secnidazole (Rx)

1-10%

Vulvovaginal candidiasis (8.4-9.6%)

Nausea (3.6-5.3%)

Headache (3.6%)

Dysgeusia (3.4%)

Diarrhea (2.5%)

Vomiting (2.5%)

Abdominal pain (2%)

Vulvovaginal pruritus (2%)

Postmarketing Reports

Reported adverse reactions were nausea, dysgeusia, abdominal pain, headache, dizziness, and vomiting when taken concomitantly with alcohol

Severe irreversible hepatotoxicity/acute liver failure (patients with Cockayne syndrome)

Contraindications

Hypersensitivity to secnidazole, excipients of the formulation, or other nitroimidazole derivatives

Patients with Cockayne syndrome

Cautions

Vulvovaginal candidiasis may occur; symptomatic vulvovaginal candidiasis may require treatment with an antifungal agent

Carcinogenicity has been seen in mice and rats treated long term with nitroimidazole derivatives, which are structurally related to secnidazole; avoid long-term use of secnidazole

Prescribing secnidazole in the absence of proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria

Avoid chronic use; carcinogenicity reported in mice and rats treated chronically with nitroimidazole derivatives, structurally related to secnidazole; significance unclear

Severe irreversible hepatotoxicity/acute liver failure with fatal outcomes reported after initiation of metronidazole in patients with Cockayne syndrome

Drug interaction overview

• Alcohol

  • Avoid alcoholic beverages and preparations containing ethanol or propylene glycol during secnidazole therapy and for 2 days after treatment is stopped
  • Nausea, vomiting, diarrhea, abdominal pain, dizziness, and headache reported when coadministered

Pregnancy

Data with secnidazole 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

Lactation

There is no information on the presence of secnidazole in human milk, the effects on the breastfed child, or the effects on milk production

Other nitroimidazole derivatives are present in human milk Because of the potential for serious adverse reactions, including tumorigenicity, advise patients that breastfeeding is not recommended during treatment with secnidazole and for 96 hr after administration of secnidazole

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Secnidazole is a nitroimidazole derivative; 5-nitroimidazoles enters the bacterial cell as an inactive prodrug where the nitro group is reduced by bacterial enzymes to radical anions

It is believed that these radical anions interfere with bacterial DNA synthesis of susceptible isolates

Absorption

Peak plasma time: 4 hr (fasted or when mixed with applesauce, pudding, or yogurt); 6 hr (high-fat meal)

Peak plasma concentration: 41.2 mcg/mL (fasted); 40.1 mcg/mL (high-fat meal); 44.1 mcg/mL (mixed with applesauce); 45.6 mcg/mL (mixed with pudding); 43.4 mcg/mL (mixed with yogurt)

AUC: 1261.5 mcg·hr/mL (fasted); 1248.2 mcg·hr/mL (high-fat meal); 1523 mcg·hr/mL (mixed with applesauce); 1447 mcg·hr/mL (mixed with pudding); 1478 mcg·hr/mL (mixed with yogurt)

Distribution

Vd: 42 L

Protein binding: <5%

Metabolism

Metabolized in vitro via oxidation by hepatic CYP450 enzyme system with ≤1% conversion to metabolites

Elimination

Clearance: 25 mL/min

Renal clearance: 3.9 mL/min

Excretion: Urine (15% unchanged)

Oral Administration

Sprinkle entire contents of the packet of secnidazole onto applesauce, yogurt, or pudding and take all the mixture within 30 minutes without chewing or crunching the granules

Drink a glass of water to aid in swallowing the mixture; secnidazole mixture is not intended to be dissolved in any liquid

Take 1 entire packet of secnidazole at one time; do not take only part of the medicine and save a portion for later

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

Avoid consumption of alcoholic beverages and preparations containing ethanol orpropylene glycol during treatment with secnidazole and for at least 2 days aftercompleting therapy

Storage

Store room temperature at 20-25°C (68-77°F); excursions permitted to 15-30ºC (59-86ºF)