Drug Interactions between fluoxetine / olanzapine and iobenguane I 123

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.

GENERALLY AVOID: Coadministration with drugs that block norepinephrine uptake or deplete norepinephrine stores may decrease iobenguane I-123 uptake in neuroendocrine tumors and lead to false-negative imaging results. Since iobenguane I-123 is subject to the same uptake and accumulation pathways as norepinephrine, drugs that alter norepinephrine disposition in adrenergic nerve terminals and presynaptic storage vesicles will likewise affect iobenguane. These drugs include antihypertensive agents that deplete norepinephrine stores or inhibit reuptake (e.g., guanethidine, reserpine, labetalol); antidepressants that inhibit norepinephrine transporter function (e.g., tricyclic antidepressants, selective serotonin reuptake inhibitors); sympathomimetic amines (e.g., phenylephrine, phenylpropanolamine, pseudoephedrine, ephedrine); central nervous stimulants (e.g., amphetamines); phenothiazines; and cocaine. Clinical studies have not determined which specific drugs may cause false-negative imaging results and whether all drugs in a specific pharmacologic class have the same potential to produce negative imaging results. Increasing the dose of iobenguane I-123 will not overcome any potential effect of these drugs.

MANAGEMENT: When medically feasible, any drug that blocks norepinephrine uptake or deplete norepinephrine stores should be discontinued for at least five biological half-lives before iobenguane I-123 administration. Patients should be monitored for the occurrence of clinically significant withdrawal symptoms, especially patients with elevated levels of circulating catecholamines and their metabolites.