SECNIDOLEX

Secnidazole is a second-generation 5-nitroimidazole antimicrobial agent.

It is structurally related to other 5-nitroimidazoles, including Metronidazole and Tinidazole, but displays improved oral absorption and a longer terminal elimination half-life than other drugs in this class.

Secnidazole is selective against many anaerobic Gram-positive and Gram-negative bacteria as well as protozoa.

Once it enters bacteria and parasites, secnidazole is activated by bacterial or parasitic enzymes to form a radical anion, thereby damaging and killing the target pathogen.

Secnidazole has been available in many other countries in Europe, Asia, South America, and Africa for decades. 3, 4 In September 2017, FDA approved secnidazole under the market name Solosec for the treatment of trichomoniasis and bacterial vaginosis.

Secnidazole is indicated for treating trichomoniasis and bacterial vaginosis in patients 12 years of age and older.

In other countries, it is also available as a with other antibacterial drugs, such as itraconazole.

Secnidazole is a broad-spectrum nitroimidazole antimicrobial drug.

It is selective against many anaerobic Gram-positive and Gram-negative bacteria and protozoa.

According to in vitro studies, secnidazole mediates antibacterial effects against Bacteroides fragilis, Trichomonas vaginalis, Entamoeba histolytica, and Giardia lamblia.

Secnidazole may prolong the

QTc interval, but not to a clinically significant extent.

Like other 5-nitroimidazole antimicrobials, the antimicrobial and antiprotozoal activity of secnidazole is accounted for by the nitro group in the imidazole ring.

Upon entering the target pathogen, the nitro group of secnidazole is reduced by bacterial or parasitic nitroreductase enzymes, producing radical anions and reactive intermediates.

Radical anions and reactive intermediates cause the depletion of thiols, DNA helix damage, disruption of bacterial or parasitic protein synthesis and replication, and ultimately, cell death of susceptible isolates of Gram positive bacteria, Gram negative bacteria and T. vaginalis. 4, 6.

Secnidazole is rapidly and completely absorbed after oral administration.

Following administration of a single oral dose of 2 g in healthy adult female subjects, the mean (SD) C max was 45.4 mcg/mL and mean (SD) systemic exposure (AUC 0-inf ) was 1331.6 mcg x hr/mL.

T max ranged from three to four hours.

Food has negligible effects on drug absorption and systemic exposure.

The apparent volume of distribution of secnidazole is approximately 42 L.

The metabolism of secnidazole has not been fully characterized.

According to in vitro studies, secnidazole is metabolized by hepatic CYP450 enzymes, with less than or equal to 1% of the parent drug converted to metabolites.

Secnidazole was found to be metabolized by CYP3A4 and CYP3A5 but to a limited extent.

Secnidazole most likely undergoes oxidation.

A hydroxymethyl metabolite and glucuronide conjugates of secnidazole have been detected in urine.

Following oral administration of a 2 g oral dose of secnidazole, approximately 15% of the drug was excreted as unchanged secnidazole in the urine.

The plasma elimination half-life for secnidazole is approximately 17 hours.

The total body clearance of secnidazole is approximately 25 mL/min.

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There is no information available regarding the LD and overdose of secnidazole.

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.

Vaginosis (female patients 12 years of age and older): Administer a single 2-gram packet of granules once orally, without regard to the timing of meals.

Trichomoniasis (patients 12 years of age and older): Administer a single 2-gram packet of granules once orally, without regard to the timing of meals.

Treat sexual partners with the same dose and at the same time.

Sprinkle entire contents of packet onto applesauce, yogurt or pudding and 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.

SOLOSEC is not intended to be dissolved in any liquid. 2.1 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. 2.2 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. 2.3 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.

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.

(secnidazole) Oral Granules, 2 g, consists of off-white to slightly yellowish granules containing secnidazole.

SOLOSEC is supplied in one unit-of-use child-resistant foil packet of granules in an individual carton.

Each packet contains 4.8 g of granules containing 2 g secnidazole.

SOLOSEC is supplied as follows

NDC 69751-400-01 carton containing one unit-of-use child-resistant 2 g foil packet.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) .

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) .

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 to 4% and to 20%, respectively.

In animal reproduction studies, pregnant rats were dosed orally with secnidazole during organogenesis (gestational days 6-17) at 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 and 300 mg/kg/day from Day of gestation through Day 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).

The safety and effectiveness of

SOLOSEC for the treatment of bacterial vaginosis have been established in pediatric patients aged to 17 years old.

Use of

SOLOSEC in this 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.

SOLOSEC for the treatment of trichomoniasis have been established in pediatric patients aged to 17 years old.

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.

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