Interaction with enzyme-inducing medicines

Unintended pregnancies may occur if liver enzyme-inducing medicines are taken with contraception.

CYP3A4 is the main liver enzyme responsible for the breakdown of contraceptives. Enzyme-inducing medicines can decrease the exposure of the contraceptive and speed up its clearance from the body. This results in loss of contraceptive efficacy.

Combined hormonal contraceptives

Combined hormonal contraceptives which include combined oral contraceptives (COCs), combined contraceptive patches and the combined contraceptive vaginal ring are less effective when given with liver enzyme-inducing medicines.

Progestogen-only contraceptives

Progestogen-only pills (POPs) and progestogen-only implants are also less effective when given with liver enzyme-inducing medicines.

Examples of enzyme-inducing medicines

Inducers of CYP3A4 include:

• Antibiotics – rifampicin and rifabutin
• Antiseizure medications- carbamazepine, eslicarbazepine acetate, oxcarbazepine, perampanel, phenobarbital, phenytoin, primidone, rufinamide and topiramate (doses of 200mg daily or higher)
• Antiretrovirals – ritonavir, efavirenz and nevirapine
• St John’s Wort

This list is not exhaustive.

To check whether a medicine induces liver enzymes, refer to sections 4.5 and 5 of the summary of product characteristics.

Clinical considerations

Consider the following points before managing the medicine interaction:

Women taking enzyme-inducing medicines

You may have a woman who is already using an enzyme-inducing medicine and wants to start contraception.

Alternative to enzyme-inducing medicine

It may be appropriate to switch to an alternative to the enzyme-inducing medicine. Discuss this with the specialist e.g. neurologist before making any changes.

Initiating contraception

Follow the recommended contraceptive method and advice for specific medicines below.

Initiating an enzyme-inducing medicine

You may have a woman who is already using a contraceptive and need to initiate an enzyme-inducing medicine. Assess the current method of contraception. Ensure the woman is following the recommended method contraceptive method (see below). If this method is not suitable, see the section on other contraceptive methods and advice for specific medicines below.

Duration of enzyme-inducing medicines

Check the intended duration of the enzyme-inducing medicine as this can affect the choice of contraception. Discuss with the woman if avoiding sex for the duration of the enzyme-inducing medicine is possible.

Recommended contraceptive method

The Faculty of Sexual and Reproductive Healthcare (FSRH) recommends to use depot medroxyprogesterone acetate or intrauterine contraception as first line instead of combined hormonal contraceptives, POPs and progestogen-only implants as they are not affected by enzyme-inducing medicines. This advice applies regardless of the potency or duration of the enzyme-inducing medicine.

Other contraceptive methods

Addition of a barrier method

For a woman using an enzyme-inducing medicine for less than 2 months, it is possible to use a barrier method if the woman wishes to continue using her existing contraception. The barrier method includes using condoms whilst taking the enzyme-inducing medicine and for at least 28 days after stopping it.

This advice applies to all enzyme-inducing medicines (regardless of potency) except the teratogen topiramate.

See the section on antiseizure medications below for advice on using COC pill (containing at least 30 micrograms ethinylestradiol) with the addition of a barrier method.

Two combined oral contraceptive pills

It is possible to use two monophasic combined oral contraceptive pills as a second line option for women taking enzyme-inducing medicines (except the potent inducers rifampicin and rifabutin as well as the teratogen topiramate). See the section on antiseizure medications below for advice on this regimen. This use is off-label.

Contraceptive methods not recommended

It is not recommended to use the following with enzyme-inducing medicines:

• two combined contraceptive patches
• two combined contraceptive rings
• two progestogen-only pills
• two progestogen-only implants

Advice for specific enzyme-inducing medicines

Antibiotics

Use the recommended method of depot medroxyprogesterone acetate or intrauterine contraception in women taking rifampicin or rifabutin as they are potent enzyme inducers.

Antiseizure medications

Use the recommended method of depot medroxyprogesterone acetate or intrauterine contraception in women taking enzyme-inducing antiseizure medications. This method is suitable for women taking topiramate which is a teratogen.

Consider the following alternative contraceptive options for women taking other enzyme-inducing antiseizure medications if clinically necessary.

Addition of a barrier method

This method is suitable for women taking antiseizure medications (except the teratogen topiramate) for a duration of less than two months and a COC pill.

Use a barrier method such as condoms in addition to the COC pill containing at least 30 micrograms ethinylestradiol.

To reduce the risk of contraceptive failure, use the COC pill:

• for 3 weeks or more without a break followed by a shortened pill-free interval of 4 days or;
• for 9 weeks without a break followed by a shortened pill-free interval of 4 days.

Continue the COC pill for a further 28 days after stopping the enzyme-inducing antiseizure medication.

Two combined oral contraceptive pills (off-label use)

This method is suitable for women taking enzyme-inducing medicines (except the teratogen topiramate) for any given duration.

The total combined ethinylestradiol from the two monophasic pills must be at least 50 micrograms per day. An example of a regimen is: using two monophasic COC pills each containing 30 micrograms ethinylestradiol (total 60 micrograms ethinylestradiol).

The BNF lists the monophasic COC pills.

To reduce the risk of contraceptive failure, use the monophasic COC pills:

• for 3 weeks or more without a break followed by a shortened pill-free interval of 4 days
• or for 9 weeks without a break followed by a shortened pill-free interval of 4 days.

Continue both contraceptive pills for a further 28 days after stopping the enzyme-inducing antiseizure medication. An additional barrier method is not required for this method.

Anti-retrovirals

Use the recommended method of depot medroxyprogesterone acetate or intrauterine contraception. Contact the HIV specialist for further advice on interaction management and refer to the University of Liverpool HIV Drug Interaction Checker.

St John’s Wort

Women should avoid taking St John’s Wort with contraceptives. If the individual wishes to continue using St John’s Wort, use the recommended method of intrauterine contraception.

Further reading

NICE CKS Contraception- combined hormonal methods has guidance on starting a COC pill, drug interactions (including women taking enzyme-inducing medicines) and monitoring required for breakthrough bleeding.

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