Nitazoxanide Tablets for Giardiasis

By Stan Deresinski, MD, FACP

Nitazoxanide (Alinia™) is a broad spectrum antiparasitic agent, previously approved for use as an oral suspension for the treatment of cryptosporidiosis and giardiasis in children.1 It has now received FDA approval as a 500 tablet for the treatment of giardiasis in adolescents and adults.2

Clinical response rates to treatment with nitazoxanide tablets in a double-blind, controlled trial in Peru and Egypt, with diarrhea caused by Giardia duodenalis lamblia, was 85% (46/54) compared to 44% (12/27) in placebo recipients. Cysts persisted in the stools of some clinical responders, however. Response rates to the oral suspension in children have been similar.2

Nitazoxanide, a nitrothiazolyl-salicylamide derivative, is a prodrug that is rapidly hydrolyzed to tizoxanide (desacetylnitazoxonide), which is then glucuronidated, with both metabolites being the active forms of the drug.4 Tizoxanide, which is > 99% bound to plasma proteins, appears to not have an inhibitory effect on cytochrome P450 enzymes.

The tablet and oral suspensions are not bioequivalent; the latter has only 70% relative bioavailability. Administration of the tablets with food is associated with an almost 2-fold increase in AUC and approximately 50% increase in Cmax of the active metabolites; the food effect is significantly less with the oral suspension. Overall, approximatley two-thirds of an oral dose of nitazoxanide is excreted as its metabolites in feces, and one-third in urine. In adults greater than 17 years of age, the Cmax of tizoxanide and tizoxanide glucuronide after administration of a singly 500 mg table with food is 10.6 ± 2.0 mcg/mL and 10.5 ± 1.4 mcg/mL, respectively. The pharmacokinetics of nitazoxanide have not been evaluated in patients with impaired renal or hepatic function.

The active metabolites of nitazoxanide are believed to interfere with the pyruvate:ferredoxin oxidoreductase enzyme-dependent electron transfer reaction. Other undefined pathways may also important. Nitazoxanide appears to be well tolerated, and is a Pregnancy Category B drug.

Other drugs available for the treatment of giardiasis include metronidazole (which has never received FDA approval for this indication), paromomycin (also not FDA-approved for this infection), and furazolidone. Quinacrine is available through some compounding pharmacies. Tinidazole had recently received approval as a single 2 gram dose for treatment of giardiasis in adults. Albendazole also has activity in patients with giardiasis.5 The most recent recommendations of The Medical Letter, for the treatment of giardiasis in adults, list 3 drugs of choice: metronidazole (250 mg tid x 5d), nitazoxanide (500 mg bid x 3d), and tinidazole (2 grams once) (ML).6 Three alternatives are listed: paromomycin, furazolidone, and quinacrine.

Overall, nitazoxanide is an useful, albeit expensive, addition to our therapeutic options in the management of patients with giardiasis.

This article was published in the October 2004 issue of Infectious Disease Alert.

Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor of Infectious Disease Alert.

References

1. Kemper CA. New FDA-Approved Agent for Cryptosporidiosis. Infect Dis Alert. June 15, 2002.

2. Alinia. http://www.fda.gov.

3. Nitazoxanide. Med Lett. 2003;45:29-31.

4. Bailey JM, et al. Nitazoxanide Treatment for Giardiasis and Cryptosporidiosis in Children. Ann Pharmacother. 2004;38:634-640.

5. Karabay O, et al. Albendazole vs Metronidazole Treatment of Adult Giardiasis: An Open Randomized Study. World J Gastroenterol. 2004;10:1215-1217.

6. Drugs for Parasitic Infections. Med Lett. August 2004.