Secnidazole

Approved Indications:

• Bacterial Vaginosis (BV):
  Indicated for the treatment of bacterial vaginosis in adult women caused by anaerobic bacteria such as Gardnerella vaginalis, Atopobium vaginae, and Mobiluncus spp.
• Amebiasis:
• Intestinal Amebiasis (Amebic Dysentery): For acute infection due to Entamoeba histolytica.
• Hepatic Amebiasis (Amebic Liver Abscess): As part of combination therapy for liver abscesses caused by E. histolytica.
• Giardiasis:
  Effective against Giardia lamblia infections in adults and pediatric patients.

Clinically Accepted (Off-Label) Uses:

• Trichomoniasis: Occasionally used for treatment of Trichomonas vaginalis, although not the first-line agent.
• Helicobacter pylori (H. pylori) Infection: Rarely included as part of multi-drug regimens when metronidazole resistance is present.

Adults:

• Bacterial Vaginosis: 2 g orally as a single dose.
• Intestinal Amebiasis: 2 g orally once daily for 1–2 days.
• Hepatic Amebiasis: 1.5 to 2 g orally once daily for 5–7 days.
• Giardiasis: 2 g orally as a single dose.

Pediatrics:

• Giardiasis/Amebiasis: 30 mg/kg orally as a single dose (maximum 2 g).
  Not indicated for bacterial vaginosis in children.

Elderly:

• Use adult dosing. Monitor renal and hepatic function; adjust dose if dysfunction is present.

Renal Impairment:

• No routine dose adjustment required, but caution is advised in severe impairment.

Hepatic Impairment:

• Use with caution. Consider dose adjustment or longer dosing interval in moderate to severe liver dysfunction.

Administration Notes:

• Administer orally with or without food.
• Preferably taken with food to minimize gastrointestinal discomfort.
• Oral granule formulation may be sprinkled on soft food (e.g., applesauce) and consumed within 30 minutes without chewing or crushing the granules.

Secnidazole is a nitroimidazole-class antimicrobial that exerts its effect by passive diffusion into anaerobic organisms and protozoa. Inside these cells, the nitro group of secnidazole undergoes reductive activation by ferredoxin-linked metabolic pathways. This reduction produces reactive nitroso intermediates that bind to DNA, causing strand breakage and inhibiting nucleic acid synthesis. The accumulation of damaged DNA ultimately results in cell death. This mechanism targets anaerobic bacteria and protozoa such as Entamoeba histolytica, Giardia lamblia, and Gardnerella vaginalis.

• Absorption: Rapidly absorbed following oral administration.
• Bioavailability: Approximately 100%.
• Time to Peak Plasma Concentration (Tmax): ~3 to 4 hours post-dose.
• Distribution: Widely distributed in body tissues and fluids, including liver and abscess cavities.
• Plasma Protein Binding: ~15%
• Metabolism: Extensively metabolized in the liver through oxidation and conjugation pathways.
• Active Metabolites: No known significant active metabolites.
• Elimination Half-life: Ranges from 17 to 29 hours, supporting single-dose administration.
• Excretion: Primarily via the urine (about 50%); minor elimination through feces.

• Pregnancy: Not assigned a formal FDA pregnancy category. Animal studies do not indicate direct teratogenicity, but human data are limited. Avoid use, particularly during the first trimester, unless clearly necessary.
• Lactation: Secnidazole is excreted into human breast milk. Because of its long half-life, breastfeeding should be discontinued during treatment and for at least 96 hours after the last dose to avoid infant exposure.
• Caution: Use only if the potential benefit outweighs the risk. Consult healthcare provider before use in pregnancy or lactation.

• Primary Class: Antiprotozoal / Antibacterial Agent
• Subclass: Nitroimidazole Derivative
• Generation: Second-generation nitroimidazole compound

• Hypersensitivity to secnidazole, other nitroimidazoles (e.g., metronidazole), or any formulation excipients
• History of blood dyscrasias related to nitroimidazole therapy
• Documented CNS disorders (e.g., seizure disorders), unless under specialist supervision
• Use during early pregnancy unless clearly justified

• Central Nervous System Effects: Risk of seizures and peripheral neuropathy; use cautiously in patients with neurologic disease.
• Superinfection: Prolonged or repeated use may lead to fungal or bacterial superinfection, including Clostridioides difficile-associated diarrhea.
• Alcohol Use: Although secnidazole has a lower risk of disulfiram-like reactions, alcohol should be avoided during and for at least 72 hours after dosing.
• Hepatic Impairment: May reduce drug clearance; close monitoring recommended.
• Monitoring: Patients with prolonged therapy or those at high risk should be monitored for hematologic abnormalities and signs of neurotoxicity.

Common (≥1%):

• Gastrointestinal: Nausea, vomiting, dyspepsia, abdominal pain, metallic or bitter taste
• Neurological: Headache, dizziness, fatigue

Less Common:

• Dermatologic: Rash, pruritus, urticaria
• Hematologic: Transient leukopenia or thrombocytopenia (rare)
• Hepatic: Elevated liver enzymes (ALT/AST)

Serious or Rare Adverse Effects:

• Neurologic: Peripheral neuropathy, seizures (rare, dose-related)
• Hypersensitivity: Anaphylactic reactions (extremely rare)
• GI Complications: Pseudomembranous colitis (very rare)

Onset & Severity:

• Most side effects are mild to moderate and transient.
• Serious events are rare and typically dose- or duration-dependent.

• Alcohol: Avoid concurrent use and for 72 hours after dosing due to potential for nausea, vomiting, and flushing (disulfiram-like reaction).
• Warfarin and Other Anticoagulants: May potentiate the anticoagulant effect, increasing bleeding risk. INR monitoring is advised.
• CYP450 System: Mild inhibitor of CYP2C9; may affect metabolism of other drugs processed by this enzyme.
• Other Nitroimidazoles: Avoid concurrent use due to increased risk of neurotoxicity.
• Enzyme Inducers (e.g., Rifampin): May reduce secnidazole plasma levels, decreasing efficacy.

• CDC STD Treatment Guidelines (2024): Secnidazole recommended as a single-dose oral therapy for bacterial vaginosis due to convenience and efficacy.
• FDA Label Revision (2023): Included precaution regarding breastfeeding and updated guidance on hepatic metabolism.
• WHO Antimicrobial Stewardship Update (2022): Recognized secnidazole as a potential alternative to metronidazole for single-dose therapy in BV and giardiasis.

• Storage Temperature: Store below 30°C (86°F).
• Humidity & Light: Store in a dry place, away from excessive moisture. Protect from direct light.
• Handling Instructions:
• Keep the container tightly closed.
• No refrigeration required.
• Do not freeze.
• Reconstitution: Not applicable. Oral granules should not be crushed or chewed. If sprinkled on food, consume immediately without chewing.