Enzyme-inducing anti-epileptic drugs and the combined pill
Carbamazepine, an anti-epileptic drug, switches on liver enzymes that break down the hormones in the combined oral contraceptive pill (taken to prevent pregnancy) faster, so the pill can fail.
Remember
Enzyme-inducing anti-epileptic drugs such as carbamazepine make the combined pill unreliable, because its hormones are cleared faster, so these women need an alternative or additional method of contraception.
An enzyme inducer is a drug that switches on the liver's drug-metabolising enzymes, so other medicines are broken down faster. The main enzyme family involved is cytochrome P450, a group of liver proteins that break down many medicines and hormones. Carbamazepine, an anti-epileptic drug that keeps seizures controlled, is a strong inducer, and it makes the liver produce more cytochrome P450 enzymes, particularly CYP3A4. Phenytoin, phenobarbital and primidone are the other main inducers, and topiramate joins them at higher doses.
The combined oral contraceptive pill contains oestrogen and a progestogen (a progesterone-like hormone), and it works by stopping the ovaries releasing an egg each month. An inducer speeds up the breakdown of both hormones, so their levels can fall below the level that reliably suppresses ovulation. A woman who takes every pill correctly can still become pregnant. This is a pharmacokinetic interaction: the anti-epileptic drug changes how the body handles the pill, rather than acting on the same target.
For a woman whose seizures are controlled on an enzyme-inducing anti-epileptic drug, the sensible approach is to change the contraception and keep the same seizure treatment. A levonorgestrel intrauterine system (a small hormone-releasing coil placed in the womb) releases its hormone locally, so enzyme inducers do not reduce its effectiveness. The progestogen-only pill is less reliable with these drugs, so it is not a safe swap.
Sodium valproate tends to inhibit liver enzymes rather than induce them, levetiracetam and gabapentin do not induce them, and lamotrigine is not a significant inducer.
Key facts
- Mechanism
- an enzyme inducer speeds up the liver's breakdown of the pill's oestrogen and progestogen, so hormone levels fall.
- Main inducers
- carbamazepine, phenytoin, phenobarbital and primidone, with topiramate at higher doses.
- Not inducers
- levetiracetam and gabapentin do not induce liver enzymes, and lamotrigine is not a significant inducer, although reduced pill effectiveness with lamotrigine cannot be excluded.
- Sodium valproate
- it tends to inhibit liver enzymes rather than induce them, so it does not lower the pill's effectiveness by induction.
- Better option
- a levonorgestrel intrauterine system releases its hormone locally in the womb, so it is not weakened by enzyme inducers.
- What to change
- change the contraception rather than the epilepsy treatment, because switching a stable anti-epileptic drug to avoid a contraception problem is the wrong trade-off.
Exam traps
- Sodium valproate does not weaken the combined pill by enzyme induction, because it tends to inhibit liver enzymes rather than induce them; its well-known warning is about harm to the baby in pregnancy.
- The progestogen-only pill is not a safe swap for the combined pill, because it is also less reliable with enzyme-inducing anti-epileptic drugs, so one affected method is swapped for another.
- A woman whose seizures are controlled should not stop her anti-epileptic drug to suit her contraception, because seizures can return and cause injury; the contraceptive method should be changed instead.
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