Drug Interaction Report

MONITOR: Coadministration of medicines targeting the prostacyclin pathway (e.g., prostacyclin (PGI2), PGI2 analogs, or selective non-prostanoid prostacyclin IP receptor agonists) with diuretics, antihypertensive agents, or other vasodilators may potentiate the hypotensive effects of these agents. The mechanism involves the additive reduction in blood pressure due to the vasodilatory effects of PGI2, PGI2 analogs or selective non-prostanoid prostacyclin IP receptor agonists on the prostacyclin pathway.

MANAGEMENT: While therapies that target the prostacyclin pathway have been used in combination with diuretics, antihypertensives, or other vasodilators in the management of pulmonary arterial hypertension, caution is recommended if they must be administered concurrently. If these drugs are used together, it is generally recommended that blood pressure be measured more frequently until a stable blood pressure pattern is observed. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their doctor if they experience dizziness, lightheadedness, syncope, orthostatic hypotension, or tachycardia. Treatment guidelines should be consulted for the optimum management of pulmonary arterial hypertension.

GENERALLY AVOID: Moderate-to-high dietary intake of potassium can cause hyperkalemia in some patients who are using angiotensin converting enzyme (ACE) inhibitors. In some cases, affected patients were using a potassium-rich salt substitute. ACE inhibitors can promote hyperkalemia through inhibition of the renin-aldosterone-angiotensin (RAA) system.

MANAGEMENT: It is recommended that patients who are taking ACE inhibitors be advised to avoid moderately high or high potassium dietary intake. Particular attention should be paid to the potassium content of salt substitutes.

Food prolongs the gastrointestinal absorption of selexipag. When taken with food, the time to peak concentration (Tmax) was delayed and peak plasma concentration (Cmax) was approximately 30% lower. Selexipag systemic exposure (AUC) and that of its active metabolite did not significantly change, however. Selexipag may be taken with or without food. Tolerability may be improved when taken with food.