ZIANA (clindamycin phosphate 1.2% and tretinoin 0.025%) Gel, is an antibiotic and retinoid combination gel product with two active ingredients. Clindamycin phosphate is a water-soluble ester of the semi-synthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic lincomycin.

The chemical name for clindamycin phosphate is Methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl-trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo-α-D-galacto-octopyranoside 2-(dihydrogen phosphate). The structural formula for clindamycin phosphate is represented below:

Clindamycin phosphate:

Molecular Formula: C₁₈H₃₄ClN₂O₈PS Molecular Weight: 504.97

The chemical name for tretinoin is 3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid (all-trans form). The structural formula for tretinoin is represented below:

Tretinoin:

Molecular Formula: C₂₀H₂₈O₂ Molecular Weight: 300.44

ZIANA Gel contains the following inactive ingredients: purified water USP, glycerin USP, carbomer 981 NF, methylparaben NF, polysorbate 80 NF, edetate disodium USP, citric acid USP, propylparaben NF, butylated hydroxytoluene NF, and tromethamine USP.

Last updated on RxList: 3/22/2007

ZIANA Gel is indicated for the topical treatment of acne vulgaris in patients 12 years or older.

At bedtime, squeeze a pea-sized amount of medication onto one fingertip, dot onto the chin, cheeks, nose, and forehead, then gently rub over the entire face. ZIANA Gel should be kept away from the eyes, the mouth, angles of the nose, and mucous membranes. ZIANA Gel is not for oral, ophthalmic, or intravaginal use.

DOSAGE FORMS AND STRENGTHS

ZIANA Gel, a combination of a lincosamide antibiotic and a retinoid, contains clindamycin phosphate 1.2% and tretinoin 0.025%, formulated as a topical gel. Each gram of ZIANA Gel contains, as dispensed, 10 mg (1%) clindamycin as phosphate, and 0.25 mg (0.025%) tretinoin in an aqueous based gel.

ZIANA Gel is available in 2 gram, 30 gram, and 60 gram tubes.

HOW SUPPLIED/STORAGE AND HANDLING

ZIANA (clindamycin phosphate 1.2% and tretinoin 0.025%) Gel is supplied as follows:

2 gram tube	NDC 99207-300-02
30 gram tube	NDC 99207-300-30
60 gram tube	NDC 99207-300-60

Storage and Handling

• Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]
• Protect from light.
• Protect from freezing.
• Keep out of the reach of children.
• Keep away from heat.
• Keep tube tightly closed.

PATIENT COUNSELING INFORMATION

See FDA-Approved Patient Labeling.

Instructions for Use

• At bedtime, the face should be gently washed with a mild soap and warm water. After patting the skin dry, apply ZIANA Gel as a thin layer over the entire face (excluding the eyes and lips).
• Patients should be advised not to use more than the recommended pea sized amount and not to apply more often than once daily (at bedtime) as this will not make for faster results and may increase irritation.
• A sunscreen should be applied every morning and reapplied over the course of the day as needed. Patients should be advised to avoid exposure to sunlight, sunlamp, ultraviolet light, and other medicines that may increase sensitivity to sunlight.

Skin Irritation

ZIANA Gel may cause irritation such as erythema, scaling, itching, burning, or stinging.

Colitis

In the event a patient treated with ZIANA Gel experiences severe diarrhea or gastrointestinal discomfort, ZIANA Gel should be discontinued and a physician should be contacted.

Manufactured for: Medicis, The Dermatology Company®
Scottsdale, AZ 85258
By: Contract Pharmaceuticals Limited Niagara
Buffalo, NY 14213
U.S. Patent 5,721,275
U.S. Patent 6,387,383
FDA rev date: 11/7/2006

Last updated on RxList: 3/22/2007

Clinical Studies Experience

Because clinical trials are conducted under prescribed conditions, adverse reaction rates observed in the clinical trial may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse reactions that appear to be related to drug use for approximating rates.

The safety data presented in Table 1 (below) reflects exposure to ZIANA Gel in 1,853 patients with acne vulgaris. Patients were 12 years and older and were treated once daily for 12 weeks. Adverse reactions that were reported in ≥1% of patients treated with ZIANA Gel were compared to adverse reactions in patients treated with clindamycin phosphate 1.2% in vehicle gel, tretinoin 0.025% in vehicle gel, and the vehicle gel alone:

Table 1: Adverse Reactions Reported in at Least 1% of Patients
Treated with ZIANA Gel: 12-Week Studies

	ZIANA Gel N=1853 N (%)	Clindamycin N=1428 N (%)	Tretinoin N=846 N (%)	Vehicle N=423 N (%)
PATIENTS WITH AT LEAST ONE AR	497 (27)	342 (24)	225 (27)	91 (22)
Nasopharyngitis	65 (4)	64 (5)	16 (2)	5 (1)
Pharyngolaryngeal pain	29 (2)	18 (1)	5 (1)	7 (2)
Dry skin	23 (1)	7 (1)	3 (<1)	0 (0)
Cough	19 (1)	21 (2)	9 (1)	2 (1)
Sinusitis	19 (1)	19 (1)	15 (2)	4 (1)
Note: Formulations used in all treatment arms were in the ZIANA vehicle gel.

Cutaneous safety and tolerance evaluations were conducted at each study visit in all of the clinical trials by assessment of erythema, scaling, itching, burning, and stinging:

Table 2: ZIANA Gel-Treated Patients with Local Skin Reactions

Local Reaction	Baseline N=1835 N (%)	End of Treatment N=1614 N (%)
Erythema	636 (35)	416 (26)
Scaling	237 (13)	280 (17)
Itching	189 (10)	70 (4)
Burning	38 (2)	56 (4)
Stinging	33 (2)	27 (2)

At each study visit, application site reactions on a scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe), and the mean scores were calculated for each of the local skin reactions. In Studies 1 and 2, 1277 subjects enrolled with moderate to severe acne, 854 subjects treated with ZIANA Gel and 423 treated with vehicle. Analysis over the twelve week period demonstrated that cutaneous irritation scores for erythema, scaling, itching, burning, and stinging peaked at two weeks of therapy, and were slightly higher for the ZIANA-treated group, decreasing thereafter.

One open-label 12-month safety study for ZIANA Gel showed a similar adverse reaction profile as seen in the 12-week studies. Eighteen out of 442 subjects (4%) reported gastrointestinal symptoms.

Concomitant Topical Medication

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. When used with ZIANA Gel, there may be increased skin irritation.

Erythromycin

ZIANA Gel should not be used in combination with erythromycin-containing products due to its clindamycin component. In vitro studies have shown antagonism between these two antimicrobials. The clinical significance of this in vitro antagonism is not known.

Neuromuscular Blocking Agents

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, ZIANA Gel should be used with caution in patients receiving such agents.

Last updated on RxList: 3/22/2007

No information provided. Please see PRECAUTIONS below and SIDE EFFECTS & DRUG INTERACTIONS.

Colitis

Systemic absorption of clindamycin has been demonstrated following topical use of this product. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical clindamycin. When significant diarrhea occurs, ZIANA Gel should be discontinued.

Severe colitis has occurred following oral or parenteral administration of clindamycin with an onset of up to several weeks following cessation of therapy. Antiperistaltic agents such as opiates and diphenoxylate with atropine may prolong and/or worsen severe colitis. Severe colitis may result in death.

Studies indicate a toxin(s) produced by clostridia is one primary cause of antibiotic-associated colitis. The colitis is usually characterized by severe persistent diarrhea and severe abdominal cramps and may be associated with the passage of blood and mucus. Stool cultures for Clostridium difficile and stool assay for C. difficile toxin may be helpful diagnostically.

Ultraviolet Light and Environmental Exposure

Exposure to sunlight, including sunlamps, should be avoided during the use of ZIANA Gel, 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. Daily use of sunscreen products and protective apparel (e.g., a hat) are recommended. Weather extremes, such as wind or cold, also may be irritating to patients under treatment with ZIANA Gel.

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category C. There are no well-controlled trials in pregnant women treated with ZIANA Gel. ZIANA Gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. ZIANA Gel was tested for maternal and developmental toxicity in New Zealand White Rabbits with topical doses of 60, 180 and 600 mg/kg/day. ZIANA Gel at 600 mg/kg/day (approximately 12 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison) was considered to be the no-observed-adverse-effect level (NOAEL) for maternal and developmental toxicity following dermal administration of ZIANA Gel for two weeks prior to artificial insemination and continuing until gestation day 18, inclusive. For purposes of comparisons of the animal exposure to human exposure, the recommended clinical dose is defined as 1 g of ZIANA Gel applied daily to a 60 kg person.

Clindamycin

Teratology (Segment II) studies using clindamycin were performed orally in rats (up to 600 mg/kg/day) and mice (up to 100 mg/kg/day) (583 and 49 times amount of clindamycin in the recommended clinical dose based on a body surface area comparison, respectively) or with subcutaneous doses of clindamycin up to 180 mg/kg/day (175 and 88 times the amount of clindamycin in the recommended clinical dose based on a body surface area comparison, respectively) revealed no evidence of teratogenicity.

Tretinoin

In oral 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 (~ 78 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison).

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 cases of temporally associated congenital malformations have been reported during two decades of clinical use of another formulation of topical tretinoin. Although no definite pattern of teratogenicity and no causal association have been established from these cases, 5 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.

Dermal tretinoin has been shown to be fetotoxic in rabbits when administered in doses 40 times the recommended human clinical dose based on a body surface area comparison. Oral tretinoin has been shown to be fetotoxic in rats when administered in doses 78 times the recommended clinical dose based on a body surface area comparison.

Nursing Mothers

It is not known whether clindamycin is excreted in human milk following use of ZIANA Gel. However, orally and parenterally administered clindamycin has been reported to appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. It is not known whether tretinoin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ZIANA Gel is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of ZIANA Gel in pediatric patients under the age of 12 have not been established.

Clinical trials of ZIANA Gel included patients 12-17 years of age. [See Clinical Studies]

Geriatric Use

Clinical studies of ZIANA Gel did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Last updated on RxList: 3/22/2007

No information provided.

ZIANA Gel is contraindicated in patients with regional enteritis, ulcerative colitis, or history of antibiotic-associated colitis.

Last updated on RxList: 3/22/2007

Mechanisms of Action

Clindamycin

[see Microbiology ].

Tretinoin

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 an open-label, multiple-dose study treating 12 subjects with moderate to severe acne, the percutaneous absorption of tretinoin following 14 consecutive daily applications of approximately 4 g of ZIANA Gel was minimal. Quantifiable tretinoin plasma concentrations ranged from 1.0 to 1.6 ng/mL, with unquantifiable plasma concentrations in 50% to 92% of subjects at any given timepoint following administration. The plasma concentrations of the key tretinoin metabolites, 13- cis -retinoic acid and 4-oxo-13-cis-retinoic acid, ranged from 1.0 to 1.4 ng/mL and from 1.6 to 6.5 ng/mL, respectively. Plasma concentrations for clindamycin generally did not exceed 3.5 ng/mL, with the exception of one subject whose plasma concentration reached 13.1 ng/mL.

Microbiology

Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing bacterial protein synthesis Clindamycin has been shown to have in vitro activity against Propionibacterium acnes, an organism which has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes was not examined in clinical trials with ZIANA Gel. P acnes resistance to clindamycin has been documented. Resistance to clindamycin is often associated with resistance to erythromycin.

NONCLINICAL TOXICOLOGY

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, mutagenicity and impairment of fertility testing of ZIANA Gel have not been performed in any species.

Clindamycin

The carcinogenicity of a 1% clindamycin phosphate gel similar to ZIANA Gel was evaluated by daily application to mice for two years. The daily doses used in this study were approximately 13 and 72 times higher than the human dose of clindamycin phosphate from ZIANA Gel, assuming complete absorption and based on a body surface area comparison. No significant increase in tumors was noted in the treated animals. For purposes of comparisons of the animal exposure to human exposure, the recommended human topical clinical dose is defined as 1 g of ZIANA Gel applied daily to a 60 kg person.

Fertility (Segment 1) studies in rats treated orally with up to 300 mg/kg/day of clindamycin (approximately 290 times the amount of clindamycin delivered from the recommended clinical dose for ZIANA Gel, based on a body surface area comparison) revealed no effects on fertility or mating ability.

Tretinoin

In two independent studies with long-term topical application of tretinoin in mice, carcinogenicity was not observed. In both studies, tretinoin was administered topically (0.025% or 0.1%) three times per week for up to two years. No carcinogenicity was observed with maximum effects of dermal amyloidosis in the basal layer of the skin.

Tretinoin has been shown to enhance photoco-carcinogenicity in properly performed specific studies, employing concurrent or intercurrent exposure to the drug and UV radiation. The contribution of clindamycin to that effect is unknown. Although the significance of these studies to humans is not clear, patients should minimize exposure to sun.

The genotoxic potential of tretinoin was evaluated in an in vitro Ames Salmonella reversion test and an in vitro chromosomal aberration assay in Chinese hamster ovary cells. Both tests were negative.

In oral Segment 1 studies in rats treated with tretinoin, the no-observed-effect-level was 2 mg/kg/day (~78 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison).

CLINICAL STUDIES

The safety and efficacy of once daily use of ZIANA Gel for treatment of acne vulgaris were assessed in three 12-week prospective, multi-center, randomized, blinded studies in patients 12 years and older. Studies 1 and 2 were of identical design, and compared ZIANA Gel to clindamycin in the vehicle gel, tretinoin in the vehicle gel, and the vehicle gel alone. Patients with mild, moderate, or severe acne were enrolled in the studies. The co-primary efficacy variables were:

(1) Mean percent change from baseline at Week 12 in

• inflammatory lesion counts,
• non-inflammatory lesion counts, and
• total lesion counts

(2) Percent of subjects who cleared or almost cleared at Week 12 as judged by an Evaluator's Global Severity (EGS) score.

The EGS scoring scale used in all of the clinical trials for ZIANA Gel is as follows:

Grade	Description
Clear	Normal, clear skin with no evidence of acne vulgaris
Almost Clear	Rare non-inflammatory lesions present, with rare non-inflamed papules (papules must be resolving and may be hyperpigmented, though not pink-red)
Mild	Some non-inflammatory lesions are present, with few inflammatory lesions (papules/pustules only; no nodulocystic lesions)
Moderate	Non-inflammatory lesions predominate, with multiple inflammatory lesions evident: several to many comedones and papules/pustules, and there may or may not be one small nodulo-cystic lesion
Severe	Inflammatory lesions are more apparent many comedones and papules/pustules, there may or may not be a few nodulocystic lesions
Very Severe	Highly inflammatory lesions predominate, variable number of comedones, many papules/pustules and many nodulocystic lesions

In Study 1, a total of 1,252 patients were enrolled, and in Study 2, a total of 1,288 patients were enrolled. The combined results are presented in Table 3.

Table 3: Efficacy Results at Week 12 in Studies 1 and 2.

	ZIANA Gel N=845	Clindamycin N=426	Tretinoin N=846	Vehicle N=423
Evaluator's Global Severity: N (%)
Patients	180	70	122	34
achieving success*	(21%)	(16%)	(14%)	(8%)
Inflammatory Lesion Count (% reduction from baseline)
Mean	48%	42%	39%	26%
Non-inflammatory Lesion Count (%reduction from baseline)
Mean	36%	27%	31%	16%
Total Lesion Count (% reduction from baseline)
Mean	41%	34%	34%	20%
* Success was defined as cleared or almost cleared at Week 12

In Study 3, ZIANA Gel was compared to clindamycin gel in a total of 2,010 patients with moderate or severe acne vulgaris (see Table 3). As with Studies 1 and 2, the co-primary endpoints were mean percent reduction in lesion counts (inflammatory, non-inflammatory and total) and the Evaluator's Global Severity score. In Study 3, success on the EGS score was assessed by the percentage of subjects who had at least 2 grades of improvement from Baseline to Week 12.

Table 4: Efficacy Results at Week 12 in Study 3

	ZIANA Gel N = 1008	Clindamycin N = 1002
Evaluator's Global Severity: N (%)
Patients achieving success*	415 (41%)	345 (34%)
Inflammatory Lesion Count (% reduction from baseline)
Mean	61%	55%
Non-inflammatory Lesion Count (% reduction from baseline)
Mean	50%	41%
Total Lesion Count (% reduction from baseline)
Mean	54%	47%
* Success was defined as at least a 2-grade improvement at Week 12 from baseline.

Last updated on RxList: 3/22/2007

PATIENT INFORMATION ZIANA (ZEE-AH-NA)
(clindamycin phosphate 1.2% and tretinoin 0.025%) Gel

IMPORTANT: Not for mouth, eye, or vaginal use.

Read the Patient Information that comes with ZIANA 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 ZIANA Gel?

ZIANA Gel is an antibiotic and retinoid combination medicine used for the skin treatment of acne in patients 12 years and older.

Who should not use ZIANA Gel? Do not use ZIANA Gel if you:

• have Crohn's Disease
• have Ulcerative Colitis
• have developed colitis with past antibiotic use

Tell your doctor:

• if you are pregnant or planning to become pregnant. It is not known if ZIANA Gel may harm your unborn baby.
• if you are breastfeeding. ZIANA Gel may pass through your milk and may harm your baby.
• about all the medicines and skin products you use:
  • ZIANA Gel should not be used with erythromycin-containing products.
  • Avoid medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect, and skin products that contain alcohol, astringents, spices or lime. These products may cause increased skin irritation if used with ZIANA GEL.

How should I use ZIANA Gel?

Use ZIANA Gel exactly as prescribed. It may take some time for you to see improvement of your acne with ZIANA Gel. Your doctor will tell you how long to use ZIANA Gel.

At bedtime:

• Wash your face gently with a mild soap and warm water.
• Pat the skin dry.
• Apply a pea-size amount of ZIANA Gel to your fingertip and spread it over your face. Gently, smooth it into your skin. Do not get ZIANA Gel in your eyes or mouth, on your lips, on the corners of your nose, or on open wounds.

In the morning:

• Apply a sunscreen and reapply during the day as needed.
• Do not apply ZIANA Gel more than once a day
• Do not use too much ZIANA Gel. Too much ZIANA Gel may irritate your skin.
• Do not wash your face more than 2 to 3 times a day. Washing your face too often or scrubbing it may make your acne worse.

Avoid:

• excessive exposure to the sun, cold, and wind. Weather extremes can dry and burn the skin. Always use a sunscreen on ZIANA Gel treated skin, even on cloudy days. Use other protective clothing such as a hat when you are in the sun.
• the use of sunlamps and tanning booths

If your face becomes sunburned, stop ZIANA Gel until your skin has healed.

What are possible side effects with ZIANA Gel?

• Skin irritation. ZIANA Gel may cause skin irritation such as dryness, redness, peeling, burning, or stinging. Stop ZIANA Gel and call your doctor if your skin becomes very red, swollen, blistered, or crusted.
• Change in skin color. ZIANA Gel may cause a temporary skin color change (lighter or darker).
• Colitis. This occurs rarely. Stop ZIANA Gel and call your doctor if you develop severe watery diarrhea, or bloody diarrhea.

Talk to your doctor about any side effect that bothers you or that does not go away.

These are not all the side effects with ZIANA Gel. Ask your doctor or pharmacist for more information.

How should I store ZIANA Gel?

• Store ZIANA Gel at room temperature, 59 to 86°F (15 to 30°C). Do not freeze.
• Keep ZIANA Gel away from heat and light.
• Keep the tube tightly closed.
• Keep ZIANA Gel and all medicines out of the reach of children

General information about ZIANA Gel

Medicines are sometimes prescribed for purposes other than those listed in patient information leaflet. Do not use ZIANA Gel for a condition for which it was not prescribed. Do not give ZIANA Gel to other people, even if they have the same symptoms you have. It may harm them.

This leaflet summarizes the most important information about ZIANA Gel. If you would like more information, talk with your doctor. You can also ask your pharmacist or doctor for information about ZIANA Gel that is written for healthcare professionals.

If you have questions about ZIANA Gel you can also call: 1-800-900-6389 (this is a toll-free number) between 10:00 a.m. and 4:00 p.m. Eastern Time, Monday through Friday.

What are the ingredients in ZIANA Gel?

Active Ingredients: clindamycin phosphate 1.2% and tretinoin 0.025%

Inactive Ingredients: purified water USP, glycerin USP, carbomer 981 NF, methylparaben NF, polysorbate 80 NF, edetate disodium USP, citric acid USP, propylparaben NF, butylated hydroxytoluene NF, and tromethamine USP.

Last updated on RxList: 3/22/2007

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.

CLINDAMYCIN/TRETINOIN GEL - TOPICAL

(klin-da-MYE-sin/TREt-i-noyn)

COMMON BRAND NAME(S): Ziana

USES: This combination medication is used to treat acne. It helps decrease the number and severity of acne pimples and helps pimples that do develop to heal more quickly. Tretinoin belongs to a class of medications called retinoids. It works by affecting the growth of skin cells. Clindamycin is an antibiotic that stops the growth of bacteria that cause acne.

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start using this medication and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

Wash your hands before applying this medication. Gently clean the affected skin with a mild/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 over the face, usually once daily at bedtime or as directed by your doctor. Be careful to avoid the eyes and lip area.

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 occurs, 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 this product, your acne might appear worse because the medication is working on pimples forming inside the skin. It may take several 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, but your risk of redness, peeling, and pain will increase.

Tell your doctor if your condition persists or worsens.

SIDE EFFECTS: Skin redness, dryness, itching, peeling, mild burning/stinging, or worsening of acne may occur during the first 2 to 4 weeks of using the medication. These effects usually decrease with continued use. A daytime moisturizer may be helpful for very dry skin (see Notes). If any of these effects persist or worsen, tell your doctor or pharmacist promptly. Your doctor may want you to decrease how often you use the medication or 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.

Tell your doctor immediately if any of these unlikely but serious side effects occur: blistering, crusting, severe burning/swelling of the skin.

This medication may be absorbed into your bloodstream and very rarely cause a severe intestinal condition (pseudomembranous colitis) due to resistant bacteria. This condition may occur weeks after treatment has stopped. Do not use anti-diarrhea products or narcotic pain medications if you have the following symptoms because these products may make them worse. Stop using this medication and tell your doctor immediately if any of these rare but very serious side effects occur: persistent diarrhea, abdominal or stomach pain/cramping, blood/mucus in your stool.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: 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 this product, tell your doctor or pharmacist if you are allergic to clindamycin or to tretinoin; or to lincomycin; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: certain intestinal problems (e.g., regional enteritis, ulcerative colitis, colitis caused by the use of antibiotics, pseudomembranous colitis, Crohn's disease).

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 this product.

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 this product with caution. Wait until the effects of such products on the skin have decreased before using this medication.

During pregnancy, this medication should be used only when clearly needed. 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 doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

This drug should not be used with the following medications because very serious interactions may occur: erythromycin products used on the skin, 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 this product.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: hair perming solutions, products that contain alcohol/lime/menthol (such as astringents, toners, shaving lotions), medicated or abrasive soaps and cleansers, products containing sulfur/resorcinol/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 this medication if the two products are applied at the same time. Talk with your doctor or pharmacist about using prescription and non-prescription benzoyl peroxide products safely.

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: This medication may be harmful if swallowed. If overdose or swallowing 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. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

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 the next day, wait until your next dose is scheduled.

STORAGE: Store with the cap tightly closed at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Gel preparations are flammable. Do not expose to heat or fire sources. Do not freeze. Keep all medicines 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.