Drugs that affect hormonal contraceptives

Most significant drug interactions with hormonal contraceptives are due to induction of cytochrome P450 liver enzymes. Enzyme-inducing drugs increase the metabolism of both estrogens and progestogens, and decrease effectiveness of all hormonal contraceptives other than levonorgestrel-releasing intrauterine contraceptive devices (IUDs) and depot medroxyprogesterone. Copper IUDs (which are nonhormonal contraceptives) are also unaffected by enzyme-inducing drugs.

Note: Levonorgestrel-releasing or copper IUDs and depot medroxyprogesterone are effective in individuals taking enzyme-inducing drugs.

Enzyme-inducing drugs that decrease the effectiveness of hormonal contraceptives include:

the antiepileptics carbamazepine, oxcarbazepine, perampanel (at doses of more than 8 mg daily), phenobarbital (phenobarbitone), phenytoin, primidone, rufinamide and topiramate (at any dose)
some drugs used to treat viral infections such as HIV, viral hepatitis and coronavirus (COVID-19)—see the University of Liverpool (UK) Drug-Drug Interaction Resource
the antibiotics rifampicin and rifabutin
some complementary medicines (eg St John’s wort)
other drugs (eg aprepitant, modafinil, bosentan).

Note: The only antibiotics that interact with hormonal contraceptives are those that induce liver enzymes (ie rifampicin and rifabutin).

Contraception in individuals taking drugs that induce liver enzymes summarises the reliability of contraception for individuals taking drugs that induce liver enzymes and the recommended actions and alternatives.

Table 1. Contraception in individuals taking drugs that induce liver enzymes
Contraceptive method	Recommended action [NB1]
combined oral contraceptive (COC)	use alternative method if possible [NB2] if a COC is used, advise all of the following: increase the daily dose of ethinylestradiol to at least 50 micrograms (ie use two tablets of a COC containing 30 micrograms of ethinylestradiol, or one COC containing 30 micrograms plus one containing 20 micrograms of ethinylestradiol) [NB3] use the active pills continuously (no hormone-free interval), or for 9 to 12 consecutive weeks followed by a shortened (4-day) hormone-free interval (see Tailored regimens) consider using a barrier method (eg condoms) as well as the COC, because contraceptive failure is still possible
vaginal ring	use alternative method [NB2]
progestogen-only oral contraceptive	use alternative method [NB2]
etonogestrel implant	use alternative method [NB2]
oral emergency contraception (levonorgestrel or ulipristal)	use a copper IUD if a copper IUD is declined or unsuitable, use a double dose of levonorgestrel emergency contraception [NB4]
levonorgestrel-releasing or copper IUD	no action required (effective)
depot medroxyprogesterone	no action required (effective)
Note: IUD = intrauterine contraceptive device NB1: The effectiveness of contraceptives may be reduced during therapy with, and for at least 4 weeks after stopping, enzyme-inducing drugs; any recommended actions should be continued for this entire duration. NB2: In individuals taking enzyme-inducing drugs, effective contraception is provided by levonorgestrel-releasing or copper IUDs, and depot medroxyprogesterone. NB3: Do not use a single combined hormonal pill containing 50 micrograms of ethinylestradiol for individuals taking drugs that induce liver enzymes because it does not contain sufficient progestogen. NB4: A double dose of levonorgestrel (3 mg, ie 2 × 1.5 mg tablets) can be used; the effectiveness in this situation is unknown and this dose is not approved by the Australian Therapeutic Goods Administration (TGA). A double dose of ulipristal is not advised.

Although griseofulvin does not induce cytochrome P450 liver enzymes, the effectiveness of hormonal contraceptives may be reduced by concurrent use. The recommended actions in Contraception in individuals taking drugs that induce liver enzymes apply while taking, and for at least 28 days after stopping, griseofulvin.

Efficacy of combined hormonal contraceptives, all progestogen-only contraceptive pills (POPs) and the etonogestrel implant may be reduced in individuals taking lamotrigine; some studies have shown a small reduction in plasma levonorgestrel concentrations and an increase in follicle stimulating hormone (FSH) and luteinising hormone (LH) concentrations. The clinical significance is not known but additional reliable use of condoms is advisable for patients using lamotrigine and combined hormonal contraception, progestogen-only pills or the etonogestrel implant. Contraceptive effectiveness of depot medroxyprogesterone acetate and levonorgestrel-releasing-IUDs is not expected to be affected by lamotrigine.