TRETINOIN CREAM USP, 0

Description

Tretinoin Cream USP, 0.05% is used for the topical treatment of acne vulgaris. Tretinoin Cream contains tretinoin in 0.05% by weight, in a hydrophilic cream vehicle of butylated hydroxytoluene, isopropyl myristate, polyoxyl stearate type II, purified water, sorbic acid, stearic acid, stearyl alcohol & xanthan gum. Chemically, tretinoin is all-trans-retinoic acid và has the following structure:


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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 và increased turnover of follicular epithelial cells causing extrusion of the comedones.

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Indications and Usage

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


Contraindications

Use of the hàng hóa should be discontinued if hypersensitivity khổng lồ any of the ingredients is noted.


Warnings

Keep out of reach of children. Keep tube tightly closed. Vì chưng not expose to lớn heat. Store at 20° to lớn 25°C (68° khổng lồ 77°F) . Protect from freezing.


General

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

Tretinoin acne treatment should be kept away from the eyes, the mouth, angles of the nose, & mucous membranes. Topical use may induce severe local erythema và peeling at the site of application. If the degree of local irritation warrants, patients should be directed khổng lồ use the medication less frequently, discontinue use temporarily, or discontinue use altogether. Tretinoin has been reported to lớn 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 và 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 tretinoin. It also is advisable to lớn "rest" a patient"s skin until the effects of such preparations subside before use of tretinoin is begun.


Carcinogenesis, Mutagenesis, Impairment to lớn Fertility

In a 91-week dermal study in which CD-1 mice were administered 0.017% & 0.035% formulations of tretinoin, cutaneous squamous cell carcinomas và papillomas in the treatment area were observed in some female mice. 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% & 0.035% formulations are 0.5 and 1.0 mg/kg/day, respectively. These doses are two & four times the maximum human systemic dose, when adjusted for total body toàn thân surface area. The biological significance of these findings is not clear because they occurred at doses that exceeded the dermal maximally tolerated dose (MTD) of tretinoin và 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 of tretinoin was administered topically to lớn mice (0.1 times the maximum human systemic dose, adjusted for total body surface area). For purposes of comparisons of the animal exposure to lớn systemic human exposure, the maximum human systemic dose is defined as 1 gram of 0.1% tretinoin applied daily to lớn a 50 kilogam person (0.02 mg tretinoin/kg toàn thân weight).

Studies in hairless albino mice suggest that concurrent exposure lớn tretinoin may enhance the tumorigenic potential of carcinogenic doses of UVB & UVA light khung a solar simulator. This effect has been 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 lớn humans is not clear, patients should minimize exposure to lớn sunlight or artificial ultraviolet irradiation sources.

The mutagenic potential of tretinoin was evaluated in the Ames assay và in the in vivo mouse micronucleus assay, both of which were negative.

In dermal Segment I 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 (4 times the maximum human systemic dose adjusted for total body toàn thân surface area), and slight (not statistically significant) increases in the number và percent of nonviable embryos in females treated with 0.25 mg/kg/day (2 times the maximum human systemic dose adjusted for total body toàn thân surface area) & above were observed. A dermal Segment III study with tretinoin has not been performed in any species. In oral Segment I và Segment III studies in rats with tretinoin, decreased survival of neonates and growth retardation were observed at doses in excess of 2 mg/kg/day (16 times the human topical dose adjusted for total body surface area).


Pregnancy Category C

Oral tretinoin has been shown lớn be teratogenic in rats, mice, hamsters, and subhuman primates. It was teratogenic and fetotoxic in Wistar rats when given orally or topically in doses greater than 1 mg/kg/day (8 times the maximum human systemic dose adjusted for total body toàn thân surface area). However, variations in teratogenic doses among various strains of rats have been reported. In the cynomolgus monkey, which metabolically is closer to humans for tretinoin than the other species examined, fetal malformations were reported at doses of 10 mg/kg/day or greater, but none were observed at 5 mg/kg/day (83 times the maximum human systemic dose adjusted for total body surface area), although increased skeletal variations were observed at all doses. A dose-related increase in embryolethality and abortion was reported. Similar results have also been reported in pigtail macaques.

Topical tretinoin in animal teratogenicity tests has generated equivocal results. There is evidence for teratogenicity (shortened or kinked tail) of topical tretinoin in Wistar rats at doses greater than 1 mg/kg/day (8 times the maximum human systemic dose adjusted for total toàn thân surface area). Anomalies (humerus: short 13%, bent 6%, os parietal incompletely ossified 14%) have also been reported when 10 mg/kg/day was topically applied.

There are other reports in New Zealand trắng rabbits administered doses of greater than 0.2 mg/kg/day (3.3 times the maximum human systemic dose adjusted for total body surface area) of an increased incidence of domed head và hydrocephaly, typical of retinoid-induced fetal malformations in this species.

In contrast, several well-controlled animals studies have shown that dermally applied tretinoin may be fetoxic, but not overly teratogenic in rats và rabbits at doses of 1.0 & 0.5 mg/kg/day, respectively (8 times the maximum human systemic dose adjusted for total body surface area in both species).

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. Thirty human cases of temporally associated congenital malformations have been reported during two decades of clinical use of tretinoin. Although no definite pattern of teratogenicity & no causal association has been established from these cases, five of the reports describe the rare birth defect category holoprosencephaly (defects associated with incomplete midline development of the forebrain). The significance of these spontaneous reports in terms of risk to the fetus is not known.


Nonteratogenic effects

Topical tretinoin has been shown to be fetotoxic in rabbits when administered 0.5 mg/kg/day (8 times the maximum human systemic dose adjusted for total body surface area). Oral tretinoin has been shown to lớn be fetotoxic, resulting in skeletal variations and increased intrauterine death in rats when administered 2.5 mg/kg/day (20 times the maximum human systemic dose adjusted for total body surface area).

There are, however, no adequate và 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 tretinoin is administered to a nursing woman.


Pediatric Use

Safety & effectiveness in pediatric patients below the age of 12 have not been established.


Geriatric Use

Safety & effectiveness in a geriatric population have not been established. Clinical studies of tretinoin did not include sufficient numbers of subjects aged 65 and over lớn determine whether they respond differently from younger patients.


Adverse Reactions

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 lớn a cấp độ the patient can tolerate. True contact allergy to lớn topical tretinoin is rarely encountered. Temporary hyper- or hypopigmentation has been reported with repeated application of tretinoin. Some individuals have been reported to lớn have heightened susceptibility to lớn sunlight while under treatment with tretinoin. To lớn date, all adverse effects of tretinoin 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 & marked redness, peeling, or discomfort may occur. Oral ingestion of the drug may lead to lớn the same side effects as those associated with excessive oral intake of vitamin A.

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Dosage and Administration

Tretinoin Cream should be applied once a day, before retiring, khổng lồ the skin where acne lesions appear, using enough to lớn cover the entire affected area lightly.

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 lớn tolerate the treatment.

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

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

Therapeutic results should be noticed after two khổng lồ 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 lớn maintain the improvement with less frequent applications, or other dosage forms.

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


Storage Conditions

Store at 20° khổng lồ 25°C (68° to lớn 77°F) . Protect from freezing.


Mfd. By: Taro Pharmaceuticals Inc.Brampton, Ontario, Canada L6T 1C1

Dist. By: Taro Pharmaceuticals U.S.A., Inc.Hawthorne, NY 10532

Issued: June, 2018PK-8728-00618-084


PATIENT INSTRUCTIONSTretinoin Cream USP, 0.05%

For Topical Use OnlyAcne TreatmentIMPORTANT

Read Directions Carefully Before Using

THIS LEAFLET TELLS YOU ABOUT TRETINOIN ACNE TREATMENT AS PRESCRIBED BY YOUR PHYSICIAN. THIS hàng hóa IS lớn BE USED ONLY ACCORDING khổng lồ YOUR DOCTOR"S INSTRUCTIONS, & IT SHOULD NOT BE APPLIED lớn OTHER AREAS OF THE body toàn thân OR khổng lồ OTHER GROWTHS OR LESIONS. THE LONG-TERM SAFETY & EFFECTIVENESS OF THIS product IN OTHER DISORDERS HAVE NOT BEEN EVALUATED. IF YOU HAVE ANY QUESTIONS, BE SURE khổng lồ ASK YOUR DOCTOR.

WARNINGS

Keep out of reach of children. Keep tube tightly closed. Vì not expose khổng lồ heat. Store at 20° lớn 25°C (68° to 77°F) . Protect from freezing.

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 lớn the sun over many years may cause premature aging of the skin & even skin cancer. The chance of these effects occurring will vary depending on skin type, the climate and the care taken to avoid overexposure lớn the sun. Therapy with tretinoin may make your skin more susceptible to lớn sunburn và other adverse effects of the sun, so unprotected exposure khổng lồ natural or artificial sunlight should be minimized.

Laboratory findings. When laboratory mice are exposed to lớn artificial sunlight, they often develop skin tumors. These sunlight-induced tumors may appear more quickly & in greater number if the mouse is also topically treated with the active ingredient in Tretinoin Cream, tretinoin. In some studies, under different conditions, however, when mice treated with tretinoin were exposed khổng lồ artificial sunlight, the incidence và rate of development of skin tumors was reduced. There is no evidence lớn 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 màn chơi which will provide you with the necessary high cấp độ of protection). For extended sun exposure, protective clothing, like a hat, should be worn. Vì not use artificial sunlamps while you are using tretinoin. If you vì chưng become sunburned, stop your therapy with tretinoin until your skin has recovered.

Avoid excessive exposure to wind or cold. Extremes of climate tend lớn dry or burn normal skin. Skin treated with tretinoin may be more vulnerable lớn these extremes. Your physician can recommend ways to lớn 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 và 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 lớn normal either when the skin was allowed lớn adjust to lớn tretinoin 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 & will recommend them to lớn 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 & hair permanent solutions. Vị 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 lớn 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 the medication.

AND WHILE YOU"RE ON TRETINOIN THERAPY

Use a mild, non-medicated soap. Avoid frequent washings và 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 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 khổng lồ use it properly. Forget about the instructions given for other products and the advice of friends. Just stick lớn the special plan your doctor has laid out for you & 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.