Rifampicin, carbamazepine, phenytoin and phenobarbital induce CYP3A4 and other enzymes by increasing their synthesis. Induction builds over several days and fades only as the extra enzyme is broken down, which typically takes around two weeks after the inducer is stopped.
So a drug whose dose was raised to overcome induction can become toxic when the inducer stops, and a drug started soon after the inducer ends may still be under-dosed. Plan for both ends: adjust when the inducer starts, and again over the fortnight after it stops.
- Expect induction to build over about a week after starting rifampicin or carbamazepine
- Expect it to wane over about two weeks after stopping
- Reduce doses that were increased to overcome induction once the inducer stops
- Monitor levels of narrow-margin drugs such as tacrolimus, warfarin and some antiepileptics across both transitions
Why it matters
Toxicity after an inducer stops is a common, predictable interaction error.
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