Table 4: ARB Drug-Drug Interactions
| Target Drug | Interacting Drug | Interaction | Recommendation | Clinical Significance Level # |
|---|---|---|---|---|
| ARBs, nebivolol/ valsartan, sacubitril/valsartan | aliskiren | increased risk for renal impairment, hyperkalemia, and hypotension with adjunctive administration most likely due to additive effects; documented in ALTITUDE trial (type 2 diabetics with renal impairment had increased stroke, renal complications, hypotension when given ARBs and aliskiren concurrently) | combined administration in diabetics contraindicated by manufacturer; avoid combination in patients with CrCl less than 60 ml/min; use cautiously together in other patients and closely monitor renal function, serum potassium levels | contraindicated (DrugReax) - 2-major (CP) |
| ARBs, nebivolol/ valsartan, sacubitril/valsartan | lithium | potential for enhanced lithium pharmacologic/adverse effects with combined administration; speculated that ARBs augment lithium reabsorption by decreasing lithium renal excretion | monitor patients for increased signs/symptoms of lithium toxicity and adjust lithium doses as necessary; may select alternate cardiovascular therapy that does not interact with lithium | major (DrugReax) - 3-moderate (CP) |
| ARBs, nebivolol/valsartan, sacubitril/valsartan | nonsteroidal anti-inflammatory drugs | combined administration may increase risk for renal function deterioration and alter response to antihypertensives, especially in volume-depleted, elderly, or renally compromised patients, due to vasodilatory prostaglandin inhibition | monitor renal function, antihypertensive efficacy when combined administration required |
moderate (DrugReax) - 3-moderate (CP) |
| ARBs, nebivolol/ valsartan, sacubitril/valsartan | potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene), potassium supplements | combined therapy may increase risk for hyperkalemia as ARBs reduce circulating aldosterone concentrations, resulting in potassium retention; elderly as well as patients with impaired renal function, diabetes, or high potassium diets may be at greater risk | measure serum potassium concentrations, monitor for signs and symptoms of hyperkalemia when administered concurrently, especially in patients with predisposing factors | moderate (DrugReax) - 2-major (CP) |
| nebivolol/valsartan | CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine) | adjunctive administration may result in enhanced nebivolol pharmacologic effects (e.g., reduced heart rate, hypotension) due to increased nebivolol serum levels as nebivolol is metabolized by CYP2D6 | combined use should be avoided; if concurrent administration necessary, monitor patients for unwanted pharmacologic/ adverse effects; adjust dosages as needed | major (DrugReax) - 2-major (CP) |
| nebivolol/valsartan | hypotensive agents | concurrent administration may result in large reductions in sympathetic activity due to added beta-blocking activity; patients may have increased orthostasis and bradycardia | avoid nebivolol use with other beta blockers; withdraw nebivolol slowly over several days in patients prescribed clonidine concurrently | 2-major, 3-moderate (CP) |
| nebivolol/valsartan | digitalis glycosides | co-administration may increase bradycardia risk as both nebivolol and digitalis glycosides reduce atrioventricular conduction and decrease heart rate | administer nebivolol with digitalis glycosides cautiously and monitor heart rate | moderate (DrugReax) - 3-moderate (CP) |
| nebivolol/valsartan | calcium channel blockers | combined use of beta blockers like nebivolol with calcium channel blockers can be useful in some circumstances; however, combined administration may result in additive negative inotropic and/or chronotropic effects | if combined therapy needed, monitor heart rate and cardiac conduction; adjust doses as necessary | moderate (DrugReax) - 3-moderate (CP) |
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- * Clinical Pharmacology