Schedule H

Oral

• Tablets: 200 mg, 500 mg

• Oral suspension: 100 mg/5 mL (powder for reconstitution)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Diarrhoea caused by Giardia lamblia (Giardiasis)

Parameter Recommendation

Starting dose 500 mg twice daily with food

Titration Not applicable

Usual maintenance dose 500 mg twice daily

Maximum dose 500 mg twice daily (1 g/day)

Duration: 3 days

Clinical Notes:

• Confirm diagnosis with stool microscopy or antigen detection before initiating therapy

• Administer with food to enhance absorption

• Response rate >85% for Giardia infections

1. Diarrhoea caused by Cryptosporidium parvum (Cryptosporidiosis)

Parameter Recommendation

Starting dose 500 mg twice daily with food

Titration Not applicable

Usual maintenance dose 500 mg twice daily

Maximum dose 500 mg twice daily (1 g/day)

Duration: 3 days (may extend to 5–7 days in immunocompromised patients)

Clinical Notes:

• Particularly useful in HIV patients with cryptosporidiosis (in addition to ART)

• Ensure adequate hydration and electrolyte replacement

• Efficacy reduced in severely immunocompromised patients

1. Intestinal Amoebiasis (Entamoeba histolytica)

Parameter Recommendation

Starting dose 500 mg twice daily with food

Titration Not applicable

Usual maintenance dose 500 mg twice daily

Maximum dose 500 mg twice daily

Duration: 3–5 days

Clinical Notes:

• May be used as alternative to metronidazole or tinidazole

• Not recommended for hepatic amoebiasis (metronidazole preferred)

• Confirm diagnosis with stool examination or antigen testing

1. Intestinal Helminthic Infections

Used when first-line agents (albendazole, mebendazole) are contraindicated, not tolerated, or unavailable. Active against Ascaris lumbricoides, Trichuris trichiura, Ancylostoma duodenale, Enterobius vermicularis, Taenia species, Hymenolepis nana, and Fasciola hepatica.

Parameter Recommendation

Starting dose 500 mg twice daily with food

Titration Not applicable

Usual maintenance dose 500 mg twice daily

Maximum dose 500 mg twice daily

Duration: 3 days for most helminths; may extend to 5–7 days for Fasciola or mixed infections

Clinical Notes:

• Not first-line for routine helminthiasis; albendazole/mebendazole preferred

• Confirm parasitic infection with stool examination before treatment

• May be useful in mixed protozoal and helminthic infections

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Clostridioides difficile Infection (mild-moderate, recurrent or metronidazole-refractory) 500 mg twice daily with food 10 days OFF-LABEL — Specialist only (Gastroenterology/ID). Based on RCTs showing comparable efficacy to vancomycin in mild-moderate CDI. Not first-line; consider when vancomycin or fidaxomicin not available/appropriate.

Viral Gastroenteritis (rotavirus, norovirus) 500 mg twice daily with food 3 days OFF-LABEL — Limited evidence from small RCTs suggesting reduction in duration of diarrhoea. Not standard practice; consider in severe/prolonged cases.

Blastocystis hominis Infection 500 mg twice daily with food 3–5 days OFF-LABEL — Used when metronidazole fails or not tolerated. Based on clinical experience and small studies.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Diarrhoea caused by Giardia lamblia / Cryptosporidium parvum / Intestinal Amoebiasis

Age-based Dosing (using oral suspension or tablets):

1–3 years ~10–15 kg 100 mg (5 mL suspension) Twice daily Suspension

4–11 years ~15–40 kg 200 mg (10 mL suspension OR 200 mg tablet) Twice daily Suspension or tablet

≥12 years >40 kg 500 mg Twice daily Tablet

Alternative Weight-based Dosing:

• 7.5 mg/kg/dose twice daily (maximum 500 mg per dose)

Parameter Recommendation

Starting dose Age/weight-based as above

Titration Not applicable

Usual maintenance dose As per age/weight table

Maximum dose 500 mg twice daily

Duration: 3 days

Clinical Notes:

• Administer with food to improve absorption

• Oral suspension preferred for children <6 years

• Shake suspension well before each dose

• Ensure confirmation of parasitic infection before treatment

Minimum Age Statement: Not recommended in infants below 12 months of age. Use in infants 1–12 months only under paediatric gastroenterologist supervision for severe/refractory parasitic infections.

Safety Monitoring:

• Monitor hydration status and electrolytes

• Watch for GI adverse effects (abdominal pain, nausea)

• Ensure resolution of symptoms; repeat stool examination if symptoms persist beyond 5 days

Secondary Indications — Paediatrics (Off-label)

Indication Age Dose Notes

Refractory Rotavirus Diarrhoea ≥1 year Age-based dosing as above; Duration: 3 days OFF-LABEL — Specialist only. Limited evidence showing reduction in duration of diarrhoea in hospitalised children. Based on small RCTs. Ensure adequate rehydration.

Cryptosporidiosis in HIV-infected Children ≥1 year 7.5 mg/kg/dose twice daily (max 500 mg); Duration: 3–14 days based on response OFF-LABEL — Paediatric ID specialist only. Efficacy reduced in severely immunocompromised; optimise ART concurrently.

Nitazoxanide is rapidly metabolised to active metabolite tizoxanide, which is primarily eliminated via biliary/faecal route with minimal renal excretion (<5%).

Mild to moderate impairment No dose adjustment required

Note: Active metabolite tizoxanide undergoes hepatic glucuronide conjugation. In significant hepatic impairment, clearance may be reduced.

• Known hypersensitivity to nitazoxanide or any excipient in the formulation

• Known allergy to other thiazolide compounds

• Hepatic impairment — metabolite cleared hepatically; monitor LFTs if prolonged use

• Diabetes mellitus — oral suspension contains sucrose; monitor glucose if large volumes used in diabetic children

• Patients with G6PD deficiency — rare reports of haemolysis; monitor if using in known G6PD-deficient patients

• Empiric use for non-parasitic diarrhoea — avoid; confirm parasitic aetiology before treatment

• Immunocompromised patients — reduced efficacy in severe immunosuppression; ensure adequate treatment of underlying condition

• Concurrent use of highly protein-bound drugs — tizoxanide is >99% protein-bound; theoretical risk of displacement interactions

• Oral suspension contains excipients (sucrose, sorbitol) — may not be suitable in hereditary fructose intolerance or sucrase-isomaltase deficiency

Parameter Recommendation

Safety Category Limited human data; animal studies do not indicate teratogenicity but data insufficient for routine use

Preferred Alternatives Metronidazole (for giardiasis/amoebiasis after first trimester); paromomycin (for giardiasis — not systemically absorbed)

When to Use May be considered in second/third trimester only if clearly needed and preferred alternatives unsuitable; avoid in first trimester if possible

Monitoring Maternal LFTs if prolonged use; standard fetal monitoring

Parameter Recommendation

Breastfeeding Compatibility Likely compatible; limited data but low systemic absorption expected

Drug Levels in Milk Unknown; expected to be low given extensive protein binding and limited systemic exposure

Preferred Alternatives Metronidazole (well-studied in lactation) for giardiasis/amoebiasis

Infant Monitoring Monitor for diarrhoea, GI upset, or poor feeding (unlikely with short course)

Parameter Recommendation

Starting dose Standard adult dose (500 mg twice daily)

Titration Not applicable

Additional Risks Age-related renal/hepatic decline (monitor if impairment present); increased dehydration risk with diarrhoeal illness; ensure adequate fluid and electrolyte replacement

Monitoring Hydration status; renal function if concurrent nephrotoxic drugs

Interacting Drug Mechanism/Effect Management

Warfarin Potential alteration of INR due to effect on gut flora (vitamin K synthesis) or theoretical protein-binding displacement Monitor INR closely during and after nitazoxanide course; adjust warfarin dose as needed

Highly protein-bound drugs (phenytoin, valproate, diazepam) Tizoxanide is >99% protein-bound; theoretical displacement risk Monitor for increased effect/toxicity of co-administered drug; clinical significance uncertain

Note: Nitazoxanide/tizoxanide do not significantly interact with cytochrome P450 enzymes. Major interactions are limited.

Interacting Drug Effect Management

Oral antidiabetic agents Diarrhoeal illness may affect absorption; sucrose in suspension may affect glucose Monitor blood glucose; adjust antidiabetic dose if needed

Immunosuppressants (tacrolimus, ciclosporin) Diarrhoea may reduce absorption of immunosuppressants Monitor immunosuppressant levels during diarrhoeal illness

Oral contraceptives Diarrhoea/vomiting may reduce absorption Advise additional contraceptive precautions during and 7 days after treatment

Metformin Additive GI effects (nausea, diarrhoea) Monitor GI tolerability

• Abdominal pain

• Nausea

• Diarrhoea (may be difficult to distinguish from underlying infection)

• Headache

• Vomiting

• Flatulence

• Discoloured urine (yellow-green) — benign, resolves after stopping

• Anorexia

• Dizziness

Adverse Effect Clinical Significance

Hypersensitivity reactions Rash, pruritus, urticaria, angioedema (rare); discontinue if occurs

Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis Very rare; discontinue immediately if mucocutaneous reaction occurs

Hepatotoxicity Elevated transaminases (rare); monitor LFTs if prolonged use; discontinue if significant elevation

Haemolytic anaemia Very rare; reported in G6PD-deficient patients; monitor if known G6PD deficiency

Thrombocytopenia Very rare; discontinue if occurs

Tachycardia Rare; mechanism unclear

Baseline:

• Stool microscopy or antigen testing to confirm parasitic infection

• Liver function tests (if hepatic impairment or prolonged therapy anticipated)

• Glucose monitoring (if diabetic and using suspension)

After Initiation/During Therapy:

• Clinical assessment of diarrhoea resolution

• Watch for adverse effects (nausea, abdominal pain)

• Monitor for hypersensitivity reactions (rash, jaundice)

Long-term (if extended therapy):

• Repeat stool examination if symptoms persist beyond 5–7 days

• LFTs if treatment extended beyond 5 days

• Assessment for superinfection

• Nizonide® (Lupin)

• Nitazet® (Cipla)

• Zintacide® (Zydus Cadila)

• Nidazox® (Aristo)

• Nitax® (Mankind)

• Nitazox® (Sun Pharma)

• Nitopar® (Micro Labs)

• Entamizole-N® (various — FDC)

Fixed-Dose Combinations (FDCs):

• Nitazoxanide + Ofloxacin

• Nitazoxanide + Albendazole

Note: FDCs should be used judiciously; avoid unless specific clinical indication for both components.

• Not included in NLEM 2022

• Not under NPPA price control

• Available in private market; limited government supply

• Significant price variation between brands

• Confirm diagnosis first: Avoid empiric use for all acute diarrhoea; best results when parasitic infection (Giardia, Cryptosporidium, amoeba) is confirmed by stool microscopy or antigen testing

• Take with food: Bioavailability significantly enhanced when administered with food; always counsel patients/caregivers to give with meals

• Yellow-green urine is benign: Warn patients about harmless discolouration of urine/sclera; prevents unnecessary concern and treatment discontinuation

• Not first-line for helminths: Albendazole/mebendazole remain first-choice for routine helminthic infections; nitazoxanide is alternative when these are contraindicated or in mixed protozoal-helminthic infections

• Avoid in neonates: Safety not established below 12 months; use only under specialist supervision in this age group

• Broad-spectrum advantage: Unique among antiparasitics for activity against protozoa, helminths, and some bacteria/viruses — useful when mixed or uncertain parasitic aetiology

nitazoxanide; antiprotozoal; giardiasis; cryptosporidiosis; amoebiasis; helminthiasis; acute diarrhoea; paediatric-safe; gastroenterology; parasitic-infection

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• API Textbook of Medicine

• IAP Guidelines for Management of Diarrhoeal Diseases

• ICMR Guidelines for Parasitic Infections

• AIIMS Antimicrobial Policy (Enteric Infections)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• International RCTs (for C. difficile and viral gastroenteritis — off-label indications only)