Drug Interaction Report

MONITOR: Concomitant ACE inhibitor therapy may potentiate the risk of nitritoid (vasomotor) reactions associated with injectable gold therapy. The mechanism of interaction is unknown, although investigators suggest that ACE inhibitors may unmask drug hypersensitivity reactions by preventing the breakdown of bradykinins. In one published case report, two patients with rheumatoid arthritis who had been treated with intramuscular sodium aurothiomalate for over 20 years without incident developed nitritoid reactions after they were started on ACE inhibitor therapy within the previous 15 months. The interaction was also suspected in several other reported cases. One patient experienced anaphylaxis and cardiac arrest after a gold injection. She had been on gold therapy for 16 months and lisinopril for 12 months. Two other cases occurred 1 to 4 weeks after starting ACE inhibitor therapy. The patients were switched to gold sodium aurothioglucose with no further problems. In general, nitritoid reactions can occur in approximately 5% of patients treated with gold. Most are transient and occur within a few minutes of drug administration within the first year of treatment. Serious sequelae including myocardial infarction have been reported.

MANAGEMENT: Patients on injectable gold therapy in combination with an ACE inhibitor should be monitored for symptoms of nitritoid reactions such as facial flushing, nausea, vomiting, and hypotension following an injection. Elderly patients in particular should be observed following treatment. Oxygen, intravenous fluids, epinephrine, steroids, and other supportive therapy may be necessary for treatment.

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.