Clindamycin Phosphate and Benzoyl Peroxide (Page 2 of 5)

6.2 Postmarketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Anaphylaxis, as well as allergic reactions leading to hospitalizations, has been reported in postmarketing use of products containing clindamycin/benzoyl peroxide.

7 DRUG INTERACTIONS

7.1 Erythromycin

Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% should not be used in combination with topical or oral erythromycin-containing products due to its clindamycin component. In vitro studies have shown antagonism between erythromycin and clindamycin. The clinical significance of this in vitro antagonism is not known.

7.2 Neuromuscular Blocking Agents

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% should be used with caution in patients receiving such agents.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no available data on Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% use in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. The limited published data on use of clindamycin in pregnant women with exposure during the first trimester are insufficient to inform a drug-associated risk of pregnancy-related adverse outcomes (see Data). In limited published 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 major birth defects.

In animal reproduction studies, clindamycin did not cause malformations or embryo-fetal development toxicity in pregnant rats and mice when administered during the period of organogenesis at systemic doses up to 240 times the maximum recommended human dose (MRHD) of 2.5 g Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5%, based on body surface area (BSA) comparisons (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of major birth defects, loss, and other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

Human Data

In limited published trials in pregnant women administered clindamycin during the first trimester of pregnancy, there was no difference in the rate of major birth defects reported among in utero exposed infants compared to unexposed infants. These data cannot definitely establish or exclude any clindamycin-associated risk during pregnancy.

Animal Data

Animal reproductive/developmental toxicity studies have not been conducted with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% or benzoyl peroxide. Developmental toxicity studies of clindamycin performed in pregnant

rats and mice administered during the period of organogenesis at oral doses of up to 600 mg/kg/day (240 and 120 times the MRHD for clindamycin, respectively, based on BSA comparisons) or subcutaneous doses of up to 200 mg/kg/day (80 and 40 times the MRHD for clindamycin, respectively, based on BSA comparisons) revealed no malformations or embryo-fetal development toxicity.

8.2 Lactation

Risk Summary

There are no data on the presence of clindamycin or benzoyl peroxide in human milk, the effects on the breastfed child, or the effects on milk production following topical administration. However, clindamycin has been reported to be present in breast milk in small amounts following oral and parenteral administration. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% and any potential adverse effects on the breastfed child from Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% or from the underlying maternal condition.

Clinical Considerations

If used during lactation and Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% is applied to the chest, care should be taken to avoid accidental ingestion by the infant.

8.4 Pediatric Use

Safety and effectiveness of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% in pediatric patients under the age of 12 have not been evaluated.

8.5 Geriatric Use

Clinical trials of clindamycin phosphate and benzoyl peroxide gel, 1.2%/2.5% did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects.

11 DESCRIPTION

Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% is a combination product with two active ingredients in a white to off-white, opaque, smooth, aqueous gel formulation intended for topical use. Clindamycin phosphate is a water-soluble ester of the semisynthetic 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-2pyrrolidinecarboxamido)-1-thio-L-threoαDgalacto-octopyranoside 2 -(dihydrogen phosphate). The structural formula or clindamycin phosphate is represented below:

Clindamycin phosphate:

structure1
(click image for full-size original)

Molecular Formula: C18 H34 ClN2 O8 PS Molecular Weight: 504.97

Benzoyl peroxide is an antibacterial and keratolytic agent. The structural formula for benzoyl peroxide is represented below:

Benzoyl peroxide:

structure2
(click image for full-size original)

Molecular Formula: C14 H10 O4 Molecular Weight: 242.23

Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% contains the following inactive ingredients: purified water, carbomer 980, propylene glycol, and potassium hydroxide. Each gram of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2%/2.5% contains 1.2% of clindamycin phosphate which is equivalent to 1% clindamycin.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Clindamycin: Clindamycin is a lincosamide antibacterial [See Microbiology (12.4) ].

Benzoyl Peroxide: Benzoyl peroxide is an oxidizing agent with bactericidal and keratolytic effects but the precise mechanism of action is unknown.

12.3 Pharmacokinetics

The systemic absorption of clindamycin was investigated in an open-label, multiple-dose trial in 16 adult subjects with moderate to severe acne vulgaris treated with 1 gram of clindamycin phosphate and benzoyl peroxide gel, 1.2%/2.5% applied to the face once daily for 30 days. Twelve subjects (75%) had at least one quantifiable clindamycin plasma concentration above the lower limit of quantification (LOQ = 0.5 ng/mL) on Day 1 or Day 30. On Day 1, the mean (± standard deviation) peak plasma concentration (Cmax ) was 0.78 ± 0.22 ng/mL (n=9 with measurable concentrations), and the mean AUC0-t was 5.29 ± 0.81 h.ng/mL (n=4). On Day 30, the mean Cmax was 1.22 ± 0.88 ng/mL (n=10), and the mean AUC0-t was 8.42 ± 6.01 h.ng/mL (n=6). Clindamycin plasma concentrations were below LOQ in all subjects at 24 hours post-dose on the three tested days (Day 1, 15, and 30).

Benzoyl peroxide has been shown to be absorbed by the skin where it is converted to benzoic acid.

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