Rifaximin

Pronunciation: (rif-AX-i-min)
Class: Anti-infective agent

Trade Names

Xifaxan
- Tablets 200 mg
- Tablets 550 mg

Pharmacology

Inhibits bacterial RNA synthesis.

Pharmacokinetics

Absorption

Systemic absorption is low. Mean C _max 3.4 ng/mL; median T _max is 0.8 h; mean AUC 12.3 ng•h/mL. Food delayed T _max from 0.75 h to 1.5 h and increased AUC 2-fold.

Distribution

Moderately bound to plasma proteins (67.5%).

Metabolism

Enzymes responsible for metabolizing rifaximin are unknown.

Elimination

The half-life is 1.8 h. Excreted primarily in feces (97% of administered dose) and 0.32% in the urine.

Special Populations

Renal Function Impairment

Pharmacokinetics have not been studied.

Hepatic Function Impairment

The mean AUC was 2-fold higher in patients with Child-Pugh class C hepatic impairment than in patients with Child-Pugh class A impairment.

Indications and Usage

Treatment of traveler's diarrhea by noninvasive strains of Escherichia coli (200 mg); reduction in risk of overt hepatic encephalopathy (550 mg).

Unlabeled Uses

Irritable bowel syndrome, recurrent Clostridium difficile –associated diarrhea.

Contraindications

Hypersensitivity to any rifamycins or any component of product.

Dosage and Administration

Hepatic Encephalopathy
Adults

PO 550 mg 2 times daily.

Traveler's Diarrhea
Adults and Children 12 y of age and older

PO 200 mg 3 times daily for 3 days.

General Advice

May be taken with or without food.

Storage/Stability

Store tablets at 59° to 86°F.

Drug Interactions

None well documented.

Adverse Reactions

CNS

Dizziness (13%); fatigue (12%); headache (10%); depression (7%); amnesia, confusional state, disturbance in attention, hypoesthesia, memory impairment, tremor (2% to 5%); abnormal dreams, insomnia, malaise, migraine, syncope, weakness (less than 2%).

Dermatologic

Pruritus (9%); rash (5%); clamminess, increased sweating, sunburn (less than 2%).

EENT

Nasopharyngitis (7%); ear pain, motion sickness, nasal passage irritation, pharyngitis, pharyngolaryngeal pain, rhinitis, rhinorrhea, tinnitus (less than 2%).

GI

Nausea (14%); abdominal pain (9%); abdominal pain upper (6%); abdominal tenderness, anorexia, dry mouth, esophageal variceal bleed, lower abdominal pain, stomach discomfort (2% to 5%); abdominal distension, blood in stool, diarrhea, dry lips, dry throat, dysentery, fecal abnormality, gingival disorder, inguinal hernia, loss of taste (less than 2%).

Genitourinary

Blood in urine, choluria, dysuria, hematuria, polyuria, proteinuria, urinary frequency (less than 2%).

Hematologic-Lymphatic

Anemia (8%); lymphocytosis, monocytosis, neutropenia (less than 2%).

Hypersensitivity

Anaphylaxis, angioneurotic edema, exfoliative dermatitis, flushing, pruritus, rash, urticaria (postmarketing).

Lab Tests

Increased AST (less than 2%).

Metabolic-Nutritional

Peripheral edema (15%); dehydration, hyperglycemia, hyperkalemia, hypoglycemia, hyponatremia, weight increase (2% to 5%); weight loss (less than 2%).

Musculoskeletal

Muscle spasms (9%); arthralgia (6%); myalgia, pain in extremity (2% to 5%); neck pain (less than 2%).

Respiratory

Dyspnea (6%); epistaxis, pneumonia, rhinitis, upper respiratory tract infection (2% to 5%); respiratory tract infection (less than 2%).

Miscellaneous

Ascites (11%); pyrexia (6%); cellulitis, chest pain, contusion, fall, flu-like illness, generalized edema, hypotension, pain, procedural pain, vertigo (2% to 5%); hot flashes, pain (less than 2%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

200 mg

Safety and efficacy not established in children younger than 12 y of age.

550 mg

Safety and efficacy not established in patients younger than 18 y of age.

Hypersensitivity

Reactions have been reported, including anaphylaxis, angioneurotic edema, and exfoliative dermatitis.

Hepatic Function

Use with extreme caution in severe hepatic failure because of increased systemic exposure.

C. difficile –associated diarrhea

Consider in patients in whom diarrhea develops subsequent to treatment.

Efficacy

Not found to be effective in treating traveler's diarrhea caused by pathogens other than E. coli or in patients with diarrhea complicated by fever and/or blood in the stool.

Overdosage

Symptoms

None well documented.

Patient Information

• Advise patients to notify health care provider if diarrhea persists more than 24 to 48 h or worsens. Advise the patient to seek medical care for fever and/or blood in the stool.
• Advise patients to contact health care provider as soon as possible if diarrhea occurs after therapy, or if it does not improve or worsens during therapy.
• Inform patients that rifaximin may be taken with or without food.
• Counsel patients that antibacterial drugs, including rifaximin, should only be used to treat bacterial infections. Inform patients that although it is common to feel better early in the course of therapy, to take the medication exactly as directed.

Copyright © 2009 Wolters Kluwer Health.