Drug Interaction Report

MONITOR: Alfuzosin may cause modest prolongation of the QTc interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. During a clinical study involving 45 healthy male subjects, average prolongation of QTc interval at peak plasma concentrations was less with single doses of alfuzosin 10 mg than with alfuzosin 40 mg, and both were less than with moxifloxacin 400 mg. Heart rate increased by an average of 5.2 bpm with alfuzosin 10 mg, 5.8 bpm with alfuzosin 40 mg, and 2.8 bpm with moxifloxacin 400 mg. Torsade de pointes has not been reported with alfuzosin. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Caution is recommended if alfuzosin is used in combination with other drugs that can prolong the QT interval. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. If taking drugs that also cause CNS or orthostatic effects (e.g., psychotropic drugs like tricyclic antidepressants, phenothiazines, and neuroleptics), patients should be made aware of the possibility of additive effects with alfuzosin and counseled to avoid activities requiring mental alertness until they know how these agents affect them.

MONITOR: Coadministration with moderate inhibitors of CYP450 3A4 may increase the plasma concentrations of alfuzosin, which is primarily metabolized by the isoenzyme. Hypotension, syncope, QT prolongation, and priapism may occur. In one study, repeated oral administration of 240 mg/day of diltiazem, a moderate CYP450 3A4 inhibitor, with 7.5 mg/day (2.5 mg three times daily) of alfuzosin increased alfuzosin peak plasma concentration (Cmax) and systemic exposure (AUC) by 50% and 30%, respectively, and increased diltiazem Cmax and AUC each by 40%. No changes in blood pressure were observed in this study.

MANAGEMENT: Caution is advised if alfuzosin is prescribed in combination with moderate CYP450 3A4 inhibitors. Pharmacologic response to alfuzosin should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the alfuzosin dosage adjusted as necessary. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, orthostasis, syncope, or tachycardia. Taking alfuzosin at bedtime may minimize the occurrence of orthostatic effects. Patients should also avoid driving or operating hazardous machinery until they know how the medication affects them.

ADJUST DOSING INTERVAL: Administration of alfuzosin with food enhances oral bioavailability. According to the manufacturer, extent of absorption is 50% higher when administered under fed conditions compared to fasting conditions.

MANAGEMENT: To ensure maximal oral absorption, alfuzosin should be administered with or immediately after a meal.