What is nitazoxanide?

What is Nitazoxanide?

Nitazoxanide is a synthetic antiprotozoal and anthelmintic medication approved by the FDA for treating diarrhea caused by Cryptosporidium parvum and Giardia lamblia in immunocompetent patients. 1

Chemical Structure and Formulation

• Nitazoxanide is chemically classified as 2-acetyloxy-N-(5-nitro-2-thiazolyl)benzamide, a nitrothiazole derivative with molecular formula C₁₂H₉N₃O₅S and molecular weight 307.3 1
• The drug is available as 500 mg tablets (ALINIA Tablets) and as an oral suspension containing 100 mg per 5 mL (ALINIA for Oral Suspension) 1
• It appears as a light yellow crystalline powder that is poorly soluble in ethanol and practically insoluble in water 1

Mechanism of Action

• Nitazoxanide interferes with the pyruvate-ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction, which is essential for anaerobic energy metabolism in susceptible organisms 2
• The drug may also activate protein kinase R (PKR), a key kinase regulating the cell's innate antiviral response, which explains its broader antimicrobial effects beyond parasites 3
• Following oral administration, nitazoxanide is rapidly hydrolyzed to its active metabolite tizoxanide (desacetyl-nitazoxanide), which then undergoes glucuronidation 1

FDA-Approved Indications

• For Cryptosporidium parvum diarrhea: The IDSA recommends nitazoxanide as primary treatment in immunocompetent children and adults 4

  • Pediatric dosing (ages 1-3 years): 100 mg orally twice daily 4
  • Pediatric dosing (ages 4-11 years): 200 mg orally twice daily 4
  • Adult dosing: 500-1000 mg orally twice daily 4
  • Clinical response rates reach 88% in immunocompetent children versus 38% with placebo 4

• For Giardia lamblia infection: The IDSA lists nitazoxanide as an approved alternative to tinidazole (first-line) 4

• Safety and efficacy are established for pediatric patients ≥1 year of age and adults 1

Spectrum of Activity

• Nitazoxanide demonstrates in vitro activity against a broad range of protozoa including Entamoeba histolytica, Giardia intestinalis, Trichomonas vaginalis, Blastocystis hominis, and Cryptosporidium parvum 5, 6
• The drug shows activity against various helminths and anaerobic bacteria 7
• It has documented antiviral properties, with clinical trials exploring its use in hepatitis B, hepatitis C, and viral gastroenteritis 3, 2

Off-Label and Investigational Uses

• Rotavirus enteritis: Recommended at 7.5 mg/kg twice daily orally, though only assessed in immunocompetent pediatric patients 3
• Cyclospora cayetanensis: Alternative treatment when trimethoprim-sulfamethoxazole cannot be used, though data is limited 4
• Cystoisospora belli: Potential second-line alternative when TMP-SMX or pyrimethamine are unsuitable 4
• Microsporidiosis (Enterocytozoon bieneusi): The CDC recommends it for HIV-infected adults 4
• Hepatitis C virus genotype 4: A trial showed 79% SVR when combined with pegylated interferon and ribavirin, though patient numbers were small 3

Pharmacokinetics

• The parent drug nitazoxanide is not detected in plasma after oral administration; only its metabolites (tizoxanide and tizoxanide glucuronide) are measurable 1
• Administration with food increases tizoxanide AUC by almost two-fold and Cmax by 50% for tablets; the suspension shows 45-50% AUC increase with food 1
• More than 99% of tizoxanide is protein-bound in plasma 1
• Approximately two-thirds of the oral dose is excreted in feces and one-third in urine 1
• No significant drug accumulation occurs with twice-daily dosing for 7 consecutive days 1

Critical Limitations in Immunocompromised Patients

• Nitazoxanide should only be used in HIV-infected patients with cryptosporidiosis when combined with effective antiretroviral therapy (cART) and CD4 count >50 cells/µL 4
• The drug has not been shown to be superior to placebo for treating C. parvum diarrhea in HIV-infected or immunodeficient patients 1
• Efficacy is markedly reduced in patients with CD4 <50/µL, and longer treatment duration (14 days) may be necessary in immunocompromised adults 8
• The drug has not been studied for G. lamblia treatment in HIV-infected or immunodeficient patients 1

Safety Profile

• Nitazoxanide is generally well tolerated with primarily mild gastrointestinal side effects 9, 6
• No documented drug-drug interactions exist at present 9
• The drug has not been studied in patients with compromised renal or hepatic function 1
• Safety in pediatric patients <1 year of age has not been established 1

Administration Considerations

• Both tablets and oral suspension must be administered with food to optimize absorption 1
• The oral suspension is not bioequivalent to tablets, with relative bioavailability of 70% 1
• A single 500 mg tablet contains more nitazoxanide than recommended for pediatric patients ≤11 years; use oral suspension for this age group 1