Clindamycin Phosphate Topical Solution, USP

CLINDAMYCIN PHOSPHATE - clindamycin phosphate solution 
Glades Pharmaceuticals, LLC

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Clindamycin Phosphate Topical Solution, USP

FOR EXTERNAL USE ONLY

DESCRIPTION

Clindamycin Phosphate Topical Solution contains clindamycin phosphate, USP at a concentration equivalent to 10 mg clindamycin per milliliter in a vehicle of isopropyl alcohol 52% v/v, propylene glycol and water. Clindamycin Phosphate Topical Solution is for topical dermatologic use.

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. It occurs as a white to off-white, hygroscopic, crystalline powder. It is freely soluble in water, slightly soluble in dehydrated alcohol, very slightly soluble in acetone and practically insoluble in chloroform, benzene, and ether. Clindamycin phosphate is odorless or practically odorless, and has a bitter taste.

Chemically, clindamycin phosphate is C18H34ClN2O8PS. It has the following structural formula:

Chemical Structure

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). (MW=504.97)

CLINICAL PHARMACOLOGY

Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts this compound 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 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.

Clindamycin activity has been demonstrated in comedones from acne patients. The mean concentration of antibiotic activity in extracted comedones after application of a Clindamycin Phosphate 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 approximately 14% to 2% following application of clindamycin.

INDICATIONS AND USAGE

Clindamycin Phosphate Topical Solution is 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.)

CONTRAINDICATIONS

Clindamycin Phosphate Topical Solution is 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.

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 pseudomembranous 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 mg 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 to 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.

PRECAUTIONS

General

Clindamycin Phosphate Topical Solution contains an alcohol base which will cause burning and irritation of the eyes. 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.

Clindamycin Phosphate Topical Solution 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

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 fertility or harm to the fetus due to clindamycin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human responses, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether clindamycin is excreted in human milk following the use of Clindamycin Phosphate Topical Solution. 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.

Pediatric Use

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

ADVERSE REACTIONS

In 18 clinical studies of various formulations of clindamycin phosphate 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 EventSolutionGelLotion
n=553 (%)n=148 (%)n=160 (%)
Burning62 (11)15 (10)17 (11)
Itching36 (7)15 (10)17 (11)
Burning/Itching60 (11)# (-)# (-)
Dryness105 (19)34 (23)29 (18)
Erythema86 (16)10 (7)22 (14)
Oiliness/Oily Skin8 (1)26 (18)12* (10)
Peeling61 (11)# (-)11 (7)
# not recorded
* of 126 subjects

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 topical clindamycin. See WARNINGS).

Abdominal pain and gastrointestinal disturbances as well as gram-negative folliculitis have also been reported in association with the use of topical formulations of clindamycin.

OVERDOSAGE

Clindamycin Phosphate Topical Solution can be absorbed in sufficient amounts to produce systemic effects. (See WARNINGS).

DOSAGE AND ADMINISTRATION

Apply a thin film of Clindamycin Phosphate Topical Solution twice daily to affected area. Keep bottle tightly closed.

HOW SUPPLIED

Clindamycin Phosphate Topical Solution containing clindamycin phosphate equivalent to 10 mg clindamycin per milliliter is available in the following size:

60 mL applicator bottle - NDA 59366-2713-6

Store at controlled room temperature, 15°C-30°C (59°F-86°F).

CAUTION

Federal law prohibits dispensing without prescription.

Questions? Please call

1-888-4GLADES

1-888-445-2337

Manufactured by Stiefel Laboratories, Inc., Coral Gables, FL 33134

for Glades Pharmaceuticals, Inc., Coral Gables, FL 33134

80794 Rev. 0696

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CLINDAMYCIN PHOSPHATE 
clindamycin phosphate   solution
Product Information
Product TypeHUMAN PRESCRIPTION DRUGNDC Product Code (Source)59366-2713
Route of AdministrationTOPICALDEA Schedule    
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
Clindamycin Phosphate (Clindamycin) Clindamycin Phosphate10 mg  in 1 mL
Inactive Ingredients
Ingredient NameStrength
No Inactive Ingredients Found
Product Characteristics
Color    Score    
ShapeSize
FlavorImprint Code
Contains    
Packaging
#NDCPackage DescriptionMultilevel Packaging
159366-2713-660 mL In 1 BOTTLENone

Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
NDANDA05080112/31/200901/01/2010

Labeler - Glades Pharmaceuticals, LLC (067604736)
Revised: 03/2010Glades Pharmaceuticals, LLC