Cleocin clindamycin phosphate 20 mg/g Cream — NDC 0009-3448-01 (Billing 00009-3448-01)

WARNINGS Pseudomembranous colitis has been reported with nearly all antibacterial agents, including clindamycin, and may range in severity from mild to life-threatening. Orally and parenterally administered clindamycin has been associated with severe colitis which may end fatally. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of orally and parenterally administered clindamycin, as well as with topical (dermal and vaginal) formulations of clindamycin.

Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of clindamycin, even when administered by the vaginal route, because approximately 5% of the clindamycin dose is systemically absorbed from the vagina. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia.Studies indicate that a toxin produced by Clostridioides difficile is a primary cause of "antibiotic-associated" colitis. After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated.

Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridioides difficile colitis. Onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment.

ADVERSE REACTIONS Clinical trials Non-pregnant Women In clinical trials involving non-pregnant women, 1.8% of 600 patients who received treatment with CLEOCIN Vaginal Cream 2% for 3 days and 2.7% of 1325 patients who received treatment for 7 days discontinued therapy due to drug-related adverse events. Medical events judged to be related, probably related, possibly related, or of unknown relationship to vaginally administered clindamycin phosphate vaginal cream 2%, were reported for 20.7% of the patients receiving treatment for 3 days and 21.3% of the patients receiving treatment for 7 days.

Events occurring in ≥1% of patients receiving clindamycin phosphate vaginal cream 2% are shown in Table 1. TABLE 1 – Events Occurring in ≥1% of Non-pregnant Patients Receiving Clindamycin Phosphate Vaginal Cream 2% Event CLEOCIN Vaginal Cream 3 Day n=600 7 Day n=1325 Urogenital Vaginal moniliasis 7.7

10.4Vulvovaginitis 6.0

4.4Vulvovaginal disorder 3.2

5.3 Trichomonal vaginitis 0

1.3Body as a Whole Moniliasis (body) 1.3

0.2Other events occurring in <1% of the clindamycin vaginal cream 2% groups include: Urogenital system : vaginal discharge, metrorrhagia, urinary tract infection, endometriosis, menstrual disorder, vaginitis/vaginal infection, and vaginal pain. Body as a whole : localized abdominal pain, generalized abdominal pain, abdominal cramps, halitosis, headache, bacterial infection, inflammatory swelling, allergic reaction, and fungal infection. Digestive system : nausea, vomiting, constipation, dyspepsia, flatulence, diarrhea, and gastrointestinal disorder.

Endocrine system : hyperthyroidism. Central nervous system : dizziness and vertigo. Respiratory system : epistaxis.

Skin : pruritus (non-application site), moniliasis, rash, maculopapular rash, erythema, and urticaria. Special senses : taste perversion. Pregnant Women In a clinical trial involving pregnant women during the second trimester, 1.7% of 180 patients who received treatment for 7 days discontinued therapy due to drug-related adverse events.

Medical events judged to be related, probably related, possibly related, or of unknown relationship to vaginally administered clindamycin phosphate vaginal cream 2%, were reported for 22.8% of pregnant patients. Events occurring in ≥1% of patients receiving either clindamycin phosphate vaginal cream 2% or placebo are shown in Table 2. TABLE 2 - Events Occurring in ≥1% of Pregnant Patients Receiving Clindamycin Phosphate Vaginal Cream 2% or Placebo Event CLEOCIN Vaginal Cream Placebo 7 DAY n=180 7 DAY n=184 Urogenital Vaginal moniliasis 13.3

7.1Vulvovaginal disorder 6.7

7.1Abnormal labor 1.1

0.5Body as a Whole Fungal infection 1.7 0 Skin Pruritus, non-application site 1.1 0 Other events occurring in <1% of the clindamycin vaginal cream 2% group include: Urogenital system : dysuria, metrorrhagia, vaginal pain, and trichomonal vaginitis. Body as a whole : upper respiratory infection. Skin : pruritus (topical application site) and erythema.

Post-marketing 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. In the post-marketing period, there have been case reports of pseudomembranous colitis with the use of clindamycin phosphate vaginal cream. Other clindamycin formulations Clindamycin vaginal cream affords minimal peak serum levels and systemic exposure (AUCs) of clindamycin compared to 100 mg oral clindamycin dosing.

Although these lower levels of exposure are less likely to produce the common reactions seen with oral clindamycin, the possibility of these and other reactions cannot be excluded presently. Data from well-controlled trials directly comparing clindamycin administered orally to clindamycin administered vaginally are not available. The following adverse reactions and altered laboratory tests have been reported with the oral or parenteral use of clindamycin: In… [Excerpted — this section continues on DailyMed.]

Drug Interactions 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.

PRECAUTIONS General CLEOCIN Vaginal Cream 2%, contains ingredients that will cause burning and irritation of the eye. In the event of accidental contact with the eye, rinse the eye with copious amounts of cool tap water. The use of CLEOCIN Vaginal Cream 2% may result in the overgrowth of nonsusceptible organisms in the vagina.

In clinical studies involving 600 non-pregnant women who received treatment for 3 days, Candida albicans was detected, either symptomatically or by culture, in 8.8% of patients. In 9% of the patients, vaginitis was recorded. In clinical studies involving 1325 non-pregnant women who received treatment for 7 days, Candida albicans was detected, either symptomatically or by culture, in 10.5% of patients.

Vaginitis was recorded in 10.7% of the patients. In 180 pregnant women who received treatment for 7 days, Candida albicans was detected, either symptomatically or by culture, in 13.3% of patients. In 7.2% of the patients, vaginitis was recorded.

Candida albicans , as reported here, includes the terms: vaginal moniliasis and moniliasis (body as a whole). Vaginitis includes the terms: vulvovaginal disorder, vulvovaginitis, vaginal discharge, trichomonal vaginitis, and vaginitis. Information for the Patient The patient should be instructed not to engage in vaginal intercourse, or use other vaginal products (such as tampons or douches) during treatment with this product.

The patient should also be advised that this cream contains mineral oil that may weaken latex or rubber products such as condoms or vaginal contraceptive diaphragms. Therefore, use of such products within 72 hours following treatment with CLEOCIN Vaginal Cream 2%, is not recommended. Drug Interactions 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. Carcinogenesis, Mutagenesis, Impairment of Fertility Long term studies in animals have not been performed with clindamycin to evaluate carcinogenic potential. Genotoxicity tests performed included a rat micronucleus test and an Ames test.

Both tests were negative. Fertility studies in rats treated orally with up to 300 mg/kg/day (31 times the human exposure based on mg/m 2 ) revealed no effects on fertility or mating ability. 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.

Clindamycin vaginal cream should be used during the first trimester of pregnancy only if clearly needed and the benefits outweigh the risks. There are no adequate and well-controlled studies in pregnant women during the first trimester of pregnancy. CLEOCIN Vaginal Cream 2% has been studied in pregnant women during the second trimester.

In women treated for seven days, abnormal labor was reported in 1.1% of patients who received clindamycin vaginal cream 2% compared with 0.5% of patients who received placebo. Reproduction studies have been performed in rats and mice using oral and parenteral doses of clindamycin up to 600 mg/kg/day (62 and 25 times, respectively, the maximum human exposure based on body surface area) and have revealed no evidence of harm to the fetus due to clindamycin. Cleft palates were observed in fetuses from one mouse strain treated intraperitoneally with clindamycin at 200 mg/kg/day (about 10 times the recommended dose based on body surface area conversions).

Since this effect was not observed in other mouse strains or in other species, the effect may be strain specific. Nursing Mothers Limited published data based on breast milk sampling reports that clindamycin appears in human breast milk in the range of less than 0.5 to 3.8 mcg/mL at dosages of 150 mg orally to 600 mg intravenously. It is not known if clindamycin is excreted in human breast milk follo… [Excerpted — this section continues on DailyMed.]