Table 2.
Clinically significant drug-drug interactions involving antihypertensives
| Object drug or drug class | Precipitant drug or drug class | Effect of interaction | Mechanism of interaction |
|---|---|---|---|
| Atorvastatin; lovastatin; simvastatin |
Diltiazem, verapamil | Increased concentrations of atorvastatin/lovastatin/simvastatin |
Diltiazem/verapamil-mediated inhibition of CYP-3A4 metabolism of atorvastatin/ lovastatin/simvastatin |
| ACE inhibitors/ARB | Diuretics (potassium-sparing), NSAIDs, potassium supplements |
Hyperkalemia; reduced renal function | Combined potassium-elevating effects; additive nephrotoxic effects |
| Antihypertensives CCB |
Vasodilators (nitrates), levodopa Erythromycin, clarithromycin |
Orthostatic hypotension Hypotension or shock |
Combined hypotensive effects Erythromycin/clarithromycin- mediated inhibition of CYP- 3A4 metabolism of CCB |
| Carbamazepine | Diltiazem, verapamil | Increased effect of carbamazepine | Reduced clearance of carbamazepine |
| Clonidine | TCA | Inhibition of antihypertensive response | Unknown |
| Clonidine | Mirtazapine | Inhibition of antihypertensive response | Mirtazapine inhibition of central α2-receptors |
| Colchicine | Diltiazem, verapamil | Increased effect of colchicine | Diltiazem/verapamil-mediated inhibition of CYP-3A4 metabolism of colchicine; diltiazem/verapamil-mediated inhibition of P-glycoprotein transport of colchicine |
| Digoxin | Diltiazem, verapamil | Increased effect of digoxin | Reduced clearance of digoxin |
| Digoxin | Diuretics (loop and thiazides) | Increased effect of digoxin | Diuretic-induced hypokalemia |
| Diuretics (potassium- sparing) |
ACE inhibitors/ARB, NSAIDs, potassium supplements |
Hyperkalemia, reduced renal function | Combined potassium-elevating effects; additive nephrotoxic effects |
| CCB (DHP) | Carbamazepine | Decreased CCB bioavailability | Enhanced CYP-3A4 mediated metabolism of CCB by carbamazepine (enzyme induction) |
| Lithium | ACE inhibitors/ARB, diuretics (thiazides) |
Increased effect of lithium | Reduced clearance of lithium |
Data from [28–30,31•]. ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blockers; CCB, calcium-channel blockers; DHP, dihydropyridine; NSAID, nonsteroidal anti-inflammatory drugs; TCA, tricyclic antidepressants.