Drug Interaction Report

MONITOR: Coadministration with darolutamide may increase the plasma concentrations of drugs that are substrates of the organic anion transporting polypeptides (OATP) 1B1 and 1B3. The proposed mechanism, based on in vitro data, involves decreased metabolic clearance due to inhibition of OATP 1B1- and 1B3-mediated hepatic uptake by darolutamide. Increased adverse reactions of the OATP 1B1 and 1B3 substrates may result.

MANAGEMENT: Caution is advised when darolutamide is used concurrently with drugs that are known OATP 1B1 and 1B3 substrates. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever darolutamide is added to or withdrawn from therapy.

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.

ADJUST DOSING INTERVAL: Food enhances the oral absorption of darolutamide. According to the prescribing information, bioavailability of darolutamide increased by 2.0 to 2.5-fold when administered with food. A similar increase in exposure was observed for the active metabolite keto-darolutamide.

MANAGEMENT: Darolutamide should be administered with food.