Drug Interaction Report

MONITOR: Limited data suggest that labetalol can increase the plasma concentrations of tricyclic antidepressants. The proposed mechanism is competition for the same metabolic pathway. In a study (n=13), imipramine AUC increased by 53% in subjects taking labetalol compared to placebo. The manufacturers of labetalol indicate that concomitant use with tricyclic antidepressants may increase the incidence of tremors and hypotensive events. Carvedilol may also interact similarly.

MANAGEMENT: Close monitoring for clinical response and tolerance is recommended whenever labetalol is added to or discontinued from an antidepressant regimen. Patients should be advised to notify their physician if they experience excessive antidepressant effects such as tremor, dry mouth, blurry vision, irregular or fast heartbeat, constipation, urinary retention, dizziness, or hypotension. Dose adjustments may be necessary.

MONITOR: Limited data suggest that the administration of clomipramine with grapefruit juice or cranberry juice may significantly increase plasma drug concentrations of clomipramine. Clomipramine is initially demethylated by CYP450 1A2, 3A3 and 3A4 before undergoing further metabolism to 8-hydroxyclomipramine. The increase in clomipramine bioavailability may stem from inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The precise mechanism by which cranberry juice exerts its effects is unknown, but may involve inhibition of CYP450 isoenzymes. This interaction has occasionally been exploited in attempts to improve symptomatic control of obsessive compulsive disorder.

MANAGEMENT: Patients receiving clomipramine therapy who ingest cranberry juice, grapefruits, or grapefruit juice should be monitored for adverse effects and undue fluctuations in plasma drug levels.

GENERALLY AVOID: The combination of ethanol and a tricyclic antidepressant may result in additive impairment of motor skills, especially driving skills. Also, one study has suggested that clomipramine metabolism is significantly impaired for several weeks or more following discontinuation of chronic alcohol consumption.

MANAGEMENT: Patients should be warned of this interaction and advised to limit their ethanol intake while taking tricyclic antidepressants. Monitoring for TCA toxicity (CNS depression, excessive anticholinergic effects, hypotension, arrhythmias) is recommended during alcohol withdrawal.