Vaginally applied clindamycin phosphate vaginal cream 2% could be absorbed in sufficient amounts to produce systemic effects.
Do not administer Clindesse (clindamycin phosphate) to individuals with a history of hypersensitivity to clindamycin or other lincosamides. Reported reactions to other formulations of clindamycin include rashes, urticaria, erythema multiforme, and anaphylactoid reactions.
History of Bowel DiseaseDo not administer Clindesse (clindamycin phosphate) to patients with regional enteritis, ulcerative colitis, or a history of Clostridium difficile-associated diarrhea.
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 practice.
The data described below reflect exposure to Clindesse (clindamycin phosphate) in 368 patients. Clindesse (clindamycin phosphate) was studied in three clinical studies: placebo-controlled (n=85), active-controlled (n=263), and single-arm (n=20). The population was female, aged 18 to 78, who were diagnosed with bacterial vaginosis. Patient demographics in the trials were 51% Caucasian, 36% Black, 10% Hispanic, and 3% Asian, other or unknown. All patients received 100 mg clindamycin phosphate cream intravaginally in a single dose.
Of the 368 women treated with a single dose of Clindesse (clindamycin phosphate) , 1.6% of the patients discontinued therapy due to adverse reactions. Adverse reactions occurred in 126 of 368 patients (34%) treated with Clindesse (clindamycin phosphate) and in 32 of 85 patients (38%) treated with placebo.
Adverse reactions occurring in ≥ 1% of patients receiving Clindesse (clindamycin phosphate) in the three clinical studies are shown in Table 1.
Table 1: Adverse Reactions Occurring in ≥ 1% of Clindesse (clindamycin phosphate) -Treated
Patients and at a Higher Rate than Placebo-Treated Patients
| Adverse Event | Clindesse (clindamycin phosphate) N=368 n (%) |
Placebo N=85 n (%) |
| Vaginosis fungal NOS* | 52 (14) | 7 (8) |
| Headache NOS | 10 (3) | 2 (2) |
| Back pain | 6 (2) | 1 (1) |
| Constipation | 4 (1) | 0 (0) |
| Urinary tract infection NOS | 4 (1) | 0 (0) |
| N = number of patients in intent-to-treat
population n (%) = number and percentage of patients with reported adverse reaction NOS = not otherwise specified * The use of clindamycin may result in the overgrowth of non-susceptible fungal organisms in the vagina and may require antifungal treatment |
Other reactions reported by < 1% of those women treated with Clindesse (clindamycin phosphate) include:
Dermatologic: Pruritic rash
Gastrointestinal: Diarrhea, vomiting
General: Fatigue
Immune System: Hypersensitivity
Nervous System: Dizziness
Reproductive System: Dysfunctional uterine bleeding, dysmennorrhea, intermenstrual bleeding, pelvic pain, vaginal burning, vaginal irritation, vulvar erythema, vulvitis, vulvovaginal discomfort, vulvovaginal dryness, vulvovaginitis
Other Clindamycin FormulationsClindesse (clindamycin phosphate) affords minimal peak serum levels and systemic exposure (AUCs) of clindamycin compared to an oral or intravenous dose of clindamycin. Data from well-controlled trials directly comparing clindamycin administered orally to clindamycin administered vaginally are not available.
The following additional adverse reactions and altered laboratory tests have been reported with the oral or parenteral use of clindamycin:
Gastrointestinal: Abdominal pain, esophagitis, nausea, Clostridium difficile-associated diarrhea
Hematopoietic: Transient neutropenia (leukopenia), eosinophilia, agranulocytosis, and thrombocytopenia have been reported. No direct etiologic relationship to concurrent clindamycin therapy could be made in any of these reports.
Hypersensitivity Reactions: Maculopapular rash, vesiculobullous rash, and urticaria have been observed during drug therapy. Generalized mild to moderate morbilliform-like skin rashes are the most frequently reported of all adverse reactions. Cases of erythema multiforme, some resembling Stevens-Johnson syndrome, have been associated with clindamycin. A few cases of anaphylactoid reactions have been reported.
Liver: Jaundice and abnormalities in liver function tests have been observed during clindamycin therapy.
Musculoskeletal: Cases of polyarthritis have been reported.
Renal: Although no direct relationship of clindamycin to renal damage has been established, renal dysfunction as evidenced by azotemia, oliguria, and/or proteinuria has been observed in rare instances.
Postmarketing ExperienceThe following adverse reactions have been identified during postapproval use of Clindesse (clindamycin phosphate). 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.
Dermatologic: Rash
Gastrointestinal: Hematochezia
Reproductive System: Vaginal erythema, vulvovaginal pruritis, vaginal discharge, vaginal swelling, vaginal bleeding, vaginal pain
Clindesse (clindamycin phosphate) is indicated for the treatment of bacterial vaginosis (formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, Corynebacterium vaginitis, or anaerobic vaginosis) in non-pregnant women.
Following a single intravaginal application of Clindesse (clindamycin phosphate) cream to 20 healthy women, the mean (range) AUC0-inf and Cmax estimates were 175 (38.6 to 541) ng/mL·hr and 6.6 (0.8 to 39) ng/mL, respectively. The mean Cmax of clindamycin for Clindesse (clindamycin phosphate) was approximately 0.3%, 0.1%, and 7.6% of that observed after the administration of a 150 mg Cleocin oral capsule (2.5 mcg/mL), a 600 mg Cleocin intravenous injection (10.9 mcg/mL), and a single dose of 100 mg of Cleocin Vaginal Cream (86.5 ng/mL), respectively. The peak serum concentration of clindamycin was attained approximately 20 hours post dosing for Clindesse (clindamycin phosphate).
Clindesse (clindamycin phosphate) should be used during pregnancy only if clearly needed. There are no adequate and well-controlled studies of Clindesse (clindamycin phosphate) in pregnant women.
Another intravaginal formulation containing 2% clindamycin phosphate 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 that clindamycin vaginal cream formulation 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 (58 and 29 times, respectively, the recommended human dose based on body surface area comparisons) and have revealed no evidence of harm to the fetus due to clindamycin.
Because animal reproduction studies are not always predictive of human response, Clindesse (clindamycin phosphate) should be used during pregnancy only if clearly needed.
Clindesse is an intravaginal cream containing clindamycin phosphate 2%. Each pre-filled, single-dose applicator delivers approximately 5 g of cream containing approximately 100 mg of clindamycin.
Storage And HandlingClindesse (clindamycin phosphate) Vaginal Cream, 2%, is available in cartons containing one single-dose, pre-filled disposable applicator (NDC 64011-124-08). Each applicator delivers approximately 5 g of vaginal cream containing approximately 100 mg of clindamycin.
Store at 20°-25°C (68°-77°F). Avoid heat above 30°C (86°F).
Manufactured by KV Pharmaceutical™ Co. for Ther-Rx™ Corporation. St. Louis, MO 63044. Revised: 12/2010
Included as part of the PRECAUTIONS section.
PRECAUTIONS Clostridium difficile-Associated Diarrhea (CDAD)Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Use with Condoms and Vaginal Contraceptive DiaphragmsThis cream contains mineral oil that may weaken latex or rubber products such as condoms or vaginal contraceptive diaphragms. Therefore, the use of such barrier contraceptives is not recommended concurrently or for 5 days following treatment with Clindesse (clindamycin phosphate). During this time period, condoms may not be reliable for preventing pregnancy or for protecting against transmission of HIV and other sexually transmitted diseases.
Patient Counseling Information Vaginal Intercourse and Use with Vaginal ProductsInstruct the patient not to engage in vaginal intercourse, or use other vaginal products (such as tampons or douches) during treatment with this product.
Use with Condoms and Vaginal Contraceptive DiaphragmsAdvise the patient that this cream contains mineral oil that may weaken latex or rubber products such as condoms or vaginal contraceptive diaphragms. Therefore, do not use barrier contraceptives concurrently or for 5 days following treatment with Clindesse (clindamycin phosphate). During this time period, condoms may not be reliable for preventing pregnancy or for protecting against transmission of HIV and other sexually transmitted diseases.
Fungal Vaginal InfectionsInform the patient that vaginal fungal infections can occur following use of Clindesse (clindamycin phosphate) and may require treatment with an antifungal drug.
Accidental Exposure to the EyeInform the patient that Clindesse (clindamycin phosphate) contains ingredients which 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 and consult a physician.
Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment of FertilityLong-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 (29 times the recommended human dose based on body surface area comparisons) revealed no effects on fertility or mating ability.
Use In Specific Populations Pregnancy Pregnancy Category BClindesse (clindamycin phosphate) should be used during pregnancy only if clearly needed. There are no adequate and well-controlled studies of Clindesse (clindamycin phosphate) in pregnant women.
Another intravaginal formulation containing 2% clindamycin phosphate 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 that clindamycin vaginal cream formulation 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 (58 and 29 times, respectively, the recommended human dose based on body surface area comparisons) and have revealed no evidence of harm to the fetus due to clindamycin.
Because animal reproduction studies are not always predictive of human response, Clindesse (clindamycin phosphate) should be used during pregnancy only if clearly needed.
Nursing MothersCaution should be exercised when Clindesse (clindamycin phosphate) is administered to a nursing woman. It is not known if clindamycin is excreted in human milk following the use of vaginally administered clindamycin. Clindamycin has been detected in human milk after oral or parenteral administration.
Because of the potential for serious adverse reactions in nursing infants, a decision to continue or discontinue nursing should take into account the importance of the drug to the mother.
Pediatric UseThe safety and efficacy of Clindesse (clindamycin phosphate) in the treatment of bacterial vaginosis in post-menarchal females have been established on the extrapolation of clinical trial data from adult women. The safety and efficacy of Clindesse (clindamycin phosphate) in pre-menarchal females have not been established.
Geriatric UseClinical studies with Clindesse (clindamycin phosphate) did not include sufficient numbers of subjects 65 years of age or older to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
The recommended dose is the complete contents of a single pre-filled applicator containing 5 g of Clindesse (clindamycin phosphate) cream administered once intravaginally at any time of the day.
Not for ophthalmic, dermal, or oral use.
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 practice.
The data described below reflect exposure to Clindesse (clindamycin phosphate) in 368 patients. Clindesse (clindamycin phosphate) was studied in three clinical studies: placebo-controlled (n=85), active-controlled (n=263), and single-arm (n=20). The population was female, aged 18 to 78, who were diagnosed with bacterial vaginosis. Patient demographics in the trials were 51% Caucasian, 36% Black, 10% Hispanic, and 3% Asian, other or unknown. All patients received 100 mg clindamycin phosphate cream intravaginally in a single dose.
Of the 368 women treated with a single dose of Clindesse (clindamycin phosphate) , 1.6% of the patients discontinued therapy due to adverse reactions. Adverse reactions occurred in 126 of 368 patients (34%) treated with Clindesse (clindamycin phosphate) and in 32 of 85 patients (38%) treated with placebo.
Adverse reactions occurring in ≥ 1% of patients receiving Clindesse (clindamycin phosphate) in the three clinical studies are shown in Table 1.
Table 1: Adverse Reactions Occurring in ≥ 1% of Clindesse (clindamycin phosphate) -Treated
Patients and at a Higher Rate than Placebo-Treated Patients
| Adverse Event | Clindesse (clindamycin phosphate) N=368 n (%) |
Placebo N=85 n (%) |
| Vaginosis fungal NOS* | 52 (14) | 7 (8) |
| Headache NOS | 10 (3) | 2 (2) |
| Back pain | 6 (2) | 1 (1) |
| Constipation | 4 (1) | 0 (0) |
| Urinary tract infection NOS | 4 (1) | 0 (0) |
| N = number of patients in intent-to-treat
population n (%) = number and percentage of patients with reported adverse reaction NOS = not otherwise specified * The use of clindamycin may result in the overgrowth of non-susceptible fungal organisms in the vagina and may require antifungal treatment |
Other reactions reported by < 1% of those women treated with Clindesse (clindamycin phosphate) include:
Dermatologic: Pruritic rash
Gastrointestinal: Diarrhea, vomiting
General: Fatigue
Immune System: Hypersensitivity
Nervous System: Dizziness
Reproductive System: Dysfunctional uterine bleeding, dysmennorrhea, intermenstrual bleeding, pelvic pain, vaginal burning, vaginal irritation, vulvar erythema, vulvitis, vulvovaginal discomfort, vulvovaginal dryness, vulvovaginitis
Other Clindamycin FormulationsClindesse (clindamycin phosphate) affords minimal peak serum levels and systemic exposure (AUCs) of clindamycin compared to an oral or intravenous dose of clindamycin. Data from well-controlled trials directly comparing clindamycin administered orally to clindamycin administered vaginally are not available.
The following additional adverse reactions and altered laboratory tests have been reported with the oral or parenteral use of clindamycin:
Gastrointestinal: Abdominal pain, esophagitis, nausea, Clostridium difficile-associated diarrhea
Hematopoietic: Transient neutropenia (leukopenia), eosinophilia, agranulocytosis, and thrombocytopenia have been reported. No direct etiologic relationship to concurrent clindamycin therapy could be made in any of these reports.
Hypersensitivity Reactions: Maculopapular rash, vesiculobullous rash, and urticaria have been observed during drug therapy. Generalized mild to moderate morbilliform-like skin rashes are the most frequently reported of all adverse reactions. Cases of erythema multiforme, some resembling Stevens-Johnson syndrome, have been associated with clindamycin. A few cases of anaphylactoid reactions have been reported.
Liver: Jaundice and abnormalities in liver function tests have been observed during clindamycin therapy.
Musculoskeletal: Cases of polyarthritis have been reported.
Renal: Although no direct relationship of clindamycin to renal damage has been established, renal dysfunction as evidenced by azotemia, oliguria, and/or proteinuria has been observed in rare instances.
Postmarketing ExperienceThe following adverse reactions have been identified during postapproval use of Clindesse (clindamycin phosphate). 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.
Dermatologic: Rash
Gastrointestinal: Hematochezia
Reproductive System: Vaginal erythema, vulvovaginal pruritis, vaginal discharge, vaginal swelling, vaginal bleeding, vaginal pain
DRUG INTERACTIONSNo formal drug interaction studies have been conducted for Clindesse (clindamycin phosphate).
Neuromuscular Blocking AgentsOrally or intravenously administered clindamycin has 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.
