CLINDESSE

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 C 18 H 34 CIN 2 O 8 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 does not comply with the pH test of the USP monograph for clindamycin phosphate vaginal cream. Structural Formula

Clindesse is a lincosamide antibacterial indicated for the treatment of bacterial vaginosis in non-pregnant women ( 1.1 ) 1.1 Treatment of Bacterial Vaginosis Clindesse 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.

The recommended dose is the complete contents of a single pre-filled applicator containing 5 g of Clindesse cream administered once intravaginally at any time of the day. Not for ophthalmic, dermal, or oral use. • For intravaginal use only • A single applicator of cream administered once intravaginally at any time of the day ( 2 ) • Not for ophthalmic, dermal, or oral use

• History of hypersensitivity to clindamycin or other lincosamides ( 4.1 ) • History of regional enteritis, ulcerative colitis, or a history of Clostridioides difficile- associated diarrhea ( 4.2 , 5.1 ) 4.1 Hypersensitivity Clindesse is contraindicated in 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 ( 6.2 )] . 4.2 History of Bowel Disease Clindesse is contraindicated in patients with regional enteritis, ulcerative colitis, or a history of Clostridioides difficile -associated diarrhea.

Most common adverse reactions reported in ≥2% of patients and at a higher rate in the Clindesse group than in the placebo group are vaginosis fungal (14%), headache (7%), back pain (5%), constipation (2%), and urinary tract infection (2%) ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Padagis ® at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 in 368 patients. Clindesse 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, 1.6% of the patients discontinued therapy due to adverse reactions. Adverse reactions occurred in 126 of 368 patients (34%) treated with Clindesse and in 32 of 85 patients (38%) treated with placebo. Adverse reactions occurring in ≥2% of patients receiving Clindesse in the placebo-controlled clinical trial are shown in Table 1. Table 1. Adverse Reactions Occurring in ≥2% of Clindesse-Treated Patients and at a Higher Rate than Placebo-Treated Patients Adverse Reactions Clindesse N=85 n (%) Placebo N=85 n (%) Vaginosis fungal NOS* 12 (14) 7 (8) Headache NOS 6 (7) 2 (2) Back Pain 4 (5) 1 (1) Constipation 2 (2) 0 (0) Urinary tract infection NOS 2 (2) 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 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 6.2 Other Clindamycin Formulations Clindesse affords minimal peak serum levels and systemic exposure (AUCs) of clindamycin compared to an oral or intravenous dose of clindamycin [see Clinical Pharmacology ( 12.3 )] . 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, Clostridioides difficile -associated diarrhea [see Warnings and Precautions ( 5.1 )] . 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. Immune System: Drug reaction with eosinophilia and systemic symptoms (DRESS) cases have been reported. 6.3 Postmarketing Experience The following adverse reactions have been identified during postapproval use of Clindesse. 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

No formal drug interaction studies have been conducted for Clindesse. Neuromuscular blocking agents: Enhanced action of neuromuscular blocking agents can occur; use with caution ( 7.1 ) 7.1 Neuromuscular Blocking Agents Orally 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.