Dalacin T

Clindamycin phosphate.

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.
Molecular formula: C₁₈H₃₄ClN₂O₈PS.
The chemical name for clindamycin phosphate is 7(S)-chloro-7-deoxylincomycin-2-phosphate (MW=504.96).
Lotion: Each mL of DALACIN T Lotion contains clindamycin phosphate equivalent to 10 mg of clindamycin base.
Topical gel: DALACIN T Topical Gel contains clindamycin phosphate, USP at a concentration equivalent to 10 mg clindamycin per gram.
Excipients/Inactive Ingredients: Lotion: In addition to clindamycin phosphate, the topical lotion contains sodium lauroyl sarcosinate, methylparahydroxybenzoate, glycerol, stearic acid, lexemul T, cetostearyl alcohol, isostearyl alcohol, and purified water.
Topical gel: In addition to clindamycin phosphate, the gel contains allantoin, carbomer 934P, methylparaben, polyethylene glycol 400, propylene glycol, sodium hydroxide, and purified water.

Pharmacology: Pharmacodynamics: Mechanism of action: Clindamycin is a lincosamide antibiotic that inhibits bacterial protein synthesis. It binds to the 50S ribosomal subunit and affects both ribosome assembly and the translation process. Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin.
Clindamycin has been shown to have in vitro activity against isolates of the following organisms; Anaerobic gram positive non spore forming bacilli, including: Propionibacterium acnes.
Pharmacodynamic effects: Efficacy is related to the time period that the agent level is above the minimum inhibitory concentration (MIC) of the pathogen (%T/MIC).
Resistance: Resistance to clindamycin in Propionibacterium acnes can be caused by mutations at the rRNA antibiotic binding site or by methylation of specific nucleotides in the 23S RNA of the 50S ribosomal subunit. These alterations can determine cross resistance to macrolides and streptogramins B (MLS_B phenotype). Macrolide-resistant isolates should be tested for inducible resistance to clindamycin using the D-zone test. Cross-resistance has been demonstrated between clindamycin and lincomycin.
The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable. Particularly in severe infections or therapy failure microbiological diagnosis with verification of the pathogen and its susceptibility to clindamycin is recommended.
Resistance is usually defined by susceptibility interpretive criteria (breakpoints) established by regulatory agencies, CLSI or EUCAST for systemically administered antibiotics. These breakpoints may be less relevant for topically administered clindamycin. Although clindamycin is not specifically cited, EUCAST has suggested that, for topically applied antimicrobials, resistance might be better defined by epidemiological cut-off values (ECOFFS) rather than the clinical breakpoints determined for systemic administration. However, MIC distributions and ECOFFS have not been published by EUCAST for P. acnes. Based on correlations between clinical results in acne patients and the clindamycin MICs for their P. acnes isolates, values as high as 256 mg/L are considered susceptible for topically administered clindamycin.
CLSI has published MIC ranges for a limited number (58) of unique clinical isolates of P. acnes collected in 2010-2012 in US hospitals; 91% of these isolates were susceptible to clindamycin (MIC ≤8 mg/L). A recent Belgian surveillance study (2011-2012) of anaerobic bacteria included 22 P. acnes isolates; 95.5% were susceptible to clindamycin. An earlier European surveillance study, which included 304 isolates of P. acnes, had reported a resistance rate of 15% to clindamycin. However, this study used a breakpoint of 0.12 mg/L; using the current breakpoint of 4 mg/L, there were no resistant isolates.
Breakpoints: CLSI and EUCAST breakpoints for Gram-positive anaerobes are listed as follows. Although the two institutions report the values differently, the resistance breakpoint is the same, because CLSI recognized a category of intermediate susceptibility (4 mg/L). As previously indicated, these breakpoints are based on use in systemic infections. (See Tables 1 and 2.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Pharmacokinetics: Clindamycin activity has been demonstrated in comedones from acne patients. The mean concentration of antibiotic activity in extracted comedones after application of clindamycin (10 mg/mL) in an isopropyl alcohol and water solution for 4 weeks was 597 mcg/g of comedonal material (range 0-1490 mcg/g). 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.
Lotion: 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.
Topical gel: Following multiple topical application of clindamycin phosphate at a concentration equivalent to 10 mg clindamycin per gram in the gel formulation, 0.053% (morning) and 0.070% (evening) of the administered dose was recovered in the urine as clindamycin. Average absolute bioavailability was 1.6% and 2.2% after morning and evening doses, respectively.
Geriatric Use: Clinical studies for topical clindamycin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Toxicology: Preclinical Safety Data: Carcinogenesis: Long term studies in animals have not been performed with clindamycin to evaluate carcinogenic potential.
Mutagenesis: Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative.
Impairment of Fertility: Fertility studies in rats treated orally with up to 300 mg/kg/day (approximately 1.1 times the highest recommended adult human dose based on mg/m²) revealed no effects on fertility or mating ability.
In oral embryo fetal development studies in rats and subcutaneous embryo fetal development studies in rats and rabbits, no developmental toxicity was observed except at doses that produced maternal toxicity.

DALACIN T Lotion/Topical Gel is indicated in the treatment of acne vulgaris.

Apply a thin film of DALACIN T Lotion/Topical Gel to the affected area of clean, dry skin twice daily. Massage into the skin is not needed. Contact with eyes and mouth should be avoided. Rinse hands after application.
Lotion: Dalacin T Lotion should be shaken immediately before using.

DALACIN T is intended for topical use only. In the event of accidental contact with sensitive surfaces (eye, abraded skin, mucous membranes), rinse affected area with copious amounts of cool water. Topically applied clindamycin phosphate can be absorbed in sufficient amounts to produce systemic effects (see PRECAUTIONS).
In the event of overdosage, general symptomatic and supportive measures are indicated as required.

DALACIN T is contraindicated in individuals with a history of hypersensitivity to clindamycin or lincomycin, or a history of antibiotic-associated colitis.

Oral and parenteral clindamycin, as well as most other antibiotics, have been associated with severe diarrhea and pseudomembranous colitis. Use of the topical formulation of clindamycin results in absorption of the antibiotic from the skin surface (see Pharmacology: Pharmacokinetics under Actions). Diarrhea and colitis have been reported infrequently with topical clindamycin. Therefore, the physician should be alert to the possible development of antibiotic-associated diarrhea or colitis. If significant or prolonged diarrhea occurs, the drug should be discontinued and appropriate diagnostic procedures and treatment provided as necessary. Large bowel endoscopy should be considered in cases of severe diarrhea. Antiperistaltic agents such as opiates and diphenoxylate with atropine may prolong and/or worsen the condition.
Effect on Ability to Drive and Use Machines: It is not expected that DALACIN T would interfere with the ability to drive or operate machinery.

Pregnancy: Oral and subcutaneous reproductive toxicity studies in rats and rabbits revealed no evidence of impaired fertility or harm to the fetus due to clindamycin, except at doses that caused maternal toxicity. Animal reproduction studies are not always predictive of human response.
In clinical trials with limited number of pregnant women, the systemic administration of clindamycin during the second and third trimesters has not been associated with an increased frequency of congenital abnormalities. However, there are no adequate and well-controlled studies using clindamycin in pregnant women during the first trimester of pregnancy and this drug should be used during pregnancy only if clearly needed.
Nursing Mothers: It is not known whether clindamycin is excreted in human breast milk following use of DALACIN T. Clindamycin has been reported to appear in human breast milk in ranges from <0.5 to 3.8 mcg/mL following systemic use.
Clindamycin has the potential to cause adverse effects on the breastfed infant's gastrointestinal flora such as diarrhea or blood in the stool, or rash. If clindamycin is required by a nursing mother, it is not a reason to discontinue breastfeeding, but an alternate drug may be preferred. 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 breastfed child from clindamycin or from the underlying maternal condition.

(See Table 3.)

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Systemic 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.

Store below 25°C. Protect from freezing.

Acne Treatment Preparations

D10AF01 - clindamycin ; Belongs to the class of topical antiinfective preparations used in the treatment of acne.

POM