Drug Interaction Report

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.

GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.