Xifaxan Indications, Dosage, Storage, Stability - Rifaximin

Xifaxan Indications, Dosage, Storage, Stability - Rifaximin

INDICATIONS AND USAGE

XIFAXAN™ Tablets are indicated for the treatment of patients (³12 years of age) with travelers’ diarrhea caused by noninvasive strains of Escherichia coli (see WARNINGS, Microbiology, and CLINICAL STUDIES).

XIFAXAN™ Tablets should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than Escherichia coli.

XIFAXAN™ Tablets can be administered orally with or without food. For travelers’ diarrhea, the recommended dose is one 200 mg tablet taken three times a day for 3 days.

XIFAXAN™ Tablets are available as circular, pink-colored, biconvex tablets containing 200 mg rifaximin, debossed with "Sx" on one side.

NDC 65649-301-03 Bottles of 30 tablets

Store XIFAXAN™ Tablets at 20–25°C (68–77°F); excursions permitted to 15–30°C (59-86°F). See USP Controlled Room Temperature.

The efficacy of rifaximin (200 mg orally taken three times a day for 3 days) was evaluated in two-randomized, multi-center, double-blind, placebo controlled studies in adult subjects with travelers’ diarrhea. One study was conducted at clinical sites in Mexico, Guatemala, and Kenya (Study 1). The other study was conducted in Mexico, Guatemala, Peru, and India (Study 2). Stool specimens were collected before treatment and 1 to 3days following the end of treatment to identify enteric pathogens. The predominant pathogen in both studies was Escherichia coli.

The clinical efficacy of rifaximin was assessed by the time to return to normal, formed stools and resolution of symptoms. The primary efficacy endpoint was time to last unformed stool (TLUS) which is defined as the time to the last unformed stool passed, after which clinical cure was declared. Table 3 displays the median TLUS and the number of patients who achieved clinical cure for the intent to treat population (ITT) of Study 1. The duration of diarrhea was significantly shorter in patients treated with rifaximin than in the placebo group. More rifaximin-treated patients were classified as clinical cures than were those in the placebo group.

Microbiological eradication (defined as the absence of a baseline pathogen in culture of stool after 72 hours of therapy) rates for Study 1 are presented in Table 4 for patients with any pathogen at baseline and for the subset of patients with Escherichia coli at baseline. Escherichia coli was the only pathogen with sufficient numbers to allow comparisons between treatment groups.

Even though rifaximin had microbiologic activity similar to placebo, it demonstrated a clinically significant reduction in duration of diarrhea and a higher clinical cure rate than placebo. Therefore, patients should be managed based on clinical response to therapy rather than microbiologic response.

Study 2 provided additional information to support the results presented for Study 1. This study also provided evidence that rifaximin-treated subjects with fever and/or blood in the stool at baseline had prolonged TLUS. These subjects had lower clinical cure rates than those without fever or blood in the stool at baseline. Many of the patients with fever and/or blood in the stool (dysentery-like diarrheal syndromes) had invasive pathogens, primarily Campylobacter jejuni, isolated in the baseline stool.

Also in this study, the majority of the rifaximin-treated subjects who had Campylobacter jejuni isolated as a sole pathogen at baseline failed treatment and the resulting clinical cure rate for these patients was 23.5% (4/17). In addition to not being different from placebo, the microbiologic eradication rates for subjects with Campylobacter jejuni isolated at baseline were much lower than the eradication rates seen for Escherichia coli.

In an unrelated Phase 1, open-label, pharmacokinetic study of oral XIFAXAN™ Tablets 200 mg taken every 8 hours for 3 days, 15 adult subjects were challenged with Shigella flexneri 2a, of whom 13 developed diarrhea or dysentery and were treated with rifaximin. Although this open-label challenge trial was not adequate to assess the effectiveness of rifaximin in the treatment of shigellosis, the following observations were noted. Eight subjects received rescue treatment with ciprofloxacin either because of lack of response to rifaximin treatment within 24 hours (2), or because they developed severe dysentery (5), or because of recurrence of Shigella flexneri in the stool (1). Five of the 13 subjects received ciprofloxacin although they did not have evidence of severe disease or relapse.

1. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. National Committee for Clinical Laboratory Standards, Sixth Edition, Wayne PA. Approved Standard NCCLS Document M7-A6 January 2003; 23 (2).

Manufactured for Salix Pharmaceuticals, Inc., Raleigh, NC 27615, under license from Alfa Wassermann S.p.A., XIFAXAN™ is a trademark of Salix Pharmaceuticals, Inc., under license from Alfa Wassermann S.p.A., Copyright © Salix Pharmaceuticals, Inc., 6255.00/June 2004 2316-25-04A