Brand Name: Xifaxan®

Generic Name: rifaximin

Indications: Xifaxan® is FDA approved to treat travelers’ diarrhea caused by Escherichia coli, hepatic encephalopathy, and irritable bowel syndrome with diarrhea.

Mechanism: A semi-synthetic derivative of rifampin, Xifaxan® inhibits bacterial protein synthesis by binding the beta-subunit of bacterial DNA-dependent RNA polymerase consequently inhibiting bacterial growth.

Pharmacokinetics: Rifaximin is mainly metabolized by CYP3A4. Peak plasma concentration is reached at about one hour. The half-life is dose-dependent and ranges between 1.83 hours and 5.63 hours. Rifaximin is excreted predominantly unchanged in the feces. Rifaximin is a substrate of CYP3A4, P-glycoprotein, OATP1A2, OATP1B1, and OATP1B3.

Adverse Reactions: The most common adverse reaction to rifaximin treating travelers’ diarrhea (≥2%) is headache. Common adverse reactions to rifaximin treating hepatic encephalopathy include peripheral edema (15%), nausea (14%), dizziness (13%), fatigue (12%), ascites (11%), muscle spasms (9%), and pruritus (9%). Common adverse reactions to rifaximin treating irritable bowel syndrome with diarrhea (≥2%) is ALT increase and nausea. Less common adverse reactions include clostridium colitis, increased blood creatine phosphokinase, and myalgia. Hypersensetivity reactions to rifaximin include exfoliative dermatitis, rash, angioneurotic edema, urticaria, flushing, pruritus, and anaphylaxis.

Product Availability: Rifaximin is available in 200 mg and 550 mg tablets.

Dosing: Dosing for travelers’ diarrhea caused by Escherichia coli is 220 mg PO TID for three days. Dosing for hepatic encephalopathy is 550 mg PO BID. Dosing for irritable bowel syndrome with diarrhea is 550 mg PO TID for 14 days, recurrent symptoms can be re-treated with this regimen twice. Rifaximin can be taken with or without food.

Special Populations: There is no available data on rifaximin use in pregnant women or lactation. Animal data shows teratogenicity at doses higher than prescribed. Rifaximin is not approved to treat travelers’ diarrhea in patient’s under 12 years of age. Rifaximin is not approved to treat hepatic encephalopathy or irritable bowel syndrome with diarrhea in patient’s under 18 years of age. No geriatric dose adjustment is required. Use rifaximin with caution in patients with severe hepatic impairment as systemic exposure is greatly increased. Renal impairment was not studied.

Drug Abuse and Dependence: Rifaximin has little to no potential for abuse.

Comparison to Similar Products2: The only other FDA approved medication for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) is alosetron (Lotronex®). Alosetron is approved for use in women only and use is restricted to prescribes enrolled in the Prometheus Prescribing Program for Lotronex®. Alosetron has a black box warning due to serious gastrointestinal adverse reactions such as ischemic colitis.

Clinical Trial Data3: Rifaximin, compared with placebo, significantly improves IBS symptoms and bloating in both male and female patients. Rifaximin provides a durable effect and has a similar adverse effect profile to placebo.

Place in Therapy4: The American College of Gastroenterology (ACG) states that rifaximin “is effective at reducing total IBS symptoms and bloating in diarrhea-predominant IBS.” The ACG monograph was released in 2014, before rifaximin was FDA approved for the treatment of IBS-D.

Cost5: Xifaxan® (rifaximin)

Strength Package Size WAC PKG price AWP PKG price AWP Unit Price200 mg 30 tablets $ 480.69 $ 576.83 $ 19.22550 mg 42 tablets $ 1282.76 $ 1539.31 $ 36.65550 mg 60 tablets $ 1832.51 $ 2199.01 $ 36.65

References: 1. Salis Pharmaceuticals. Xifaxan® package insert. Bridgewater, NJ: 2015, November. 2. Prometheus Laboratories Inc. Lotronex® package insert. San Diego, CA: 2014, March.3. Pimentel M, Lembo A, Chey WD, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364:22-32. 4. Ford AC, Moayyedi P, Lacy BE, et al. American college of gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014;109:S2-S26. 5. Redbook Online [online database]. Greenwood Village, CO: Truven Health Analytics. http://www.micromedexsolutions.com/micromedex2/librarian/ND_T/evidencexpert/ND_PR/evidencexpert/CS/34DCE5/ND_AppProduct/evidencexpert/DUPLICATIONSHIELDSYNC/172387/ND_PG/evidencexpert/ND_B/evidencexpert/ND_P/evidencexpert/PFActionId/redbook.ShowProductSearchResults?SearchTerm=XIFAXAN&searchType=redbookProductName&searchTermId=16888&searchContent=%24searchContent&searchFilterAD=filterADActive&searchFilterRepackager=filterExcludeRepackager&searchPattern=%5Exifaxan.