Atralin

Dosage Forms And Strengths

Gel, 0.05%

Each gram of Atralin Gel contains 0.5 mg (0.05%) tretinoin in a translucent to opaque, pale yellow topical gel.

Atralin (tretinoin) Gel, 0.05% is a translucent to opaque, pale yellow topical gel and available as:

45 g tubes (NDC 13548-070-45)

Storage And Handling

Store at controlled room temperature 20° - 25°C (68° - 77°F) with excursions permitted between 15°-30°C (59°-86°F). Protect from freezing. Keep out of reach of children.

Manufactured for: Valeant Pharmaceuticals North America LLC, Bridgewater, NJ 08807 by: DPT Laboratories, Ltd., San Antonio, TX 78215. Revised: 08/2014

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, but cutaneous levels of tretinoin in excess of physiologic concentrations occur following application of a tretinoin-containing topical drug product.

Although tretinoin activates three members of the retinoid 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 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.

Pharmacokinetics

In two (2) studies, the plasma levels of tretinoin and its major metabolites (13-cis-retinoic acid and 4-oxo-13-cisretinoic acid) were investigated in a total of 14 patients (age: 13 – 25 years) with severe acne, who applied 4 g ± 0.5 g (range 3.5 g – 4.5 g) of Atralin Gel once daily to face, back and chest, as compared to a mean of 0.71 g (range of 0.07 – 3.71 g) applied in the controlled clinical trials. Blood samples were taken at baseline and immediately prior to treatment on days 1, 5, 10 and 14. On Day 14, the final study day, samples also were taken 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours, post-treatment.

The plasma concentrations of tretinoin and its metabolites could be measured (LOQ = 0.5 ng/mL for all three analytes) in all patients at all time points. The range of plasma concentrations of tretinoin and its metabolites, 13-cisretinoic acid and all-trans-4-oxo-retinoic acid at baseline and after multiple once daily applications of Atralin Gel, 0.05% for 14 days are given in Table 2 (below). Although some patients had increased concentrations of tretinoin or its metabolites over baseline values, no consistent increase in these concentrations were observed across patients.

Table 2: Concentrations of active and metabolites at Baseline and at Day 14 after exposure to Atralin Gel, 0.05%

Clinical Studies

Clinical Trials

The safety and efficacy of Atralin Gel used once daily before bedtime for the treatment of mild to moderate acne vulgaris were assessed in two 12-week prospective, multi-center, randomized, controlled trials. Subjects in these two trials ranged from 10 to 65 years of age, were approximately 52% female, 48% male, and were 74% Caucasian, 15% Black or African American, 3% Asian, and 8% Other.

Efficacy results at Week 12 are presented in Table 3. Success on the 6-point Global Severity Score is defined as a score of 0 (clear) or 1 (very mild). In Trial 2, subjects were also required to have at least two grades reduction from baseline for success. 'Very mild' acne is defined as: skin almost clear; rare non-inflammatory lesions present, with rare non-inflamed papules (papules may be hyperpigmented, though not pink-red, less than 4 lesions). The database was not large enough to assess whether there were differences in effects in age, gender, or race subgroups.

Table 3: Efficacy Results at Week 12 in Trials 1 and 2

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

You should not use tretinoin topical if you are allergic to it.

It is not known whether tretinoin topical will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether tretinoin topical passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Avoid exposure to sunlight or tanning beds. Tretinoin topical can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors, even on a cloudy day.

Avoid getting this medication in your eyes, nose, mouth, or in the creases of your nose.

Avoid using skin products that can cause irritation, such as harsh soaps, shampoos, or skin cleansers, hair coloring or permanent chemicals, hair removers or waxes, or skin products with alcohol, spices, astringents, or lime.

Avoid using other medications on the areas you treat with tretinoin topical unless your doctor tells you to.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using tretinoin topical and call your doctor at once if you have:

• severe burning, stinging, or irritation of treated skin;

• severe redness, swelling, blistering, peeling, or crusting;

Your skin may be more sensitive to weather extremes such as cold and wind while using this medicine.

Common side effects may include:

• mild warmth or stinging where the medicine was applied; or

• changes in color of treated skin.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Read the Atralin User Reviews »

© Atralin Patient Information is supplied by Cerner Multum, Inc. and Atralin Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Animal models have revealed evidence of teratogenicity and fetotoxicity. Some species have shown delayed ossification, supernumerary ribs, hydrocephaly, domed heads, increased fetal resorption, and/or increased intrauterine death at doses of at least 4 times the maximum human dose. There are no controlled data in human pregnancy. There are approximately 30 human case reports with evidence of congenital malformations, including holoprosencephaly. The significance of these malformations to the fetus is unknown. AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

This drug should not be used during pregnancy unless clearly needed and the benefit outweighs the risk to the fetus. AU TGA pregnancy category: D US FDA pregnancy category: C Comment: Use of adequate methods of contraception should be encouraged.

Some experts state that risk to the nursing infant is considered low as this drug is poorly absorbed after application.

Use is not recommended and a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Unknown Excreted into animal milk: Unknown Comments: -The effects in the nursing infant are unknown. -If this drug is used during breastfeeding, patients should ensure that infants do not come into contact with treated areas. -Ointments should not be applied to the breast prior to breastfeeding; if necessary, water-miscible cream or gel products should be used.

Summary of Use during Lactation

Tretinoin has not been studied during breastfeeding. Breastfeeding should probably be avoided after oral use. Because it is poorly absorbed after topical application, it is considered a low risk to the nursing infant.[1][2][3] Ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated. Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking.[4]

Drug Levels

Maternal Levels. Relevant published information was not found as of the revision date.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

(Acne) Azelaic Acid, Benzoyl Peroxide, Clindamycin, Erythromycin

References

1. Leachman SA, Reed BR. The use of dermatologic drugs in pregnancy and lactation. Dermatol Clin. 2006;24:167-97. PMID: 16677965

2. Zip C. Common sense dermatological drug suggestions for women who are breast-feeding. Skin Therapy Lett. 2002;7:5-7. PMID: 12007012

3. Butler DC, Heller MM, Murase JE. Safety of dermatologic medications in pregnancy and lactation: Part II Lactation. J Am Acad Dermatol. 2014;70:417.e1-417.e10. PMID: 24528912

4. Noti A, Grob K, Biedermann M et al. Exposure of babies to C(15)-C(45) mineral paraffins from human milk and breast salves. Regul Toxicol Pharmacol. 2003;38:317-25. PMID: 14623482