DrugindexOnline^{2nd edition}

Pronouncation: (nye-tah-ZOX-ah-nide)
Class: Antiprotozoal

Trade Names:
Alinia
- Tablets 500 mg
- Oral suspension 100 mg per 5 mL

Mechanism of Action

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. Pharmacokinetics of tizoxanide following administration of nitazoxanide 500 mg tablet with food in adults or children 12 yr of age and older is: C _max 10.6 and 9.1 mcg/mL, respectively; T _max is 3 and 4 hr, respectively; AUC is 41.9 and 39.5 mcg•hr/mL. For tizoxanide glucuronide, corresponding values are: C _max 10.5 and 7.3 mcg/mL, respectively; T _max of 4.5 and 4 hr, respectively; AUC of 63 and 46.5 mcg•hr/mL, respectively. Absorption of tizoxanide following administration of the oral suspension with food to children 4 to 11 yr of age or 1 to 3 yr of age is: C _max 3 and 3.11 mcg/mL, respectively; T _max 2 and 3.5 hr, respectively; AUC 13.5 and 11.7 mcg•hr/mL, respectively. For tizoxanide glucuronide, corresponding values are: C _max 2.84 and 3.64 mcg/mL, respectively; T _max 4 hr in both age groups; and AUC 16.9 and 19 mcg•hr/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.

Indications and Usage

Treatment of diarrhea caused by Giardia lamblia or Cryptosporidium parvum .

Contraindications

Standard considerations.

Dosage and Administration

Diarrhea caused by G. lamblia
Adults and Children 12 yr of age and older

PO 500 mg q 12 hr with food.

Children 4 to 11 yr of age

PO 10 mL (200 mg) q 12 hr with food.

Children 1 to 3 yr of age

PO 5 mL (100 mg) q 12 hr with food.

Diarrhea caused by C. parvum
Children 4 to 11 yr of age

PO 10 mL (200 mg) q 12 hr with food.

Children 1 to 3 yr of age

PO 5 mL (100 mg) q 12 hr with food.

General Advice

• Nitazoxanide tablets and oral suspension are not bioequivalent. The relative bioavailability of the suspension compared to tablet is 70%.
• Administer with food to minimize GI side effects and increase absorption.
• Shake suspension well before measuring dose.

Storage/Stability

Store tablets, unsuspended powder, and reconstituted oral suspension at controlled room temperature (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.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache (3%).

GI

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

Precautions

Pregnancy

Category B .

Lactation

Not established.

Children

Safety and efficacy not established for treatment of C. parvum in patients 12 yr of age and older.

Oral suspension

Safety and efficacy not established in children younger than 1 yr of age.

Tablet

Not for use 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

Because nitazoxanide was not studied in patients with impaired hepatic or renal function, use with caution in patients with hepatic, biliary, or renal disease.

Tablet administration

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

Patient Information

• Explain name, dose, action, and potential side effects of drug.
• 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 side effects 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; 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 side effects to health care provider.
• Advise women to notify health care provider if pregnant, planning to become pregnant, or breastfeeding.
• Instruct patient not to take any prescription or OTC medications, herbal preparations, or dietary supplements unless advised by health care provider.
• Advise patient that follow-up visits may be required to monitor therapy and to keep appointments.