Drug Interaction Report

MONITOR: Additive hypotensive effects may occur when ACE inhibitors are used in combination with alpha-blockers. In the presence of ACE inhibition, the risk and/or severity of first-dose effects associated with alpha-blockers such as postural hypotension and syncope may be increased. In a study of six healthy subjects, mean blood pressure (systolic/diastolic) declined by 27/28 mmHg and 19/22 mmHg when a single 2 mg dose of bunazosin was given one hour after enalapril 10 mg and 2.5 mg, respectively, compared to a 9.5/6.7 mmHg decrease following bunazosin 2 mg or enalapril 10 mg alone. Potentiation of first-dose response has also been reported with prazosin administered in the presence of enalapril.

MANAGEMENT: Caution is advised during coadministration of these agents, particularly when initiating an alpha-blocker in the presence of an ACE inhibitor. Small initial dosages of the alpha-blocker should be considered and gradually titrated to desired effect, while the ACE inhibitor dosage may also need to be reduced. Hemodynamic responses should be monitored, especially during the first few weeks of therapy. Taking the alpha-blocker at bedtime may minimize the occurrence of orthostatic effects. 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, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.

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.

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of silodosin. The effect of a moderate-fat, moderate-calorie meal on silodosin pharmacokinetics was variable and decreased silodosin maximum plasma concentration (Cmax) by approximately 18% to 43% and systemic exposure (AUC) by 4% to 49% across three different studies. The maximum effect of food (i.e., coadministration with a high-fat, high-calorie meal) on the pharmacokinetics of silodosin was not evaluated. Safety and efficacy clinical trials for silodosin were always conducted in the presence of food intake.

MANAGEMENT: Patients should be instructed to take silodosin with a meal to reduce the risk of adverse events.