Nitazoxanide

Pronunciation: (nye-ta-ZOX-a-nide)
Class: Antiprotozoal

Trade Names

Alinia
- Tablets 500 mg
- Suspension, oral 100 mg per 5 mL

Pharmacology

Interferes with pyruvate:ferredoxin oxidoreductase enzyme-dependent electron transfer reaction, which is essential to anaerobic energy metabolism.

Pharmacokinetics

Absorption

After ingestion, nitazoxanide is converted to the active metabolites tizoxanide and tizoxanide glucuronide. Bioavailability of the suspension is 70% compared with the tablet.

Adults and children 12 yr of age and older

Following administration of nitazoxanide 500 mg tablet with food in adults or children 12 yr of age and older, C _max is 10.6 and 9.1 mcg/mL, respectively; T _max is 3 and 4 h, respectively; AUC is 41.9 and 39.5 mcg•h/mL. For tizoxanide glucuronide, C _max is 10.5 and 7.3 mcg/mL, respectively; T _max is 4.5 and 4 h, respectively; AUC is 63 and 46.5 mcg•h/mL, respectively.

Children 1 to 11 yr of age

Following administration of nitazoxanide 500 mg tablet with food in children 4 to 11 yr of age or 1 to 3 yr of age, C _max is 3 and 3.11 mcg/mL, respectively; T is _max 2 and 3.5 h, respectively; AUC is 13.5 and 11.7 mcg•h/mL, respectively. For tizoxanide glucuronide, C is _max is 2.84 and 3.64 mcg/mL, respectively; T _max is 4 h in both age groups; and AUC is 16.9 and 19 mcg•h/mL, respectively.

Distribution

Tizoxanide is more than 99% protein bound.

Metabolism

Nitazoxanide is rapidly hydrolyzed to an active metabolite, tizoxanide, which then undergoes conjugation, primarily by glucuronidation, to an active metabolite.

Elimination

Approximately 67% of the oral dose of nitazoxanide is excreted in the feces and 33% in the urine. Tizoxanide is excreted in the urine, bile, and feces, while tizoxanide glucuronide is excreted in the urine and bile.

Special Populations

Renal Function Impairment

The pharmacokinetics in patients with impaired renal function have not been studied.

Hepatic Function Impairment

The pharmacokinetics in patients with impaired hepatic function have not been studied.

Indications and Usage

Treatment of diarrhea caused by Giardia lamblia or Cryptosporidium parvum .

Contraindications

Hypersensitivity to nitazoxanide or any ingredient in the formulations.

Dosage and Administration

Diarrhea
Adults and Children 12 yr of age and older

PO 500 mg every 12 h for 3 days.

Children 4 to 11 yr of age

PO 10 mL (200 mg) every 12 h for 3 days.

Children 1 to 3 yr of age

PO 5 mL (100 mg) every 12 h for 3 days.

General Advice

• Nitazoxanide tablets and oral suspension are not bioequivalent. The relative bioavailability of the suspension compared with the tablet is 70%.
• Do not use administer tablets in children 11 yr of age and younger.
• Administer with food to minimize GI adverse reactions and increase absorption.
• Shake suspension well before measuring dose.

Storage/Stability

Store at 59° to 86°F. Discard any unused suspension after 7 days.

Drug Interactions

Highly protein-bound drugs (eg, warfarin)

May compete for binding sites, transiently increasing the effects of the displaced drug.

Adverse Reactions

CNS

Headache (3%).

GI

Abdominal pain (8%); diarrhea (4%); nausea (3%); vomiting (1%).

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established in children younger than 1 yr of age. Do not administer the tablets in children 11 yr of age or younger.

Elderly

Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Special Risk Patients

Use with caution in patients with hepatic, biliary, or renal disease, or combined renal and hepatic disease.

HIV-infected or immunodeficient patients

Nitazoxanide tablets and oral suspension have not been studied for the treatment of diarrhea cause by G. Iamblia in HIV-infected or immunodeficient patients. Nitazoxanide tablets and oral suspension have not been shown to be superior to placebo for the treatment of diarrhea caused by C. parvum in HIV-infected or immunodeficient patients.

Tablet administration

A single tablet contains a greater amount of nitazoxanide than recommended for dosing in children and should not be used in patients 11 yr of age or younger.

Patient Information

• Instruct patient to take exactly as prescribed and not to change the dose or discontinue therapy unless advised by health care provider.
• Advise patient to take prescribed dose with food to minimize GI adverse reactions and increase absorption.
• Advise patient or caregiver using oral suspension to shake suspension well before measuring dose; measure and administer prescribed dose using dosing syringe, dosing spoon, or dosing cup; and discard any remaining suspension after 7 days.
• Instruct patient or caregiver to notify health care provider if diarrhea does not improve or worsens.
• Advise patient to report any other bothersome adverse reactions to health care provider.
• Advise diabetic patients and caregivers that the oral suspension contains 1.48 g of sucrose per 5 mL.

Copyright © 2009 Wolters Kluwer Health.