Label: TRETINOIN gel
TRETINOIN cream

For External Use Only.

Not For Ophthalmic Use.

Rx Only

Prescribing Information

Tretinoin Gel, USP and Tretinoin Cream, USP are used for the topical treatment of acne vulgaris. Each gram of tretinoin gel contains tretinoin in either of two strengths, 0.025% (0.25 mg) or 0.01% (0.1 mg) in a gel vehicle of hydroxypropyl cellulose, butylated hydroxytoluene, and alcohol 90% w/w. Each gram of tretinoin cream contains tretinoin in either of three strengths, 0.1% (1 mg), 0.05% (0.5 mg), or 0.025% (0.25 mg) in a hydrophilic cream vehicle of: stearic acid, isopropyl myristate, polyoxyl 40 stearate, stearyl alcohol, xanthan gum, sorbic acid, butylated hydroxytoluene, and purified water. Chemically, tretinoin is all-trans-retinoic acid. It has a molecular weight of 300.44 and has the following structural formula:

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.

Tretinoin gel and cream are 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.

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

GELS ARE FLAMMABLE. AVOID FIRE, FLAME OR SMOKING DURING USE. Keep out of reach of children. Keep tube tightly closed. Do not expose to heat or store at temperatures above 120°F (49°C).

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 a tretinoin preparation. Some individuals have been reported to have heightened susceptibility to sunlight while under treatment with tretinoin. To date, all adverse effects of tretinoin have been reversible upon discontinuance of therapy (see Dosage and Administration Section).

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.

Tretinoin gel or cream should be applied once a day, before retiring, to the skin where acne lesions appear, using enough to cover the entire affected area lightly. 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 tretinoin preparations may use cosmetics, but the areas to be treated should be cleansed thoroughly before the medication is applied (see Precautions).

Tretinoin Gel, USP

Tretinoin Cream, USP

Tretinoin Gel, USP: store below 30°C (86°F).

Tretinoin Cream, USP: store below 27°C (80°F)

Manufactured by Padagis®
Yeruham, Israel

www.padagis.com

Rev 12-23
08T00 RC PH7

Acne Treatment

IMPORTANT Read Directions Carefully Before Using

THIS LEAFLET TELLS YOU ABOUT 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

TRETINOIN GELS ARE FLAMMABLE. AVOID FIRE, FLAME OR SMOKING DURING USE. Keep out of reach of children. Keep tube tightly closed. Do not expose to heat or store at temperatures above 120°F (49°C).

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 chances of these effects occurring will vary depending on skin type, the climate and the care taken to avoid overexposure to the sun. Therapy with tretinoin 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 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 tretinoin 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 tretinoin. If you do become sunburned, stop your therapy with tretinoin 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 tretinoin 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 tretinoin and consult your physician.

There have been reports that, in some patients, areas treated with tretinoin 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 tretinoin or therapy was discontinued.

Use other medication only on your doctor’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 tretinoin 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 tretinoin in pregnant women. If you are pregnant, think you are pregnant, or are nursing a baby, consult your physician before using this medication.

AND WHILE YOU’RE ON TRETINOIN 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 20-30 minutes before applying tretinoin. 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 TRETINOIN

To get the best results with tretinoin 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 tretinoin 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 tretinoin 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 tretinoin 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.

•

Tretinoin 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 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.

•

Tretinoin 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 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.

•

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

Tretinoin works deep inside your skin and this takes time. You cannot make tretinoin work any faster by applying more than one dose each day, but an excess amount of tretinoin 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 tretinoin 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 tretinoin.

If tretinoin 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 tretinoin 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 tretinoin, call our toll-free number: 1-866-634-9120.

Manufactured by Padagis®
Yeruham, Israel

www.padagis.com

Rev 12-23
08T00 RC PH7

NDC 0574-2325-45

Rx Only

Tretinoin Gel, USP 0.025%

NET WT 45 g

The following image is a placeholder representing the product identifier that is either affixed or imprinted on the drug package label during the packaging operation.

NDC 0574-2301-45

Rx Only

Tretinoin Gel, USP 0.01%

NET WT 45 g

The following image is a placeholder representing the product identifier that is either affixed or imprinted on the drug package label during the packaging operation.

NDC 0574-2201-20

Rx Only

Tretinoin Cream, USP 0.1%

NET WT 20 g

The following image is a placeholder representing the product identifier that is either affixed or imprinted on the drug package label during the packaging operation.

NDC 0574-2205-20

Rx Only

Tretinoin Cream, USP 0.05%

NET WT 20 g

The following image is a placeholder representing the product identifier that is either affixed or imprinted on the drug package label during the packaging operation.

NDC 0574-2225-20

Rx Only

Tretinoin Cream, USP 0.025%

NET WT 20 g

The following image is a placeholder representing the product identifier that is either affixed or imprinted on the drug package label during the packaging operation.