Introduction
Nitazoxanide is a broad-spectrum antiparasitic and antiviral agent first approved by the FDA in 2002. It belongs to the thiazolide class of drugs and represents a significant advancement in the treatment of protozoal infections, particularly cryptosporidiosis and giardiasis. Originally developed as a veterinary antiparasitic, nitazoxanide has demonstrated clinical utility in human medicine with a favorable safety profile.
Mechanism of Action
Nitazoxanide exerts its antiparasitic effects through interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme pathway, which is essential for anaerobic energy metabolism in protozoa and bacteria. The active metabolite, tizoxanide, inhibits this electron transfer reaction, disrupting the energy metabolism of susceptible organisms. Additionally, research suggests nitazoxanide may demonstrate antiviral activity by inhibiting the maturation of viral hemagglutinin and modulating host cell signaling pathways.
Indications
FDA-Approved Indications:- Treatment of diarrhea caused by Cryptosporidium parvum in immunocompetent patients aged 1 year and older
- Treatment of diarrhea caused by Giardia lamblia in patients aged 1 year and older
- Treatment of other intestinal protozoan infections (including Entamoeba histolytica, Blastocystis hominis)
- Clostridium difficile-associated diarrhea
- Helicobacter pylori eradication (as part of combination therapy)
- Treatment of viral gastroenteritis caused by rotavirus and norovirus
- Investigational use for chronic hepatitis B and C infections
Dosage and Administration
Oral Administration Only:- Available as 500 mg tablets and powder for oral suspension (100 mg/5 mL)
- Adults and adolescents (≥12 years): 500 mg twice daily with food for 3 days
- Children (4-11 years): 200 mg (10 mL) twice daily with food for 3 days
- Children (1-3 years): 100 mg (5 mL) twice daily with food for 3 days
- Renal impairment: No dosage adjustment required
- Hepatic impairment: Use with caution; consider dosage reduction in severe impairment
- Elderly: No specific dosage recommendations; use standard dosing
- Pregnancy: Category B; use only if potential benefit justifies potential risk
- Breastfeeding: Limited data; use with caution
Pharmacokinetics
Absorption: Rapidly hydrolyzed to active metabolite tizoxanide after oral administration. Food significantly increases bioavailability (approximately doubles AUC). Distribution: Tizoxanide is highly protein-bound (>99.9%). Limited data on tissue distribution. Metabolism: Extensive first-pass metabolism via hydrolysis to tizoxanide, which undergoes glucuronidation. Elimination: Primarily excreted in urine as tizoxanide glucuronide, with some biliary excretion. Elimination half-life of tizoxanide is approximately 1-4 hours.Contraindications
- Hypersensitivity to nitazoxanide or any component of the formulation
- Concomitant use with strong CYP3A4 inducers (may significantly reduce efficacy)
Warnings and Precautions
- Hepatic effects: Monitor liver function in patients with pre-existing liver disease
- Renal impairment: Use caution in severe renal impairment due to limited data
- Diabetic patients: Oral suspension contains sucrose (1.48 g per 5 mL)
- Immunocompromised patients: Limited efficacy data in immunocompromised hosts
- Bacterial superinfections: May occur during treatment of parasitic infections
Drug Interactions
Significant Interactions:- Warfarin: Potential increased anticoagulant effect; monitor INR closely
- Highly protein-bound drugs: Potential displacement interactions (e.g., phenytoin, valproic acid)
- CYP3A4 inducers: Reduced nitazoxanide concentrations (e.g., rifampin, carbamazepine, phenytoin)
- CYP3A4 inhibitors: Possible increased nitazoxanide concentrations
Adverse Effects
Common (≥1%):- Gastrointestinal: Abdominal pain, nausea, diarrhea
- Neurological: Headache, dizziness
- Other: Discolored urine (yellow-orange)
- Allergic reactions: Rash, pruritus
- Hepatic: Transaminase elevations
- Renal: Limited reports of renal impairment
- Severe hypersensitivity reactions
- Significant hepatotoxicity
- Pancreatitis
Monitoring Parameters
- Clinical response to therapy (reduction in diarrheal symptoms)
- Hydration status, especially in pediatric patients
- Liver function tests in patients with pre-existing liver disease or prolonged therapy
- Complete blood count with prolonged use
- Signs of hypersensitivity reactions
Patient Education
- Take with food to enhance absorption and reduce gastrointestinal upset
- Complete full course of therapy even if symptoms improve
- Urine may appear yellow-orange; this is normal and harmless
- Report any signs of allergic reaction (rash, itching, swelling)
- Maintain adequate hydration during treatment for diarrhea
- Inform healthcare provider of all medications being taken
- Store suspension at room temperature and discard after 7 days
References
1. FDA Prescribing Information: Alinia (nitazoxanide) tablets and oral suspension 2. Rossignol JF. Nitazoxanide: a first-in-class broad-spectrum antiviral agent. Antiviral Res. 2014;110:94-103. 3. Anderson VR, Curran MP. Nitazoxanide: a review of its use in the treatment of gastrointestinal infections. Drugs. 2007;67(13):1947-1967. 4. Stockis A, et al. Nitazoxanide pharmacokinetics and tolerability in man during 7 days dosing. J Clin Pharmacol. 2002;42(10):1136-1145. 5. Hemphill A, et al. Nitazoxanide: a broad-spectrum thiazolide anti-infective agent. Expert Rev Anti Infect Ther. 2006;4(5):781-790. 6. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Nitazoxanide; [updated 2023]. 7. Micromedex® Healthcare Series [Internet]. Greenwood Village (CO): Truven Health Analytics. Nitazoxanide; [updated 2023].