Retin-A

Ortho-McNeil Janssen Pharmaceuticals, Inc.

Retin-A (tretinoin) Cream • Gel • Liquid

FULL PRESCRIBING INFORMATION: CONTENTS*

• Description
• Clinical Pharmacology
• Retin-A Indications and Usage
• Contraindications
• Precautions
  • General
  • Drug Interactions
  • Carcinogenesis
  • Pregnancy
  • Nursing Mothers
• Side Effects
• Overdosage
• Dosage and Administration
• How Supplied
  • Storage Conditions
• PATIENT INSTRUCTIONS
• PRINCIPAL DISPLAY PANEL - 20 g Carton
• PRINCIPAL DISPLAY PANEL - 20 g Carton
• PRINCIPAL DISPLAY PANEL - 20 g Carton
• PRINCIPAL DISPLAY PANEL - 15 g Carton
• PRINCIPAL DISPLAY PANEL - 15 g Carton

FULL PRESCRIBING INFORMATION

For Topical Use Only

Description

RETIN-A Gel, Cream and Liquid, containing tretinoin are used for the topical treatment of acne vulgaris. RETIN-A Gel contains tretinoin (retinoic acid, vitamin A acid) in either of two strengths, 0.025% or 0.01% by weight, in a gel vehicle of butylated hydroxytoluene, hydroxypropyl cellulose and alcohol (denatured with tert-butyl alcohol and brucine sulfate) 90% w/w. RETIN-A (tretinoin) Cream contains tretinoin in either of three strengths, 0.1%, 0.05%, or 0.025% by weight, in a hydrophilic cream vehicle of stearic acid, isopropyl myristate, polyoxyl 40 stearate, stearyl alcohol, xanthan gum, sorbic acid, butylated hydroxytoluene, and purified water. RETIN-A Liquid contains tretinoin 0.05% by weight, polyethylene glycol 400, butylated hydroxytoluene and alcohol (denatured with tert-butyl alcohol and brucine sulfate) 55%. Chemically, tretinoin is all-trans-retinoic acid and has the following structure:

Clinical Pharmacology

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.

Retin-A Indications and Usage

RETIN-A is indicated for topical application in the treatment of acne vulgaris. The safety and efficacy of the long-term use of this product in the treatment of other disorders have not been established.

Contraindications

Use of the product should be discontinued if hypersensitivity to any of the ingredients is noted.

Precautions

General

If a reaction suggesting sensitivity or chemical irritation occurs, use of the medication should be discontinued. Exposure to sunlight, including sunlamps, should be minimized during the use of RETIN-A, and patients with sunburn should be advised not to use the product until fully recovered because of heightened susceptibility to sunlight as a result of the use of tretinoin. Patients who may be required to have considerable sun exposure due to occupation and those with inherent sensitivity to the sun should exercise particular caution. Use of sunscreen products 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.

RETIN-A (tretinoin) acne treatment should be kept away from the eyes, the mouth, angles of the nose, and mucous membranes. Topical use may induce severe local erythema and peeling at the site of application. If the degree of local irritation warrants, patients should be directed to use the medication less frequently, discontinue use temporarily, or discontinue use altogether. Tretinoin has been reported to cause severe irritation on eczematous skin and should be used with utmost caution in patients with this condition.

Drug Interactions

Concomitant topical medication, medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect, and products with high concentrations of alcohol, astringents, spices or lime should be used with caution because of possible interaction with tretinoin. Particular caution should be exercised in using preparations containing sulfur, resorcinol, or salicylic acid with RETIN-A. It also is advisable to "rest" a patient's skin until the effects of such preparations subside before use of RETIN-A is begun.

Carcinogenesis

Long-term animal studies to determine the carcinogenic potential of tretinoin have not been performed. Studies in hairless albino mice suggest that tretinoin may accelerate the tumorigenic potential of weakly carcinogenic light from a solar simulator. In other studies, when lightly pigmented hairless mice treated with tretinoin were exposed to carcinogenic doses of UVB light, the incidence and rate of development of skin tumors was reduced. Due to significantly different experimental conditions, no strict comparison of these disparate data is possible. Although the significance of these studies to man is not clear, patients should avoid or minimize exposure to sun.

Pregnancy

Teratogenic effects

Pregnancy Category C

Oral tretinoin has been shown to be teratogenic in rats when given in doses 1000 times the topical human dose. Oral tretinoin has been shown to be fetotoxic in rats when given in doses 500 times the topical human dose.

Topical tretinoin has not been shown to be teratogenic in rats and rabbits when given in doses of 100 and 320 times the topical human dose, respectively (assuming a 50 kg adult applies 250 mg of 0.1% cream topically). However, at these topical doses, delayed ossification of a number of bones occurred in both species. These changes may be considered variants of normal development and are usually corrected after weaning. There are no adequate and well-controlled studies in pregnant women. Tretinoin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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 RETIN-A is administered to a nursing woman.

GELS ARE FLAMMABLE. Note: Keep away from heat and flame. Keep tube tightly closed.

Side Effects

The skin of certain sensitive individuals may become excessively red, edematous, blistered, or crusted. If these effects occur, the medication should either be discontinued until the integrity of the skin is restored, or the medication should be adjusted to a level the patient can tolerate. True contact allergy to topical tretinoin is rarely encountered. Temporary hyper- or hypopigmentation has been reported with repeated application of RETIN-A. Some individuals have been reported to have heightened susceptibility to sunlight while under treatment with RETIN-A. To date, all adverse effects of RETIN-A have been reversible upon discontinuance of therapy (see Dosage and Administration Section).

Overdosage

If medication is applied excessively, no more rapid or better results will be obtained and marked redness, peeling, or discomfort may occur. Oral ingestion of the drug may lead to the same side effects as those associated with excessive oral intake of Vitamin A.

Dosage and Administration

RETIN-A Gel, Cream or Liquid should be applied once a day, before retiring, to the skin where acne lesions appear, using enough to cover the entire affected area lightly. Liquid: The liquid may be applied using a fingertip, gauze pad, or cotton swab. If gauze or cotton is employed, care should be taken not to oversaturate it to the extent that the liquid would run into areas where treatment is not intended. Gel: Excessive application results in "pilling" of the gel, which minimizes the likelihood of over application by the patient.

Application may cause a transitory feeling of warmth or slight stinging. In cases where it has been necessary to temporarily discontinue therapy or to reduce the frequency of application, therapy may be resumed or frequency of application increased when the patients become able to tolerate the treatment.

Alterations of vehicle, drug concentration, or dose frequency should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance.

During the early weeks of therapy, an apparent exacerbation of inflammatory lesions may occur. This is due to the action of the medication on deep, previously unseen lesions and should not be considered a reason to discontinue therapy.

Therapeutic results should be noticed after two to three weeks but more than six weeks of therapy may be required before definite beneficial effects are seen.

Once the acne lesions have responded satisfactorily, it may be possible to maintain the improvement with less frequent applications, or other dosage forms.

Patients treated with RETIN-A (tretinoin) acne treatment may use cosmetics, but the area to be treated should be cleansed thoroughly before the medication is applied. (See Precautions.)

How Supplied

RETIN-A (tretinoin) is supplied as:

Storage Conditions

RETIN-A Liquid, 0.05%, and RETIN-A Gel, 0.025% and 0.01%: store below 86°F. RETIN-A Cream, 0.1%, 0.05%, and 0.025%: store below 80°F.

Rx Only

Ortho Dermatologics™

Marketed by: Ortho Dermatologics™

Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.,

Los Angeles, CA 90045

Manufactured by: DRAXIS Specialty Pharmaceuticals, Inc., Qc, Canada H9H 4J4

©OMJPI 2010 30012823 Made in Canada 201691

PATIENT INSTRUCTIONS

Retin-A^®
(tretinoin)

Acne Treatment

IMPORTANT

Read Directions Carefully Before Using

Cream • Gel • Liquid

For Topical Use Only

THIS LEAFLET TELLS YOU ABOUT RETIN-A (TRETINOIN) ACNE TREATMENT AS PRESCRIBED BY YOUR PHYSICIAN. THIS PRODUCT IS TO BE USED ONLY ACCORDING TO YOUR DOCTOR'S INSTRUCTIONS, AND IT SHOULD NOT BE APPLIED TO OTHER AREAS OF THE BODY OR TO OTHER GROWTHS OR LESIONS. THE LONG-TERM SAFETY AND EFFECTIVENESS OF THIS PRODUCT IN OTHER DISORDERS HAVE NOT BEEN EVALUATED. IF YOU HAVE ANY QUESTIONS, BE SURE TO ASK YOUR DOCTOR.

WARNINGS AND PRECAUTIONS

The effects of the sun on your skin. As you know, overexposure to natural sunlight or the artificial sunlight of a sunlamp can cause sunburn. Overexposure to the sun over many years may cause premature aging of the skin and even skin cancer. The chance of these effects occurring will vary depending on skin type, the climate and the care taken to avoid overexposure to the sun. Therapy with RETIN-A may make your skin more susceptible to sunburn and other adverse effects of the sun, so unprotected exposure to natural or artificial sunlight should be minimized.

Laboratory findings. When laboratory mice are exposed to artificial sunlight, they often develop skin tumors. These sunlight-induced tumors may appear more quickly and in greater number if the mouse is also topically treated with the active ingredient in RETIN-A, tretinoin. In some studies, under different conditions, however, when mice treated with tretinoin were exposed to artificial sunlight, the incidence and rate of development of skin tumors was reduced. There is no evidence to date that tretinoin alone will cause the development of skin tumors in either laboratory animals or humans. However, investigations in this area are continuing.

Use caution in the sun. When outside, even on hazy days, areas treated with RETIN-A should be protected. An effective sunscreen should be used any time you are outside (consult your physician for a recommendation of an SPF level which will provide you with the necessary high level of protection). For extended sun exposure, protective clothing, like a hat, should be worn. Do not use artificial sunlamps while you are using RETIN-A. If you do become sunburned, stop your therapy with RETIN-A until your skin has recovered.

Avoid excessive exposure to wind or cold. Extremes of climate tend to dry or burn normal skin. Skin treated with RETIN-A may be more vulnerable to these extremes. Your physician can recommend ways to manage your acne treatment under such conditions.

Possible problems. The skin of certain sensitive individuals may become excessively red, swollen, blistered or crusted. If you are experiencing severe or persistent irritation, discontinue the use of RETIN-A and consult your physician.

There have been reports that, in some patients, areas treated with RETIN-A developed a temporary increase or decrease in the amount of skin pigment (color) present. The pigment in these areas returned to normal either when the skin was allowed to adjust to RETIN-A or therapy was discontinued.

Use other medication only on your physician's advice. Only your physician knows which other medications may be helpful during treatment and will recommend them to you if necessary. Follow the physician's instructions carefully. In addition, you should avoid preparations that may dry or irritate your skin. These preparations may include certain astringents, toiletries containing alcohol, spices or lime, or certain medicated soaps, shampoos and hair permanent solutions. Do not allow anyone else to use this medication.

Do not use other medications with RETIN-A which are not recommended by your doctor. The medications you have used in the past might cause unnecessary redness or peeling.

If you are pregnant, think you are pregnant or are nursing an infant: No studies have been conducted in humans to establish the safety of RETIN-A in pregnant women. If you are pregnant, think you are pregnant, or are nursing a baby, consult your physician before using this medication.

GELS ARE FLAMMABLE. Note: Keep away from heat and flame. Keep tube tightly closed.

AND WHILE YOU'RE ON RETIN-A THERAPY

Use a mild, non-medicated soap. Avoid frequent washings and harsh scrubbing. Acne isn't caused by dirt, so no matter how hard you scrub, you can't wash it away. Washing too frequently or scrubbing too roughly may at times actually make your acne worse. Wash your skin gently with a mild, bland soap. Two or three times a day should be sufficient. Pat skin dry with a towel. Let the face dry 20 to 30 minutes before applying RETIN-A. Remember, excessive irritation such as rubbing, too much washing, use of other medications not suggested by your physician, etc., may worsen your acne.

HOW TO USE RETIN-A (TRETINOIN)

To get the best results with RETIN-A therapy, it is necessary to use it properly. Forget about the instructions given for other products and the advice of friends. Just stick to the special plan your doctor has laid out for you and be patient. Remember, when RETIN-A is used properly, many users see improvement by 12 weeks. AGAIN, FOLLOW INSTRUCTIONS – BE PATIENT – DON'T START AND STOP THERAPY ON YOUR OWN – IF YOU HAVE QUESTIONS, ASK YOUR DOCTOR.

To help you use the medication correctly, keep these simple instructions in mind.

• Apply RETIN-A once daily before bedtime, or as directed by your physician. Your physician may advise, especially if your skin is sensitive, that you start your therapy by applying RETIN-A every other night. First, wash with a mild soap and dry your skin gently. WAIT 20 to 30 MINUTES BEFORE APPLYING MEDICATION; it is important for skin to be completely dry in order to minimize possible irritation.
• It is better not to use more than the amount suggested by your physician or to apply more frequently than instructed. Too much may irritate the skin, waste medication and won't give faster or better results.
• Keep the medication away from the corners of the nose, mouth, eyes and open wounds. Spread away from these areas when applying.
• Cream: Squeeze about a half inch or less of medication onto the fingertip. While that should be enough for your whole face, after you have some experience with the medication you may find you need slightly more or less to do the job. The medication should become invisible almost immediately. If it is still visible, you are using too much. Cover the affected area lightly with RETIN-A (tretinoin) Cream by first dabbing it on your forehead, chin and both cheeks, then spreading it over the entire affected area. Smooth gently into the skin.
• Gel: Squeeze about a half inch or less of medication onto the fingertip. While that should be enough for your whole face, after you have some experience with the medication you may find you need slightly more or less to do the job. The medication should become invisible almost immediately. If it is still visible, or if dry flaking occurs from the gel within a minute or so, you are using too much. Cover the affected area lightly with RETIN-A (tretinoin) Gel by first dabbing it on your forehead, chin and both cheeks, then spreading it over the entire affected area. Smooth gently into the skin.
• Liquid: RETIN-A (tretinoin) Liquid may be applied to the skin where acne lesions appear, spreading the medication over the entire affected area, using a fingertip, gauze pad, or cotton swab. If gauze or cotton is employed, care should be taken not to oversaturate it to the extent that the liquid would run into areas where treatment is not intended (such as corners of the mouth, eyes, and nose).
• It is recommended that you apply a moisturizer or a moisturizer with sunscreen that will not aggravate your acne (noncomedogenic) every morning after you wash.

WHAT TO EXPECT WITH YOUR NEW TREATMENT

RETIN-A works deep inside your skin and this takes time. You cannot make RETIN-A work any faster by applying more than one dose each day, but an excess amount of RETIN-A may irritate your skin. Be patient.

There may be some discomfort or peeling during the early days of treatment. Some patients also notice that their skin begins to take on a blush.

These reactions do not happen to everyone. If they do, it is just your skin adjusting to RETIN-A and this usually subsides within two to four weeks. These reactions can usually be minimized by following instructions carefully. Should the effects become excessively troublesome, consult your doctor.

BY THREE TO SIX WEEKS, some patients notice an appearance of new blemishes (papules and pustules). At this stage it is important to continue using RETIN-A.

If RETIN-A is going to have a beneficial effect for you, you should notice a continued improvement in your appearance after 6 to 12 weeks of therapy. Don't be discouraged if you see no immediate improvement. Don't stop treatment at the first signs of improvement.

Once your acne is under control you should continue regular application of RETIN-A until your physician instructs otherwise.

IF YOU HAVE QUESTIONS

All questions of a medical nature should be taken up with your doctor. For more information about RETIN-A (tretinoin), call our toll-free number: 800-426-7762. Call between 9:00 a.m. and 3:00 p.m. Eastern Time, Monday through Friday.

Ortho Dermatologics™

Marketed by: Ortho Dermatologics™

Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.,

Los Angeles, CA 90045

Manufactured by: DRAXIS Specialty Pharmaceuticals, Inc., Qc, Canada H9H 4J4

©OMJPI 2010 30012823 Made in Canada 201691

PRINCIPAL DISPLAY PANEL - 20 g Carton

NDC 0062-0165-01

Retin-A^® Cream
(tretinoin) 0.025%

Contains: Tretinoin 0.025%, stearic acid, isopropyl
myristate, polyoxyl 40 stearate, stearyl alcohol, xanthan
gum, sorbic acid, butylated hydroxytoluene,
and purified water

For Topical Use only   NET WT. 20g
Rx only
Dosage: See package insert.
Store below 80° F.
Warning: Keep out of reach of children.

Ortho Dermatologics
Marketed by: Ortho Dermatologics
Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.
Los Angeles, CA 90045

PRINCIPAL DISPLAY PANEL - 20 g Carton

NDC 0062-0175-12

Retin-A^® Cream
(tretinoin) 0.05%

Contains: Tretinoin 0.05%, stearic acid, isopropyl
myristate, polyoxyl 40 stearate, stearyl alcohol, xanthan
gum, sorbic acid, butylated hydroxytoluene,
and purified water

For Topical Use only   NET WT. 20g
Rx only
Dosage: See package insert.
Store below 80° F.
Warning: Keep out of reach of children.

Ortho Dermatologics
Marketed by: Ortho Dermatologics
Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.
Los Angeles, CA 90045

PRINCIPAL DISPLAY PANEL - 20 g Carton

NDC 0062-0275-23

Retin-A^® Cream
(tretinoin) 0.1%

Contains: Tretinoin 0.1%, stearic acid, isopropyl
myristate, polyoxyl 40 stearate, stearyl alcohol, xanthan
gum, sorbic acid, butylated hydroxytoluene,
and purified water

For Topical Use only   NET WT. 20g
Rx only
Dosage: See package insert.
Store below 80° F.
Warning: Keep out of reach of children.

Ortho Dermatologics
Marketed by: Ortho Dermatologics
Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.
Los Angeles, CA 90045

PRINCIPAL DISPLAY PANEL - 15 g Carton

NDC 0062-0575-44

Retin-A^® Gel
(tretinoin) 0.01%

Contains: Tretinoin 0.01%, hydroxypropyl cellulose,
butylated hydroxytoluene, alcohol, (denatured with tert-
butyl alcohol and brucine sulfate) 90% w/w.

For topical Use Only   NET WT. 15g
Rx only
Dosage: See package insert.
Store below 86° F.
Warning: Keep out of reach of children.

Ortho Dermatologics
Marketed by: Ortho Dermatologics
Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.
Los Angeles, CA 90045

PRINCIPAL DISPLAY PANEL - 15 g Carton

NDC 0062-0475-42

Retin-A^® Gel
(tretinoin) 0.025%

Contains: Tretinoin 0.01%, hydroxypropyl cellulose,
butylated hydroxytoluene, alcohol, (denatured with tert-
butyl alcohol and brucine sulfate) 90% w/w.

For topical Use Only   NET WT. 15g
Rx only
Dosage: See package insert.
Store below 86° F.
Warning: Keep out of reach of children.

Ortho Dermatologics
Marketed by: Ortho Dermatologics
Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.
Los Angeles, CA 90045