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CLINICAL PHARMACOLOGY Mechanism of Action Clindamycin is an antibacterial drug [see Microbiology] Pharmacokinetics 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) . Microbiology Mechanism of Action Clindamycin inhibits bacterial protein synthesis at the level of the bacterial ribosome. The antibiotic binds preferentially to the 50S ribosomal subunit and affects the process of peptide chain initiation. Although clindamycin phosphate is inactive in vitro , in vivo hydrolysis converts this compound to the antibacterially active clindamycin. Activity In Vitro Clindamycin is an antibacterial agent active in vitro against most strains of the following organisms that have been reported to be associated with bacterial vaginosis: Bacteroides spp. Gardnerella vaginalis Mobiluncus spp. Mycoplasma hominis Peptostreptococcus spp. Standard methodology for the susceptibility testing of the potential bacterial vaginosis pathogens has not been defined. Culture and sensitivity testing of bacteria are not routinely performed to establish the diagnosis of bacterial vaginosis [see Clinical Studies]. Clinical Studies Two clinical studies were conducted to evaluate the efficacy of Clindesse (clindamycin phosphate) for the treatment of bacterial vaginosis. A clinical diagnosis of bacterial vaginosis was defined by the presence of a homogeneous vaginal discharge that (a) has a pH of greater than 4.5, (b) emits a “fishy” amine odor when mixed with a 10% KOH solution, and (c) contains clue cells on microscopic examination. Gram's stain results consistent with a diagnosis of bacterial vaginosis include (a) markedly reduced or absent Lactobacillus morphology, (b) predominance of Gardnerella morphotype, and (c) absent or few white blood cells. In a randomized, double-blind, placebo-controlled, clinical study involving 144 non-pregnant female patients aged 18 to 64 with a baseline Nugent score ≥ 4, Clindesse (clindamycin phosphate) demonstrated statistically significantly higher cure rates over placebo as measured by therapeutic cure, clinical cure, and Nugent score cure (Table 2) assessed at 21-30 days after administration of the drug. Therapeutic cure was a composite endpoint which required both clinical cure and Nugent score cure. Clinical cure required normal vaginal discharge, vaginal pH < 4.7, < 20% clue cells on wet mount preparation, and negative “whiff” test (detection of amine odor on addition of 10% KOH solution to sample of the vaginal discharge). A Nugent score of 0-3 was considered a Nugent score cure. The Nugent scoring is based on microscopic examination of the Gram's stained vaginal smears for quantification of specific bacterial morphotypes. Cure rates were consistently higher for Clindesse (clindamycin phosphate) compared to placebo for the following demographic subsets: age, race, height, weight, sexual behavior, and recalcitrant infection status. Table 2: Efficacy of Clindesse (clindamycin phosphate) for Treatment of Bacterial Vaginosis in a Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study Outcome Clindesse N=78 Placebo N=66 Treatment Difference† (%) [97.5% Confidence Interval] % Cure % Cure Therapeutic Cure 29.5 3.0 26.5 [14.0, 39.0] Clinical Cure 41.0 19.7 21.3 [4.7, 38.0] Nugent Score Cure 44.9 6.1 38.8 [24.6, 53.1] N = number of patients in treatment group (modified intent-to-treat population defined as all subjects randomized who received at least one dose of study medication, and who had a baseline Nugent score of at least 4) †Treatment difference = Clindesse (clindamycin phosphate) minus placebo cure rates In a second controlled clinical study involving 432 patients aged 18 to 78 with a baseline Nugent score of ≥ 4, 221 women self-administered a single dose of Clindesse (clindamycin phosphate) , and 211 women self-administered a single daily dose of a formulation of clindamycin vaginal cream for 7 days. A single dose of Clindesse (clindamycin phosphate) was shown to be similar to 7 daily doses of the clindamycin vaginal cream for treatment of bacterial vaginosis as measured by therapeutic cure, clinical cure or Nugent score cure assessed at 21-30 days after administration of the drug in the modified intent-to-treat population (Table 3) and for the per protocol population (Table 4). The study endpoints were identical to those described above for the placebo-controlled study. Statistical analyses did not reveal any significant differences when controlling for the following demographic variables: age, race, height, weight, sexual behavior, and recalcitrant infection status. The cure rates reported in the clinical studies with Clindesse (clindamycin phosphate) were based on resolution of 4 out of 4 Amsel criteria and a Nugent score of < 4, while the criteria for cure in previous clinical studies with the clindamycin vaginal cream were based solely on resolution of 2 out of 4 Amsel criteria, resulting in higher reported rates of cure for bacterial vaginosis. Table 3: Efficacy of Clindesse (clindamycin phosphate) in Treatment of Bacterial Vaginosis in a Randomized, Investigator-Blind, Active-Controlled Comparative Study – Modified-Intent-to-Treat Outcome Clindesse Single Dose N=221 Clindamycin Vaginal Cream (7 doses) N=211 Treatment Difference† (%) [95% Confidence Interval] % Cure % Cure Therapeutic Cure 33.0 37.0 -3.9 [-12.9, 5.1] Clinical Cure 53.4 54.0 -0.6 [-10.0, 8.8] Nugent Score Cure 45.7 49.3 -3.6 [-13.1, 5.8] †Treatment difference = Clindesse (clindamycin phosphate) minus clindamycin vaginal cream cure rates N = number of patients in treatment group (modified intent-to-treat population defined as all subjects randomized who received at least one dose of study medication, and who had a baseline Nugent score of at least 4) Table 4: Efficacy of Clindesse (clindamycin phosphate) in Treatment of Bacterial Vaginosis in a Randomized, Investigator-Blind, Active-Controlled Comparative Study – Per Protocol Outcome Clindesse Single Dose N=126 Clindamycin Vaginal Cream (7 doses) N=125 Treatment Difference† (%) [95% Confidence Interval] % Cure % Cure Therapeutic Cure 42.1 45.6 -3.5 [-15.8, 8.7] Clinical Cure 64.3 63.2 1.1 [-10.8, 13.0] Nugent Score Cure 56.5‡ 57.7‡ -1.3 [-13.6, 11.1] † Treatment difference = Clindesse (clindamycin phosphate) minus clindamycin vaginal cream cure rates N = number of patients in treatment group (per protocol population defined as all subjects included in the modified intent-to-treat population who completed the study without significant protocol violation) ‡ Four subjects (2 from each treatment group) did not have complete Nugent scores and were not included in the Nugent Score cure analysis

Find Lowest Prices on Clindesse® (clindamycin phosphate) DESCRIPTION Clindamycin phosphate, a lincosamide, is a water soluble ester of the semi-synthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic lincomycin. The chemical name for clindamycin phosphate is methyl 7-chloro- 6,7,8-trideoxy-6(1-methyl- trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L- threo-(alpha)-D-galacto- octopyranoside 2-(dihydrogen phosphate). It has a molecular weight of 504.96, and the molecular formula is C18H34CIN2O8 PS. The structural formula is represented below: Clindesse is a semi-solid, white cream, which contains clindamycin phosphate, USP, at a concentration equivalent to 20 mg clindamycin base per gram. The cream also contains edetate disodium, glycerol monoisostearate, lecithin, methylparaben, microcrystalline wax, mineral oil, polyglyceryl-3-oleate, propylparaben, purified water, silicon dioxide and sorbitol solution. Clindesse (clindamycin phosphate) does not comply with the pH test of the USP monograph for clindamycin phosphate vaginal cream.

INDICATIONS Treatment of Bacterial Vaginosis 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. DOSAGE AND ADMINISTRATION 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. HOW SUPPLIED Dosage Forms And Strengths 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 Handling Clindesse (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). [See USP Controlled Room Temperature.] Avoid heat above 30°C (86°F). Manufactured by KV Pharmaceutical™ Co. for Ther-Rx™ Corporation. St. Louis, MO 63044. Revised: 12/2010

PATIENT INFORMATION Clindesse (clin-DESS) (clindamycin phosphate) Vaginal Cream, 2% For vaginal use only. Do not put Clindesse (clindamycin phosphate) in your eyes, mouth, or on your skin. Read this patient information before you start using Clindesse (clindamycin phosphate) . There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment. What is Clindesse (clindamycin phosphate) ? Clindesse (clindamycin phosphate) is a vaginal cream medicine used to treat bacterial vaginal infections in women who are not pregnant. It is not known if Clindesse (clindamycin phosphate) is safe and effective in pregnant women. It is not known if Clindesse (clindamycin phosphate) is safe and effective in females who have not yet reached puberty. Who should not use Clindesse (clindamycin phosphate) ? Do not use Clindesse (clindamycin phosphate) if you: have had an allergic reaction to clindamycin or other lincosamide antibiotic medicines or are allergic to any of the ingredients in Clindesse (clindamycin phosphate) . See the end of this leaflet for a complete list of ingredients in Clindesse (clindamycin phosphate) . have had bowel problems such as: inflammation of your intestines (enteritis) inflammation of your colon (colitis) diarrhea due to a Clostridum difficile infection (CDAD) Talk to your healthcare provider before using this medicine if you have any of these conditions. What should I tell my healthcare provider before using Clindesse (clindamycin phosphate) ? Before you use Clindesse (clindamycin phosphate) , tell your healthcare provider if you: are pregnant or plan to become pregnant. It is not known if Clindesse (clindamycin phosphate) will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if Clindesse (clindamycin phosphate) passes into your breast milk. You and your healthcare provider should decide if you will take Clindesse (clindamycin phosphate) or breast feed. Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Clindesse (clindamycin phosphate) may affect how other medicines work, and other medicines may affect how Clindesse (clindamycin phosphate) works. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I use Clindesse (clindamycin phosphate) ? Use Clindesse (clindamycin phosphate) exactly as your healthcare provider tells you. Insert Clindesse (clindamycin phosphate) in the vagina one time. See the “Patient Instructions for Use” at the end of this leaflet. Insert all of the Clindesse (clindamycin phosphate) cream into your vagina. Do not use Clindesse (clindamycin phosphate) after the expiration date on the package. Do not get Clindesse (clindamycin phosphate) in your eyes. If you accidently get Clindesse (clindamycin phosphate) in your eyes rinse your eyes with cool tap water right away and call your healthcare provider. What should I avoid while using Clindesse (clindamycin phosphate) ? After you insert Clindesse (clindamycin phosphate) you should: not have vaginal intercourse or use of other vaginal products (such as tampons or douches) for at least 7 days. not use barrier contraceptive products for 5 days. Barrier contraceptives include condoms or contraceptive diaphragms used for birth control or to protect yourself against HIV or other sexually transmitted diseases. Clindesse (clindamycin phosphate) contains mineral oil that may weaken latex or rubber products such as condoms or vaginal contraceptive diaphragms. What are the possible side effects of Clindesse (clindamycin phosphate) ? Clindesse (clindamycin phosphate) may cause serious side effects, including diarrhea. One type of diarrhea is caused by an infection in your intestines called Clostridium difficile-associated diarrhea (CDAD). If you have diarrhea after you use Clindesse (clindamycin phosphate) , call your healthcare provider. The most common side effects of Clindesse (clindamycin phosphate) include: fungal infection in your vagina. You may need to take an anti-fungal medicine if you get a fungal infection. headache back pain constipation urinary tract infection Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of Clindesse (clindamycin phosphate) . For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1800-FDA-1088. How should I store Clindesse (clindamycin phosphate) ? Store Clindesse (clindamycin phosphate) at 68°F to 77°F (20°C to 25°C). Keep Clindesse (clindamycin phosphate) and all medicines out of the reach of children. General information about the safe and effective use of Clindesse (clindamycin phosphate) . Medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. Do not use Clindesse (clindamycin phosphate) for a condition for which it was not prescribed. Do not give Clindesse (clindamycin phosphate) to other people, even if they have the same symptoms you have. It may harm them. This leaflet summarizes the most important information about Clindesse (clindamycin phosphate) . If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Clindesse (clindamycin phosphate) that is written for health professionals. For more information, go to www.clindesse (clindamycin phosphate) .com or call 1-877-567-7676. What are the ingredients in Clindesse? Active ingredient: clindamycin phosphate Inactive ingredients: edetate disodium, glycerol monoisostearate, lecithin, methylparaben, microcrystalline wax, mineral oil, polyglyceryl-3-oleate, propylparaben, purified water, silicon dioxide and sorbitol solution Patient Instructions for Use Clindesse (clin-DESS) (clindamycin phosphate) Vaginal Cream, 2% For vaginal use only. Do not put Clindesse (clindamycin phosphate) in your eyes, mouth, or on your skin. It is important that you read and follow these directions on how to use Clindesse (clindamycin phosphate) vaginal cream properly. Clindesse (clindamycin phosphate) comes in a single-dose, pre-filled, disposable applicator that gives you a certain amount of clindamycin cream to be inserted into your vagina. Step 1. Prepare the applicator. Peel back the protective foil and remove the pre-filled applicator. Do not remove the tip. The applicator is made to be used with the tip in place. Do not use the applicator if the tip has been removed (see Figure 1). Activate the plunger before you use it. To activate the plunger, pull the ring back to fully extend the plunger while you firmly hold the applicator (see Figure 2). Step 2. Insert the applicator. Gently insert the applicator into your vagina as far as it will comfortably go (see Figure 3). Figure 3 Step 3. Apply the cream. Push the plunger in until all of the cream goes into your vagina (see Figures 4 and 5). Figure 4 and Figure 5 Step 4. Remove the empty applicator from your vagina and throw it away in the trash.

OVERDOSE Vaginally applied clindamycin phosphate vaginal cream 2% could be absorbed in sufficient amounts to produce systemic effects [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS]. CONTRAINDICATIONS Hypersensitivity 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 [see ADVERSE REACTIONS]. History of Bowel Disease Do not administer Clindesse (clindamycin phosphate) to patients with regional enteritis, ulcerative colitis, or a history of Clostridium difficile-associated diarrhea.

SIDE EFFECTS Clinical Study Experience 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

WARNINGS 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 [see ADVERSE REACTIONS]. Use with Condoms and Vaginal Contraceptive Diaphragms This 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 Products Instruct 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 Diaphragms Advise 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 [see WARNINGS AND PRECAUTIONS]. Fungal Vaginal Infections Inform the patient that vaginal fungal infections can occur following use of Clindesse (clindamycin phosphate) and may require treatment with an antifungal drug [see ADVERSE REACTIONS]. Accidental Exposure to the Eye Inform 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 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 (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 B 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. Nursing Mothers Caution 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 Use The 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 Use Clinical 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.