Alinia

Generic Name: Nitazoxanide
Class: Antiprotozoals, Miscellaneous
VA Class: AP109
Chemical Name: 2-acetyloxy-N-(5-nitro-2-thiazolyl)benzamide
Molecular Formula: C12H9N3 O5 S
CAS Number: 55981-09-4

Introduction

Antiprotozoal; nitrothiazolyl-salicylamide derivative.1 2

Uses for Alinia

Cryptosporidiosis

Treatment of diarrhea caused by Cryptosporidium parvum in immunocompetent adults, adolescents, and children ≥1 year of age;1 12 designated an orphan drug by FDA for this use.13 A drug of choice for treatment of cryptosporidiosis in adults and pediatric patients who do not have HIV infection.12

Anti-infectives may suppress the infection, but none has been found to reliably eradicate Cryptosporidium.4 6 15 16

Safety and efficacy not established for treatment of diarrhea caused by C. parvum in immunocompromised individuals (including HIV patients);1 has not been more effective than placebo in such patients.1 2 12 15 CDC, NIH, IDSA, and others state that the most appropriate treatment for cryptosporidiosis in HIV-infected individuals is the use of potent antiretroviral agents (to restore immune function) and symptomatic treatment of diarrhea.6 15 16

Slideshow: View Frightful (But Dead Serious) Drug Side Effects

Giardiasis

Treatment of diarrhea caused by Giardia lamblia (also known as G. duodenalis or G. intestinalis) in immunocompetent adults, adolescents, and children ≥1 year of age.1 Designated an orphan drug by FDA for treatment of intestinal giardiasis.13

Metronidazole, tinidazole, and nitazoxanide are drugs of choice for treatment of giardiasis.12

Safety and efficacy not established for treatment of giardiasis in immunocompromised individuals (including HIV patients).1

Cestode (Tapeworm)Infections

Has been used for treatment of infections caused by Hymenolepis nana (dwarf tapeworm).14 Praziquantel is drug of choice;12 nitazoxanide is an alternative.12

Nematode (Roundworm) Infections

Has been used for treatment of ascariasis caused by Ascaris lumbricoides.14 Albendazole, ivermectin, and mebendazole are drugs of choice for ascariasis.12

Has been used for treatment of trichuriasis caused by Trichuris trichiura (whipworm).14 Mebendazole is drug of choice;12 alternatives are albendazole and ivermectin.12

Alinia Dosage and Administration

Administration

Oral Administration

Administer orally twice daily with food.1

Reconstitution

Reconstitute powder for oral suspension at the time of dispensing by adding the amount of water specified on the container in 2 portions; shake well after each addition.1

Reconstituted suspension contains 100 mg/5 mL.1

Shake suspension well prior to administration of each dose.1

Oral suspension is the appropriate dosage form for children ≤11 years of age.1 The amount of nitazoxanide in the tablet (500 mg) exceeds the recommended dosage in this age group.1

Dosage

Nitazoxanide tablets and oral suspension are not bioequivalent.1

Pediatric Patients

Cryptosporidiosis
Oral

Children 1–3 years of age: 100 mg every 12 hours for 3 days.1 12

Children 4–11 years of age: 200 mg every 12 hours for 3 days.1 12

Children ≥12 years of age: 500 mg every 12 hours for 3 days.1 12

Giardiasis
Oral

Children 1–3 years of age: 100 mg every 12 hours for 3 days.1 12

Children 4–11 years of age: 200 mg every 12 hours for 3 days.1 12

Children ≥12 years of age: 500 mg every 12 hours for 3 days.1 12

Cestode (Tapeworm) Infections
Hymenolepsis nana Infections
Oral

Children 1–3 years of age: 100 mg twice daily for 3 days.12 14

Children 4–11 years of age: 200 mg twice daily for 3 days.12 14

Children ≥12 years of age: 500 mg daily for 3 days.12

Adults

Cryptosporidiosis
Oral

500 mg every 12 hours for 3 days.1 12

Giardiasis
Oral

500 mg every 12 hours for 3 days.1

Cestode (Tapeworm) Infections
Hymenolepsis nana Infections
Oral

500 mg daily for 3 days.12

Cautions for Alinia

Contraindications

  • Hypersensitivity to nitazoxanide or any ingredient in the formulation.1

Warnings/Precautions

General Precautions

Diabetes Mellitus

Individuals with diabetes mellitus and/or their caregivers should be informed that reconstituted nitazoxanide oral suspension contains 1.48 g of sucrose/5 mL.1

Immunodeficiency

Has not been more effective than placebo for treatment of diarrhea caused by C. parvum in HIV-infected or immunocompromised patients.1 2 12 15

Safety and efficacy for treatment of diarrhea caused by Giardia notestablished in immunocompromised individuals, including those with HIV infection.1

Specific Populations

Pregnancy

Category B.1

Lactation

Not known whether distributed into milk.1 Caution advised if used in nursing women.1

Pediatric Use

Safety and efficacy not established in children <1 year of age.1

Geriatric Use

Experience in those ≥65 years of age insufficient to determine whether they respond differently than younger adults.1

The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease or drug therapy should be considered.1 Caution advised in geriatric patients with renal and/or hepatic impairment.1

Hepatic Impairment

Use with caution;1 pharmacokinetics not evaluated.1

Renal Impairment

Use with caution;1 pharmacokinetics not evaluated.1

Common Adverse Effects

Abdominal pain, diarrhea, nausea, vomiting, headache.1

Interactions for Alinia

Protein-bound Drugs

Pharmacokinetic interaction possible with other highly protein-bound drugs; use with caution in patients receiving highly protein-bound drugs with a narrow therapeutic index (e.g., warfarin).1

Drugs Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interaction unlikely; does not inhibit CYP isoenzymes.1

Alinia Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from GI tract and hydrolyzed to tizoxanide.1 Both nitazoxanide and tizoxanide have antiprotozoal activity.1 10

Peak plasma concentrations of tizoxanide and tizoxanide glucuronide attained within 1–4 hours; nitazoxanide undetectable in plasma.1

The tablets and oral suspension are not bioequivalent.1 Bioavailability of the oral suspension is 70% relative to that of the tablet.1

Food

Food increases extent of absorption.1

Distribution

Plasma Protein Binding

>99%.1

Elimination

Metabolism

Rapidly hydrolyzed to tizoxanide;1 tizoxanide subsequently undergoes conjugation, principally by glucuronidation.1

Elimination Route

Tizoxanide eliminated in urine, bile, and feces;1 tizoxanide glucuronide eliminated in urine and bile.1

Special Populations

Pharmacokinetics not studied in patients with hepatic or renal impairment.1

Stability

Storage

Oral

For Suspension

25°C (may be exposed to 15–30°C).1

After reconstitution, store in tight container at 25°C (may be exposed to 15–30°C); discard after 7 days.1

Tablets

25°C (may be exposed to 15–30°C).1

Actions

  • Both nitazoxanide and its metabolite, tizoxanide, have antiprotozoal activity.10

  • Antiprotozoal activity may be related principally to interference with the pyruvate:ferredoxin 2-oxidoreductase enzyme-dependent electron transfer reaction essential to anaerobic energy metabolism in susceptible organisms.1

  • Active against sporozoites and oocysts of Cryptosporidium parvum and trophozoites of Giardia lamblia (also known as G. duodenalis or G. intestinalis).1

  • Also active against some other organisms, including Entamoeba histolytica,10 Trichomonas vaginalis,10 and certain anaerobic and microaerophilic gram-positive and gram-negative bacteria (e.g., Helicobacter pylori).10

Advice to Patients

  • Importance of taking with food.1

  • Advise diabetic patients and/or their caregivers that the oral suspension contains sucrose.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Nitazoxanide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

For suspension

100 mg/5 mL

Alinia

Romark

Tablets

500 mg

Alinia

Romark

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Alinia 500MG Tablets (ROMARK PHARMACEUTICALS): 60/$1,425.99 or 180/$4,006.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Romark Pharmaceuticals. Alinia (nitazoxanide) tablets and for oral suspension prescribing information. Tampa, FL: 2005 Jun.

2. Amadi B, Mwiya M, Musuku J et al. Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised controlled study. Lancet. 2002; 360:1375-80. [IDIS 488791] [PubMed 12423984]

3. Rossignol J-F A, Ayoub A, Ayers MS. Treatment of diarrhea caused by Cryptosporidium parvum: a prospective randomized, double-blind, placebo-controlled study of nitazoxanide. J Infect Dis. 2001; 184:103-6. [IDIS 466301] [PubMed 11398117]

4. Committee on Infectious Diseases, American Academy of Pediatrics. Redbook: 2003 report of the Committee on Infectious Diseases. 26th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003:255-7, 283-5.

5. Scott K G-E, Meddings JB, Kirk DR et al. Intestinal infection with Giardia spp. reduces epithelial barrier function in a myosin light chain kinase-dependent fashion. Gastroenterol. 2002; 123:1179-90.

6. Chen XM, Keithly JS, Paya CV et al. Cryptosporidiosis. N Engl J Med. 2002; 346:1723-31. [PubMed 12037153]

7. Kosek M, Alcantara C, Lima AAM et al. Cryptosporidiosis: an update. Lancet Infect Dis. 2001; 1:262-9. [PubMed 11871513]

8. Guerrant RL, Gilder TV, Steiner TS et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis. 2001; 32:331-50. [IDIS 466024] [PubMed 11170940]

9. Centers for Disease Control and Prevention. Diagnosis and management of foodborne illness. A primer for physicians. MMWR Morb Mortal Wkly Rep. 2001; 50(No. RR-2):1-69. [PubMed 11215787]

10. Adagu IS, Nolder D, Warhurst DC et al. In vitro activity of nitazoxanide and related compounds against isolates of Giardia intestinalis, Entamoeba histolytica, and Trichomonas vaginalis. J Antimicrob Chemother. 2002; 49:103-14. [PubMed 11751773]

11. Romark Laboratories, Tampa, FL: personal communication.

12. Anon. Drugs for parasitic infections. Med Lett Drugs Ther. Aug 2004. From the Medical Letter web site ().

13. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD; 2002 Oct 15. From FDA web site (). Accessed 2003 Feb 24.

14. Juan JO, Lopez Chegne N, Gargala G et al. Comparative clinical studies of nitazoxanide, albendazole and praziquantel in the treatment of ascariasis, trichuriasis and hymenolepiasis in children from Peru. Trans R Soc Trop Med Hyg. 2002; 96:193-6. [PubMed 12055813]

15. Centers for Disease Control and Prevention. Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America. MMWR Morb Mortal Wkly Rep. 2004; 53(No. RR-15):1-112.

16. Centers for Disease Control and Prevention. Treating opportunistic infections among HIV-exposed and infected children: recommendations from CDC, the National Institutes of Health, and the Infectious Diseases Society of America. MMWR Morb Mortal Wkly Rep. 2004; 53(No. RR-14):1-92.

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