Nitazoxanide (Monograph)

Brand name: Alinia
Drug class: Antiprotozoals, Cryptosporidiosis
Chemical name: 2-acetyloxy-N-(5-nitro-2-thiazolyl)benzamide
Molecular formula: C₁₂H₉N₃ O₅ S
CAS number: 55981-09-4

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Antiprotozoal; nitrothiazolyl-salicylamide derivative.

Uses for Nitazoxanide

Cryptosporidiosis

Treatment of diarrhea caused by Cryptosporidium parvum in immunocompetent adults, adolescents, and children ≥1 year of age. Designated an orphan drug by FDA for treatment of cryptosporidiosis.

Recommended as drug of choice for treatment of cryptosporidiosis.

Although safety and efficacy not established for treatment of diarrhea caused by C. parvum in HIV-infected or other immunodeficient patients, nitazoxanide has been used for treatment of cryptosporidiosis in such individuals. CDC, NIH, IDSA, and others state that the most appropriate treatment for cryptosporidiosis in HIV-infected individuals is potent antiretroviral therapy (to restore immune function) and supportive care and symptomatic treatment of diarrhea. These experts state that adjunctive use of nitazoxanide can be considered for treatment of cryptosporidiosis in HIV-infected adults, adolescents, or children^{† [off-label]} receiving effective antiretroviral therapy; however, do not use nitazoxanide in HIV-infected patients not receiving antiretroviral therapy.

Giardiasis

Treatment of diarrhea caused by Giardia intestinalis (also known as G. lamblia or G. duodenalis) in immunocompetent adults, adolescents, and children ≥1 year of age. Designated an orphan drug by FDA for treatment of intestinal giardiasis.

Metronidazole, tinidazole, and nitazoxanide are the drugs of choice for treatment of giardiasis; alternatives include paromomycin (especially in pregnant women), furazolidone (no longer commercially available in US), or quinacrine (not commercially available in US).

Safety and efficacy not established for treatment of diarrhea caused by Giardia in HIV-infected or other immunodeficient patients. CDC, NIH, and IDSA state that tinidazole and nitazoxanide are drugs of choice for treatment of giardiasis in HIV-infected infants and children^{† [off-label]} and metronidazole is the preferred alternative in these patients.

Amebiasis

Has been used for treatment of amebiasis caused by Entamoeba ^{† [off-label]}. Designated an orphan drug by FDA for treatment of intestinal amebiasis.

Regimen of choice for symptomatic intestinal amebiasis or extraintestinal disease is treatment with a nitroimidazole derivative (tinidazole or metronidazole) followed by treatment with a luminal amebicide (iodoquinol or paromomycin).

Although nitazoxanide has been effective in some patients with mild to moderate intestinal amebiasis, data are limited and some clinicians state that additional study is needed.

Isosporiasis (Cystoisosporiasis)

Has been used in some patients for treatment of isosporiasis^{† [off-label]} (also known as cystoisosporiasis) caused by Isospora belli (Cystoisospora belli).

Co-trimoxazole is drug of choice for treatment of infections caused by I. belli (C. belli); pyrimethamine and ciprofloxacin are recommended alternatives.

Although data are limited, some experts state that nitazoxanide is a potential alternative for treatment of isosporiasis (cystoisosporiasis) in HIV-infected infants and children^{† [off-label]} who cannot tolerate co-trimoxazole.

Cestode (Tapeworm) Infections

Has been used for treatment of hymenolepiasis caused by Hymenolepis nana^† (dwarf tapeworm).

Praziquantel is drug of choice for infections caused by H. nana; niclosamide (not commercially available in US) and nitazoxanide are recommended as alternatives.

Nematode (Roundworm) Infections

Has been used for treatment of ascariasis^† caused by Ascaris lumbricoides. Albendazole, mebendazole, and ivermectin are the drugs of choice for ascariasis.

Has been used for treatment of trichuriasis^† caused by Trichuris trichiura (whipworm). Albendazole is drug of choice for trichuriasis; recommended alternatives are mebendazole and ivermectin.

Trematode (Fluke) Infections

Has been used for treatment of fascioliasis caused by Fasciola hepatica^† (sheep liver fluke).

Triclabendazole is considered drug of choice for fascioliasis and bithionol (not commercially available in US) and nitazoxanide are recommended as alternatives.

Nitazoxanide Dosage and Administration

Administration

Oral Administration

Administer orally twice daily with food.

Do not use nitazoxanide 500-mg tablets in pediatric patients ≤11 years of age; amount of drug contained in the tablets exceeds recommended dosage in this age group.

Reconstitution

Reconstitute powder for oral suspension at time of dispensing by adding 48 mL of water according to the manufacturer's directions. Tap the bottle to loosen the powder and add the water in 2 portions; shake vigorously after each addition.

Reconstituted suspension contains 100 mg/5 mL.

Shake suspension well prior to administration of each dose.

Dosage

Nitazoxanide tablets and oral suspension are not bioequivalent.

Pediatric Patients

Cryptosporidiosis

Oral

Children 1–3 years of age: 100 mg every 12 hours for 3 days.

Children 4–11 years of age: 200 mg every 12 hours for 3 days.

Children ≥12 years of age: 500 mg every 12 hours for 3 days.

HIV-infected pediatric patients^† receiving optimized antiretroviral regimen: CDC, NIH, and IDSA recommend 100 mg twice daily in those 1–3 years of age, 200 mg twice daily in those 4–11 years of age, and 500 mg twice daily in those ≥12 years of age. Recommended duration is 3–14 days.

Giardiasis

Oral

Children 1–3 years of age: 100 mg every 12 hours for 3 days.

Children 4–11 years of age: 200 mg every 12 hours for 3 days.

Children ≥12 years of age: 500 mg every 12 hours for 3 days.

HIV-infected pediatric patients^†: CDC, NIH, and IDSA recommend 100 mg every 12 hours in those 1–3 years of age, 200 mg every 12 hours in those 4–11 years of age, and 500 mg every 12 hours in those ≥12 years of age. Recommended duration is 3 days.

Isosporiasis (Cystoisosporiasis)†

Oral

HIV-infected pediatric patients^†: CDC, NIH, and IDSA recommend 100 mg every 12 hours in those 1–3 years of age, 200 mg every 12 hours in those 4–11 years of age, and 500 mg every 12 hours in those ≥12 years of age. Recommended duration is 3 days.

Cestode (Tapeworm) Infections†

Hymenolepiasis†

Oral

Children 1–3 years of age: 100 mg twice daily for 3 days.

Children 4–11 years of age: 200 mg twice daily for 3 days.

Children ≥12 years of age: 500 mg twice daily for 3 days.

Nematode (Roundworm) Infections†

Ascariasis†

Oral

Children 1–3 years of age: 100 mg twice daily for 3 days.

Children 4–11 years of age: 200 mg twice daily for 3 days.

Children ≥12 years of age: 500 mg twice daily for 3 days.

Trichuriasis†

Oral

Children 1–3 years of age: 100 mg twice daily for 3 days.

Children 4–11 years of age: 200 mg twice daily for 3 days.

Trematode (Fluke) Infections†

Fascioliasis†

Oral

Children 1–3 years of age: 100 mg twice daily for 7 days.

Children 4–11 years of age: 200 mg twice daily for 7 days.

Children ≥12 years of age: 500 mg twice daily for 7 days.

Adults

Cryptosporidiosis

Oral

500 mg every 12 hours for 3 days.

HIV-infected adults^† receiving optimized antiretroviral regimen: CDC, NIH, and IDSA recommend 0.5–1 g twice daily for 14 days.

Giardiasis

Oral

500 mg every 12 hours for 3 days.

Cestode (Tapeworm) Infections†

Hymenolepiasis†

Oral

500 mg twice daily for 3 days.

Trematode (Fluke) Infections†

Fascioliasis†

Oral

500 mg twice daily for 7 days.

Cautions for Nitazoxanide

Contraindications

• Hypersensitivity to nitazoxanide or any ingredient in the formulation.

Warnings/Precautions

General Precautions

Immunodeficiency

Has not been more effective than placebo for treatment of diarrhea caused by C. parvum in HIV-infected or other immunodeficient individuals.

Not evaluated for treatment of diarrhea caused by Giardia in HIV-infected or other immunodeficient individuals.

Specific Populations

Pregnancy

Data not available on use of nitazoxanide in pregnant women to inform a drug-associated risk.

In animal reproduction studies, no evidence of teratogenicity or fetotoxicity when nitazoxanide was given to pregnant rats and rabbits during organogenesis at exposures 30 and 2 times, respectively, the human exposure at recommended human dosage of 500 mg twice daily based on body surface area.

Lactation

Not known whether distributed into human milk, affects milk production, or affects breast-fed child.

Consider developmental and health benefits of breast-feeding along with the mother's clinical need for nitazoxanide and potential adverse effects on the breast-fed infant from the drug or the underlying maternal condition.

Pediatric Use

Safety and efficacy not established in children <1 year of age.

Nitazoxanide oral suspension: Safety and efficacy for treatment of diarrhea caused by C. parvum or Giardia established in pediatric patients 1–17 years of age.

Nitazoxanide tablets: Safety and efficacy for treatment of diarrhea caused by C. parvum or Giardia established in pediatric patients 12–17 years of age. Do not use the 500-mg tablets in pediatric patients ≤11 years of age since the tablets contain a greater amount of the drug than is recommended in this age group.

Geriatric Use

Experience in those ≥65 years of age insufficient to determine whether they respond differently than younger individuals.

Consider the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease or drug therapy in this age group.

Hepatic Impairment

Use with caution; pharmacokinetics not evaluated.

Renal Impairment

Use with caution; pharmacokinetics not evaluated.

Common Adverse Effects

Abdominal pain, headache, chromaturia, nausea.

Drug Interactions

Protein-bound Drugs

Possible pharmacokinetic interactions with other highly protein-bound drugs; monitor closely if used concomitantly with highly protein-bound drugs with a narrow therapeutic index. (See Specific Drugs under Interactions.)

Drugs Metabolized by Hepatic Microsomal Enzymes

Does not inhibit CYP isoenzymes.

Specific Drugs

Nitazoxanide Pharmacokinetics

Absorption

Bioavailability

Following oral administration, nitazoxanide is rapidly hydrolyzed to an active metabolite, tizoxanide, which is converted to tizoxanide glucuronide.

Peak plasma concentrations of tizoxanide and tizoxanide glucuronide usually attained within 1–5 and 2–8 hours, respectively; nitazoxanide undetectable in plasma.

The tablets and oral suspension are not bioequivalent. Bioavailability of the oral suspension is 70% relative to that of the tablet.

Food

Administration of nitazoxanide with food increases tizoxanide and tizoxanide glucuronide AUCs.

Distribution

Plasma Protein Binding

Tizoxanide: >99%.

Elimination

Metabolism

Rapidly hydrolyzed to tizoxanide; tizoxanide subsequently undergoes conjugation, primarily by glucuronidation.

Elimination Route

Tizoxanide eliminated in urine, bile, and feces; tizoxanide glucuronide eliminated in urine and bile.

Half-life

Nitazoxanide: 6 minutes.

Tizoxanide: 1.2–1.5 hours after single dose with food; 1.8–6.4 hours after repeated doses with food.

Tizoxanide glucuronide: 1.9–2.9 hours after single dose with food; 3.5–5.6 hours after repeated doses with food.

Special Populations

Pharmacokinetics not studied in patients with hepatic or renal impairment.

Stability

Storage

Oral

For Suspension

25°C (may be exposed to 15–30°C).

After reconstitution, store at room temperature; discard after 7 days.

Tablets

25°C (may be exposed to 15–30°C).

Actions and Spectrum

• Nitazoxanide and its metabolite, tizoxanide, have antiprotozoal activity.

• Antiprotozoal activity may be related principally to interference with the pyruvate:ferredoxin 2-oxidoreductase enzyme-dependent electron transfer reaction essential to anaerobic energy metabolism in susceptible organisms.

• Protozoa: Active against sporozoites and oocysts of Cryptosporidium parvum and trophozoites of Giardia intestinalis (also known as G. lamblia or G. duodenalis). Also active against Entamoeba histolytica, Trichomonas vaginalis, Cyclospora cayetanensis, and Isospora belli (Cystoisospora belli).

• Other organisms: Active against certain helminths, including some cestodes (tapeworms). Although clinical importance unclear, active in vitro against some anaerobic and microaerophilic gram-positive and gram-negative bacteria, including Clostridioides difficile (formerly known as Clostridium difficile) and Helicobacter pylori and also active against some viruses.

Advice to Patients

• Advise patients to take nitazoxanide tablets or oral suspension with food.

• Advise patients using the oral suspension to keep container tightly closed and shake the suspension well prior to each dose. Inform patients that the oral suspension may be stored at room temperature for up to 7 days and to discard any unused portion after that time.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses. Importance of avoiding concomitant use of warfarin.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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