Most serious pharmacokinetic interactions in everyday practice involve a small number of strong CYP3A inhibitors and inducers. Learning them covers a large share of the risk.
Strong inhibitors: clarithromycin, ketoconazole and itraconazole, and ritonavir or cobicistat. Strong inducers: rifampicin, carbamazepine and phenytoin. Grapefruit juice is a moderate intestinal inhibitor.
- Before adding clarithromycin, an azole or a ritonavir-boosted regimen, check for CYP3A substrates such as simvastatin, tacrolimus, some calcium channel blockers, apixaban and rivaroxaban.
- Rifampicin can reduce levels of many drugs, including DOACs, hormonal contraceptives and tacrolimus, within days.
- When an inducer is stopped, the effect wears off over one to two weeks; substrate levels can rise.
- Prefer azithromycin over clarithromycin when an interaction is a concern.
Why it matters
A handful of drugs cause most of the pharmacokinetic interactions that hurt patients.
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