Drug Interaction Report

MONITOR: The use of mTOR (mammalian target of rapamycin) inhibitors has been associated with the development of angioedema, and coadministration with other drugs that are also known to cause angioedema such as ACE inhibitors, angiotensin II receptor antagonists, and renin inhibitors may increase the risk. In a pooled analysis of everolimus oncology clinical trials, the incidence of angioedema in patients taking everolimus with an ACE inhibitor was 6.8% compared to 1.3% in the control arm with an ACE inhibitor. The onset of angioedema may sometimes be delayed. According to the product labeling for temsirolimus, angioneurotic edema-type reactions have occurred two months after initiation of therapy in some patients who received concomitant ACE inhibitors.

MANAGEMENT: Clinicians and patients should be aware of the potential for increased risk of angioedema when mTOR inhibitors are prescribed with other drugs that are also known to cause angioedema. Patients should be advised to promptly discontinue these medications and seek medical attention if they develop signs or symptoms suggestive of angioedema such as swelling of the face, extremities, eyes, lips, or tongue, and difficulty swallowing or breathing.

GENERALLY AVOID: Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs). ARBs can promote hyperkalemia through inhibition of angiotensin II-induced aldosterone secretion. Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia.

MANAGEMENT: Patients should receive dietary counseling and be advised to not use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician. If salt substitutes are used concurrently, regular monitoring of serum potassium levels is recommended. Patients should also be advised to seek medical attention if they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs.