CLEOCIN® Vaginal Ovules Warnings and Precautions

(clindamycin)

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 CLEOCIN Vaginal Ovules, because approximately 30% 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.

PRECAUTIONS

General

The use of CLEOCIN Vaginal Ovules may result in the overgrowth of nonsusceptible organisms in the vagina. In clinical studies using CLEOCIN Vaginal Ovules, treatment-related moniliasis was reported in 2.7% and vaginitis in 3.6% of 589 nonpregnant women. Moniliasis, as reported here, includes the terms: vaginal or nonvaginal moniliasis and fungal infection. Vaginitis includes the terms: vulvovaginal disorder, vaginal discharge, and vaginitis/vaginal infection.

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 these suppositories use an oleaginous base that may weaken latex or rubber products such as condoms or vaginal contraceptive diaphragms. Therefore, the use of such products within 72 hours following treatment with CLEOCIN Vaginal Ovules 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/m2) 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 ovules 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 of CLEOCIN Vaginal Ovules 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 7 days, abnormal labor was reported more frequently in patients who received CLEOCIN Vaginal Cream compared to those receiving placebo (1.1% vs. 0.5% of patients, respectively).

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 dose 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 following the use of vaginally administered clindamycin phosphate.

Clindamycin has the potential to cause adverse effects on the breast-fed infant's gastrointestinal flora. If clindamycin is required by a nursing mother, it is not a reason to discontinue breastfeeding, but an alternate drug may be preferred. Monitor the breast-fed infant for possible adverse effects on the gastrointestinal flora, such as diarrhea, candidiasis (thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis.

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 breast-fed child from clindamycin or from the underlying maternal condition.

Pediatric Use

The safety and efficacy of CLEOCIN Vaginal Ovules in the treatment of bacterial vaginosis in post-menarchal females have been established on the extrapolation of clinical trial data from adult women. When a post-menarchal adolescent presents to a health professional with bacterial vaginosis symptoms, a careful evaluation for sexually transmitted diseases and other risk factors for bacterial vaginosis should be considered. The safety and efficacy of CLEOCIN Vaginal Ovules in pre-menarchal females have not been established.

Geriatric Use

Clinical studies of CLEOCIN Vaginal Ovules did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

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Warnings and Precautions

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 CLEOCIN Vaginal Ovules, because approximately 30% 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.

PRECAUTIONS

General

The use of CLEOCIN Vaginal Ovules may result in the overgrowth of nonsusceptible organisms in the vagina. In clinical studies using CLEOCIN Vaginal Ovules, treatment-related moniliasis was reported in 2.7% and vaginitis in 3.6% of 589 nonpregnant women. Moniliasis, as reported here, includes the terms: vaginal or nonvaginal moniliasis and fungal infection. Vaginitis includes the terms: vulvovaginal disorder, vaginal discharge, and vaginitis/vaginal infection.

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 these suppositories use an oleaginous base that may weaken latex or rubber products such as condoms or vaginal contraceptive diaphragms. Therefore, the use of such products within 72 hours following treatment with CLEOCIN Vaginal Ovules 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/m2) 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 ovules 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 of CLEOCIN Vaginal Ovules 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 7 days, abnormal labor was reported more frequently in patients who received CLEOCIN Vaginal Cream compared to those receiving placebo (1.1% vs. 0.5% of patients, respectively).

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 dose 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 following the use of vaginally administered clindamycin phosphate.

Clindamycin has the potential to cause adverse effects on the breast-fed infant's gastrointestinal flora. If clindamycin is required by a nursing mother, it is not a reason to discontinue breastfeeding, but an alternate drug may be preferred. Monitor the breast-fed infant for possible adverse effects on the gastrointestinal flora, such as diarrhea, candidiasis (thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis.

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 breast-fed child from clindamycin or from the underlying maternal condition.

Pediatric Use

The safety and efficacy of CLEOCIN Vaginal Ovules in the treatment of bacterial vaginosis in post-menarchal females have been established on the extrapolation of clinical trial data from adult women. When a post-menarchal adolescent presents to a health professional with bacterial vaginosis symptoms, a careful evaluation for sexually transmitted diseases and other risk factors for bacterial vaginosis should be considered. The safety and efficacy of CLEOCIN Vaginal Ovules in pre-menarchal females have not been established.

Geriatric Use

Clinical studies of CLEOCIN Vaginal Ovules did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

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