Calcium-channel blockers in current clinical usage affect slow L-type channel. They are usually classified by their chemical structure, which determines their selectivity for vascular smooth muscle over myocardium, and hence their potential to slow heart rate (negative inotropic activity) see table 1 below,(below). Interactions due to additive inotropic effects will therefore apply only to benzothiazepine (diltiazem) and phenylalkylamine-type (verapamil) calcium-channel blockers, and usually not to dihydropyridine-type (e.g. nifedipine) calcium-channel blockers. All three types of calcium-channel blocker will have additive hypotensive effects with other drugs with blood-pressure lowering activity.
Calcium-channel blockers also undergo interactions due to altered metabolism. Both verapamil and diltiazem are principally metabolised by cytochrome P450 isoenzyme CYP3A4, and also inhibit this enzyme (see table 2 below,). They are therefore affected by drugs that induce or inhibit CYP3A4,and also themselves interact with drugs metabolised by CYP3A4.
Many of dihydropyridine-type calcium-channel blockers are also metabolised by CYP3A4, and are affected by inducers or inhibitors of this isoenzyme. However,they do not generally inhibit CYP3A4, or other isoenzymes to a clinically relevant extent. The exception is perhaps nicardipine,which may cause a clinically relevant inhibition of CYP3A4 (see table 2 below,).
This section is primarily concerned with those interactions where activity of calcium-channel blockers is changed by presence of another drug. Where calcium-channel blocker is affecting agent, relevant monograph is usually categorised under heading of affected drug.
Mibefradil is a calcium-channel blocker that acts on fast T-type calcium channel. It was thought that practical problems of implementing all warnings relating to these interactions were too difficult and risky
Amlodipine,Barnidipine, Benidipine, Felodipine, Isradipine, Lacidipine, Lercanidipine, Manidipine, Nicardipine, Nifedipine, Nilvadipine, Nimodipine,† Nisoldipine, Nitrendipine
Gallopamil,Verapamil
†Nimodipine crosses blood-brain barrier and therefore affects cerebral blood vessels, and is used for cerebral ischaemia.
| Table 1 Classification of calcium-channel blockers that act on slow L-type channels | |||
|---|---|---|---|
| Class | Rate limiting? | Effect on AV or SA node | Examples |
| Dihydropyridine | No | Little or none | Amlodipine, Barnidipine, Benidipine, Felodipine, Isradipine, Lacidipine, Lercanidipine, Manidipine, Nicardipine, Nifedipine, Nilvadipine, Nimodipine,† Nisoldipine, Nitrendipine |
| Benzothiazepine | Yes | Depression (negative inotropic activity) | Diltiazem |
| Phenylalkylamine | Yes | Depression (negative inotropic activity) | Gallopamil, Verapamil |
| Table 2 Drugs affecting or metabolised by isoenzyme CYP3A4 | the cytochrome P450 | |
|---|---|---|
| Inhibitors | Aprepitant Azoles Itraconazole Ketoconazole Voriconazole Cimetidine Delavirdine Diltiazem Grapefruit juice Imatinib | Macrolides Clarithromycin Erythromycin Troleandomycin Nefazodone Nicardipine Protease inhibitors SSRIs Fluoxetine Verapamil |
| Table 3 Drugs affecting or metabolised by isoenzyme CYP3A4 | the cytochrome P450 | |
|---|---|---|
| Inhibitors | Aprepitant Azoles Itraconazole Ketoconazole Voriconazole Cimetidine Delavirdine Diltiazem Grapefruit juice Imatinib | Macrolides Clarithromycin Erythromycin Troleandomycin Nefazodone Nicardipine Protease inhibitors SSRIs Fluoxetine Verapamil |