Is there an interaction between Rifaximine and oral contraceptives like Minulet (Ethinyl Estradiol and Gestodene)?

No Clinically Significant Interaction Between Rifaximin and Oral Contraceptives

Rifaximin does not interact with oral contraceptives like Minulet (ethinyl estradiol and gestodene), and you can safely take both medications together without requiring additional contraceptive precautions. 1, 2

Key Evidence

Rifaximin is Different from Other Rifamycins

The critical distinction is that rifaximin is NOT the same as rifampin or rifabutin, which DO significantly reduce oral contraceptive effectiveness. 3

• Rifampin and rifabutin are potent enzyme inducers that accelerate the metabolism of oral contraceptives through hepatic CYP3A4 induction, leading to subtherapeutic hormone levels and contraceptive failure 3, 4
• Women taking rifampin or rifabutin should add barrier contraception methods 3
• Rifaximin, however, has minimal systemic absorption (less than 0.4% bioavailability) and acts primarily in the gastrointestinal tract 1

Direct Clinical Evidence for Rifaximin

A well-designed pharmacokinetic study specifically evaluated rifaximin's effect on oral contraceptives:

• 28 healthy women received ethinyl estradiol 0.07 mg/norgestimate 0.5 mg alone, then with rifaximin 200 mg three times daily for 3 days 2
• No changes were observed in the pharmacokinetics of ethinyl estradiol, norgestrel, or 17-deacetyl norgestimate when administered with rifaximin 2
• The 90% confidence intervals for all bioavailability parameters ranged from 86-118%, well within the predefined equivalence range of 80-125% 2
• This confirms no clinically meaningful interaction 2

FDA Drug Label Confirmation

The FDA-approved rifaximin drug label explicitly states:

• "Results showed that the pharmacokinetics of single doses of ethinyl estradiol and norgestimate were not altered by rifaximin" 1
• In vitro studies showed rifaximin did not inhibit CYP3A4 at therapeutic concentrations 1
• While rifaximin showed CYP3A4 induction at 0.2 µM in vitro, clinical studies with midazolam (a sensitive CYP3A4 substrate) showed no clinically meaningful effect 1

Important Caveats

Dosing Regimen Considerations

• The contraceptive interaction study used rifaximin 200 mg three times daily for 3 days (the travelers' diarrhea regimen) 1, 2
• The FDA label notes that the effect of rifaximin 550 mg twice daily (hepatic encephalopathy regimen) on oral contraceptives was not specifically studied 1
• However, given the minimal systemic absorption and lack of CYP3A4 inhibition, no interaction would be expected at higher doses 1

Don't Confuse Rifamycins

This is a common clinical pitfall: Healthcare providers may incorrectly assume all rifamycin antibiotics interact similarly with oral contraceptives 4

• Only rifampin and rifabutin require additional contraceptive precautions 3, 4
• Rifaximin and rifalazil do not alter hormone pharmacokinetics 4
• The tetracycline class of antibiotics also does NOT reduce oral contraceptive effectiveness, despite widespread misconception 3, 5

General Antibiotic Misconceptions

While not directly relevant to rifaximin, it's worth noting that the concern about broad-spectrum antibiotics reducing oral contraceptive efficacy is largely unfounded 3, 5:

• Only rifampin and griseofulvin are documented to reduce oral contraceptive effectiveness 3
• Despite case reports, clinical pharmacokinetic studies have failed to demonstrate that common antibiotics alter oral contraceptive blood levels 5, 6

Clinical Bottom Line

You can confidently continue taking Minulet while on rifaximin without any additional contraceptive measures. 1, 2 The evidence is clear and direct, with both pharmacokinetic data and FDA labeling supporting the absence of interaction. No backup contraception is needed, and no dose adjustments are required for either medication.