FDA label 23476395-d7ce-4bac-a4f7-e8eaefa28d15

5 WARNINGS AND PRECAUTIONS • C. difficile -associated diarrhea: Discontinue and evaluate if diarrhea occurs ( 5.1 ) • Rubber or latex products: Do not use barrier contraceptives (condoms or vaginal contraceptive diaphragms) concurrently or for 5 days following treatment. Condoms may not be reliable for preventing pregnancy or for protecting against transmission of HIV and other sexually transmitted diseases during this time ( 5.2 ) 5.1 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 ( 6.2 )] . 5.2 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. During this time period, condoms may not be reliable for preventing pregnancy or for protecting against transmission of HIV and other sexually transmitted diseases.

6 ADVERSE REACTIONS 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 Ther-Rx Corporation at 1-877-567-7676 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 Event Clindesse N=85 n (%) Placebo N=85 n (%) 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 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) 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 ( 12.1 )] . 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 [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. 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

<table ID="_Refid_3e016e02-2e79-43f5-a80e-b4033daa5" width="100%"><caption>Table 1. Adverse Reactions Occurring in &#x2265;2% of Clindesse-Treated Patients and at a Higher Rate than Placebo-Treated Patients</caption><col width="33%"/><col width="33%"/><col width="33%"/><thead><tr><th align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><content styleCode="bold">Adverse Event</content></th><th align="center" styleCode="Rrule Botrule Toprule " valign="top"><content styleCode="bold">Clindesse</content> <content styleCode="bold">N=85</content> <content styleCode="bold">n (%)</content></th><th align="center" styleCode="Rrule Botrule Toprule " valign="top"><content styleCode="bold">Placebo</content> <content styleCode="bold">N=85</content> <content styleCode="bold">n (%)</content></th></tr></thead><tfoot><tr><td align="left" colspan="3" styleCode="Botrule" valign="top">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</td></tr></tfoot><tbody><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Vaginosis fungal NOS*</paragraph></td><td align="center" styleCode="Rrule Toprule Botrule " valign="top"><paragraph>12 (14)</paragraph></td><td align="center" styleCode="Rrule Toprule Botrule " valign="top"><paragraph>7 (8)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Headache NOS</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6 (7)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (2)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Back pain</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>4 (5)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (1)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Constipation</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (2)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph>Urinary tract infection NOS</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (2)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr></tbody></table>