Atralin Gel is a translucent to opaque, pale yellow topical gel containing 0.05% tretinoin, by weight. Other components of this formulation are benzyl alcohol, butyl paraben, butylated hydroxytoluene, carbomer 940, ethyl paraben, fish collagen hydrolyzates, glycerin, iso-butyl paraben, methylparaben, octoxynol 9, phenoxyethanol, propylparaben, purified water, sodium hyaluronate, and trolamine.

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 family of compounds, and a metabolite of Vitamin A. Tretinoin has a molecular weight of 300.44. Tretinoin has the following structure:

The contribution to efficacy of individual components of the vehicle has not been evaluated.

Last updated on RxList: 8/16/2007

Atralin Gel is a retinoid indicated for topical treatment of acne vulgaris.

Important Limitations of Use

The safety and efficacy of the use of this product in the treatment of any other disorders have not been evaluated.

Atralin Gel should be applied once daily, before bedtime, to the skin where acne lesions appear, using a thin layer to cover the entire affected area. Atralin Gel should be kept away from the eyes, the mouth, paranasal creases, and mucous membranes. Application of excessive amounts of gel will not provide incremental efficacy.

Patients treated with Atralin Gel may use cosmetics, but the areas to be treated should be cleansed thoroughly before the medication is applied.

Dosage Forms And Strengths

0.05% weight/weight topical gel, in 45 gram tubes

HOW SUPPLIED/STORAGE AND HANDLING

Atralin (tretinoin) Gel, 0.05% is 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.

Marketed by: CORIA LABORATORIES, LTD., Fort Worth, TX 76107
Manufactured by: DPT LABORATORIES, LTD., San Antonio, TX 78215
FDA rev date: 7/26/2007

Last updated on RxList: 8/16/2007

Clinical Studies Experience

Because clinical trials are conducted under prescribed 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.

In two randomized, controlled trials, 674 subjects received treatment for up to 12 weeks with Atralin Gel [see CLINICAL STUDIES]. In these studies, 50% of the subjects who were treated with Atralin Gel reported one or more adverse reactions; 30% of the subjects reported treatment-related adverse reactions. In the vehicle group, 29% of the 487 randomized subjects reported at least one adverse reaction; 5% of the subjects reported events that were treatment-related. There were no serious, treatment-related adverse reactions reported by subjects in any of the treatment groups.

Selected adverse reactions that occurred in at least 1% of subjects in the two studies combined, are shown in Table 1 (below). Most skin-related adverse reactions first appear during the first two weeks of treatment with Atralin Gel, and the incidence rate for skin-related reactions peaks around the second and third week of treatment. In some subjects the skin-related adverse reactions persists throughout the treatment period.

Table 1. Number of Subjects with Selected Adverse Reactions (Occurring in At Least 1% of Subjects)

Event	Atralin Gel (n = 674)	Vehicle Gel (n = 487)
Dry Skin	109 (16%)	8 (2%)
Peeling/Scaling/ Flaking Skin	78 (12%)	7 (1%)
Skin Burning Sensation	53 (8%)	8 (2%)
Erythema	47 (7%)	1 (< 1%)
Pruritus	11 (2%)	3 (1%)
Pain of Skin	7 (1%)	0 (0%)
Sunburn	7 (1%)	3 (1%)

When treating with Atralin Gel, caution should be exercised with the use of concomitant topical medication, medicated or abrasive soaps and cleansers, products that have a strong drying effect, and products with high concentrations of alcohol, astringents, spices, or lime. Particular caution should be exercised with the concomitant use of topical over-the-counter acne preparations containing benzoyl peroxide, sulfur, resorcinol, or salicylic acid. Allow the effects of such preparations to subside before use of Atralin Gel is begun.

Last updated on RxList: 8/16/2007

Included as part of the PRECAUTIONS section.

PATIENT COUNSELING INFORMATION
[See FDA-Approved Patient Labeling]

Pregnancy

Instruct female patients to inform the treating physician of any plans to become pregnant. If the patient becomes pregnant, discontinue use and inform the treating physician immediately. Atralin Gel should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Skin Irritation

Warn patients of the drying and irritation effects often seen during treatment. Direct patients to continue use of the medication if these effects are tolerable.

Caution patients against application of Atralin Gel around the eyes, mouth, paranasal creases, and mucous membranes as this skin is especially prone to irritation.

Skin Care Regimen

Instruct patients to clean the affected areas with an appropriate cleanser before applying Atralin Gel.

Patients may use moisturizers that are non-comedogenic, and should avoid products that could be drying or irritating.

Patients may also wear cosmetics while being treated with Atralin Gel. However, they should be instructed to remove the cosmetics and clean the area thoroughly before applying Atralin Gel.

Sun Exposure

Instruct patients to avoid direct exposure to the sun or sunlamps and to use sunscreen.

Skin Irritation

The skin of certain individuals may become dry, red, or exfoliated while using Atralin Gel. If the degree of irritation warrants, patients should be directed to temporarily reduce the amount or frequency of application of the medication, discontinue use temporarily, or discontinue use all together. Efficacy at reduced frequencies of application has not been established. If a reaction suggesting sensitivity occurs, use of the medication should be discontinued. Mild to moderate skin dryness may also be experienced; if so, use of an appropriate moisturizer during the day may be helpful.

Tretinoin has been reported to cause severe irritation on eczematous or sunburned skin and should be used with caution in patients with these conditions.

Topical over-the-counter acne preparations, concomitant topical medication, medicated cleansers, topical products with alcohol or astringents, when used with Atralin Gel, should be used with caution. [see DRUG INTERACTIONS].

Ultraviolet Light and Environmental Exposure

Unprotected exposure to sunlight, including sunlamps, should be minimized during the use of Atralin Gel. Patients who normally experience high levels of sun exposure, and those with inherent sensitivity to sun, should be warned to exercise caution. Use of sunscreen products of at least SPF 15 and protective clothing over treated areas is recommended when exposure cannot be avoided.

Weather extremes, such as wind or cold, also may be irritating to patients under treatment with tretinoin.

Fish Allergies

Atralin Gel contains soluble fish proteins and should be used with caution in patients with known sensitivity or allergy to fish. Patients who develop pruritus or urticaria should contact their health care provider.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, photocarcinogenicity and mutagenicity testing of Atralin Gel have not been performed in any species.

In a 91-week dermal study in which mice were administered 0.017% and 0.035% formulations of tretinoin in a different formulation, cutaneous squamous cell carcinomas and papillomas in the treatment area were observed in some female mice. These concentrations are near the tretinoin concentration of Atralin Gel. A dose-related 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, (1.5 and 3 mg/m², respectively, approximately 2 and 4 times the clinical dose based on body surface area comparison). The biological significance of these findings is not clear because they occurred at doses that exceeded the dermal maximum tolerated dose (MTD) 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 (0.075 mg/m² approximately 0.1 times the clinical dose, based on body surface area comparison) of tretinoin was administered topically to mice.

Studies in hairless albino mice with a different formulation 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 was confirmed in a later study in pigmented mice, and dark pigmentation did not overcome the enhancement of photocarcinogenesis 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.

The genotoxic potential of tretinoin was evaluated in an in vitro bacterial reversion test, an in vitro chromosomal aberration assay in human lymphocytes and in an in vivo rat micronucleus assay. All tests were negative.

In dermal fertility studies of another tretinoin formulation in rats, slight (not statistically significant) decreases in sperm count and motility were seen at 0.5 mg/kg/day (3 mg/m², approximately 4 times the clinical dose based on body surface area comparison), and slight (not statistically significant) increases in the number and percent of nonviable embryos in females treated with 0.25 mg/kg/day and above (1.5 mg/m², approximately 2 times the clinical dose based on body surface area comparison), were observed.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no well-controlled trials in pregnant women treated with Atralin Gel. Atralin Gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Atralin Gel at doses of 0.1, 0.3 and 1 g/kg/day was tested for maternal and developmental toxicity in pregnant Sprague-Dawley rats by dermal application. The dose of 1 g/kg/day was approximately 4 times the clinical dose assuming 100% absorption and based on body surface area comparison. Possible tretinoin-associated teratogenic effects (craniofacial abnormalities (hydrocephaly), asymmetrical thyroids, variations in ossification, and increased supernumerary ribs) were noted in the fetuses of Atralin Gel treated animals. These findings were not observed in control animals. Other maternal and reproductive parameters in the Atralin Gel treated animals were not different from control. For purposes of comparison of the animal exposure to human exposure, the clinical dose is defined as 2 g of Atralin Gel applied daily to a 50 kg person.

Oral tretinoin has been shown to be teratogenic in rats, mice, rabbits, hamsters and nonhuman primates. Tretinoin was teratogenic in Wistar rats when given orally in doses greater than 1 mg/kg/day (approximately 8 times the clinical dose based on body surface area comparison). In the cynomolgus monkey, fetal malformations were reported for doses of 10 mg/kg/day, but none were observed at 5 mg/kg/day (approximately 80 times the clinical dose based on body surface area comparison), although increased skeletal variations were observed at all doses. Dose-related increases in embryolethality and abortion also were reported. Similar results have also been reported in pigtail macaques.

Topical tretinoin in a different formulation has generated equivocal results in animal teratogenicity tests. There is evidence for teratogenicity (shortened or kinked tail) of topical tretinoin in Wistar rats at doses greater than 1 mg/kg/day (approximately 8 times the clinical dose assuming 100% absorption and based on body surface area comparison). Anomalies (humerus: short 13%, bent 6%, os parietal incompletely ossified 14%) have also been reported when 10 mg/kg/day (approximately 160 times the clinical dose assuming 100% absorption and based on body surface area comparison ) was topically applied. Supernumerary ribs have been a consistent finding in rats when dams were treated topically or orally with retinoids.

With widespread use of any drug, a small number of birth defect reports associated temporally with the administration of the drug would be expected by chance alone. Cases of temporally associated congenital malformations have been reported with use of other topical tretinoin products. The significance of these spontaneous reports in terms of risk to the fetus is not known.

Nonteratogenic effects on fetuses

Oral tretinoin has been shown to be fetotoxic in rats when administered in doses 20 times the clinical dose based on a body surface area comparison. Topical tretinoin has been shown to be fetotoxic in rabbits when administered in doses 8 times the clinical dose based on a body surface area comparison.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Atralin Gel is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in children below the age of 10 have not been established.

A total of 381 pediatric subjects (aged 10 to 16 years), treated with Atralin Gel were enrolled into the two clinical studies. Across these two studies, comparable safety and efficacy were observed between pediatric and adult subjects.

Geriatric Use

Safety and effectiveness in a geriatric population have not been established. Clinical studies of Atralin Gel did not include any subjects over age 65 to determine whether they respond differently from younger subjects.

Last updated on RxList: 8/16/2007

No information provided.

None

Last updated on RxList: 8/16/2007

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 (RAR α, RAR β, and RAR γ) 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-cis-retinoic 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-cis-retinoic 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%

Compound	Baseline Concentration Range (ng/ml)	Day 14 Concentration Range (ng/ml)
Tretinoin	0.68-1.62	0.69-2.88
13-cis-retinoic acid	0.67-1.79	0.51-2.26
4-oxo-13-cis-retinoic acid	0.82-5.92	0.59-6.96

Clinical Studies

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 studies. Subjects in these two studies 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 Study 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 Studies 1 and 2

Study 1	Atralin Gel N=375	Vehicle N=185
Global Severity Score Success*	78 (21%)	23 (12%)
Non-Inflammatory Facial Lesions
Mean Baseline Count	50.7	52.4
Mean Absolute Reduction	21.8	10.3
Mean Percent Reduction	43%	21%
Inflammatory Facial Lesions
Mean Baseline Count	23.4	23.9
Mean Absolute Reduction	9.7	5.8
Mean Percent Reduction	41%	26%
Total Facial Lesions
Mean Baseline Count	74.1	76.3
Mean Absolute Reduction	31.4	16.1
Mean Percent Reduction	43%	22%
Study 2	Atralin Gel N=299	Vehicle N=302
Global Severity Score Success**	69 (23%)	42 (14%)
Non-Inflammatory Facial Lesions
Mean Baseline Count	51.9	52.7
Mean Absolute Reduction	18.7	10.8
Mean Percent Reduction	37%	20%
Inflammatory Facial Lesions
Mean Baseline Count	22.9	23.4
Mean Absolute Reduction	7.0	4.0
Mean Percent Reduction	30%	17%
Total Facial Lesions
Mean Baseline Count	74.8	76.1
Mean Absolute Reduction	25.7	14.7
Mean Percent Reduction	35%	19%
*Success was defined as 0 (clear) or 1 (very mild) ** Success was defined as 0 (clear) or 1 (very mild) with at least 2 grades reduction from baseline

Last updated on RxList: 8/16/2007

FDA-Approved Patient Labeling

Atralin™
(A-truh-lin)
(tretinoin) Gel, 0.05%

For Skin Use Only
Important: Not for mouth, eye, or vaginal use.

Read the patient information that comes with Atralin Gel before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your acne or treatment.

What is Atralin Gel?

Atralin Gel is a prescription medicine used on the skin to treat acne. Acne is a condition in which the skin has blackheads, whiteheads, and other pimples.

Atralin Gel may not be right for you. Tell your doctor about all of your health conditions, including if you:

• are allergic to fish
• have a skin condition called eczema
• are pregnant or planning to become pregnant. Atralin Gel may harm your fetus (unborn baby).
• are breastfeeding. It is not known if Atralin Gel passes into breast milk and to your baby.

Tell your doctor about all the medicines you take including prescription and nonprescription medicines, vitamins and herbal supplements. Some medicines can make your skin more sensitive to sunlight.

Know the medicines you take. Keep a list of your medicines with you to show your doctor. Your doctor will decide if you can use Atralin Gel with your other medicines.

Tell your doctor about all of the skin products you use. Your doctor will tell you which skin products you can use with Atralin Gel. You should avoid using skin products that can dry or irritate your skin because skin dryness and irritation are increased with Atralin Gel. Skin products that can dry and irritate your skin include:

• products that contain alcohol, astringents, or spices
• acne medicines that contain benzoyl peroxide, sulfur, resorcinol, or salicylic acid
• medicated soap or skin cleansers

How should I use Atralin Gel?

• Wash your skin with mild, non-medicated soap and dry your skin gently. Apply Atralin once a day before bedtime.
• Squeeze a small amount of Atralin Gel (about the size of a pea) on your fingertip. Apply Atralin Gel , using a thin layer to cover the entire affected area.. Smooth Atralin Gel gently into your skin.
• Do not put Atralin Gel, near your mouth, eyes, on the corners of your nose, or on open sores. Spread Atralin away from these areas when putting Atralin on your skin.
• Do not use more Atralin Gel than your doctor has prescribed. Do not use Atralin Gel more often than your doctor has told you. Too much Atralin Gel may irritate or increase the irritation of your skin, and will not give faster or better results.
• You can use a facial cream or lotion of SPF 15 or higher each morning after washing your face. Follow your doctor's advice because you need to use a cream or lotion that will not make your acne worse. You may use cosmetics with Atralin Gel. However, clean your face before using cosmetics and remove cosmetics from your skin before using Atralin Gel. Talk to your doctor about recommended cosmetics.
• You may not see improvement right away. Atralin Gel may work better for some patients than for others.
• Once your acne is under control you should continue to use Atralin Gel as your doctor instructs you to do.

What should I avoid while using Atralin Gel?

Spend as little time as possible in the sun. Use a daily sunscreen with a SPF 15 rating or higher, protective clothing, and a wide brimmed hat to protect you from sunlight. When outside, even on hazy days, areas treated with Atralin Gel should be protected. Do not use sunlamps or tanning beds. Atralin Gel may make you get sunburned more easily. If you do get sunburned, stop using Atralin Gel until your skin is completely back to normal. Talk to your doctor about how to protect your skin if you must be in sunlight a lot.

Avoid cold weather and wind as much as possible, and use clothing to protect you from the weather. Skin treated with Atralin Gel may dry out or get wind burned more easily.

What are the possible side effects of Atralin Gel?

The most common side effect with Atralin Gel is skin irritation. This can include dry skin, burning, redness, excessive flaking or peeling. Some of these side effects may go away or bother you less after you have used Atralin Gel for a few weeks. Tell your doctor if these side effects become a problem. Your doctor may ask you to stop using Atralin Gel for a while, change the amount of Atralin Gel you are using, or have you use Atralin GEL less than once a day.

These are not all the side effects possible with Atralin Gel. For more information, ask your doctor or pharmacist.

How do I store Atralin Gel?

Store Atralin Gel at controlled room temperature 20° - 25°C (68° - 77°F) with excursions permitted between 15°-30°C (59°-86°F).

Protect from freezing.

Keep Atralin Gel and all medicines out of the reach of children.

General Information about Atralin Gel

Do not allow anyone else to use this medicine. Medicines are sometimes prescribed for conditions not mentioned in patient information leaflets. Do not use Atralin Gel for a condition for which it was not prescribed by your doctor. Do not share Atralin Gel with other people, even if they have the same condition you have. It may harm them.

What are the ingredients of Atralin Gel?

Active ingredient: tretinoin

Inactive ingredients: benzyl alcohol, butyl paraben, butylated hydroxytoluene, carbomer 940, ethyl paraben, fish collagen hydrolyzates, glycerin, iso-butyl paraben, methylparaben, octoxynol 9, phenoxyethanol, propylparaben, purified water, sodium hyaluronate, and trolamine.

This leaflet gives the most important information about Atralin Gel. For more information about Atralin Gel, talk with your doctor. You can ask your doctor or pharmacist for the information about Atralin Gel that is written for health professionals. You can also contact Coria Laboratories. Ltd. by calling their toll-free number: 1-866-819-9007.

Last updated on RxList: 8/16/2007

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

TRETINOIN - TOPICAL

(tret-ih-NO-in)

COMMON BRAND NAME(S): Retin-A

USES: This medication is used to treat acne. It may decrease the number and severity of acne pimples and promote quick healing of pimples that do develop. Tretinoin belongs to a class of medications called retinoids. It works by affecting the growth of skin cells.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

Other forms of this medication are used to improve the appearance of the skin and minimize fine wrinkles. Your doctor may also use this medication to treat other conditions.

HOW TO USE: Read the Patient Information Leaflet if one is available from your pharmacist. Consult your doctor or pharmacist if you have questions.

Wash your hands before applying this medication. Gently clean the affected skin with a mild or soapless cleanser and pat dry. Use your fingertips to apply a small amount of medication (about the size of a pea) in a thin layer, usually once daily at bedtime or as directed by your doctor. A gauze pad or cotton swab can be used to apply the liquid. For some preparations, you should wait 20-30 minutes after cleaning your face before applying this medication. Consult the label directions, the Patient Information Leaflet, or your pharmacist if you have any questions.

Use this medication on the skin only. Do not apply to the inner lip area or inside the nose/mouth. Do not apply to cut, scraped, sunburned, or eczema-affected skin.

Avoid getting this medication in your eyes. If this medication gets into your eyes, flush with large amounts of water. Call your doctor if eye irritation develops. Wash your hands after using the medication to avoid accidentally getting it in your eyes.

During the first few weeks of using tretinoin, your acne might appear worse because the medication is working on pimples forming inside the skin. It may take up to 8-12 weeks to notice results from this medication.

Use it regularly in order to get the most benefit from it. To help you remember, use it at the same time each day. Do not use a larger amount or use it more frequently than recommended. Your skin will not improve any faster, and it will increase the risk of developing redness, peeling and pain.

This medication is available in different strengths and forms (e.g., gel, cream, solution). The best type of medication for you to use will depend on the condition of your skin and your response to therapy. Inform your doctor if your condition persists or worsens.

SIDE EFFECTS: A brief sensation of warmth or stinging may occur immediately after applying the medication. Skin redness, dryness, itching, scaling, mild burning, or worsening of acne may occur during the first 2-4 weeks of using the medication. These effects usually decrease with continued use. A daytime moisturizer may be helpful for excessive dry skin (see Notes).

If any of these effects persist or worsen, notify your doctor or pharmacist promptly. Your doctor may want you to decrease how often you use tretinoin, change the strength or type, or have you stop using it.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Notify your doctor if you experience: blistering, crusting, severe burning/swelling of the skin, eye redness and watering (conjunctivitis), eyelid swelling, skin discoloration.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using tretinoin, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: eczema.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Weather extremes such as wind or cold may also be irritating to the skin. Use a sunscreen daily, and wear protective clothing when outdoors. Wait until your skin has completely recovered from a sunburn before using tretinoin.

Avoid electrolysis, waxing and chemical depilatories for hair removal on the treated areas while using this product.

If you have recently used products containing sulfur, resorcinol or salicylic acid, use tretinoin with caution. Wait until the effects of such products on the skin have decreased before using tretinoin.

This medication is not recommended for use during pregnancy. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: See also Precautions section.

Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medications because very serious interactions may occur: products containing alpha hydroxy acid, products containing glycolic acid.

If you are currently using medications containing the ingredients listed above, tell your doctor or pharmacist before starting tretinoin.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: hair perming solutions, alcohol/lime/menthol-containing products (such as astringents, toners, shaving lotions), medicated or abrasive soaps and cleansers, products containing sulfur, resorcinol or salicylic acid, soaps and cosmetics with a strong drying effect, other drugs that may increase your sensitivity to sunlight (e.g., fluoroquinolones such as ciprofloxacin, tetracyclines, thiazide water pills such as hydrochlorothiazide, sulfa drugs such as sulfamethoxazole, phenothiazines such as chlorpromazine).

Benzoyl peroxide can be very irritating and may decrease the effectiveness of tretinoin if the two products are applied at the same time. Talk with your doctor or pharmacist about the safe use of prescription and non-prescription benzoyl peroxide products (e.g., Pro-Activ, Clearasil).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. This medicine may be harmful if swallowed. Symptoms of overdose may include excessive redness, peeling, and discomfort.

NOTES: Do not share this medication with others.

Cosmetics may be used, but clean skin thoroughly before applying the medication.

Some cosmetics and soaps may worsen your acne. Moisturizers may be safe to use. When buying cosmetics, moisturizers or other skin care products, check the label for "non-comedogenic" or "non-acnegenic." These products are unlikely to worsen your acne. Ask your doctor or pharmacist which products are safe to use. Remember, acne is not caused by dirt. Cleaning your skin too often or too vigorously can irritate your skin and worsen acne.

MISSED DOSE: If you forget to use this medication, use it as soon as you remember if you remember the same day. If you don't remember until morning, wait until your next dose is scheduled.

STORAGE: Store at room temperature between 59-77 degrees F (15-25 degrees C) away from light and moisture. Gel preparations are flammable. Do not expose to heat or fire sources. Do not smoke during use. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.