Drug Interaction Report

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.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of copanlisib. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of copanlisib by certain compounds present in grapefruit. When a single 60 mg intravenous dose of copanlisib was administered to cancer patients in combination with the potent CYP450 3A4 and P-gp inhibitor, itraconazole (200 mg once daily for 10 days), mean copanlisib peak plasma concentration (Cmax) did not change but systemic exposure (AUC) increased by 53%. The interaction has not been studied with grapefruit juice. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to copanlisib may increase the risk of adverse effects such as nausea, vomiting, diarrhea, stomatitis, hyperglycemia, hypertension, noninfectious pneumonitis, cutaneous reactions (e.g., exfoliative dermatitis, maculopapular rash), anemia, neutropenia, thrombocytopenia, and infections.

MANAGEMENT: Patients should avoid the consumption of grapefruit and grapefruit juice during treatment with copanlisib.