Drug Information

Drug Interaction:

Clinical studies with interaction with drugs metabolised by human cytochrome P450 isoenzymes are not expected

Rifaximin did not significantly affect the pharmacokinetics of midazolam either presystemically or systemically

No effect of rifaximin on the presystemic metabolism of an oral anticontraceptive containing ethinyl estradiol and norgestimate

Indication:

XIFAXANR (rifaximin) Tablets

Initial U.S. Approval: 2004

To reduce the development of drug-resistant bacteria and maintain

the effectiveness of XIFAXAN and other antibacterial drugs,

XIFAXAN should be used only to treat or prevent infections that are proven

or strongly suspected to be caused by bacteria.

RECENT MAJOR CHANGES

Indications and Usage, Hepatic Encephalopathy (1.2) 03/2010

Dosage and Administration, Hepatic Encephalopathy (2.2) 03/2010

LIST OF DRUGS DURING 2006

Sr.No- 113

Name of the Drug- Rifaximine 200mg tablets Pharmacological Classification- For infections diarrheoa in adults

Date of Approval- 28-08-2006

Approved by U.S.FDA on 30-12-2006 (Ref- FDA approved List)

New Drugs Approved by (DCI) Drug Controller GENERAL - India For Marketing

(Ref- IDMA Publication)

Name of Drug Indication Date of Approval

1.Rifaximin 400mg 18-07-2009

Addl.Indcn

For the treatment of Hepatic Encephalopathy

2.Rifaximin Dispersible tablet 200mg 26-11-2009

For infections Diarrhea in adults

3.Rifaximin 200mg tablets 28-08-2006

For infections Diarrhea in adults

Travellers diarrhea

Adverse Reaction:

Cardiovascular- chest pain, hot flushes CNS - abnormal dreams, dizziness, migraine, syncope

Dermatologic- clamminess, increased sweating, rash, dry lips, dry throat, dysentry

GU- blood in urine, dysuria, hematuria, polyuria, urinary frequency

Hematologic- lymphocytosis, monocytosis, neutropenia

Musculoskeletal - arthalgia, muscle spasms, myalgia, neck pain

Contra-Indications:

CONTRAINDICATIONS

History of hypersensitivity to rifaximin, rifamycin antimicrobial agents,

or any of the components of XIFAXAN

WARNINGS AND PRECAUTIONS

Travelers Diarrhea Not Caused by E. coli: XIFAXAN was not effective

in diarrhea complicated by fever and/or blood in the stool or diarrhea

due to pathogens other than E. coli.

If diarrhea symptoms get worse or persist for more than 24-48 hours,

discontinue XIFAXAN and consider alternative antibiotics

Clostridium difficile-Associated Diarrhea: Evaluate if diarrhea occurs after

therapy or does not improve or worsens during therapy

Hepatic Impairment: Use with caution in patients with severe (Child-Pugh C)

hepatic impairment

Concomitant P-glycoprotein inhibitor: Caution should be exercised when

concomitant use of rifaximin and a P-glycoprotein inhibitor is needed

Dosages/ Overdosage Etc:

Indication-

Travelers diarrhea

Dosage-

200mg taken 3 times a day for 3 days

INDICATIONS AND USAGE

XIFAXAN is a rifamycin antibacterial indicated for:

The treatment of patients (. 12 years of age) with travelers¡¦ diarrhea (TD) caused

by noninvasive strains of Escherichia coli

Reduction in risk of overt hepatic encephalopathy (HE) recurrence in

patients . 18 years of age

Limitations of Use in TD:

Do not use in patients with diarrhea complicated by fever or blood

in the stool or diarrhea due to pathogens other than Escherichia coli

DOSAGE AND ADMINISTRATION

Travelers¡¦ diarrhea: One 200 mg tablet taken orally three times a day for 3 days,

with or without food

Hepatic encephalopathy: One 550 mg tablet taken orally two times a day,

with or without food

DOSAGE FORMS AND STRENGTHS

200 mg and 550 mg tablets

Patient Information:

PATIENT COUNSELING INFORMATION

1. 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

2. 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

2. Administration with Food

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

3. 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.

4 Severe Hepatic Impairment

Patients should be informed that in patients with severe hepatic impairment

(Child-Pugh C) there is an increase in systemic exposure to XIFAXAN .

Manufactured for:

Salix Pharmaceuticals, Inc.

Raleigh, NC 27615

XIFAXAN® is a trademark of Salix Pharmaceuticals, Inc., under license

Pharmacology/ Pharmacokinetics:

Pharmacodynamics-

Rifaxim acts by binding to the beta-subunit of the bacterial DNA-dependent

RNA polymerase resulting in inhibition of bacterial RNA synthesis. It has a

broad spectrum of activity against aerobic and anaerobic gram-positive

and gram-negative micro-organisms.

Pharmacokinetics-

Upon oral administration , rifaximin gets poorly absorbed 0.4% in human

gatro-intestinal tract with high luminal activity. It is primarily excreted

unchanged in the feces. The bioavailabilty of rifaximin varies throughout

the gastro-intestinal tract in connection with the solubilization because

of its highly detectable fecal concentrationdue to its poor absorption.

Interaction with Food:

Rifaximin can be administered with or without food

Pregnancy and lactation:

USE IN SPECIFIC POPULATIONS

1. Pregnancy

Pregnancy Category C

There are no adequate and well controlled studies in pregnant women. Rifaximin has

been shown to be teratogenic in rats and rabbits at doses that caused maternal

toxicity. XIFAXAN tablets should be used during pregnancy only if the potential

benefit justifies the potential risk to the fetus.

Administration of rifaximin to pregnant rats and rabbits at dose levels that caused

2. Nursing Mothers

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, 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.

3. Pediatric Use

The safety and effectiveness of XIFAXAN 200 mg in pediatric patients with

travelers’ diarrhea lessthan 12 years of age have not been established.

The safety and effectiveness of XIFAXAN 550 mg for HE have not been

established in patients < 18

4. Geriatric Use

Clinical studies with rifaximin 200 mg for travelers’ diarrhea did not include

sufficient numbers of patients aged 65 and over to determine whether they

respond differently than younger subjects.

Rifaximin - @-Antibacterial- (Aug 2006)

Drug Interaction

Indication

Adverse Reaction

Contra-Indications

Dosages/ Overdosage Etc

Patient Information

Pharmacology/ Pharmacokinetics

Interaction with Food

Pregnancy and lactation