Solosec Drug Information

Recommended Dosage for Bacterial Vaginosis

The recommended dosage of SOLOSEC for the treatment of bacterial vaginosis in female patients 12 years of age and older is a single 2-gram packet of granules taken once orally, without regard to the timing of meals .

Recommended Dosage for Trichomoniasis

The recommended dosage of SOLOSEC for the treatment of trichomoniasis in patients 12 years of age and older is a single 2-gram packet of granules taken once orally, without regard to the timing of meals . Since trichomoniasis is a sexually transmitted disease, treat sexual partners with the same dose and at the same time .

Instructions for the Preparation and

Administration of SOLOSEC Open the SOLOSEC packet by folding over the corner (marked by an arrow) and tearing across the top. Sprinkle the entire contents of the SOLOSEC packet onto applesauce, yogurt or pudding . The granules will not dissolve. Consume all of the mixture within 30 minutes without chewing or crunching the granules.

A glass of water may be taken after the administration of SOLOSEC to aid in swallowing. The granules are not intended to be dissolved in any liquid. Avoid consumption of alcoholic beverages and preparations containing ethanol or propylene glycol during treatment with SOLOSEC and for at least 2 days after completing therapy.

Clinical Trials 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. Bacterial Vaginosis The safety data described below reflect exposure to 629 patients, of whom 558 received a 2 g dose of SOLOSEC. SOLOSEC was evaluated in four clinical trials of female patients diagnosed with bacterial vaginosis: two placebo-controlled trials (Trial 1 n=215, Trial 2 n=189) and two uncontrolled safety trials (Trial 3 n=321, Trial 4 n=40). Most Common Adverse Reactions in Trials 1 and 2 All patients in Trial 1 and Trial 2 received a single oral dose of study medication or placebo. Trial 1 evaluated a 1 g (this dose is not approved) dose (n=71) and a 2 g dose (n=72) of SOLOSEC in patients aged 18 to 54 years.

Trial 2 evaluated a 2 g dose (n=125) in patients aged 18 to 54 years. Patients in the placebo-controlled trials were primarily Black or African American (54%) or Caucasian (41%). Among 197 patients treated with a single 2 g dose of SOLOSEC in the two placebo-controlled trials, Trial 1 and 2, adverse reactions were reported by approximately 29% of patients. Table 1 displays the most common adverse reactions (≥ 2% in SOLOSEC-treated patients) in these two trials.

There were no deaths in the trials. Table 1: Adverse Reactions Occurring (≥ 2 % SOLOSEC-Treated Patients) in the Pooled Placebo-Controlled Trials 1 and 2 in Adult Women with Bacterial Vaginosis Adverse Reaction SOLOSEC N=197 n (%) Placebo N=136 n (%) Vulvovaginal candidiasis 19 4 Headache 7 2 Nausea 7 1 Diarrhea 5 1 Abdominal pain 4 2 Vulvovaginal pruritus 4 2 Most Common Adverse Reactions in Trial 3 Among the 321 patients in an uncontrolled trial, Trial 3, adverse reactions were reported in 30% of patients. Vulvovaginal candidiasis (8.4%), nausea (5.3%), vomiting (2.5%) and dysgeusia (3.4%) were the most common adverse reactions reported in this trial.

Two SOLOSEC-treated patients in Trial 3 discontinued due to vulvovaginal candidiasis. Most Common Adverse Reactions in Trial 4 In Trial 4, the safety of SOLOSEC was evaluated in a multicenter, uncontrolled, open-label study evaluating the safety and tolerability of SOLOSEC in 40 pediatric patients between the ages of 12 and less than 18 years old all of whom were treated with a 2 g single dose of SOLOSEC. Most patients in this study were either White (60%) or Black/African-American (38%).The overall safety findings of a SOLOSEC 2 g dose in patients aged 12 to 17 years are consistent with findings in adult patients aged 18 to 65 years old. There were no deaths, severe adverse reactions, or discontinuations due to adverse reactions.

Adverse reactions occurring in at least one SOLOSEC-treated pediatric patient included: nausea and abdominal pain. Trichomoniasis The safety of SOLOSEC was evaluated in 147 female patients with trichomoniasis who participated in Trial 5, a placebo controlled, double blind trial, of whom 143 (97.3%) patients completed the 'Test of Cure' (TOC) visit. In this trial, 74 patients received a single 2-gram oral dose of SOLOSEC, and 73 patients received placebo.

The mean age of the patients in this study was 37.7 years, with a range of 15 to 65 years. Most of the patients were Black or African American (134/147; 91.2%). In the primary phase of Trial 5, i.e., baseline to TOC visit, one SOLOSEC-treated patient was discontinued from the study due to nausea and productive cough. Most Common Adverse Reactions A total of 11 patients (14.9%) who received SOLOSEC and 16 patients (21.9%) in the placebo group reported adverse reactions, respectively.

Vulvovaginal candidiasis was reported in 2 patients (2.7%) in the SOLOSEC-treated group and in none of the patients in the placebo group.

Postmarketing Experience

The following adverse reactions have been reported during use of SOLOSEC and other 2 g formulations of secnidazole outside of the United States. 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. Adverse Reactions with SOLOSEC Nervous System Disorders: Dysgeusia Nausea, vomiting, diarrhea, abdominal pain, dizziness, and headache have been reported when SOLOSEC was taken concomitantly with alcohol. . Metronidazole, Another Nitroimidazole Agent, Structurally Related to Secnidazole Cases of severe irreversible hepatotoxicity/acute liver failure, including cases with fatal outcomes with very rapid onset after initiation of systemic use of metronidazole, another nitroimidazole agent structurally related to secnidazole, have been reported in patients with Cockayne syndrome (latency from drug start to signs of liver failure as short as 2 days).

Oral Contraceptives

There was no clinically significant drug interaction between secnidazole and the combination oral contraceptive, ethinyl estradiol plus norethindrone . SOLOSEC can be co-administered with combination oral contraceptives (e.g., ethinyl estradiol plus norethindrone).

Alcohol Alcoholic beverages and preparations containing ethanol or propylene glycol should be

avoided during SOLOSEC therapy and for 2 days after treatment is stopped. Nausea, vomiting, diarrhea, abdominal pain, dizziness, and headache have been reported when SOLOSEC was taken concomitantly with alcohol .

Pregnancy Risk Summary Limited available data with SOLOSEC use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. In animal reproduction studies, there were no adverse developmental outcomes when secnidazole was administered orally to pregnant rats and rabbits during organogenesis at doses up to 4 times the clinical dose (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In animal reproduction studies, pregnant rats were dosed orally with secnidazole during organogenesis (gestational days 6-17) at 100, 300 and 1000 mg/kg/day, up to 4 times the clinical dose based on AUC comparisons. Animals showed no evidence of adverse developmental outcomes, but maternal toxicity (including reduced body weight gain) was observed at and above 300 mg/kg/day.

In rabbits, no evidence of adverse developmental outcomes was observed when oral doses of secnidazole were administered to dams during organogenesis (gestational days 7-20) at doses up to 100 mg/kg/day (about 0.1 times the clinical dose, based on AUC comparisons). Secnidazole was associated with maternal toxicity (reduced food consumption and markedly reduced body weight gain) in dams at 100 mg/kg/day. In a peri- and post-natal development study in rats, secnidazole was administered at 30, 100 and 300 mg/kg/day from Day 6 of gestation through Day 20 of lactation. Secnidazole was not associated with any adverse effects on gestation, parturition, lactation or on subsequent development of first generation (F1) and second generation (F2) offspring at these doses, equivalent to up to 1.4 times the clinical dose based on AUC comparisons.

Maternal toxicity (reduced gestational body weight gain) was evident at doses of 100 mg/kg and above (about 0.3 times the clinical dose based on AUC comparisons).

Pediatric Use The safety and effectiveness of SOLOSEC for the treatment of bacterial vaginosis have been established in pediatric patients aged 12 to 17 years old. Use of SOLOSEC in this age group is supported by evidence from a multicenter, open-label safety study in 40 pediatric female patients with bacterial vaginosis and evidence from adequate and well-controlled studies in adult women . The safety and effectiveness of SOLOSEC for the treatment of trichomoniasis have been established in pediatric patients aged 12 to 17 years old. Use of SOLOSEC in this group is based on the extrapolation of clinical trial data from adult women with trichomoniasis, four open-label trials in males with trichomoniasis, and an open-label safety study in pediatric female patients with bacterial vaginosis .The safety and effectiveness of SOLOSEC in pediatric patients below the age of 12 years have not been established.

4. CONTRAINDICATIONS SOLOSEC is contraindicated: In patients who have shown hypersensitivity to secnidazole, or other nitroimidazole derivatives. In patients with Cockayne syndrome: Severe irreversible hepatotoxicity/acute liver failure with fatal outcomes have been reported after initiation of metronidazole, another nitroimidazole drug, structurally related to secnidazole, in patients with Cockayne syndrome . History of hypersensitivity to secnidazole, or other nitroimidazole derivatives. Patients with Cockayne syndrome.