Emergency Contraception and Enzyme Inducers

Enzyme-inducing medicines speed the liver metabolism of levonorgestrel and ulipristal acetate and lower their effect. Use of oral emergency contraception with these medicines is category 1, meaning no safety restriction, but efficacy is reduced. The copper IUD is unaffected and is the preferred option.

Common inducers. Rifampicin, rifabutin, phenytoin, phenobarbital, primidone, carbamazepine, oxcarbazepine, efavirenz, nevirapine, griseofulvin and St John's wort. These are frequent in patients treated for tuberculosis, HIV and epilepsy.

Mechanism. Induction of the CYP3A4 enzyme lowers drug levels. The effect continues for about 28 days after the inducer is stopped.

Effectiveness. After oral emergency contraception in the general population, 1 to 2 in 100 women become pregnant. Rates are expected to be higher during induction. With the copper IUD, fewer than 1 in 100 become pregnant.

Return to fertility. Immediate.

History. Ask every patient for current and recent medicines in the past 28 days, including herbal products and treatment for tuberculosis, HIV and epilepsy.

Eligibility. Enzyme inducers are category 1 for emergency contraception. Cardiovascular disease, angina, migraine and severe liver disease are category 2.

Choosing the option.

• Copper IUD first, within 5 days. It is unaffected by inducers.

• If the IUD is declined or unavailable: levonorgestrel 3 mg as a single dose (two 1.5 mg tablets together). Evidence for this dose is limited.

• Ulipristal acetate loses efficacy with strong inducers and is avoided when the other options exist.

Counselling points for the clinician. Explain that the oral option is less reliable and that a pregnancy test 3 weeks later is important. Obtain consent and protect confidentiality. Offer condoms for dual protection.

Interactions to note. Dolutegravir and tenofovir do not induce relevant enzymes.

Special groups.

• HIV: the copper IUD is acceptable in stable patients on treatment.

• Tuberculosis: rifampicin lowers hormone levels for the whole course and about 28 days after.

• Epilepsy: enzyme-inducing antiseizure medicines lower oral hormone levels.

• Breastfeeding: the copper IUD does not affect milk.

Regimens.

• Copper IUD: copper T 380A, inserted once within 5 days of intercourse or of expected ovulation. Immediate protection, lasts up to 12 years, no backup, no interactions.

• Levonorgestrel: 3 mg by mouth as one dose (two 1.5 mg tablets together), as soon as possible within 120 hours. One course for each episode. Duration of protection is the episode only.

• Ulipristal acetate: 30 mg by mouth as one dose within 120 hours, only when the IUD and levonorgestrel are not possible. No progestin for 5 days after.

Pregnancy exclusion. Pregnancy is reasonably excluded when there has been no unprotected intercourse since the last normal menses and menses are not overdue. A test is not needed before one recent episode.

Vomiting. Within 2 hours of a dose, repeat it with an antiemetic. After more than 2 hours, give nothing further.

Starting ongoing contraception. Choose a method that holds up during induction.

• Copper IUD, levonorgestrel IUD and injectable (150 mg intramuscularly every 13 weeks): category 1.

• Implant: category 2.

• Combined and progestin-only pills: category 3 with rifampicin and enzyme-inducing antiseizure medicines, and category 2 with efavirenz and nevirapine.

• Timing: injectable the same day with 7 days of backup; IUD the same day; implant within 7 days of the next menses with condoms or pills until then.

Follow up. Test 3 weeks after the episode if menses have not started. Continue the effective method for 28 days after the inducer stops.

Expected effects. Nausea, headache, abdominal pain and altered menses. Menses may be early or late by a few days.

Antiemetic regimen. Ondansetron 4 mg by mouth as one dose, repeated once after 8 hours if needed. Maximum 12 mg in 24 hours, for no more than 2 days. Limit to 8 mg in 24 hours in severe liver disease. No kidney adjustment is needed. Avoid in congenital long QT syndrome. In pregnancy use only when the benefit is clear. Short courses are acceptable in breastfeeding.

Failure. Oral failure is more likely during induction. A positive test needs assessment for ectopic pregnancy when pain or bleeding is present. The dose does not harm the pregnancy.

Common errors. Not asking about tuberculosis or antiseizure medicines, giving levonorgestrel 1.5 mg alone without discussing the IUD, and stopping the effective method too early after the inducer ends.

Referral and escalation. Refer for severe lower abdominal pain, fainting or a positive pregnancy test with pain or bleeding. Refer patients on antiseizure medicines or antiretrovirals for review of long-term contraception.