Drug Interactions between alfuzosin and fluoxetine / olanzapine

MONITOR: It is uncertain whether olanzapine causes clinically significant prolongation of the QT interval. In pooled studies of adults as well as pooled studies of adolescents, there were no significant differences between olanzapine and placebo in the proportion of patients experiencing potentially important changes in ECG parameters, including QT, QTcF (Fridericia-corrected), and PR intervals. In clinical trials, clinically meaningful QTc prolongations (QTcF >=500 msec at any time post-baseline in patients with baseline QTcF <500 msec) occurred in 0.1% to 1% of patients treated with olanzapine, with no significant differences in associated cardiac events compared to placebo. Published studies have generally reported no significant effect of olanzapine on QTc interval, although both QTc prolongation and QTc shortening have also been reported. There have been a few isolated case reports of QT prolongation in patients receiving olanzapine. However, causality is difficult to establish due to confounding factors such as concomitant use of drugs that cause QT prolongation and underlying conditions that may predispose to QT prolongation (e.g., hypokalemia, congenital long QT syndrome, preexisting conduction abnormalities).

MANAGEMENT: Some authorities recommend caution when olanzapine is used with drugs that are known to cause QT prolongation. ECG monitoring may be advisable in some cases, such as in patients with a history of cardiac arrhythmias or congenital or family history of long QT syndrome. 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.

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: Phenothiazines, tricyclic antidepressants (TCAs), and some antipsychotic (neuroleptic) agents may potentiate the blood pressure lowering capabilities of other drugs with hypotensive effects due to their peripheral alpha-1 adrenergic blocking activity. Orthostatic hypotension and syncope associated with vasodilation may occur, particularly during initial dosing and/or parenteral administration of the phenothiazine, TCA, or neuroleptic. The severity of this interaction may be affected by the agent's affinity for the alpha-1 adrenoceptor. One in vitro study demonstrated an affinity for the alpha-1 adrenoceptor for some of these medications that was similar to, or greater than, those of alpha blocker medications used to treat hypertension. Examples of drugs evaluated in this study with a high affinity included amitriptyline, clomipramine, chlorpromazine, clozapine, doxepin, flupenthixol, lurasidone, nortriptyline, perphenazine, paliperidone, quetiapine, risperidone, sertindole, and ziprasidone. On the other hand, examples of those with lower affinities included aripiprazole, lofepramine, protriptyline, sulpiride, and amisulpride.

MANAGEMENT: Close clinical monitoring for development of hypotension is recommended if phenothiazines, tricyclic antidepressants (TCAs), or certain antipsychotic (neuroleptic) agents are used in patients receiving antihypertensive medications or vasodilators. A lower starting dosage and slower titration of the phenothiazine, TCA, or neuroleptic may be appropriate, especially in the elderly. It may also be advisable to consider using a phenothiazine, TCA, or neuroleptic medication with a lower affinity for the alpha-1 adrenoceptor when possible. Patients should be counseled to avoid rising abruptly from a sitting or recumbent position and to notify their healthcare provider 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.