Rifampicin, carbamazepine, phenytoin and St John's wort induce CYP3A4 and other enzymes and transporters. Induction depends on making new enzyme, so it builds over several days and, after the inducer stops, fades over one to two weeks as the extra enzyme is cleared.
This has two consequences. A short course of an inducer can still lower levels of affected drugs well beyond its last dose, and a drug whose dose was raised to overcome induction can become toxic when the inducer stops unless the dose is brought back down.
- Expect induction to build over several days after starting rifampicin or carbamazepine.
- Expect the effect to persist for one to two weeks after the inducer is stopped.
- Reduce doses that were increased to overcome induction as the inducer wears off.
- Rifabutin is a weaker inducer than rifampicin and is sometimes used to limit interactions.
- Check interactions with warfarin, DOACs, tacrolimus, antiretrovirals and hormonal contraception first.
Why it matters
Most harm from induction happens at the transitions, not while the patient is stable on both drugs.
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