Mechanism of Action of Nitazoxanide
The antiprotozoal activity of nitazoxanide is believed to be due to interference with the pyruvate, ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction which is essential to anaerobic energy metabolism. Nitazoxanide is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that nitazoxanide inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), all folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Nitazoxanide is transported into cells by both the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, nitazoxanide is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process that occurs in tumor cells and, to a lesser extent, in normal tissues. Polyglutamated metabolites have an increased intracellular half-life resulting in prolonged drug action in malignant cells.
Indications of Nitazoxanide
- Dwarf Tapeworm Infection (Hymenolepis nana)
- Ascariasis
- Amebiasis
- Diarrhea with vomiting
- Giardiasis
- Ascariasis
- Cestode infections
- Clostridium difficile infection recurrence
- Cryptosporidiosis infection
- Diarrhea caused by Cryptosporidium parvum
- Diarrhea caused by Giardia lamblia
- Giardiasis
- Trichuriasis
- For the treatment of diarrhea in adults and children caused by the protozoa Giardia lamblia, and for the treatment of diarrhea in children caused by the protozoan, Cryptosporidium parvum.
- Nitazoxanide has not been shown to be superior to placebo medication for the management of diarrhea caused by Cryptosporidium parvum in patients with HIV/immunodeficiency
Contra-Indications of Nitazoxanide
- Nitazoxanide is contraindicated only in individuals who have experienced a hypersensitivity reaction to nitazoxanide or the inactive ingredients of a nitazoxanide formulation
Dosage of Nitazoxanide
Strengths: 500 mg ,100 mg/5 mL
Amebiasis
- 500 mg twice daily with food for 3 days.
- 1000 mg twice daily with food for 14 days or until diarrhea resolves.
Cryptosporidiosis
- 500 mg twice daily with food for 3 days.
- 1000 mg twice daily with food for 14 days or until diarrhea resolves.
Giardiasis
- 500 mg twice daily with food for 3 days.
- 1000 mg twice daily with food for 14 days or until diarrhea resolves.
Cryptosporidiosis
- 12 to 47 months: 100 mg (5 mL) by mouth with food every 12 hours for 3 days.
- 4 to 11 years: 200 mg (10 mL) with food every 12 hours for 3 days.
- Greater than or equal to 12 years: 500 mg twice daily with food for 3 days.
Pediatric Giardiasis
- 12 to 47 months: 100 mg (5 mL) by mouth with food every 12 hours for 3 days.
- 4 to 11 years: 200 mg (10 mL) with food every 12 hours for 3 days.
- Greater than or equal to 12 years: 500 mg twice daily with food for 3 days.
Ascariasis
- 2 to 3 years: 100 mg/5 mL
- 4 to 11 years: 200 mg/10 mL
Hymenolepis nana
- to 3 years: 100 mg/5 mL
- 4 to 11 years: 200 mg/10 mL
Pediatric Amebiasis
- 500 mg twice daily with food for 3 days.
Side Effects of Nitazoxanide
The most common side effects
- Abdominal or stomach cramps
- dizziness or lightheadedness
- heartburn
- Stomach pain, especially if it comes along with fever and diarrhea or constipation
- Yellowing of the skin or eyes
- Loss of appetite
- Constipation
- Chest pain or discomfort
- lightheadedness, dizziness, or fainting
- unusual tiredness or weakness
- fast, pounding, or irregular heartbeat or pulse
- increased watering of mouth
- lightheadedness
- constipation;
- vision changes;
- breast swelling (in men or women); or
- decreased sex drive, impotence, or difficulty having an orgasm.
- blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
- restless muscle movements in your eyes, tongue, jaw, or neck;
Common
- Drowsiness and lightheadedness the day after taking the medicine.
- Confusion.
- Numbed emotions.
- Visual disturbances such as blurred vision or double vision.
- Shaky movements and unsteady walk (ataxia).
- Muscle weakness.
- Dizziness.
- A headache.
- Skin rashes.
- Disturbances of the gut such as diarrhea, constipation, nausea, vomiting or abdominal pain.
- Changes in sex drive.
- Low blood pressure (hypotension).
- Blood disorders.
- Unexpected aggression, restlessness or irritability.
- Nightmares or hallucinations
Rare
- agitation
- anxiety
- behavioral changes, including aggressiveness, angry outbursts,
- confusion
- increased trouble sleeping
- muscle spasms
- shortness of breath
- difficult or labored breathing
- difficulty with swallowing
- dizziness, faintness, or lightheadedness
- frequent urination
- hallucinations
- bloating or swelling of the face, arms, hands, lower legs, or feet
- blurred vision
- hives or welts, itching, or skin rash
- the increased volume of pale, dilute urine
Drug Interactions of Nitazoxanide
Nitazoxanide may interact with following drugs, supplements, & may change the efficacy of drugs
- barbiturates (e.g., phenobarbital, butalbital)
- benzodiazepines (e.g., diazepam, lorazepam)
- phenothiazines (e.g., perphenazine, fluphenazine)
- quinidine
- ritonavir
- tricyclic antidepressants (e.g., amitriptyline, nortriptyline)
Pregnancy & Lactation of Nitazoxanide
FDA Pregnancy Category B
There are no data with nitazoxanide in human pregnancy to inform a drug-associated risk. Animal reproductive studies performed in rats and rabbits at doses up to 2 and 30 times the recommended daily human dose demonstrated no evidence of teratogenicity or fetotoxicity due to nitazoxanide.
There is no information about the presence of nitazoxanide in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for nitazoxanide and any potential adverse effects on the breastfed infant from nitazoxanide or the mother’s underlying condition.
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References
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