Drug interactions between Elavil and Prozac Weekly

GENERALLY AVOID: Coadministration with fluoxetine may significantly increase the plasma concentrations of some tricyclic antidepressants (TCAs). The proposed mechanism is fluoxetine inhibition of CYP450 2D6, the isoenzyme responsible for the metabolic clearance of many antidepressant and psychotropic drugs. Seizures and delirium have been reported, as well as a fatality attributed to fluoxetine-induced chronic amitriptyline toxicity. Pharmacodynamically, the combination of fluoxetine (or any other selective serotonin reuptake inhibitor) and a TCA may potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5HT1A receptors.

MANAGEMENT: In general, the use of fluoxetine (or other SSRIs) with TCAs should be avoided if possible, or otherwise approached with caution if potential benefit is deemed to outweigh the risk. Pharmacologic response and plasma TCA levels should be monitored more closely whenever fluoxetine is added to or withdrawn from therapy in patients stabilized on their existing antidepressant regimen, and the TCA dosage adjusted as necessary. Patients should be monitored closely for signs and symptoms of TCA toxicity (e.g., sedation, dry mouth, blurred vision, constipation, urinary retention) and/or excessive serotonergic activity (e.g., CNS irritability, altered consciousness, confusion, myoclonus, ataxia, abdominal cramping, hyperpyrexia, shivering, pupillary dilation, diaphoresis, hypertension, and tachycardia). Due to the long half-life of fluoxetine and its active metabolite, norfluoxetine, the risk of interaction may persist for several weeks after discontinuation of fluoxetine.