Rifaximin

Although dosing change is not anticipated, caution should be used in patients with impaired renal function.

An in vitro study suggested that rifaximin is a moderate substrate of P-glycoprotein(P-gp) and metabolized by CYP3A4. It is unknown whether concomitant drugs which inhibit P-gp and/or CYP3A4 can increase the systemic exposure of rifaximin.

Use with caution in patients with severe (Child-Pugh C) hepatic impairment and in patients with MELD (Model for End-Stage Liver Disease) score >25.

In healthy subjects, co-administration of a single dose of ciclosporin (600 mg), a potent P-glycoprotein inhibitor, with a single dose of rifaximin (550 mg) resulted in 83-fold and 124-fold increases in rifaximin mean C_max and AUC_∞. The clinical significance of this increase in systemic exposure is unknown.

Both decreases and increases in international normalized ratio have been reported in patients maintained on warfarin and prescribed rifaximin. If co-administration is necessary, the international normalized ratio should be carefully monitored with the addition or withdrawal of rifaximin. Adjustments in the dose of oral anticoagulants may be necessary.

There is no or limited data from the use of rifaximin in pregnant women. Animal studies showed transient effects on ossification and skeletal variations in the foetus. The clinical relevance of these findings in humans is unknown. As a precautionary measure, use of rifaximin during pregnancy is not recommended.

It is unknown whether rifaximin/metabolites are excreted in human milk. A risk to the breast-fed child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from rifaximin therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility

Animal studies do not indicate direct or in direct harmful effects with respect to male and female fertility.

In clinical controlled trials dizziness and somnolence have been reported but rifaximin has negligible influence on the ability to drive and use machines.