Get your patient on Clindamycin Phosphate - Clindamycin Phosphate aerosol, Foam (Clindamycin Phosphate)

Risk Summary

There are no available data on clindamycin phosphate foam use in pregnant women to inform a drug-associated risk for adverse developmental outcomes.

Animal reproduction studies have not been conducted with clindamycin phosphate foam. No evidence of fetal harm or malformations was observed in pregnant rats and mice administered daily subcutaneous or oral doses of clindamycin salts during organogenesis at doses that produced exposures up to 84 and 42 times, respectively, the maximum recommended human dose (MRHD) of clindamycin phosphate foam based on body surface area (BSA) comparisons and assuming 100% absorption [see Data] .

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

Reproduction studies have been conducted in rats and mice using subcutaneous or oral doses of clindamycin phosphate, clindamycin hydrochloride or clindamycin palmitate hydrochloride administered daily during organogenesis at doses up to the equivalent of 432 mg/kg/day clindamycin phosphate. These studies produced no evidence of fetal harm or malformations in rats or mice at exposures 84 or 42 times, respectively, the MRHD of clindamycin phosphate (i.e., 5 milliliters of clindamycin phosphate foam) based on BSA comparison and assuming 100% absorption.

Risk Summary

There is no information on the presence of clindamycin in human milk, or the effects on the breast-fed child, or the effects on milk production following use of clindamycin phosphate foam. However, orally and parenterally administered clindamycin has been reported to appear in breast milk.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for clindamycin phosphate foam and any potential adverse effects on the breast-fed child from clindamycin phosphate foam or from the underlying maternal condition.

Clinical Considerations

If used during lactation and clindamycin phosphate foam is applied to the chest, care should be taken to avoid accidental ingestion by the infant.

Safety and effectiveness of clindamycin phosphate foam in children under the age of 12 have not been studied.

The clinical study with clindamycin phosphate foam did not include sufficient numbers of subjects aged 65 and over to determine if they respond differently than younger subjects.

Systemic absorption of clindamycin has been demonstrated following topical use of this product. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical clindamycin. If significant diarrhea occurs, clindamycin phosphate foam should be discontinued [ see Adverse Reactions (6.2 ) ].

Severe colitis has occurred following oral or parenteral administration of clindamycin with an onset of up to several weeks following cessation of therapy. Antiperistaltic agents such as opiates and diphenoxylate with atropine may prolong and/or worsen severe colitis. Severe colitis may result in death.

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. Stool cultures for Clostridium difficile and stool assay for C. difficile toxin may be helpful diagnostically.

Clindamycin phosphate foam can cause irritation. Concomitant topical acne therapy should be used with caution since a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents. If irritation or dermatitis occurs, clindamycin should be discontinued.

Avoid contact of clindamycin phosphate foam with eyes, mouth, lips, other mucous membranes or areas of broken skin. If contact occurs, rinse thoroughly with water.

Clindamycin phosphate foam should be prescribed with caution in atopic individuals.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

A total of 439 subjects with mild to moderate acne vulgaris were treated once daily for 12 weeks with clindamycin phosphate foam.

The incidence of adverse reactions occurring in ≥ 1% of the subjects in clinical trials comparing clindamycin phosphate foam and its vehicle is presented in Table 1.

In a contact sensitization study, none of the 203 subjects developed evidence of allergic contact sensitization to clindamycin phosphate foam.

The following adverse reactions have been identified during post approval use of clindamycin phosphate foam: application site pain, application site erythema, diarrhea, urticaria, abdominal pain, hypersensitivity, rash, abdominal discomfort, nausea, seborrhea, application site rash, dizziness, pain of skin, colitis (including pseudomembranous colitis), and hemorrhagic diarrhea. 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.

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. Orally and parenterally administered clindamycin have been associated with severe colitis, which may end fatally.

Clindamycin phosphate foam should not be used in combination with topical or oral erythromycin-containing products due to possible antagonism to its clindamycin component. In vitro studies have shown antagonism between these two antimicrobials. The clinical significance of this in vitro antagonism is not known.

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

Mechanism of action of clindamycin in acne vulgaris is unknown [see Microbiology (12.4 )].

Pharmacodynamics of clindamycin phosphate foam is unknown.

In an open label, parallel group study in 24 subjects with acne vulgaris, 12 subjects (3 male and 9 female) applied 4 grams of clindamycin phosphate foam once-daily for five days, and 12 subjects (7 male and 5 female) applied 4 grams of a clindamycin gel, 1%, once daily for five days. On Day 5, the mean C _max and AUC _{(0 to 12)} were 23% and 9% lower, respectively, for clindamycin phosphate foam than for the clindamycin gel, 1%.

Following multiple applications of clindamycin phosphate foam, less than 0.024% of the total dose was excreted unchanged in the urine over 12 hours on Day 5.

No microbiology studies were conducted in the clinical trials with this product.

Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing protein synthesis. Clindamycin has been shown to have in vitro activity against Propionibacterium acnes ( P. acnes ), an organism that has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes was not examined in clinical studies with clindamycin phosphate foam. P. acnes resistance to clindamycin has been documented.

Inducible Clindamycin Resistance

The treatment of acne with antimicrobials is associated with the development of antimicrobial resistance in P. acnes as well as other bacteria (e.g. Staphylococcus aureus, Streptococcus pyogenes ). The use of clindamycin may result in developing inducible resistance in these organisms. This resistance is not detected by routine susceptibility testing.

Cross Resistance:

Resistance to clindamycin is often associated with resistance to erythromycin.

The carcinogenicity of a 1.2% clindamycin phosphate gel similar to clindamycin phosphate foam was evaluated by daily topical administration to mice for two years. The topical doses used in this study were approximately 3 and 15 times higher than the MRHD of clindamycin phosphate from clindamycin phosphate foam, based on BSA comparison and assuming 100% absorption. No significant increase in tumors was noted in the treated animals.

The genotoxic potential of clindamycin was evaluated in an in vitro Ames assay and in an in vivo rat micronucleus test. Both tests were negative.

Reproduction studies in rats using oral doses of clindamycin hydrochloride or clindamycin palmitate hydrochloride have revealed no evidence of impaired fertility.

Clindamycin Phosphate Foam, 1% contains clindamycin phosphate, USP equivalent to 10 mg clindamycin per gram. The white thermolabile hydroethanolic aerosol foam is available as follows.

100 gram aerosol can - NDC 68462-605-94

50 gram aerosol can - NDC 68462-605-27

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Flammable. Avoid fire, flame or smoking during and immediately following application.

Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperature above 120°F (49°C).

Keep out of reach of children.