RxPRODUCT NEWS: PROFILE: Alinia (nitazoxanide)

Giardia intestinalis and Cryptosporidiumparvum infectionsare 2 of the leading causes ofpersistent diarrhea in humans.^1,2These organisms are transmittedthrough water, food, or personal contact.They are responsible for >200million illnesses annually in the UnitedStates and are an increased causeof mortality throughout the world.^1,2These infections may produce symptomsof diarrhea, abdominal pain,cramping, and/or bloating.² Alinia(nitazoxanide), marketed by RomarkLaboratories, has received FDAapproval for the treatment of giardiasis,as well as the treatment ofC parvum-induced diarrhea in childrenfrom 1 to 11 years of age.^3,4

Pharmacology

Alinia is a first-in-class, broad-spectrumantiparasitic drug.^4,5 It interfereswith the pyruvate ferredoxin oxidoreductaseenzyme-dependent electrontransfer reaction, which plays a majorrole in anaerobic metabolism.⁶ It is anitrothiazolyl-salicylamide derivativeand a prodrug, converting to theactive metabolite, tizoxanide.^3,7 These2 components also exhibit activityagainst intestinal parasites and bacterialpathogens.²

Clinical Trials

A prospective, randomized, double-blind,placebo-controlled study evaluatedthe efficacy of Alinia in the treatmentof diarrhea caused by C parvum.⁸Fifty adults and adolescents (>11 yearsof age) were given 500 mg of Alinia orplacebo twice daily for 3 days, while50 children (&#8804;11 years old) received100 mg, 200 mg, or matching placebotwice daily for 3 days. Efficacy wasmeasured by resolution of diarrheaafter 7 days. Of the 99 patients whocompleted the study, resolutionoccurred in 39 of 49 patients (80%) inthe active group versus 20 of 49 (41%)in the placebo group (P<.0001).⁸ Stoolsamples also were examined for post-treatmentC parvum oocytes. In thisportion of the study, 67% of thepatients receiving active treatmentand 22% of the patients receivingplacebo had no oocyst detection(P<.0001).⁸

A second randomized, placebo-controlledstudy was designed to assessthe safety and efficacy of Alinia in thetreatment of diarrhea caused by Gintestinalis, Entamoeba histolytica,and/or Entamoeba dispar.² Eighty-nineadults and adolescents (12-65 years ofage) were given Alinia 500 mg orplacebo twice daily for 3 days. Theclinical response rate in the Aliniagroup was 81%, compared with 40%in the placebo group (P<.0002).² Resolutionof diarrhea took a median of 3days in the active group, while 60% ofthe patients in the placebo group stillhad diarrhea during the follow-upperiod. Parasitologic cure wasachieved for 71% of those treatedwith Alinia. No patients in the placeboarm showed parasitologic cure(P<.0001).²

Safety

Overall, Alinia is well-tolerated. Alladverse effects reported have beenmild or transient in nature. The mostcommon adverse events reported areabdominal pain, dyspepsia, worseningdiarrhea, discoloration of urine,drowsiness, dizziness, and nausea.^2,3The safety of Alinia in HIV-positivepatients and in patients with hepatic,bilary, or renal impairment has notbeen established; therefore, use inthese patient populations is contraindicated.

Alinia is supplied as a 100-mg/5-mLsuspension containing 1.48 g of sucroseper 5 mL. Due to this significantamount of sucrose, Alinia also is contraindicatedin diabetic patients. Aliniais a Pregnancy Category B agent.

Outlook

Alinia is a safe and effective treatmentoption for the resolution of giardiasisand cyclosporidiosis-inducedpersistent diarrhea. A 3-day treatmentregimen reduces the duration of diarrheaand oocyst excretion in patientswith persistent diarrhea caused by Cparvum and giardiasis.⁸ Alinia hasshown greater efficacy when treatingpersistent diarrhea over placebo andalso has shown favorable results incases where traditional therapy mayprove resistant.³ The beneficial safetyand efficacy profile of Alinia giveshealth care practitioners anotherviable therapeutic treatment optionfor giardiasis and cyclosporidiosis.

Drs. Faria and Soo are both senior researchpharmacists with the Investigational DrugService at Brigham and Women's Hospital,Boston, Mass. Dr. Faria also is a seniorhuman research specialist at PartnersHealthCare System. Mr. Weidner is afourth-year pharmacy student fromNortheastern University, currently workingon a cooperative program at the Brighamand Women's Hospital in the InvestigationalDrug Service.

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