Subject: Xifaxan® (rifaximin)

Status	Drug	PR	PR-QL	PR-AL	ST	M EX‡
FE	Xifaxan®  (rifaximin)	X	X			X

Policy:

1. Precertification Criteria

Under some plans, including plans that use an open or closed formulary, Xifaxan is subject to precertification.   If precertification requirements apply Aetna considers Xifaxan to be medically necessary for those members who meet any of the following precertification criteria: 

A. A documented diagnosis of traveler's diarrhea caused by noninvasive strains of Escherichia coli (non-bloody diarrhea without fever)

OR

B.  A documented diagnosis of hepatic encephalopathy

AND  
C. A documented:


• Contraindication to one preferred alternative agent indicated for the member's condition OR
• Intolerance to one preferred alternative agent indicated for the member's condition OR
• Allergy to one preferred alternative agent indicated for the member's condition OR
• Failure of an adequate trial of two weeks of one preferred alternative agent indicated for the member's condition

AND


Based on manufacturer labeling and/or standard reference compendia3, the usual dosage of Xifaxan for the treatment of travelers' diarrhea caused by noninvasive strains of E. coli in adults and adolescents 12 years of age or older is 200 mg 3 times daily for 3 days and Xifaxan has also been given in a dosage of 600-1200 mg daily (usually in 3 divided doses) for 7-21 days for the treatment of hepatic encephalopathy in adults.  A quantity of Xifaxan will be considered medically necessary as indicated in the table below.

Drug	Maximum Daily Dose/ Dosing Interval	Dosage Strength	Quantity Limits
Xifaxan	200 mg/ three times daily	200 mg	9 tablets in 30 days (Traveler's diarrhea)
Xifaxan	1200 mg/ three times daily	200 mg	180 tablets in 30 days (Hepatic encephalopathy)





For coverage of additional quantities, a member's treating physician must request prior authorization through the Aetna Pharmacy Management Precertification Unit. Additional quantities of Xifaxan will be considered medically necessary for those members who meet ANY of the following criteria:

• Member's physician provides documentation (controlled clinical trial) from the peer-reviewed medical literature for use of a higher dose.
  



2. Medical Exception Criteria

Xifaxan is currently listed on the Aetna Formulary Exclusions List.* Therefore, Xifaxan is excluded from coverage for members enrolled in prescription drug benefits plans that use a closed formulary, unless a medical exception is granted.  Aetna considers Xifaxan to be medically necessary for those members who meet the following criteria:

A. A documented diagnosis of traveler's diarrhea caused by noninvasive strains of Escherichia coli (non-bloody diarrhea without fever)

OR

B.  A documented diagnosis of hepatic encephalopathy

AND

C.  A documented:

• Contraindication to one preferred alternative agent indicated for the member's condition OR
• Intolerance to one preferred alternative agent indicated for the member's condition OR
• Allergy to one preferred alternative agent indicated for the member's condition OR
• Failure of an adequate trial of two weeks of one preferred alternative agent indicated for the member's condition
  
  

Indication	Preferred Alternatives
Traveler’s Diarrhea	azithromycin ciprofloxacin
Hepatic encephalopathy	lactulose

Place of Service:

Outpatient

The above policy is based on the following references:

1. Olin BR, editor. Drugs Facts and Comparisons (electronic online version). St. Louis: J.B. Lippincott Company, 2006.
2. USPDI Drug Information for the HealthCare Professional (online through Stat!Ref). Thomson MICROMEDEX, Greenwood Village, Colorado; 2006.
3. McEvoy GK, editor. AHFS Drug Information (online through Stat!Ref). American Society of Health-Systems Pharmacists, Bethesda, Maryland; 2006.
4. Package Information Insert.  Xifaxan Tablets, Salix Pharmaceuticals, Raleigh, NC. June 2004.
5. Package Information Insert.  Ciprofloxacin Tablets and Oral Suspension, Bayer Pharmaceuticals, West Haven, CT. 2004.
6. Package Information Insert.  Zithromax Tablets and Oral Suspension, Pfizer Labs, NY, NY. January 2004Medical Economics, Inc., PDR Electronic Library. Thomson Medical Economics, Montvale, NJ; 2003.
7. DuPont HL, Jiang ZD, et al. Rifaximin versus ciprofloxacin for treatment of traveler's diarrhea: a randomized, double-blind clinical trial.  Clin Infect Dis.  2001 Dec 1;33 (11):1807-15.
8. DuPont HL, Ericsson CD, et al.  Rifaximin: a nonabsorbed antimicrobial in the therapy of travelers' diarrhea.  Digestion.  1998 Nov-Dec;59(6):708-14.
9. Lima, A.  Tropical diarrhea:  new developments in traveller's diarrhea.  Curr Opin Infect Dis.  2001 Oct;14(5):547-52
10. Massa P, Vallerino E, Dodero M. Treatment of hepatic encephalopathy with rifaximin: double blind, double dummy study versus lactulose.  Eur J Clin Res. 1993 Feb;4:7-18.
11. Giacomo F, Francesco A, Michele N, et al. Rifaximin in the treatment of hepatic encephalopathy.  Eur J Clin Res. 1993 June;4:57-66.
12. Xifaxan Formulary Dossier.  Salix Pharmaceuticals, 2004.
13. Riordan SM, Williams R. Treatment of hepatic encephalopathy. N Engl J Med. 1997;337:473-9.
14. Williams R, James OF, Warnes TW et al. Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy: a double-blind, randomized, dose-finding multi-centre study. Eur J Gastroenterol Hepatol. 2000;12:203-8.
15. Puxeddu A, Quartini M, Massimetti A et al. Rifaximin in the treatment of chronic hepatic encephalopathy. Curr Med Res Opin. 1995;13:274-81.
16. Pedretti G, Calzetti C, Missale G et al. Rifaximin versus neomycin on hyperammoniemia in chronic portal systemic encephalopathy of cirrhotics. A double-blind, randomized trial. Ital J Gastroenterol. 1991;23:175-8.
17. Bucci L, Palmieri GC. Double-blind, double-dummy comparison between treatment with rifaximin and lactulose in patients with medium to severe degree hepatic encephalopathy. Curr Med Res Opin. 1993;13:109-18.
18. Centers for Disease Control website. Travelers' diarrhea.  Accessed June 21, 2006 http://www.cdc.gov/travel/other/drug_for_td_approval_2004.htm
19. Centers for Disease Control website. Travelers' Diarrhea- General Information. http://www.cdc.gov/ncidod/dbmd/diseaseinfo/travelersdiarrhea_g.htm

 

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

November 12, 2007