Pharmacy Times

RxPRODUCT NEWS: PROFILE: Alinia (nitazoxanide)

Author: Claudio Faria, PharmD; Carolyn Soo, PharmD; and Nathaniel Weidner

Giardia intestinalis and Cryptosporidium parvum infections are 2 of the leading causes of persistent diarrhea in humans.1,2 These organisms are transmitted through water, food, or personal contact. They are responsible for >200 million illnesses annually in the United States and are an increased cause of mortality throughout the world.1,2 These infections may produce symptoms of diarrhea, abdominal pain, cramping, and/or bloating.2 Alinia (nitazoxanide), marketed by Romark Laboratories, has received FDA approval for the treatment of giardiasis, as well as the treatment of C parvum-induced diarrhea in children from 1 to 11 years of age.3,4

Pharmacology

Alinia is a first-in-class, broad-spectrum antiparasitic drug.4,5 It interferes with the pyruvate ferredoxin oxidoreductase enzyme-dependent electron transfer reaction, which plays a major role in anaerobic metabolism.6 It is a nitrothiazolyl-salicylamide derivative and a prodrug, converting to the active metabolite, tizoxanide.3,7 These 2 components also exhibit activity against intestinal parasites and bacterial pathogens.2

Clinical Trials

A prospective, randomized, double-blind, placebo-controlled study evaluated the efficacy of Alinia in the treatment of diarrhea caused by C parvum.8 Fifty adults and adolescents (>11 years of age) were given 500 mg of Alinia or placebo twice daily for 3 days, while 50 children (≤11 years old) received 100 mg, 200 mg, or matching placebo twice daily for 3 days. Efficacy was measured by resolution of diarrhea after 7 days. Of the 99 patients who completed the study, resolution occurred in 39 of 49 patients (80%) in the active group versus 20 of 49 (41%) in the placebo group (P<.0001).8 Stool samples also were examined for post-treatment C parvum oocytes. In this portion of the study, 67% of the patients receiving active treatment and 22% of the patients receiving placebo had no oocyst detection (P<.0001).8

A second randomized, placebo-controlled study was designed to assess the safety and efficacy of Alinia in the treatment of diarrhea caused by G intestinalis, Entamoeba histolytica, and/or Entamoeba dispar.2 Eighty-nine adults and adolescents (12-65 years of age) were given Alinia 500 mg or placebo twice daily for 3 days. The clinical response rate in the Alinia group was 81%, compared with 40% in the placebo group (P<.0002).2 Resolution of diarrhea took a median of 3 days in the active group, while 60% of the patients in the placebo group still had diarrhea during the follow-up period. Parasitologic cure was achieved for 71% of those treated with Alinia. No patients in the placebo arm showed parasitologic cure (P<.0001).2

Safety

Overall, Alinia is well-tolerated. All adverse effects reported have been mild or transient in nature. The most common adverse events reported are abdominal pain, dyspepsia, worsening diarrhea, discoloration of urine, drowsiness, dizziness, and nausea.2,3 The safety of Alinia in HIV-positive patients and in patients with hepatic, bilary, or renal impairment has not been established; therefore, use in these patient populations is contraindicated.

Alinia is supplied as a 100-mg/5-mL suspension containing 1.48 g of sucrose per 5 mL. Due to this significant amount of sucrose, Alinia also is contraindicated in diabetic patients. Alinia is a Pregnancy Category B agent.

Outlook

Alinia is a safe and effective treatment option for the resolution of giardiasis and cyclosporidiosis-induced persistent diarrhea. A 3-day treatment regimen reduces the duration of diarrhea and oocyst excretion in patients with persistent diarrhea caused by C parvum and giardiasis.8 Alinia has shown greater efficacy when treating persistent diarrhea over placebo and also has shown favorable results in cases where traditional therapy may prove resistant.3 The beneficial safety and efficacy profile of Alinia gives health care practitioners another viable therapeutic treatment option for giardiasis and cyclosporidiosis.

Drs. Faria and Soo are both senior research pharmacists with the Investigational Drug Service at Brigham and Women's Hospital, Boston, Mass. Dr. Faria also is a senior human research specialist at Partners HealthCare System. Mr. Weidner is a fourth-year pharmacy student from Northeastern University, currently working on a cooperative program at the Brigham and Women's Hospital in the Investigational Drug Service.

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