Cleocin T

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 dermatologic events [see table below]. Number of Patients Reporting Events Treatment Emergent Adverse Event Solution n=553(%) Gel n=148(%) Lotion n=160(%) # not recorded 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 of 126 subjects (10) Peeling 61 (11) # ( – ) 11 ( 7) Orally and parenterally administered clindamycin has been associated with severe colitis which may end fatally. Cases of diarrhea, bloody diarrhea and colitis (including pseudomembranous colitis) have been reported as adverse reactions in patients treated with oral and parenteral formulations of clindamycin and rarely with topical clindamycin (see WARNINGS ). Abdominal pain, gastrointestinal disturbances, gram-negative folliculitis, eye pain and contact dermatitis have also been reported in association with the use of topical formulations of clindamycin.

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

DESCRIPTION CLEOCIN T Topical Solution and CLEOCIN T Topical Lotion contain clindamycin phosphate, USP, at a concentration equivalent to 10 mg clindamycin per milliliter. CLEOCIN T Topical Gel contains clindamycin phosphate, USP, at a concentration equivalent to 10 mg clindamycin per gram. Each CLEOCIN T Topical Solution pledget applicator 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, propylene glycol, sodium hydroxide, and purified water. The lotion contains cetostearyl alcohol (2.5%); glycerin; glyceryl stearate SE (with potassium monostearate); isostearyl alcohol (2.5%); methylparaben (0.3%); sodium lauroyl sarcosinate; stearic acid; and purified water. The structural formula is represented below: 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). Chemical Structure

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 pledget may be used. Each pledget should be used only once and then be discarded. Lotion: Shake well immediately before using. Pledget: Remove pledget from foil just before use. Do not use if the seal is broken. Discard after single use. Keep all liquid dosage forms in containers tightly closed.

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 , WARNINGS and ADVERSE REACTIONS ).

WARNINGS Orally and parenterally administered clindamycin 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 colitis) have been reported with the use of topical and systemic clindamycin. 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. Endoscopic examination may reveal pseudomembranous colitis. Stool culture for Clostridium difficile and stool assay for C. difficile 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 concurrently, 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.

OVERDOSAGE Topically applied CLEOCIN T can be absorbed in sufficient amounts to produce systemic effects (see WARNINGS ).

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.

CLINICAL PHARMACOLOGY Mechanism of Action The mechanism of action of clindamycin in treating acne vulgaris is unknown. Pharmacokinetics Following multiple topical applications of clindamycin phosphate at a concentration equivalent to 10 mg clindamycin per mL in an isopropyl alcohol and water solution, very low levels of clindamycin are present in the serum (0–3 ng/mL) and less than 0.2% of the dose is recovered in urine as clindamycin. Although clindamycin phosphate is inactive in vitro , rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin. Microbiology Clindamycin inhibits bacterial protein synthesis by binding to the 23S RNA of the 50S subunit of the ribosome. Clindamycin is bacteriostatic. Antimicrobial Activity Clindamycin is active in vitro against most isolates of Propionibacterium acnes; however, the clinical significance is unknown. Resistance Resistance to clindamycin is most often caused by modification of specific bases of the 23S ribosomal RNA. Cross-resistance between clindamycin and lincomycin is complete. Because the binding sites for these antibacterial drugs overlap, cross resistance is sometimes observed among lincosamides, macrolides and streptogramin B. Macrolide-inducible resistance to clindamycin occurs in some isolates of macrolide-resistant bacteria.

Mechanism of Action The mechanism of action of clindamycin in treating acne vulgaris is unknown.

Pharmacokinetics Following multiple topical applications of clindamycin phosphate at a concentration equivalent to 10 mg clindamycin per mL in an isopropyl alcohol and water solution, very low levels of clindamycin are present in the serum (0–3 ng/mL) and less than 0.2% of the dose is recovered in urine as clindamycin. Although clindamycin phosphate is inactive in vitro , rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin.

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Cleocin T clindamycin phosphate CLINDAMYCIN PHOSPHATE CLINDAMYCIN ISOPROPYL ALCOHOL PROPYLENE GLYCOL WATER Cleocin T clindamycin phosphate CLINDAMYCIN PHOSPHATE CLINDAMYCIN CETOSTEARYL ALCOHOL GLYCERIN ISOSTEARYL ALCOHOL METHYLPARABEN SODIUM LAUROYL SARCOSINATE STEARIC ACID WATER Cleocin T clindamycin phosphate CLINDAMYCIN PHOSPHATE CLINDAMYCIN ALLANTOIN CARBOMER HOMOPOLYMER TYPE B (ALLYL PENTAERYTHRITOL CROSSLINKED) METHYLPARABEN POLYETHYLENE GLYCOL 400 PROPYLENE GLYCOL SODIUM HYDROXIDE WATER

NDA050600

Cleocin T

clindamycin phosphate

0009-3329

HUMAN PRESCRIPTION DRUG

TOPICAL

Microbiology Clindamycin inhibits bacterial protein synthesis by binding to the 23S RNA of the 50S subunit of the ribosome. Clindamycin is bacteriostatic. Antimicrobial Activity Clindamycin is active in vitro against most isolates of Propionibacterium acnes; however, the clinical significance is unknown. Resistance Resistance to clindamycin is most often caused by modification of specific bases of the 23S ribosomal RNA. Cross-resistance between clindamycin and lincomycin is complete. Because the binding sites for these antibacterial drugs overlap, cross resistance is sometimes observed among lincosamides, macrolides and streptogramin B. Macrolide-inducible resistance to clindamycin occurs in some isolates of macrolide-resistant bacteria.

PRINCIPAL DISPLAY PANEL - 30 mL Bottle Label Pfizer NDC 0009-3116-01 Cleocin T ® clindamycin phosphate topical solution, USP 1%* Solution for topical use only 30 mL Rx only PRINCIPAL DISPLAY PANEL - 30 mL Bottle Label

For External Use

Geriatric Use Clinical studies for CLEOCIN T did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Nursing Mothers It is not known whether clindamycin is excreted in breast milk following use of CLEOCIN T. However, orally and parenterally administered clindamycin has been reported to appear in breast milk. Clindamycin has the potential to cause adverse effects on the breast-fed infant's gastrointestinal flora. Monitor the breast-fed infant for possible adverse effects on the gastrointestinal flora, such as diarrhea, candidiasis (thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for clindamycin and any potential adverse effects on the breast-fed child from clindamycin or from the underlying maternal condition. Clinical Considerations If used during lactation and CLEOCIN T is applied to the chest, care should be taken to avoid accidental ingestion by the infant.

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

Pregnancy Teratogenic effects In clinical trials with pregnant women, the systemic administration of clindamycin during the second and third trimesters has not been associated with an increased frequency of congenital abnormalities. There are no adequate studies in pregnant women during the first trimester of pregnancy. Clindamycin should be used during the first trimester of pregnancy only if clearly needed.

Teratogenic effects In clinical trials with pregnant women, the systemic administration of clindamycin during the second and third trimesters has not been associated with an increased frequency of congenital abnormalities. There are no adequate studies in pregnant women during the first trimester of pregnancy. Clindamycin should be used during the first trimester of pregnancy only if clearly needed.

HOW SUPPLIED CLEOCIN T Topical Solution containing clindamycin phosphate equivalent to 10 mg clindamycin 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: 60 gram tube—NDC 0009-3331-01 30 gram tube—NDC 0009-3331-02 CLEOCIN T Topical Lotion containing clindamycin phosphate equivalent to 10 mg clindamycin per milliliter is available in the following size: 60 mL plastic squeeze bottle—NDC 0009-3329-01 Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP]. Protect from freezing.

Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP]. Protect from freezing.

General CLEOCIN T Topical Solution contains an alcohol base which will cause burning and irritation of the eye. In the event of accidental contact with sensitive surfaces (eye, abraded skin, mucous membranes), 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 caution in atopic individuals.

PRECAUTIONS General CLEOCIN T Topical Solution contains an alcohol base which will cause burning and irritation of the eye. In the event of accidental contact with sensitive surfaces (eye, abraded skin, mucous membranes), 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 caution 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 In clinical trials with pregnant women, the systemic administration of clindamycin during the second and third trimesters has not been associated with an increased frequency of congenital abnormalities. There are no adequate studies in pregnant women during the first trimester of pregnancy. Clindamycin should be used during the first trimester of pregnancy only if clearly needed. Nursing Mothers It is not known whether clindamycin is excreted in breast milk following use of CLEOCIN T. However, orally and parenterally administered clindamycin has been reported to appear in breast milk. Clindamycin has the potential to cause adverse effects on the breast-fed infant's gastrointestinal flora. Monitor the breast-fed infant for possible adverse effects on the gastrointestinal flora, such as diarrhea, candidiasis (thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for clindamycin and any potential adverse effects on the breast-fed child from clindamycin or from the underlying maternal condition. Clinical Considerations If used during lactation and CLEOCIN T is applied to the chest, care should be taken to avoid accidental ingestion by the infant. Pediatric Use Safety and effectiveness in pediatric patients under the age of 12 have not been established. Geriatric Use Clinical studies for CLEOCIN T did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.