Drug Interactions and Contraceptive Failure

Some medicines speed the metabolism of contraceptive steroids through liver enzyme induction and lower contraceptive effectiveness. Pregnancy in a patient on a hormonal method and one of these medicines raises the question of an interaction. Methods that do not depend on liver metabolism are not affected, including depot medroxyprogesterone acetate, the copper device and the levonorgestrel intrauterine device.

Interacting medicines. Rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital, primidone, topiramate, oxcarbazepine, efavirenz, nevirapine, ritonavir and ritonavir-boosted protease inhibitors, griseofulvin and St John’s wort.

Not interacting with oral or implant methods. Dolutegravir, raltegravir, abacavir, tenofovir, zidovudine, lamivudine, emtricitabine, etravirine, rilpivirine and most other antibiotics.

Effect in the other direction. Combined pills lower the level of lamotrigine, which can loosen seizure control.

History. Full medication list including herbal products, start and stop dates, method, adherence, vomiting and diarrhoea, pregnancy symptoms, unprotected sex.

Differential diagnosis. Interaction, missed or late doses, malabsorption from vomiting or diarrhoea over 2 days, device expulsion, incorrect use, and pregnancy present before the method.

Investigations. Pregnancy test, with ultrasound to exclude ectopic pregnancy when there is pain or bleeding. Device check if relevant.

Eligibility categories.

Pregnant. Manage the pregnancy as one during method use: confirm, locate, exclude ectopic pregnancy and remove an implant or intrauterine device where appropriate.

Not pregnant and unprotected sex in the last 5 days. Offer emergency contraception. The copper intrauterine device inserted within 5 days is the most effective and is not affected by interactions. If only pills are available, levonorgestrel 1.5 mg orally as a single dose within 120 hours is used, and a dose of 3 mg is considered for patients taking enzyme inducers. Ulipristal acetate 30 mg is less effective with enzyme inducers.

Change of method. Switch to an unaffected method.

• DMPA 150 mg intramuscularly every 13 weeks, or 104 mg subcutaneously every 13 weeks. Repeat injection allowed up to 4 weeks late.
• Copper device (up to 12 years for the T 380A) or levonorgestrel 52 mg device (5 years).
• Norethisterone enanthate 200 mg intramuscularly every 8 weeks, up to 2 weeks late, is a category 2 choice.

If the patient stays on a pill or implant. Add condoms for the whole course of the interacting medicine and for 28 days after stopping it.

Treatment course dependent. Short courses of rifampicin or rifabutin still need backup for the duration plus 28 days.

Review of the interacting medicine. Where an alternative non-inducing medicine exists, such as dolutegravir in place of efavirenz, discuss with the treating clinician.

Documentation. Record the interaction and the plan.

Follow up. Review in 2 to 4 weeks after switching. Confirm adherence and absence of pregnancy.

Method decisions. For a patient who will need long term treatment with an enzyme inducer, favour DMPA, a copper device or a levonorgestrel device. For a patient on tuberculosis treatment who is also living with HIV, review both regimens for interaction.

Referral and escalation. Refer pregnancy with a displaced device, suspected ectopic pregnancy, patients on complex antiretroviral or antiseizure regimens whose management needs specialist input, and teratogenic exposure.