Alinia - General Information
Alinia, also known by the brand name Alinia, is a synthetic nitrothiazolyl-salicylamide derivative and an anti-protozoal agent. It is approved for treatment of infectious diarrhea caused by Cryptosporidium parvum and Giardia lamblia in patients 1 year of age and older. Following oral administration it is rapidly hydrolyzed to its active metabolite, tizoxanide, which is 99% protein bound. Peak concentrations are observed 1–4 hours after administration. It is excreted in the urine, bile and feces. Untoward effects include abdominal pain, vomiting and diarrhea. [Wikipedia]
Pharmacology of Alinia
Alinia 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. Alinia 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.
Alinia for patients
Nitazoxanide should be taken with food. Diabetic patients should be aware that the oral suspension contains 1.48 g of sucrose/5 ml.
Tizoxanide is highly bound to plasma protein (>99.9%). Therefore, caution should be used when administering nitazoxanide concurrently with other highly plasma protein-bound drugs with narrow therapeutic indices, as competition for binding sites may occur (e.g., warfarin). In vitro metabolism studies have demonstrated that tizoxanide has no significant inhibitory effect on cytochrome P450 enzymes. Although no drug-drug interaction studies have been conducted in vivo, it is expected that no significant interaction would occur when nitazoxanide is co-administered with drugs that either are metabolized by or inhibit cytochrome P450 enzymes.
Alinia Tablets and Alinia for Oral Suspension are contraindicated in patients with a prior hypersensitivity to nitazoxanide or any other ingredient in the formulations.
Additional information about Alinia
Alinia Indication: 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 protozoa Cryptosporidium parvum.
Mechanism Of Action: 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. Studies have shown that the PFOR enzyme from Giardia lamblia directly reduces nitazoxanide by transfer of electrons in the absence of ferredoxin. The DNA-derived PFOR protein sequence of Cryptosporidium parvum appears to be similar to that of Giardia lamblia. Interference with the PFOR enzyme-dependent electron transfer reaction may not be the only pathway by which nitazoxanide exhibits antiprotozoal activity.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Nitazoxanide
Synonyms: Nitazoxanida [Inn-Spanish]; Nitazoxanid; Nitazoxanidum [Inn-Latin]; Tizoxanide Glucuronide; NTZ; 2-Acetyloxy-N-[(5-nitro-2-thiazolyl)]benzamide; 2-(Acetolyloxy)-N-(5-nitro-2-thiazolyl)benzamide
Drug Category: Antiparasitic Agents
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Nitazoxanide: Alinia; Fental; Phavic-1;
Absorption: The relative bioavailability of the suspension compared to the tablet was 70%. When administered with food the AUC and Cmax increased by two-fold and 50%, respectively, for the tablet and 45 to 50% and ≤ 10%, respectively, for the oral suspension.
Toxicity (Overdose): In acute studies in rodents and dogs, the oral LD50 was higher than 10,000 mg/kg. Single oral doses of up to 4000 mg nitazoxanide have been administered to healthy adult volunteers without significant adverse effects.
Protein Binding: Very High (greater than 99%), bound to proteins. Binding is not affected by degree of renal impairment.
Biotransformation: Rapidly hydrolyzed to an active metabolite, tizoxanide (desacetyl-nitazoxanide), followed by conjugation, primarily by glucuronidation to tizoxanide glucuronide.
Half Life: 3.5 hours in patients with normal renal function
Dosage Forms of Alinia: Tablet Oral
Chemical IUPAC Name: [2-[(5-nitro-1,3-thiazol-2-yl)carbamoyl]phenyl] acetate
Chemical Formula: C12H9N3O5S
Nitazoxanide on Wikipedia: http://en.wikipedia.org/wiki/Nitazoxanide
Organisms Affected: Protozoa