NITAZOXANIDE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Interferes with pyruvate:ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reactions, essential for anaerobic metabolism in certain pathogens.

What the body does with it

Metabolism	Primarily hepatic, via hydrolysis to tizoxanide (active metabolite) and subsequent glucuronidation; CYP450 involvement minimal.
Excretion	Nitazoxanide is primarily excreted in feces (approximately 66%) and urine (approximately 33%). Renal elimination accounts for about 33% of the dose, primarily as the active metabolite tizoxanide (glucuronide conjugates), while fecal excretion accounts for approximately 66%, mostly as tizoxanide and its conjugates.
Half-life	The terminal elimination half-life of the active metabolite tizoxanide is approximately 1.5–2 hours in adults and 2–4 hours in children. Clinical context: The short half-life supports twice-daily dosing; accumulation is minimal with normal dosing intervals.
Protein binding	Nitazoxanide is highly protein-bound (greater than 99%) to albumin. The major active metabolite tizoxanide also shows high protein binding (>99%).
Volume of Distribution	The apparent volume of distribution (Vd/F) is approximately 2.0 L/kg, indicating extensive distribution beyond plasma into tissues. Clinical meaning: This suggests good penetration into tissues and intracellular compartments, relevant for treating intracellular pathogens like Cryptosporidium.
Bioavailability	Oral bioavailability of nitazoxanide is not formally determined due to rapid first-pass metabolism; however, the active metabolite tizoxanide reaches peak plasma concentrations within 1–4 hours, indicating near-complete absorption and extensive first-pass metabolism. The tablet and suspension formulations are considered bioequivalent.
Onset of Action	Oral administration: Clinical effect (antiprotozoal activity) begins within 1–2 hours after ingestion, corresponding to peak plasma concentrations of tizoxanide at about 1–4 hours. For Cryptosporidium or Giardia infections, symptom improvement is typically observed within 24–72 hours.
Duration of Action	Duration of therapeutic effect: Approximately 12–24 hours, corresponding to the dosing interval (every 12 hours). Clinical note: The drug is given for 3–14 days depending on the infection; sustained efficacy requires strict adherence to the full course.

Classification & Brands

Dosing & administration

500 mg orally twice daily for 3 days for treatment of diarrhea caused by Cryptosporidium parvum or Giardia lamblia; for chronic giardiasis, 500 mg twice daily for 10 days.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment; data insufficient for severe renal impairment (CrCl <30 mL/min), use with caution.
Liver impairment	No formal recommendations; contraindicated in Child-Pugh Class C (severe hepatic impairment) due to lack of safety data; use with caution in Child-Pugh Class A and B.
Pediatric use	For children aged 1-3 years: 100 mg (5 mL suspension) twice daily; aged 4-11 years: 200 mg (10 mL suspension) twice daily; for 3 days. Weight-based: approximately 7.5 mg/kg twice daily.
Geriatric use	No specific dose adjustment; use with caution due to increased risk of adverse effects (e.g., gastrointestinal, renal) and potential for polypharmacy; monitor renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

No significant drug interactions Can cause abdominal pain and diarrhea.

Breastfeeding	Excretion into human milk unknown; M/P ratio not established. Use with caution in nursing mothers due to potential for adverse effects in infants (e.g., diarrhea, nausea). Consider benefits of breastfeeding and importance of drug to mother.
Teratogenic Risk	Pregnancy Category B. Animal studies at up to 20 times the human dose revealed no evidence of harm to the fetus. No adequate, well-controlled studies in pregnant women. Use only if clearly needed. First trimester: minimal data but no reported malformations. Second/third trimester: no known risk based on limited human data.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Common Effects	Abdominal pain
Serious Effects

Absolute Contraindications

History of hypersensitivity to nitazoxanide or any excipients. Renal or hepatic impairment (relative caution).

Clinical Precautions

Precautions

May cause hepatotoxicity; monitor liver function tests. Avoid use in patients with hepatic impairment. May cause QT prolongation; caution in patients with cardiac disease or electrolyte imbalances. Immunocompromised patients may require prolonged or repeat courses.

Clinical Tips & Counseling

Drug interactions

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