Rifaximin

Antibiotic Class: 

Rifamycin (structural analogue of rifampin)

Antimicrobial Spectrum:

Escherichia coli, Clostridium difficile

Mechanism of Action:

Rifamycins bind to and inhibit DNA-dependant RNA polymerase

Pharmacodynamics:

Most likely concentration-dependant killing (peak/MIC and AUC/MIC)

Pharmacokinetics:

Cmax (fasting): 0.004 mcg/L; Tmax: 1.2 ± 0.5 hours; Half-life: 5.8 ± 4.3 hours; AUC: 0.018 (mcg*h/mL)

    * Note: Rifaximin should NOT be used for systemic infection since less than 0.4% is absorbed after oral administration

Adverse Effects:

CNS: headache was seen with both rifaximin and placebo in clinical trials

Allergic: hypersensitivity reactions, allergic dermatitis, and angioneurotic edema have been described uncommonly

Dosage:

PO: 200 mg tablets

Dosing in adults:

For Traveler’s diarrhea: 200mg tablet PO q8h

Dosing in pediatrics:

Not FDA approved for patients < 12 years of age

Disease state based dosing:

Hepatic failures: No change in dosing, due to limited systemic absorption

Renal failures: Not studied in this population. No change expected due to limited systemic absorption

Contraindications/Warnings/Precautions:

NOT effective in patients with Traveler’s diarrhea due to Campylobacter jejuni, and unproven when caused by Shigella spp. and Salmonella spp.

Rifaximin should be discontinued if diarrhea persists or worsens over 24 to 48 hours 

Drug Interactions:

Rifamixin, like other rifamycins, is an inducer of CYP3A4 isoenzymes. Little effect is expected, due to limited systemic absorption

Limited drug-drug interaction studies have shown the following:

Midazolam: No difference in midazolam systemic exposure when coadministered either IV or PO with rifaximin.

Oral contraception: Single dose studies have been conducted with rifaximin and 0.07 ethinyl estradiol and 0.5mg norgestimate, and showed that the kinetics of the oral contraceptive were not altered.

Pregnancy:

Category C: Risk unknown. Human studies inadequate.

Monitoring Requirements:

Efficacy: Resolution of diarrhea in Traveler’s diarrhea

Brand names/Manufacturer:

Xifaxan - Salix Pharmaceuticals, USA

Dermodis – Farmades, Italy

Flonorm - Schering-Plough, Mexico

Normix - Alfa Wassermann, Czech Republic, Hungary, Italy

Rifacol - Prodotti Formenti, Italy, Germany

Spiraxin - Bama, Spain

Zaxine - Cantabria, Spain