Drug interactions between amiloride and Diovan

MONITOR CLOSELY: Concomitant use of angiotensin II receptor blockers (ARBs) and potassium-sparing diuretics may increase the risk of hyperkalemia. Inhibition of angiotensin II results in decreased aldosterone secretion, which can lead to increases in serum potassium that may be additive with that induced by potassium-sparing diuretics. Life-threatening and fatal hyperkalemia can occur, especially when the combination is used in patients with risk factors such as renal impairment, diabetes, old age, severe or worsening heart failure, dehydration, and concomitant use of other agents that block the renin-angiotensin-aldosterone system or otherwise increase serum potassium levels. Individually, both ARBs and potassium-sparing diuretics have been associated with hyperkalemia in patients with renal impairment. ARBs may also cause deterioration of renal function in patients with chronic heart failure, and the risk is increased if they are sodium-depleted or dehydrated secondary to excessive diuresis. A retrospective analysis of the incidence of hyperkalemia in the CHARM study (Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity) found that the addition of candesartan to standard medical therapy for heart failure was associated with a 2- to 3-fold increase in risk of hyperkalemia, which was further amplified by cotreatment with spironolactone or ACE inhibitors.

MANAGEMENT: Caution is advised if angiotensin II receptor blockers must be used concurrently with potassium-sparing diuretics, particularly in patients with renal impairment, diabetes, old age, severe or worsening heart failure, dehydration, or concomitant therapy with other agents that increase serum potassium such as nonsteroidal anti-inflammatory drugs, beta-blockers, cyclosporine, heparin, tacrolimus, trimethoprim, and licorice. Serum potassium and renal function should be checked prior to initiating therapy and regularly thereafter, and potassium supplementation as well as the use of potassium-containing salt substitutes should be avoided unless absolutely necessary and the benefits outweigh the potential risks. Patients should be given counseling on the appropriate levels of potassium and fluid intake, and advised to seek medical attention if they experience signs and symptoms of hyperkalemia such as nausea, vomiting, weakness, listlessness, tingling of the extremities, paralysis, confusion, weak pulse, and a slow or irregular heartbeat. If spironolactone is prescribed with an ARB, some investigators recommend that its dosage not exceed 25 mg/day in high-risk patients.