CLINDAMYCIN PHOSPHATE- clindamycin phosphate_cream

CLINICAL PHARMACOLOGY
Clindamycin is an antibacterial drug (see MICROBIOLOGY. Following a once a day intravaginal dose of 100 mg of clindamycin phosphate vaginal cream 2%, administered to 6 healthy female volunteers for 7 days, approximately 5% (range 0. 6% to 11%) of the administered dose was absorbed systemically. The peak serum clindamycin concentration observed on the first day averaged 18 ng/mL (range 4 to 47 ng/mL) and on day 7 it averaged 25 ng/mL (range 6 to 61 ng/mL). These peak concentrations were attained approximately 10 hours post-dosing (range 4en dash24 hours). Following a once a day intravaginal dose of 100 mg of clindamycin phosphate vaginal cream 2%, administered for 7 consecutive days to 5 women with bacterial vaginosis, absorption was slower and less variable than that observed in healthy females. Approximately 5% (range 2% to 8%) of the dose was absorbed systemically. The peak serum clindamycin concentration observed on the first day averaged 13 ng/mL (range 6 to 34 ng/mL) and on day 7 it averaged 16 ng/mL (range 7 to 26 ng/mL). These peak concentrations were attained approximately 14 hours post-dosing (range 4en dash24 hours). There was little or no systemic accumulation of clindamycin after repeated vaginal dosing of clindamycin phosphate vaginal cream 2%. The systemic half-life was 1. Clindamycin inhibits bacterial protein synthesis by binding to the 23S RNA of the 50S subunit of the ribosome. Clindamycin is predominantly bacteriostatic. Although clindamycin phosphate is inactive in vitro in vivo Resistance to clindamycin is most often caused by modification of the target site on the ribosome, usually by chemical modification of RNA bases by point mutations in RNA or occasionally in proteins. Cross resistance has been demonstrated between lincosamides, macrolides and streptogramins B in some organisms. Cross resistance has been demonstrated between clindamycin and lincomycin. Culture and sensitivity testing of bacteria are not routinely performed to establish the diagnosis of bacterial vaginosis (see INDICATIONS AND USAGE Gardnerella vaginalis, Mobiluncus Mycoplasma hominis The following in vitro in vitro Bacteroides Gardnerella vaginalis Mobiluncus Mycoplasma hominis Peptostreptococcus.
Mechanism of Action
Clindamycin is an antibacterial drug (see MICROBIOLOGY .
Pharmacokinetics
Following a once a day intravaginal dose of 100 mg of clindamycin phosphate vaginal cream 2%, administered to 6 healthy female volunteers for 7 days, approximately 5% (range 0.6% to 11%) of the administered dose was absorbed systemically. The peak serum clindamycin concentration observed on the first day averaged 18 ng/mL (range 4 to 47 ng/mL) and on day 7 it averaged 25 ng/mL (range 6 to 61 ng/mL). These peak concentrations were attained approximately 10 hours post-dosing (range 4en dash24 hours). Following a once a day intravaginal dose of 100 mg of clindamycin phosphate vaginal cream 2%, administered for 7 consecutive days to 5 women with bacterial vaginosis, absorption was slower and less variable than that observed in healthy females. Approximately 5% (range 2% to 8%) of the dose was absorbed systemically. The peak serum clindamycin concentration observed on the first day averaged 13 ng/mL (range 6 to 34 ng/mL) and on day 7 it averaged 16 ng/mL (range 7 to 26 ng/mL). These peak concentrations were attained approximately 14 hours post-dosing (range 4en dash24 hours). There was little or no systemic accumulation of clindamycin after repeated vaginal dosing of clindamycin phosphate vaginal cream 2%. The systemic half-life was 1.5 to 2.6 hours.
MICROBIOLOGY
Clindamycin inhibits bacterial protein synthesis by binding to the 23S RNA of the 50S subunit of the ribosome. Clindamycin is predominantly bacteriostatic. Although clindamycin phosphate is inactive in vitro in vivo Resistance to clindamycin is most often caused by modification of the target site on the ribosome, usually by chemical modification of RNA bases by point mutations in RNA or occasionally in proteins. Cross resistance has been demonstrated between lincosamides, macrolides and streptogramins B in some organisms. Cross resistance has been demonstrated between clindamycin and lincomycin. Culture and sensitivity testing of bacteria are not routinely performed to establish the diagnosis of bacterial vaginosis (see INDICATIONS AND USAGE Gardnerella vaginalis, Mobiluncus Mycoplasma hominis The following in vitro in vitro Bacteroides Gardnerella vaginalis Mobiluncus Mycoplasma hominis Peptostreptococcus.

Clindamycin phosphate vaginal cream 2%, is indicated in the treatment of bacterial vaginosis (formerly referred to as Haemophilus Gardnerella Corynebacterium CLINICAL STUDIES NOTE: Lactobacillus Gardnerella Other pathogens commonly associated with vulvovaginitis, eg, Trichomonas vaginalis, Chlamydia trachomatis, N. gonorrhoeae, Candida albicans, Herpes simplex

DOSAGE AND ADMINISTRATION
The recommended dose is one applicatorful of clindamycin phosphate vaginal cream 2%, (5 grams containing approximately 100 mg of clindamycin phosphate) intravaginally, preferably at bedtime, for 3 or 7 consecutive days in non-pregnant patients and for 7 consecutive days in pregnant patients. (See CLINICAL STUDIES
INSTRUCCIONES PARA LA PACIENTE
Este envase contiene aplicadores de plástico desechables. Los aplicadores están diseñados para la administración apropiada de la crema en la vagina. Remueva la tapa del tubo de crema y enrosque el aplicador de plástico al tubo. Exprima el tubo suavemente desde el extremo inferior y fuerce el medicamento al aplicador. El aplicador estará lleno cuando el émbolo llega a su máxima longitud. Desenrosque el aplicador del tubo y vuelva a poner la tapa. Acuéstese de espalda y agarrando firmemente el aplicador, introdúzcalo en la vagina tanto como sea posible sin causar molestias. Empuje lentamente el émbolo hasta que se detenga. Saque el aplicador cuidadosamente de la vagina y descártelo. RECUERDE APLICARSE UN APLICADOR LLENO TODAS LAS NOCHES AL ACOSTARSE, O DE ACUERDO CON LAS INDICACIONES DE SU MEDICO. 0 Figure Figure.

ADVERSE REACTIONS
In clinical trials involving non-pregnant women, 1. 8% of 600 patients who received treatment with clindamycin phosphate 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 en dash Events Occurring in >=1% of Non-pregnant Patients Receiving Clindamycin Phosphate Vaginal Cream 2% Clindamycin Phosphate Vaginal Cream Event 3 Day n=600 7 Day n=1325 Urogenital Vaginal moniliasis 7. 4 Vulvovaginitis 6. 4 Vulvovaginal disorder 3. 3 Trichomonal vaginitis 0 1. 3 Body as a Whole Moniliasis (body) 1. 2 Other events occurring in <1% of the clindamycin vaginal cream 2% groups include: Urogenital system: Body as a whole: Digestive system: Endocrine system: Central nervous system: Respiratory system: Skin: Special senses: 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 Clindamycin Phosphate Vaginal Cream Placebo Event 7 DAY n=180 7 Day n=184 Urogenital Vaginal moniliasis 13. 1 Vulvovaginal disorder 6. 1 Abnormal labor 1. 5 Body 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: Body as a whole: Skin: 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. 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 Infections and Infestations: Clostridioides difficile Gastrointestinal: WARNINGS Hematopoietic: Hypersensitivity Reactions: Liver: Musculoskeletal: Renal: Immune System:.
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.

Clindamycin phosphate vaginal cream 2%, is contraindicated in individuals with a history of hypersensitivity to clindamycin, lincomycin, or any of the components of this vaginal cream. Clindamycin phosphate vaginal cream 2%, is also contraindicated in individuals with a history of regional enteritis, ulcerative colitis, or a history of "antibiotic-associated" colitis.

Pregnancy
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. Clindamycin phosphate 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 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
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
Clinical studies for clindamycin phosphate vaginal cream 2% did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

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.

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 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 Onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment.
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
Clinical trials
In clinical trials involving non-pregnant women, 1. 8% of 600 patients who received treatment with clindamycin phosphate 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 en dash Events Occurring in >=1% of Non-pregnant Patients Receiving Clindamycin Phosphate Vaginal Cream 2% Clindamycin Phosphate Vaginal Cream Event 3 Day n=600 7 Day n=1325 Urogenital Vaginal moniliasis 7. 4 Vulvovaginitis 6. 4 Vulvovaginal disorder 3. 3 Trichomonal vaginitis 0 1. 3 Body as a Whole Moniliasis (body) 1. 2 Other events occurring in <1% of the clindamycin vaginal cream 2% groups include: Urogenital system: Body as a whole: Digestive system: Endocrine system: Central nervous system: Respiratory system: Skin: Special senses: 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 Clindamycin Phosphate Vaginal Cream Placebo Event 7 DAY n=180 7 Day n=184 Urogenital Vaginal moniliasis 13. 1 Vulvovaginal disorder 6. 1 Abnormal labor 1. 5 Body 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: Body as a whole: Skin:.
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 Infections and Infestations: Clostridioides difficile Gastrointestinal: WARNINGS Hematopoietic: Hypersensitivity Reactions: Liver: Musculoskeletal: Renal: Immune System:
OVERDOSAGE
Vaginally applied clindamycin phosphate vaginal cream 2% could be absorbed in sufficient amounts to produce systemic effects. (See WARNINGS
CLINICAL STUDIES
In two clinical studies involving 674 evaluable non-pregnant women with bacterial vaginosis comparing Clindamycin phosphate vaginal cream 2% for 3 or 7 days, the clinical cure rates, determined at 1 month posttherapy, ranged from 72% to 81% for the 3-day treatment and 84% to 86% for the 7-day treatment. Clindamycin Phosphate Vaginal Cream 2% 3 Day Clindamycin Phosphate Vaginal Cream 2% 7 Day US Study 94/131 72% 110/128 86% European Study 161/199 81% 181/216 84% In a clinical study involving 249 evaluable pregnant patients in the second and third trimester treated for 7 days, the clinical cure rate, determined at 1 month posttherapy, was 60% (77/129) in the clindamycin arm and 9% (11/120) for the vehicle arm. The determination of clinical cure was based on the absence of a "fishy" amine odor when the vaginal discharge was mixed with a 10% KOH solution and the absence of clue cells on microscopic examination.

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