Strong CYP3A4 inducers — rifampicin, carbamazepine, phenytoin, phenobarbital and primidone, and St John's wort — lower the levels of many co-prescribed drugs. Unlike inhibition, which acts within a dose or two, induction builds over about one to two weeks as new enzyme is made, and wears off over a similar period after the inducer is stopped.
That timing is where harm happens. A dose raised to overcome induction becomes too high once the inducer is withdrawn, as with warfarin, tacrolimus or some antiretrovirals after a course of rifampicin.
- When starting a strong inducer, expect co-prescribed substrate levels to fall over one to two weeks.
- When stopping one, plan to reduce doses that were raised to compensate, over a similar period.
- Monitor levels or effect of narrow-therapeutic-index drugs through both transitions.
- Ask about St John's wort and other herbal products, which patients may not mention.
Why it matters
The interaction that harms is often the one that ends, not the one that begins.
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