Drug interactions between Inderal LA and Prozac

MONITOR: Limited clinical data suggest that selective serotonin reuptake inhibitors (SSRIs) may potentiate the pharmacologic effects of some beta-blockers. There have been case reports of patients stabilized on beta-blocker therapy who developed bradycardia, hypotension, and complete heart block following the addition of a SSRI, subsequently requiring discontinuation of one or both agents and/or institution of a permanent pacemaker. The interaction is also corroborated by data from in vitro and clinical studies involving paroxetine and metoprolol conducted by one group of investigators. The proposed mechanism is SSRI inhibition (competitive and/or noncompetitive) of CYP450 2D6, the isoenzyme responsible for the metabolic clearance of beta-blockers such as carvedilol, labetalol, metoprolol, nebivolol, propranolol, and timolol. Paroxetine and norfluoxetine (the active metabolite of fluoxetine), in particular, are potent inhibitors of CYP450 2D6 and may be more likely than other SSRIs to cause the interaction. On the other hand, fluvoxamine is a potent inhibitor of CYP450 1A2 and may significantly interact with propranolol, which is a substrate of both CYP450 2D6 and 1A2.

MANAGEMENT: During concomitant therapy with SSRIs, a lower initial dosage and more cautious titration of the beta-blocker may be appropriate. Cardiac function should be closely monitored and the beta-blocker dosage adjusted accordingly, particularly following initiation, discontinuation or change of dosage of SSRI in patients who are stabilized on their beta-blocker regimen. Due to the long half-life of fluoxetine and its active metabolite, norfluoxetine, the risk of an interaction may exist for an extended period (up to several weeks) after discontinuation of fluoxetine. To avoid the interaction, use of beta-blockers that are primarily eliminated by the kidney such as atenolol, acebutolol, betaxolol, carteolol, and nadolol may be considered.