DRUG INTERACTIONS

 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).

U.S. FDA APPROVED  DRUGS DURING 2017

ADVERSE REACTIONS 

 Most common adverse reactions observed in clinical trials (incidence = 2%) were vulvo-vaginal candidiasis, headache, nausea, dysgeusia, vomiting, diarrhea, abdominal pain, and vulvovaginal pruritus. 

CONTRAINDICATIONS

History of hypersensitivity to secnidazole, other ingredients of the formulation, or other nitroimidazole derivatives. 

WARNING AND PRECAUTIONS

 • Vulvo-vaginal candidiasis may develop with SOLOSEC and require treatment with an antifungal agent

• Potential Risk for Carcinogenicity: Carcinogenicity has been seen in mice and rats treated chronically with nitroimidazole derivatives, which are structurally related to secnidazole. It is unclear if the positive tumor findings in lifetime rodent studies indicate a risk to patients taking a single dose of SOLOSEC to treat bacterial vaginosis. Avoid chronic use

PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Administration Instructions-

Instruct the patient:

• To sprinkle the entire contents of the packet of SOLOSEC onto applesauce, yogurt or pudding and take all the mixture within 30 minutes without chewing or crunching the granules.

• That after consuming the mixture, they may take a glass of water to aid in swallowing.

• That SOLOSEC is not intended to be dissolved in any liquid.

Advise the patient that SOLOSEC may be taken without regard to the timing of meals.

Lactation-   

Advise women not to breastfeed during treatment with SOLOSEC and to discontinue breastfeeding for 96 hours following the administration of SOLOSEC. Also, advise a nursing mother that she may choose to pump and discard her milk for 96 hours after administration of SOLOSEC and feed her infant stored human milk or formula 

 Vulvo-Vaginal Candidiasis- 

Advise the patient that use of SOLOSEC may result in vulvo-vaginal candidiasis that may require treatment with an antifungal agent

Drug Resistance-

Patients should be counseled that antibacterial drugs including SOLOSEC should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When SOLOSEC is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed.

Skipping doses or not completing the full course of therapy may                                     (1) decrease the effectiveness of the immediate treatment and                                       (2) increase the likelihood that bacteria will develop resistance and will not be treatable by SOLOSEC or other antibacterial drugs in the future.

Distributed by: Symbiomix Therapeutics LLC Newark, NJ 07103

Manufactured by: Catalent Pharma Solutions Somerset, NJ 08873

CLINICAL PHARMACOLOGY

1 Mechanism of Action-

SOLOSEC is a nitroimidazole antimicrobial drug

2. Pharmacodynamics-

Secnidazole exposure-response relationships and the time course of pharmacodynamic response are unknown.

Cardiac Electrophysiology-                                                                                          The effect of secnidazole on the QTc interval was evaluated in a Phase 1 randomized, double blind, placebo- and positive-controlled four-period crossover thorough QTc study in 52 healthy adult subjects following single oral granule doses of 2 g and 6 g (3-times the recommended dose).

Although there was a positive relationship of the QTc interval with secnidazole concentrations, there was no clinically relevant increase in the QTc interval following either dose.

3. Pharmacokinetics-                                                                                                        A single oral dose of 2 g of SOLOSEC in healthy adult female subjects, following an overnight fast and admixed with (4 oz) of applesauce, resulted in a mean (SD) secnidazole peak plasma concentration (Cmax) of 45.4 (7.64) mcg/mL and mean (SD) systemic exposure (AUC0-inf) of 1331.6 (230.16) mcg•hr/mL. Median (range) time to peak concentration (Tmax) was 4.0 (3.0-4.0) hours.

Following administration of the 2-g dose, mean secnidazole plasma concentrations decreased to 22.1 mcg/mL at 24 hours, 9.2 mcg/mL at 48 hours, 3.8 mcg/mL at 72 hours, and 1.4 mcg/mL at 96 hours.

Absorption-                                                                                                                 Effect of Food Administration of 2 g of SOLOSEC admixed with applesauce followed by ingestion of a high-fat meal (approximately 150 protein calories, 250 carbohydrate calories, and 500-600 fat calories) resulted in no significant change in the rate (Cmax) and extent (AUC) of secnidazole exposure as compared to administration when admixed with applesauce and taken under fasted conditions.

There was no effect of admixing SOLOSEC with pudding and yogurt as compared to admixing with applesauce

Distribution-                                                                                                                      The apparent volume of distribution of secnidazole is approximately 42 L. The plasma protein binding of secnidazole is <5%.

Elimination-                                                                                                                    The total body clearance of secnidazole is approximately 25 mL/min. The renal clearance of secnidazole is approximately 3.9 mL/min. The plasma elimination half-life for secnidazole is approximately 17 hours.

Metabolism-                                                                                                          Secnidazole is metabolized in vitro via oxidation by human hepatic CYP450 enzyme system with = 1% conversion to metabolites.

Excretion-                                                                                                                    Approximately 15% of a 2-g oral dose of SOLOSEC is excreted as unchanged secnidazole in the urine.

 USE IN SPECIFIC POPULATIONS

1. 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 

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.

2.Breast feeding-

Because of the potential for serious adverse reactions, including tumorigenicity, advise patients that breastfeeding is not recommended during treatment with SOLOSEC and for 96 hours (based on half-life) after administration of SOLOSEC. 

Clinical Considerations- A nursing mother may choose to pump and discard her milk during treatment with SOLOSEC and for 96 hours after administration of SOLOSEC and feed her infant stored human milk or formula.

3.Pediatric Use

The safety and effectiveness of SOLOSEC in pediatric patients below the age of 18 years have not been established.

4.Geriatric Use-

Clinical studies with secnidazole did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.