Retin-a-micro

RETIN-A MICRO^® is indicated for the topical treatment of acne vulgaris in adults and pediatric patients 12 years of age and older.

For topical use only. Not for oral, ophthalmic, or intravaginal use.

• •Prior to RETIN-A MICRO use, thoroughly cleanse area(s) with a mild, non-medicated cleanser then pat the skin dry.
• •When applying RETIN-A MICRO, keep away from the eyes, the mouth, paranasal creases of the nose, and mucous membranes.
• •Apply a thin layer of RETIN-A MICRO (0.04%, 0.06%, 0.08%, or 0.1%) 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

  5.1 Local Skin Irritation

  RETIN-A MICRO can cause local skin irritation, including excessive dryness, redness, swelling, peeling, itching, blistering, burning, or stinging

  [see Adverse Reactions (6.1)]

  . Use of RETIN-A MICRO 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 RETIN-A MICRO.

  To reduce the risk of local skin irritation, instruct RETIN-A MICRO-treated patients to:

  • •Avoid use of RETIN-A MICRO in areas affected by eczema.
  • •Minimize or avoid use of RETIN-A MICRO 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. RETIN-A MICRO 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 RETIN-A MICRO 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 RETIN-A MICRO treatment.

  If severe local skin irritation occurs, discontinue RETIN-A MICRO use temporarily or permanently.

  Efficacy of RETIN-A MICRO at reduced frequencies of application has not been established.

  ]
  .

Improvements in acne lesions may be noticed after two weeks of RETIN-A MICRO therapy, but more than seven weeks of therapy may be needed for sustained benefit.

If RETIN-A MICRO was temporarily discontinued due to local adverse reactions, RETIN-A MICRO therapy may be resumed upon resolution of local adverse reactions.

Gel (white to very pale yellow and opaque):

• •0.04% (0.4 mg of tretinoin per gram)
• •0.06% (0.6 mg of tretinoin per gram)
• •0.08% (0.8 mg of tretinoin per gram)
• •0.1% (1 mg of tretinoin per gram).

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

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 (microsponge) 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 (microsponge) during organogenesis at 10 to 19 times the MRHD [

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.

Pregnant rats were treated with 0.1% tretinoin gel (microsponge) 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 (microsponge) 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 (microsponge) 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 organogenesis has been shown to cause malformations in the offspring of rats, mice, rabbits, hamsters, and nonhuman primates. Fetal malformations and death were observed when tretinoin was orally administered to pregnant rats during organogenesis at doses greater than 1 mg/kg/day (10 times the MRHD based on BSA comparison). Fetal malformations were reported at doses of 10 mg/kg/day or greater when administered to pregnant cynomolgus monkeys, but none were observed at 5 mg/kg/day (95 times the MRHD based on BSA comparison), although increased skeletal variations were observed at all doses. Dose-dependent increases in embryolethality and abortion also were reported. Similar results have also been reported in pigtail macaques.

In peri- and postnatal development studies in rats with oral tretinoin, decreased survival of neonates and growth retardation were observed at doses in excess of 2 mg/kg/day (19 times the MRHD based on BSA comparison).

Oral tretinoin has been shown to be fetotoxic in rats when administered at doses 24 times the MRHD based on BSA comparison.

Topical tretinoin has been shown to be fetotoxic in rabbits when administered at doses 10 times the MRHD based on BSA comparison.

• •
  Local Skin Irritation
  : RETIN-A MICRO can cause local skin irritation, including excessive dryness, redness, swelling, peeling, itching, blistering, burning, or stinging (
  5.1 Local Skin Irritation

  RETIN-A MICRO can cause local skin irritation, including excessive dryness, redness, swelling, peeling, itching, blistering, burning, or stinging

  [see Adverse Reactions (6.1)]

  . Use of RETIN-A MICRO 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 RETIN-A MICRO.

  To reduce the risk of local skin irritation, instruct RETIN-A MICRO-treated patients to:

  • •Avoid use of RETIN-A MICRO in areas affected by eczema.
  • •Minimize or avoid use of RETIN-A MICRO 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. RETIN-A MICRO 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 RETIN-A MICRO 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 RETIN-A MICRO treatment.

  If severe local skin irritation occurs, discontinue RETIN-A MICRO use temporarily or permanently.

  Efficacy of RETIN-A MICRO at reduced frequencies of application has not been established.
  )
• •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 RETIN-A MICRO treatment, an apparent exacerbation of inflammatory lesions may occur. If RETIN-A MICRO is tolerated, this should not be considered a reason to discontinue therapy. (
  5.2 Initial Worsening of Inflammatory Acne Vulgaris

  During the early weeks of RETIN-A MICRO treatment, an apparent exacerbation of inflammatory acne vulgaris lesions may occur. If RETIN-A MICRO is tolerated, initial worsening of inflammatory acne vulgaris lesions should not be considered a reason to discontinue therapy.
  )
• •
  Photosensitivity
  : RETIN-A MICRO 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 Photosensitivity

  RETIN-A MICRO can cause photosensitivity. Advise patients to avoid or minimize unnecessary exposure to ultraviolet (UV) light, including sunlight and sunlamps, while using RETIN-A MICRO. Advise patients with sunburn to not use RETIN-A MICRO 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.
  )