Which Antibiotics Decrease Oral Contraceptive Efficacy
Rifampin and rifabutin are the only antibiotics that definitively decrease the efficacy of oral contraceptives, while broad-spectrum antibiotics (including tetracyclines, penicillins, and cephalosporins) do NOT reduce contraceptive effectiveness. 1
Rifampin and Rifabutin: The Only Proven Culprits
Rifampin is a potent inducer of hepatic cytochrome P450 enzymes that accelerates the metabolism of both estrogen and progestins, substantially reducing their systemic exposure and contraceptive efficacy. 2, 3
Management for Rifampin/Rifabutin Users:
Add barrier contraception (condoms) consistently during rifampin therapy and for at least one full menstrual cycle after completing treatment for short-term courses 2
Switch to depot medroxyprogesterone acetate (DMPA/Depo-Provera), which is classified as Category 1 with rifampin—meaning its effectiveness is NOT decreased by rifampin and remains a reliable hormonal option 1, 2
Switch to a copper IUD for long-term rifampin therapy, as it is unaffected by enzyme induction and provides highly effective non-hormonal contraception 2
All other hormonal methods are compromised: combined oral contraceptives, patches, rings, implants, and progestin-only pills all have reduced efficacy with rifampin 1, 2
Broad-Spectrum Antibiotics: No Interaction
The tetracycline class of antibiotics has NOT been shown to reduce the effectiveness of oral contraceptives when taken concomitantly. 1
Broad-spectrum antibiotics, antifungals, and antiparasitics are classified as Category 1 (no restrictions) for use with all forms of hormonal contraception, including combined oral contraceptives, progestin-only pills, DMPA, and implants 1
This includes commonly prescribed antibiotics such as amoxicillin, ampicillin, doxycycline, tetracycline, azithromycin, and fluoroquinolones 1
Griseofulvin: Possible but Uncertain Interaction
Griseofulvin is mentioned alongside rifampin as potentially interacting with oral contraceptives, though the evidence is less robust. 1
The 2016 American Academy of Dermatology guidelines list griseofulvin as an antiinfective that may lessen oral contraceptive effectiveness 1
Consider backup contraception when prescribing griseofulvin, though the interaction is not as well-established as with rifampin 1
Critical Clinical Pitfalls to Avoid
The widespread misconception that common antibiotics reduce oral contraceptive efficacy is NOT supported by evidence and leads to unnecessary anxiety and potentially unwanted pregnancies from discontinuing reliable contraception. 1, 2
Do NOT advise backup contraception for patients taking tetracyclines, penicillins, cephalosporins, macrolides, or fluoroquinolones with oral contraceptives 1
Rifampin is unique among antibiotics—extensive literature reviews find no definitive evidence of decreased contraceptive effectiveness with any antibiotic except rifampin (and possibly griseofulvin) 2
The theoretical concern about antibiotics disrupting gut flora and interfering with enterohepatic recirculation of ethinyl estradiol has not been substantiated in clinical studies 1
Other Important Drug Interactions (Non-Antibiotics)
While not antibiotics, be aware that certain anticonvulsants (phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine) and some antiretrovirals (NNRTIs, ritonavir-boosted protease inhibitors) also reduce oral contraceptive efficacy through enzyme induction. 1