Although in vitro studies demonstrated the potential of rifaximin to interact with cytochrome
P450 3A4 (CYP3A4), a clinical drug-drug interaction study demonstrated that rifaximin did not significantly affect
the pharmacokinetics of midazolam either presystemically or systemically. An additional clinical drug-drug
interaction study showed no effect of rifaximin on the presystemic metabolism of an oral contraceptive containing
ethinyl estradiol and norgestimate. Therefore, clinical interactions with drugs metabolized by human cytochrome P450
isoenzymes are not expected.