Avage

In human dermal safety studies, tazarotene 0.05% and 0.1% creams did not induce allergic contact sensitization, phototoxicity or photoallergy.

The most frequent treatment-related adverse reactions ( ≥ 5%) reported during the clinical trials with AVAGE® (TAZAROTENE) Cream 0.1% in the treatment of facial fine wrinkling, mottled hypo- and hyperpigmentation, and benign facial lentigines were limited to the skin. Those occurring in >10%, in descending order, included: desquamation, erythema, burning sensation, and dry skin. Events occurring in ≥ 1% to ≤ 10% of patients, in descending order included: skin irritation, pruritus, irritant contact dermatitis, stinging, acne, rash or cheilitis. Common adverse events observed in the clinical trials are presented in the following table:

TABLE OF ADVERSE EVENTS SEEN IN CLINICAL TRIALS WITH AVAGE® (TAZAROTENE) Cream 0.1% 

A few patients reported adverse events at Week 0; however, for patients who were treated with AVAGE® (tazarotene) the highest number of new reports for each adverse event was at Week 2.

When combining data from the two pivotal studies, 5.3% of patients in the tazarotene cream group and 0.9% of patients in the vehicle group discontinued due to adverse events.

Overall, 20/567 (3.5%) patients in the AVAGE® (TAZAROTENE) Cream 0.1% group and 16/564 (2.8%) patients in the vehicle group reported adverse events (including edema, irritation, and inflammation) directly related to the eye or eyelid. The majority of these conditions were mild.

Take Avage exactly as prescribed.

Agave comes in topical cream form and is applied to the affected skin once a day at bedtime to lightly cover the entire face including the eyelids if desired. 

Facial moisturizers may be used as frequently as desired. If any makeup is present it should be removed before applying Avage. If the face is washed or a bath or shower is taken prior to application, the skin should be dry before applying the cream. If emollients or moisturizers are used, they can be applied either before or after application of Avage ensuring that the first cream or lotion has absorbed into the skin and has dried completely.

Avage does not eliminate or prevent wrinkles, repair sun-damaged skin, reverse photo aging, or restore more youthful or younger skin and daily use beyond 52 weeks has not been investigated in clinical trials.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of Avage at the same time.

Tazarotene topical can harm an unborn baby or cause birth defects. Do not use if you are pregnant. You must have a negative pregnancy test within 2 weeks before starting this treatment.

Stop using this medicine and tell your doctor right away if you become pregnant, if you stop using birth control, or if you miss a menstrual period.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Stinging.
• Dry skin.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Embryofetal Toxicity

Based on data from animal reproduction studies, retinoid pharmacology and the potential for systemic absorption, Avage Cream may cause fetal harm when administered to a pregnant female and is contraindicated during pregnancy. Safety in pregnant females has not been established. The potential risk to the fetus outweighs the potential benefit to the mother from Avage Cream use during pregnancy; therefore, discontinue Avage Cream as soon as pregnancy is recognized. Tazarotene elicits malformations and developmental effects associated with retinoids after topical and oral administration to pregnant rats and rabbits during organogenesis. However, limited case reports of pregnancy in females enrolled in clinical trials for Avage Cream have not reported a clear association with tazarotene and major birth defects or miscarriage risk [see Contraindications (4), Use in Specific Populations (8.1)].

Systemic exposure to tazarotenic acid is dependent upon the extent of the body surface area treated. In patients treated topically over sufficient body surface area, exposure could be in the same order of magnitude as in these orally treated animals. Although there may be less systemic exposure in the treatment of the face alone due to less surface area for application, tazarotene is a teratogenic substance in animals, and it is not known what level of exposure is required for teratogenicity in humans [see Clinical Pharmacology (12.3)].

Advise pregnant females of the potential risk to a fetus. Obtain a pregnancy test within 2 weeks prior to Avage Cream therapy. Initiate Avage Cream therapy during a menstrual period. Advise females of reproductive potential to use effective contraception during treatment with Avage Cream [see Dosage and Administration (2), Use in Specific Populations (8.3)].

Local Irritation and Hypersensitivity Reactions

Local tolerability reactions (including blistering and skin desquamation) and hypersensitivity adverse reactions (including urticaria) have been observed with topical tazarotene. Application of Avage Cream may cause excessive irritation in the skin of certain sensitive individuals. Some individuals may experience excessive pruritus, burning, skin redness, or peeling. If these adverse reactions occur, discontinue the medication until the integrity of the skin is restored, or reduce the dosing to an interval the patient can tolerate. Closely monitor the frequency of application by carefully observing the therapeutic response and skin tolerance.

Avoid concomitant use of topical medications and cosmetics that have a strong drying effect. It is also advisable to “rest” a patient's skin until the effects of such preparations subside before use of Avage Cream is begun.

Avoid using Avage Cream on eczematous skin because such use may cause severe irritation.

Weather extremes, such as wind or cold, may be more irritating to patients using Avage Cream.

Photosensitivity and Risk of Sunburn

Because of heightened burning susceptibility, minimize exposure to ultraviolet rays (including sunlight and sun lamps) during the use of Avage Cream. Patients must be warned to use sunscreens and protective clothing when using Avage Cream. Advise patients with sunburn not to use Avage Cream until the sunburn is fully recovered.

Patients who may have considerable sun exposure because of their occupation and those patients with inherent sensitivity to sunlight should exercise particular caution when using Avage Cream.

Avoid using Avage Cream if the patient is also taking drugs known to be photosensitizers (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the increased possibility of augmented photosensitivity.

Lentigo Maligna

Some facial pigmented lesions are not lentigines, but rather lentigo maligna, a type of melanoma. Before application of Avage Cream, carefully assess facial pigmented lesions of concern by a qualified physician (e.g., dermatologist) to exclude a diagnosis of lentigo maligna.

The following serious adverse reactions are discussed in more detail in other sections of the labeling:

• Embryofetal toxicity [see Warnings and Precautions (5.1)]
• Photosensitivity and Risk of Sunburn [see Warnings and Precautions (5.3)]

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.

The most frequent adverse reactions reported with Avage Cream, 0.1% that occurred in greater than 10% of subjects, included desquamation, erythema, burning sensation, and dry skin (in descending order). Reactions that occurred in 1 to 10% of subjects, included skin irritation, pruritus, irritant contact dermatitis, stinging, rash, and cheilitis (in descending order). Common adverse events that occurred at a rate of at least 1% and at a higher rate in the Avage Cream group than in the vehicle group in the clinical trials are presented in the following table.

A few subjects reported adverse events at Week 0; however, for patients who were treated with Avage Cream, the highest number of new reports for each adverse event was at Week 2.

When combining data from the two trials, 5.3% of subjects in the Avage Cream group and 0.9% of subjects in the vehicle group discontinued because of adverse events.

Overall, 20/567 (3.5%) subjects in the Avage Cream group and 16/564 (2.8%) subjects in the vehicle group reported adverse events (including edema, irritation, and inflammation) directly related to the eye or eyelid. The majority of these conditions were mild.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of tazarotene. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skin and subcutaneous tissue disorders: blister, dermatitis, urticaria, skin exfoliation, skin discoloration (including skin hyperpigmentation or skin hypopigmentation), swelling at or near application sites, and pain.

Avage Cream, 0.1% is for topical use and contains the active ingredient, tazarotene. Each gram of Avage Cream, 0.1% contains 1 mg of tazarotene in a white cream base.

Tazarotene is a member of the acetylenic class of retinoids. Chemically, tazarotene is

ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)ethynyl] nicotinate. The compound has an empirical formula of C21H21NO2S and molecular weight of 351.46. The structural formula is shown below:

Avage Cream contains the following inactive ingredients: benzyl alcohol 1%, carbomer homopolymer type B; carbomer 1342, edetate disodium, medium chain triglycerides, mineral oil, purified water, sodium thiosulfate, sorbitan monooleate, and sodium hydroxide to adjust pH.

Carcinogenesis, Mutagenesis, Impairment of Fertility

A long term study of tazarotene following oral administration of 0.025, 0.050, and 0.125 mg/kg/day to rats showed no indications of increased carcinogenic risks. Based on pharmacokinetic data from a shorter term study in rats, the highest dose of 0.125 mg/kg/day was anticipated to give systemic exposure in the rat equivalent to the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream 0.1%.

A long-term topical application study of up to 0.1% tazarotene in a gel formulation in mice, terminated at 88 weeks, showed that dose levels of 0.05, 0.125, 0.25, and 1 mg/kg/day (reduced to 0.5 mg/kg/day for males after 41 weeks due to severe dermal irritation) revealed no apparent carcinogenic effects when compared to vehicle control animals. Systemic exposure at the highest dose represented 8 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream 0.1%.

Tazarotene was non-mutagenic in the Ames assay and did not produce structural chromosomal aberrations in a human lymphocyte assay. Tazarotene was also non-mutagenic in the CHO/HGPRT mammalian cell forward gene mutation assay and was non-clastogenic in the in vivo mouse micronucleus test.

No impairment of fertility occurred in rats when male animals were treated for 70 days prior to mating and female animals were treated for 14 days prior to mating and continuing through gestation and lactation with topical doses of tazarotene gel up to 0.125 mg/kg/day. Based on data from another study, the systemic drug exposure in the rat would be equivalent to the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream 0.1%.

No impairment of mating performance or fertility was observed in male rats treated for 70 days prior to mating with oral doses of up to 1 mg/kg/day tazarotene, which represented 4 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream 0.1%.

No effect on parameters of mating performance or fertility was observed in female rats treated for 15 days prior to mating and continuing through day 7 of gestation with oral doses of tazarotene up to 2 mg/kg/day. However, there was a significant decrease in the number of estrous stages and an increase in developmental effects at that dose, which represented 7 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream 0.1% [see Use in Specific Populations (8.1)].

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Embryofetal Toxicity

Inform females of reproductive potential of the potential risk to a fetus. Advise these patients to use effective contraception during treatment with Avage Cream. Advise patients to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1, 8.3)].

Photosensitivity and Risk of Sunburn

Advise patients to avoid excessive sun exposure and to use of sunscreens and protective measures (hat, visor). Advise patients to avoid using Avage if also taking other medicines may increase sensitivity to sunlight.

Important Administration Instructions

Advise patients of the following:

1. Use Avage Cream on the face once per day, at bedtime.
2. Avage Cream is for topical use only. Do not apply to eyes, mouth, or other mucous membranes. The cream may cause severe redness, itching, burning, stinging, and peeling. Avoid accidental transfer of Avage Cream into eyes, mouth, or other mucous membranes. If contact with mucous membranes occurs, rinse thoroughly with water. Seek medical attention if eye irritation continues. Wash hands thoroughly after applying Avage Cream.
3. Gently wash face with a mild soap before applying the cream.
4. Dry skin before applying the cream.
5. Apply only a small pea sized amount (about 1/4 inch or 5 millimeter diameter) to lightly cover the entire face.
6. Apply emollients or moisturizers before or after tazarotene cream and ensure that the first cream or lotion has absorbed into the skin and dried completely.
7. In the morning, apply a moisturizing sunscreen.

© 2017 Allergan. All rights reserved.
All trademarks are the property of their respective owners.
Irvine, CA 92612
Made in the U.S.A.

73291US11

NDC 0023-9236-30 Rx Only

Avage®
(tazarotene) CREAM, 0.1%

30 grams

For Dermatologic Use Only
Not for Ophthalmic Use

ALLERGAN®

Tazarotene topical can harm an unborn baby or cause birth defects. Do not use if you are pregnant. You must have a negative pregnancy test within 2 weeks before starting this treatment. Use effective birth control while using tazarotene topical.

Stop using this medication and tell your doctor right away if you become pregnant, if you stop using birth control, or if you miss a menstrual period.

Women who use tazarotene topical should start the medication during a menstrual period.

Avoid exposure to sunlight or tanning beds. Tazarotene topical can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 15 or higher) when you are outdoors.

Do not use tazarotene topical on skin that is sunburned, windburned, dry, chapped, or irritated. Also avoid using this medication in wounds or on areas of eczema. Wait until these conditions have fully healed before using tazarotene topical.

Ask a doctor before using other skin products that might dry or irritate your skin.

Applies to tazarotene topical: topical cream, topical foam, topical gel/jelly

Along with its needed effects, tazarotene topical (the active ingredient contained in Avage) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking tazarotene topical:

• Burning or stinging of the skin (severe)
• changes in color of the treated skin
• deep grooves or lines in the skin
• dryness, itching, peeling, or redness of the skin (severe)
• pain or swelling of the treated skin
• skin rash (in patients with psoriasis only)

Some side effects of tazarotene topical may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Burning or stinging after application
• dryness, itching, peeling, or redness of the skin (mild)