About XIFAXAN

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Product Description

XIFAXAN® Tablets contain rifaximin, a semi-synthetic, nonsystemic antibiotic. The chemical name for rifaximin is (2S,16Z,18E,20S,21S,22R,23R,24R,25S,26S,27S,28E)-5,6,21,23,25- pentahydroxy-27-methoxy-2,4,11,16,20,22,24,26-octamethyl-2,7-( poxypentadeca-[1,11,13] trienimino)benzofuro[4,5-e]pyrido[1,2-α]-benzimidazole-1,15(2H)-dione,25-acetate. The empirical formula is C₄₃H₅₁N₃O₁₁ and its molecular weight is 785.9.

XIFAXAN Tablets for oral administration are film-coated and contain 200 mg of rifaximin. Inactive ingredients are colloidal silicon dioxide, disodium edetate, glycerol palmitostearate, hypromellose, microcrystalline cellulose, propylene glycol, red iron oxide, sodium starch glycolate, talc, and titanium dioxide.

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Contraindications and Warnings

Contraindications

XIFAXAN Tablets are contraindicated in patients with a hypersensitivity to rifaximin, any of the rifamycin antimicrobial agents, or any of the components in XIFAXAN Tablets.

Warnings

XIFAXAN Tablets were not found to be effective in patients with diarrhea complicated by fever and/or blood in the stool or diarrhea due to pathogens other than Escherichia coli.

XIFAXAN Tablets are not effective in cases of travelers’ diarrhea due to Campylobacter jejuni. The effectiveness of XIFAXAN Tablets in travelers’ diarrhea caused by Shigella spp. and Salmonella spp. has not been proven. XIFAXAN Tablets should not be used in patients where Campylobacter jejuni, Shigella spp., or Salmonella spp. may be suspected as causative pathogens.

XIFAXAN Tablets should be discontinued if diarrhea symptoms get worse or persist more than 24-48 hours and alternative antibiotic therapy should be considered.

Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to lifethreatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is the primary cause of "antibiotic-associated colitis."

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile.

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Precautions

General

The use of antibiotics may promote the overgrowth of nonsusceptible organisms. Should superinfection occur during therapy, appropriate measures should be taken.

Information for Patients

Patients should be advised that XIFAXAN Tablets may be taken with or without food. Patients should be advised that XIFAXAN Tablets should be discontinued if their diarrhea persists more than 24-48 hours or worsens, or if they have fever and/or blood in the stool that they should seek medical care.

Drug-Drug Interactions

Although in vitro studies demonstrated the potential of rifaximin to interact with cytochrome P450 3A4 (CYP3A4), a clinical drug-drug interaction study demonstrated that rifaximin did not significantly affect the pharmacokinetics of midazolam either presystemically or systemically. An additional clinical drug-drug interaction study showed no effect of rifaximin on the presystemic metabolism of an oral contraceptive containing ethinyl estradiol and norgestimate. Therefore, clinical interactions with drugs metabolized by human cytochrome P450 isoenzymes are not expected.

Carcinogenesis, Mutagenesis. Impairment of Fertility

Carcinogenicity studies were not conducted. Rifaximin was not genotoxic in the bacterial reverse mutation assay, chromosomal aberration assay, rat bone marrow micronucleus assay, and the CHO/HGPRT mutation assay. There was no effect on fertility in male or female rats following the administration of rifaximin at doses up to 300 mg/kg (approximately 5 times the clinical dose, adjusted for body surface area).

Pregnancy-Teratogenic Effects (Pregnancy Category C)

Rifaximin was teratogenic in rats at doses of 150 to 300 mg/kg (approximately 2.5 to 5 times the clinical dose, adjusted for body surface area) and in rabbits at doses of 62.5 to 1000 mg/kg (approximately 2 to 33 times the clinical dose, adjusted for body surface area). These effects include cleft palate, agnatha, jaw shortening, hemorrhage, eye partially open, small eyes, brachygnathia, incomplete ossification, and increased thoracolumbar vertebrae. There are no adequate and well controlled studies in pregnant women. XIFAXAN Tablets should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.

Use During Lactation

It is not known whether rifaximin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from XIFAXAN® Tablets, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of XIFAXAN Tablets in pediatric patients less than 12 years of age have not been established.

Geriatric Use

Clinical studies of XIFAXAN® Tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects.

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Adverse Reactions

The safety of XIFAXAN Tablets 200 mg taken three times a day (TID) was evaluated in 320 patients in two placebo-controlled clinical trials with 95% of patients receiving at least three days of treatment with XIFAXAN Tablets. All adverse events for XIFAXAN Tablets 200 mg TID that occurred at a frequency = 2% in the two placebo-controlled trials combined are provided in Table 2. (These include adverse events that may be attributable to the underlying disease.)

All Adverse Events With an Incidence ≥2% Among Patients Receiving XIFAXAN Tablets, 600mg/day, in Placebo-Controlled Studies

MedDRA Preferred Term	Number (%) of Patients
	XIFAXAN Tablets, 600mg/day (N = 320)	Placebo N = 228
Flatulence Headache Abdominal Pain NOS Rectal Tenesmus Defecation Urgency Nausea Constipation Pyrexia Vomiting NOS	36 (11.3%) 31 (9.7%) 23 (7.2%) 23 (7.2%) 19 (5.9%) 17 (5.3%) 12 (3.8%) 10 (3.1%) 7 (2.2%)	45 (19.7%) 21 (9.2%) 23 (10.1%) 20 (8.8%) 21 (9.2%) 19 (8.3%) 8 (3.5%) 10 (4.4%) 4 (1.8%)

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Overdosage

No specific information is available on the treatment of overdosage with XIFAXAN Tablets. In clinical studies at doses higher than the recommended dose (> 600 mg/day), adverse events were similar to the recommended dose (200 mg taken three times a day) and to placebo. In the case of overdosage, discontinue XIFAXAN Tablets, treat symptomatically, and institute supportive measures as required.

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Dosage and Administration

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.

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How Supplied

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

NDC 65649-301-41 Bottles of 100 tablets

NDC 65649-301-05 Carton of 100 Tablets, Unit Dose

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

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