CLEOCIN T Topical Solution and CLEOCIN T Topical Lotion contain clindamycin phosphate, USP, at a concentration equivalent to 10 mg clin- damycin per milliliter. CLEOCIN T Topical Gel con- tains clindamycin phosphate, USP, at a concen- tration equivalent to 10 mg clindamycin per gram. Each CLEOCIN T Topical Solution pledget appli- cator contains approximately 1 mL of topical solution. 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 solution contains isopropyl alcohol 50% v/v, propylene glycol, and water. The gel contains allantoin, carbomer 934P, methylparaben, polyethylene glycol 400, propy- lene glycol, sodium hydroxide, and purified water. The lotion contains cetostearyl alcohol (2.5%); glycerin; glyceryl stearate SE (with potassium monostearate); isostearyl alcohol (2.5%); methyl- paraben (0.3%); sodium lauroyl sarcosinate; stearic acid; and purified water. The structural formula is represented below: The chemical name for clindamycin phos- phate is Methyl 7-chloro-6,7,8-trideoxy-6-(1- methyl-trans-4-propyl-L-2-pyrrolidinecarboxam- ido)-1-thio-L-threo-_-D-galacto-octopyranoside 2-(dihydrogen phosphate).

CLINICAL PHARMACOLOGY

Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts this com- pound to the antibacterially active clindamycin. Cross resistance has been demonstrated between clindamycin and lincomycin. Antagonism has been demonstrated between clindamycin and erythromycin. Following multiple topical applications of clin- damycin phosphate at a concentration equivalent to 10 mg clindamycin per mL in an isopropyl alco- hol and water solution, very low levels of clin- damycin are present in the serum (0-3 ng/mL) and less than 0.2% of the dose is recovered in urine as clindamycin. Clindamycin activity has been demonstrated in comedones from acne patients. The mean con- centration of antibiotic activity in extracted come- dones after application of CLEOCIN T Topical Solution for 4 weeks was 597 mcg/g of comedonal material (range 0-1490). Clindamycin in vitro inhibits all Propionibacterium acnes cultures tested (MICs 0.4 mcg/mL). Free fatty acids on the skin surface have been decreased from approx- imately 14% to 2% following application of clin- damycin.

INDICATIONS AND USAGE

CLEOCIN T Topical Solution, CLEOCIN T Topical Gel and CLEOCIN T Topical Lotion are indicated in the treatment of acne vulgaris. In view of the potential for diarrhea, bloody diarrhea and pseudomembranous colitis, the physician should consider whether other agents are more appropriate. (See CONTRAINDICATIONS, WARN- INGS and ADVERSE REACTIONS.)

CONTRAINDICATIONS

CLEOCIN T Topical Solution, CLEOCIN T Topical Gel and CLEOCIN T Topical Lotion are contraindicated in individuals with a history of hyper- sensitivity to preparations containing clindamycin or lincomycin, a history of regional enteritis or ulcer- ative colitis, or a history of antibiotic-associated colitis.

WARNINGS

Orally and parenterally administered clin- damycin has been associated with severe colitis which may result in patient death. Use of the topical formulation of clindamycin results in absorption of the antibiotic from the skin surface. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous coli- tis) have been reported with the use of topi- cal and systemic clindamycin.

Studies indicate a toxin(s) produced by clostridia is one primary cause of antibiotic- associated colitis. The colitis is usually char- acterized by severe persistent diarrhea and severe abdominal cramps and may be asso- ciated with the passage of blood and mucus. Endoscopic examination may reveal pseu- domembranous colitis. Stool culture for Clostridium difficile and stool assay for C. dif- ficile toxin may be helpful diagnostically.

When significant diarrhea occurs, the drug should be discontinued. Large bowel endoscopy should be considered to establish a definitive diagnosis in cases of severe diarrhea.

Antiperistaltic agents such as opiates and diphenoxylate with atropine may prolong and/or worsen the condition. Vancomycin

has been found to be effective in the treatment of antibiotic-associated pseudomembranous colitis produced by Clostridium difficile. The usual adult dosage is 500 milligrams to 2 grams of vancomycin orally per day in three to four divided doses administered for 7 to 10 days. Cholestyramine or colestipol resins bind vancomycin in vitro. If both a resin and vancomycin are to be administered concur- rently, it may be advisable to separate the time of administration of each drug.

Diarrhea, colitis, and pseudomembranous colitis have been observed to begin up to several weeks following cessation of oral and parenteral therapy with clindamycin.

PRECAUTIONS

General

CLEOCIN T Topical Solution contains an alco- hol base which will cause burning and irritation of the eye. In the event of accidental contact with sen- sitive surfaces (eye, abraded skin, mucous mem- branes), bathe with copious amounts of cool tap water. The solution has an unpleasant taste and caution should be exercised when applying medication around the mouth. CLEOCIN T should be prescribed with cau- tion in atopic individuals.

Drug Interactions

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

Pregnancy: Teratogenic effects--Pregnancy Category B

Reproduction studies have been performed in rats and mice using subcutaneous and oral doses of clindamycin ranging from 100 to 600 mg/kg/day and have revealed no evidence of impaired fer- tility or harm to the fetus due to clindamycin. There are, however, no adequate and well-controlled stud- ies in pregnant women. Because animal repro- duction studies are not always predictive of human response, this drug should be used dur- ing pregnancy only if clearly needed.

Nursing Mothers

It is not known whether clindamycin is excreted in human milk following use of CLEOCIN T. However, orally and parenterally administered clin- damycin 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 dis- continue the drug, taking into account the impor- tance of the drug to the mother.

Pediatric Use

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

ADVERSE REACTIONS

In 18 clinical studies of various formulations of CLEOCIN T using placebo vehicle and/or active comparator drugs as controls, patients experienced a number of treatment emergent adverse der- matologic events [see table below]. Number of Patients Reporting Events

Treatment

Emergent Solution Gel Lotion Adverse Event n=553(%) n=148(%) n=160(%)

Burning 62 (11) 15 (10) 17 (11) Itching 36 ( 7) 15 (10) 17 (11) Burning/Itching 60 (11) # ( - ) # ( - ) Dryness 105 (19) 34 (23) 29 (18) Erythema 86 (16) 10 ( 7) 22 (14) Oiliness/Oily Skin 8 ( 1) 26 (18) 12 * (10) Peeling 61 (11) # ( - ) 11 ( 7)

# not recorded

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f 126 subjects

Orally and parenterally administered clin- damycin has been associated with severe colitis which may end fatally. (see WARNINGS). Abdominal pain and gastrointestinal dis- turbances as well as gram-negative folli- culitis have also been reported in association with the use of topical formulations of clin- damycin.

OVERDOSAGE

Topically applied CLEOCIN T can be absorbed in sufficient amounts to produce sys- temic effects. (See WARNINGS.)

DOSAGE AND ADMINISTRATION

Apply a thin film of CLEOCIN T Topical Solution, CLEOCIN T Topical Lotion, CLEOCIN T Topical Gel, or use a CLEOCIN T Topical Solution pledget for the application of CLEOCIN T twice daily to affected area. More than one pled- get may be used. Each pledget should be used only once and then be discarded. single use. Keep all liquid dosage forms in containers tightly closed.

HOW SUPPLIED

CLEOCIN T Topical Solution containing clin- damycin phosphate equivalent to 10 mg clinda- mycin per milliliter is available in the following sizes: 30 mL applicator bottle -- NDC 0009-3116-01 60 mL applicator bottle -- NDC 0009-3116-02 Carton of 60 single-use pledget applicators -- NDC 0009-3116-14 CLEOCIN T Topical Gel containing clindamycin phosphate equivalent to 10 mg clindamycin per gram is available in the following sizes:

gram

CLEOCIN T Topical Lotion containing clin- damycin phosphate equivalent to 10 mg clin- damycin per milliliter is available in the following size:

plastic squeeze bottle -- NDC 0009-3329-01 Store at controlled room temperature 20deg to 25degC

Pharmacia & Upjohn Company A subsidiary of Pharmacia Corporation Kalamazoo, MI 49001, USA Revised May 2002 811 373 831

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This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature.

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For External Use

DESCRIPTION

CLINICAL PHARMACOLOGY

INDICATIONS AND USAGE

CONTRAINDICATIONS

WARNINGS

When significant diarrhea occurs, the drug should be discontinued. Large bowel endoscopy should be considered to establish a definitive diagnosis in cases of severe diarrhea.

Antiperistaltic agents such as opiates and diphenoxylate with atropine may prolong and/or worsen the condition. Vancomycin

Diarrhea, colitis, and pseudomembranous colitis have been observed to begin up to several weeks following cessation of oral and parenteral therapy with clindamycin.

PRECAUTIONS

General

Drug Interactions

Pregnancy: Teratogenic effects--Pregnancy Category B

Nursing Mothers

Pediatric Use

ADVERSE REACTIONS

Treatment

Emergent Solution Gel Lotion Adverse Event n=553(%) n=148(%) n=160(%)

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OVERDOSAGE

DOSAGE AND ADMINISTRATION

HOW SUPPLIED

gram

gram

mL