OBAGI- tretinoin cream
YS PLUS CORPORATION
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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 % (0.1mg)
in a gel vehicle of hydroxypropyl cellulose, butylated hydroxytoluene, and alcohol (denatured with
tert - butyl alcohol and brucine sulfate) 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, xantham gum, sorbic
acid, butylated hydroxytoluene, and purified water. Chemically, tretinoin is all - trans - retinoic acid. It has a molecular
weight of 300.44.
Although the exact mode of action of tretinoin is unknown, current evidence suggest that topical
tretinoin decreases cohesiveness of follicular eipthelial cells with decreased micromedo 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.
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 ).
General
If a reaction suggesting sensitivity or chemical irritation occurs, use of the medication
should be discontinued. Exposure to sunlight, including sunlamos, should be minimized during the use of
tretinoin, and patients with sunburns should be advised not to use this product until fully recored
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.
Tretinoin preparations for 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
In a 91 - week dermal study in which CD - 1 mice were administered 0.017 % and 0.035 % formulations of
tretinoin, cutaneous squamous cell carcinomas and 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 % and 0.035 %
formulations are 0.5 and 1.0 mg /kg / day, respectively. These doses are two and four times the
maximum human systemic dose, when adjusted for total body 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 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 of tretinoin was administered topically to mice ( 0.1 times the maximum human
systemic dose, adjusted for total body surface area ). For purposes of comparisons of the animal
exposure to systemic human exposure, the maximum human systemic dose is defined as 1 gram of
0.1 % tretinoin applied daily to a 50 kg person ( 0.02 mg tretinoin / kg body weight).
Studies in hairless albino mice suggest that concurrent exposure to tretinoin may enhance the
tumorigenic potential of carcinogenic doses of UVB and UVA light form a solar stimulator. 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 to
humans is not clear, patients should minimize exposure to sunlight or artificial ultraviolet radiation sources.
The mutagenic potential of tretinoin was evaluated in the Ames assay and in the invivomouse micronucleus assay, both of
which were negative.
In dermal Segment I fertility studies of tretinoin 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 surface area ), and
slight ( not statistically significant) increases in the number and percent of nonviable embryos in females treated with 0.25 mg / kg /day
( 2 times the maximum human systemic dose adjusted for total body surface area ) and above were observed. A dermal Segment III study
with tretinoin has not been performed has not been performed in any species. In oral Segment I and 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
Teratongenic Effects
Pregnancy Category C
Oral tretinoin ha sbeen shown to 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
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 malfomrations were reported at doses of 10 mg / kr / day
(83 times the maximumhuman systemic dose adjusted for total body surface area), although skeletal variations were observed at all doses. A dose - related
increase in embryolethality and abortion were reported. Similar reuslts have been reported in pigtail macaques.
Topical tretinoin in animal teratogenecity tests have 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 e maximum human systemic dose adjusted for total body surface area). Anomalies
(humerous: 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 White rabbits administered in 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 and hydrocephaly, typical of reinoid - induced fetal malformations in this species.
In contrast, several well - controlled animal studies have shown that dermally applied tretinoin may be fetotoxic, but not overly teratogenic in rats and rabbits at
doses of 1.0 and 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 reprots 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 teratogenecity and no causal association has been established form these cases, five of the reports describe therare 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 tretinoinhas been shown to be ferotoxic 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 be fetotoxic, resulting in skeletal variations and increased intrauterine death in rats when administered
2.5 mg / kg / day ( 20 mes the maximum human systemic dose adjusted for total body surface area).
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 tretinoin
is used by a nursing woman.
Pediatric Use
Safety and effectiveness in pediatric patients below the age of 12 have not been established.
Geriatric Use
Safety and effectiveness in a geriatric populationhave not been established. Clinical studies of tretinoin did not include sufficient numbers of subjects
aged 65 and over to determine whether they respond differently from younger patients.
The skin if certain sensitive individuals may become excessively red, edamatous, 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 susceptibility to sunlight while under
treatment with tretinoin. To date, alldverse 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 weeks of erapy, 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
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
Acne Treatment
IMPORTANT
Read Directions Carefully Before Using
Rx Only
For External Use Only
Not for Ophthalmic Use
READ DIRECTIONS CAREFULLY BEFORE USING
THIS LEAFLET TELLS YOU ABOUT TRETINOIN ACNE TREATMENT AS PRESCRIBED BY YOUR PHYSICIAN. THIS PRODUCT
IS TO BE SUED 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.
WARINGS
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 kinow, overexposure to natural sunlight or artificial sunlight of a sunlamp can cause sunburn.
Overexposure to the sun over many eyars 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 given 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 mors
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 aniamls or humans. However, investigators 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 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 therpay 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 of necessayr. 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 establlsh 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 b y 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 simply 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 importasnt for skin to be completely dry in order to minimize possible irritation.
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 mjore than one dose each day, but
an excessive amount of tretinoin may irritate your skin. Be patient.
There may be some doscomfort or peeling during the early days of treatment. Some patients may also notice that their skin begins to take on a blush.
These reactions do not happen to everyone. If they do, 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,
sonsult your doctor.
BY THREE TO SIX WEEKS, some patients notice an appearance of new blemishes ( papules and postules ). 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 or a medical nature should be taken up with your doctor. For more information about tretinoin, call our toll - free number: 866 - 488 - 7429.
Call between 9:00 a.m. and 3:00 p.m. Eastern Time, Monday through Friday.
OBAGI
tretinoin cream |
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Labeler - YS PLUS CORPORATION (843007597) |