Cytochrome P450 3A4
Also known as: CYP3A4, CYP3A
Enzyme of the cytochrome P450 complex (family 3, subfamily A) responsible for metabolising about half of the drugs currently in use. It is located mainly in the liver and small intestine.
It is the most frequent target in interactions: drugs that inhibit it (e.g. ketoconazole, clarithromycin, grapefruit juice) raise substrate concentrations; drugs that induce it (e.g. rifampicin, carbamazepine, phenytoin) lower them and may cause loss of efficacy.
Substrates: simvastatin, atorvastatin, ciclosporin, tacrolimus, sirolimus, clarithromycin, erythromycin, midazolam, sildenafil, tadalafil, nifedipine, verapamil, diltiazem, ivabradine, pimozide.
Inhibitors: ketoconazole, itraconazole, fluconazole (weak), clarithromycin, erythromycin, ritonavir, amiodarone, diltiazem, verapamil, grapefruit juice.
Inducers: rifampicin, carbamazepine, phenytoin, phenobarbital, St John's wort (hypericum), dexamethasone.
In clinical practice, inhibition is the most relevant mechanism: combinations with strong inhibitors require dose reduction or monitoring (e.g. simvastatin + clarithromycin, ivabradine + ketoconazole, tacrolimus + diltiazem).
DailyMed/FDA (NIH/NLM) — approved labels; EMC-UK (MHRA) — SmPC; PubMed (NIH/NLM)
