Xifaxan

Rifaximin may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

1. nausea
2. stomach pain
3. dizziness
4. excessive tiredness
5. headache
6. muscle tightening
7. joint pain

Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately:

1. watery or bloody diarrhea that may occur along with stomach cramps and fever during your treatment or for 2 months afterward
2. hives
3. rash
4. itching
5. difficulty breathing or swallowing
6. swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
7. hoarseness

Rifaximin may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

XIFAXAN tablets contain rifaximin, a non-aminoglycoside semi-synthetic, nonsystemic antibiotic derived from rifamycin SV. Rifaximin is a structural analog of rifampin. 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-(epoxypentadeca-[1,11,13]trienimino)benzofuro[4,5-e]pyrido[1,2-á]-benzimidazole-1,15(2H)-dione,25-acetate. The empirical formula is C43H51N3O11 and its molecular weight is 785.9. The chemical structure is represented below:

XIFAXAN tablets for oral administration are film-coated and contain 200 mg or 550 mg of rifaximin.

Inactive Ingredients

Each 200 mg tablet contains colloidal silicon dioxide, disodium edetate, glycerol palmitostearate, hypromellose, microcrystalline cellulose, propylene glycol, red iron oxide, sodium starch glycolate, talc, and titanium dioxide.

Each 550 mg tablet contains colloidal silicon dioxide, glycerol palmitostearate, microcrystalline cellulose, polyethylene glycol/macrogol, polyvinyl alcohol, red iron oxide, sodium starch glycolate, talc, and titanium dioxide.

No specific information is available on the treatment of overdosage with XIFAXAN. In clinical studies at doses higher than the recommended dose (greater than 600 mg per day for TD, greater than 1100 mg per day for HE or greater than 1650 mg per day for IBS-D), adverse reactions were similar in subjects who received doses higher than the recommended dose and placebo. In the case of overdosage, discontinue XIFAXAN, treat symptomatically, and institute supportive measures as required.

Persistent Diarrhea

For those patients being treated for travelers' diarrhea, discontinue XIFAXAN if diarrhea persists more than 24-48 hours or worsens. Advise the patient to seek medical care for fever and/or blood in the stool [see WARNINGS AND PRECAUTIONS].

Clostridium difficile-Associated Diarrhea

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including XIFAXAN, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibiotics alters the normal flora of the colon which may lead to C. difficile. Patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If diarrhea occurs after therapy or does not improve or worsens during therapy, advise patients to contact a physician as soon as possible [see WARNINGS AND PRECAUTIONS].

Administration with Food

Inform patients that XIFAXAN may be taken with or without food.

Antibacterial Resistance

Counsel patients that antibacterial drugs including XIFAXAN should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When XIFAXAN is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by XIFAXAN or other antibacterial drugs in the future.

Severe Hepatic Impairment

Inform patients with severe hepatic impairment (Child-Pugh Class C) that there is an increase in systemic exposure to XIFAXAN [see WARNINGS AND PRECAUTIONS].

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Xifaxan is a prescription medication used to treat traveler’s diarrhea and irritable bowel syndrome (IBS) with diarrhea. It is also used to reduce the recurrence of hepatic encephalopathy in adults. Xifaxan should not be used if diarrhea is accompanied by fever or blood in the stool.

Xifaxan belongs to a group of drugs called antibiotics. These drugs work by stopping the growth of bacteria that cause diarrhea and by stopping the growth of bacteria that produce toxins that worsen liver disease.

This medication comes in tablet form and is taken 2 to 3 times a day, depending on the indication. It can be taken with or without food.

Common side effects of Xifaxan include headache, swelling of the extremities, nausea, dizziness, and fatigue.

Xifaxan can also cause dizziness. Do not drive or operate heavy machinery until you know how Xifaxan affects you.

Xifaxan is part of the drug class:

• Other antibiotics for topical use

Take Xifaxan exactly as prescribed.

Xifaxan comes in tablet form and is taken 2 to 3 times daily.

It may be taken with or without food.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of Xifaxan at the same time.

• Store Xifaxan at room temperature.
• Keep this and all medicines out of the reach of children.

• Like other rifamycins, rifaximin inhibits RNA synthesis in susceptible bacteria by binding to the β subunit of bacterial DNA-dependent RNA polymerase.1 11

• Escherichia coli: Active in vitro and in clinical infections (i.e., infectious diarrhea) against enterotoxigenic E. coli (ETEC) and enteroaggregative E. coli (EAEC).1 11 26 31 33 Although clinical importance unknown, also active in vitro against other E. coli strains, including enterohemorrhagic, enteroinvasive, enteropathogenic, and Hep-2 adherent strains.2 11 33

• Other bacteria: Although clinical importance unknown, has some in vitro activity against Aeromonas,2 11 26 31 Bacillus,2 11 Bacteroides,2 11 Bifidobacterium,2 11 Campylobacter jejuni,2 11 26 Enterobacter cloacae,2 11 Fusobacterium,2 11 Helicobacter,2 11 Klebsiella pneumoniae,2 11 Plesiomonas shigelloides,2 11 26 31 Peptostreptococcus,2 11 Prevotella,2 11 Salmonella,2 11 26 Shigella (including S. dysenteriae, S. flexneri, S. sonnei),2 11 26 33 Vibrio,2 11 31 32 and Yersinia enterocolitica.2 11

• Resistance to rifaximin has been produced in vitro in E. coli (ETEC and EAEC strains).29 Rifaximin resistance also reported in various clinical isolates of E. coli from patients with travelers' diarrhea or inflammatory bowel disease,26 27 28 30 including some patients who previously received the drug.27 Clinical isolates of Campylobacter,26 28 Salmonella,31 and Shigella28 31 with in vitro resistance to rifaximin also reported. Although some strains of Clostridium difficile susceptible to rifaximin in vitro, clinical isolates resistant to rifaximin (some with high-level resistance) reported.34 35

• Resistance generally is associated with mutations in the rpoB gene1 27 34 that change the binding site on DNA-dependent RNA polymerase and decrease rifaximin binding affinity.1 Presence of efflux pumps also appears to cause or contribute to development of rifaximin resistance in some organisms.27

• Cross-resistance between rifaximin and other classes of anti-infectives not observed.1

• Tell all of your health care providers that you take Xifaxan. This includes your doctors, nurses, pharmacists, and dentists.
• Do not use longer than you have been told. A second infection may happen.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Xifaxan is contraindicated in patients with a hypersensitivity to rifaximin, any of the rifamycin antimicrobial agents, or any of the components in Xifaxan. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema, and anaphylaxis [see Adverse Reactions ( 6.2)] .

Take Xifaxan exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take Xifaxan with or without food.

Use this medicine for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antibiotics. Rifaximin will not treat a viral infection such as the flu or a common cold.

Call your doctor if your symptoms do not improve after 24 hours, or if they get worse while using this medicine.

Xifaxan does not treat all bacterial forms of traveler's diarrhea.

Store at room temperature away from moisture and heat.

Usual Adult Dose for Traveler's Diarrhea:

200 mg orally 3 times a day for 3 days

Comments:
-Should not use in patients with diarrhea complicated by fever and/or blood in the stool or diarrhea caused by pathogens other than Escherichia coli

Use: For the treatment of travelers' diarrhea due to noninvasive strains of E coli

Usual Adult Dose for Hepatic Encephalopathy:

550 mg orally twice a day

Comments:
-In trials, lactulose was used concomitantly in 91% of patients; differences in treatment effect of patients not using concomitant lactulose could not be assessed.

Use: For reduction in risk of overt hepatic encephalopathy recurrence

Usual Pediatric Dose for Traveler's Diarrhea:

12 years or older: 200 mg orally 3 times a day for 3 days

Comments:
-Should not use in patients with diarrhea complicated by fever and/or blood in the stool or diarrhea caused by pathogens other than E coli

Use: For the treatment of travelers' diarrhea due to noninvasive strains of E coli