Drug Interaction Report

MONITOR: The coadministration of nesiritide with ACE inhibitors may result in an increase in symptomatic hypotension due to possible additive pharmacodynamic effects in the vasculature. In a clinical trial in which patients were treated with either nesiritide or nitroglycerin therapy, the frequency of symptomatic hypotension was 6% in patients who also received an oral ACE inhibitor, compared to 1% in patients who did not.

MANAGEMENT: Whether used alone or with other agents, nesiritide should be administered only in settings where blood pressure can be closely monitored. The dosage should be reduced or the drug discontinued in patients who develop hypotension.

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.

ADJUST DOSING INTERVAL: Administration with food decreased the biotransformation of perindopril to its active metabolite, perindoprilat, resulting in a decrease of perindoprilat bioavailability by 35% and a reduction in the plasma ACE inhibition curve of approximately 20%. When administered as part of a combination product with amlodipine and taken with food, perindopril and perindoprilat absorption rates have decreased by 18% and 14%, respectively, versus fasting. No effect of food on the extent of unmetabolized perindopril absorption has been observed.

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. Some authorities recommend administering perindopril before a meal, preferably in the morning. According to the prescribing information, the combination product containing perindopril and amlodipine may be taken with or without food.