Usage
Nitazoxanide is an antiprotozoal agent prescribed for the treatment of diarrhea caused by Giardia lamblia or Cryptosporidium parvum in immunocompetent patients. It is also used off-label for other parasitic infections like amebiasis, ascariasis, and some viral infections. Its pharmacological classification is antiprotozoal. The drug interferes with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction, which is essential to the anaerobic energy metabolism of the targeted parasites.
Alternate Names
The drug is also known by its brand name, Alinia. There are no widely used alternate generic names.
How It Works
Pharmacodynamics: Nitazoxanide inhibits the PFOR enzyme, disrupting anaerobic energy metabolism in susceptible protozoa. The drug and its metabolite, tizoxanide, are active against both Giardia and Cryptosporidium organisms.
Pharmacokinetics: Following oral administration, nitazoxanide is rapidly hydrolyzed in the intestinal wall and plasma to its active metabolite, tizoxanide. Tizoxanide is over 99.9% bound to plasma proteins. Peak plasma concentrations of tizoxanide and its glucuronide metabolite occur 1-4 hours after ingestion. It is primarily metabolized by glucuronidation in the liver. Nitazoxanide is eliminated in both urine (approximately 33%) and feces (approximately 67%). The elimination half-life of tizoxanide is about 1-1.6 hours.
Mode of Action: Nitazoxanide and its active metabolite, tizoxanide, interfere with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme. This enzyme is crucial for anaerobic energy metabolism in certain protozoan parasites, and its inhibition leads to parasite death. This mechanism of action is particularly effective against organisms such as Giardia lamblia and Cryptosporidium parvum. The PFOR enzyme is not present in humans, contributing to the drug’s selective toxicity.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: The primary mechanism of action is the inhibition of the PFOR enzyme.
Elimination Pathways: Nitazoxanide is metabolized primarily by hepatic glucuronidation, after which it is eliminated through both renal and fecal routes (approximately 33% in urine and 67% in feces).
Dosage
Standard Dosage
Adults:
500 mg (one tablet or 25 mL oral suspension) every 12 hours with food for 3 days.
Children:
- 1-3 years: 100 mg (5 mL oral suspension) every 12 hours with food for 3 days.
- 4-11 years: 200 mg (10 mL oral suspension) every 12 hours with food for 3 days.
- 12 years and older: 500 mg (one tablet or 25 mL oral suspension) every 12 hours with food for 3 days.
Special Cases:
- Elderly Patients: Use with caution due to potential age-related decline in hepatic, renal, or cardiac function. Dose adjustments may be required.
- Patients with Renal Impairment: Use with caution. No specific dose adjustments are available, but monitoring is recommended.
- Patients with Hepatic Dysfunction: Use with caution. No specific dose adjustments are available, but monitoring is recommended.
- Patients with Comorbid Conditions: Use with caution in patients with HIV infection or other immunodeficiencies, diabetes, or other chronic conditions.
Clinical Use Cases
Nitazoxanide is not indicated for the clinical use cases listed (intubation, surgical procedures, mechanical ventilation, ICU use, emergency situations).
Dosage Adjustments
Dose adjustments may be necessary for elderly patients and those with renal or hepatic impairment based on individual patient characteristics and clinical response. Monitor patients closely for adverse reactions.
Side Effects
Common Side Effects
Abdominal pain, headache, nausea, vomiting, flatulence, discolored urine (chromaturia).
Rare but Serious Side Effects
Allergic reactions (hypersensitivity), severe skin reactions.
Long-Term Effects
No specific long-term adverse effects have been reported with short-term nitazoxanide therapy.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include hypersensitivity reactions, potentially involving rash, itching, angioedema, and difficulty breathing.
Contraindications
Hypersensitivity to nitazoxanide or any components of the formulation.
Drug Interactions
Nitazoxanide can interact with highly protein-bound drugs with narrow therapeutic indices (e.g., warfarin). It may also interact with some medications metabolized by CYP450 enzymes. No specific CYP450 interactions have been definitively characterized. Caution is advisable when co-administering nitazoxanide with other medications. Consult drug interaction resources for the most up-to-date information.
Pregnancy and Breastfeeding
No adequate human data are available to inform the drug-associated risk during pregnancy. Animal studies have not shown evidence of teratogenicity or fetotoxicity. Limited information suggests low levels of the metabolite tizoxanide may be excreted in breast milk, but the risk to infants is considered low, especially those older than two months. Caution is recommended, and alternative agents may be preferred, especially while breastfeeding newborns or preterm infants.
Drug Profile Summary
- Mechanism of Action: Inhibits pyruvate:ferredoxin oxidoreductase (PFOR), disrupting anaerobic energy metabolism in susceptible protozoa.
- Side Effects: Abdominal pain, headache, nausea, vomiting, discolored urine. Rarely, hypersensitivity reactions.
- Contraindications: Hypersensitivity to nitazoxanide.
- Drug Interactions: May interact with highly protein-bound drugs, particularly warfarin.
- Pregnancy & Breastfeeding: Limited data suggest low risk, but caution is recommended.
- Dosage: Adults and children 12 years and older: 500 mg every 12 hours for 3 days; children 1-3 years: 100 mg every 12 hours for 3 days; children 4-11 years: 200 mg every 12 hours for 3 days. All doses should be taken with food.
- Monitoring Parameters: Monitor for resolution of symptoms, adverse reactions, and potential drug interactions.
Popular Combinations
No routinely recommended drug combinations are associated with nitazoxanide.
Precautions
Pre-screen for allergies, hepatic or renal dysfunction, and other relevant medical conditions. Exercise caution in patients with HIV, other immunodeficiencies, or diabetes. Advise patients to take nitazoxanide with food. No restrictions on driving or operating machinery are typically associated with nitazoxanide.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Nitazoxanide?
A: Adults and children 12 years and older: 500 mg every 12 hours with food for 3 days. Children 1-3 years: 100 mg every 12 hours with food for 3 days. Children 4-11 years: 200 mg every 12 hours with food for 3 days.
Q2: How does Nitazoxanide work?
A: It inhibits the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme, disrupting the anaerobic energy metabolism of certain parasites.
Q3: What are the common side effects of Nitazoxanide?
A: Common side effects include abdominal pain, headache, nausea, vomiting, and discolored urine.
Q4: Is Nitazoxanide safe for pregnant or breastfeeding women?
A: Limited data suggest low risk, but caution is recommended. Consult a healthcare professional for guidance.
Q5: What are the contraindications for Nitazoxanide?
A: Known hypersensitivity to nitazoxanide is a contraindication.
Q6: Does Nitazoxanide interact with other medications?
A: It may interact with highly protein-bound drugs, particularly warfarin. Consult drug interaction resources for specific information.
Q7: How should Nitazoxanide be administered?
A: Administer orally with food. The oral suspension should be reconstituted according to the manufacturer’s instructions.
Q8: What should I do if a dose is missed?
A: Take the missed dose as soon as possible, unless it is almost time for the next scheduled dose. Do not double doses.
Q9: Is nitazoxanide effective against all types of diarrhea?
A: No. It is specifically indicated for diarrhea caused by Giardia lamblia and Cryptosporidium parvum. It is not effective against bacterial or viral causes of diarrhea.
