did not overcome the enhancement of photo carcinogenesis by 0.05% tretinoin. Although the significance of these studies to humans is not clear, patients should minimize exposure to sunlight or artificial ultraviolet irradiation sources [ see Warnings and Precautions (5.3) ]. The genotoxic potential of tretinoin was evaluated in the Ames assay and an in vivo mouse micronucleus assay.
Both tests were negative. The components of the microspheres have shown potential for genetic toxicity and fetal malformation. EGDMA, a component of the excipient acrylates copolymer, was positive for induction of structural chromosomal aberrations in an in vitro chromosomal aberration assay in mammalian cells in the absence of metabolic activation, and negative for genetic toxicity in the Ames assay, and an in vivo mouse micronucleus assay.
In fertility studies in rats with oral tretinoin, the no-observable effect level was 2 mg/kg/day (19 times the MRHD based on BSA comparison).
📄 Package Label / Principal Display Panel ▾
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 21922- 043 -40 Tretinoin Gel (Microsphere), 0.08% PUMP For Topical Use Only Net wt. 50 g Rx only NDC 21922- 042 -40 Tretinoin Gel (Microsphere), 0.06% PUMP For Topical Use Only Net wt. 50 g Rx only crt carton-0-06