Drug Interactions between fluoxetine and paroxetine

GENERALLY AVOID: Fluoxetine and paroxetine are both substrates as well as inhibitors of the CYP450 2D6 isoenzyme. During coadministration or sequential use without a sufficient washout period, plasma concentrations of both drugs may be increased due to competitive inhibition and saturation of CYP450 2D6. Enhanced drug effects may also occur because of duplicative pharmacodynamic activities. In particular, increased serotonergic effects may potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MANAGEMENT: Concomitant use of fluoxetine and paroxetine should generally be avoided. Lower dosages and/or more gradual titration should be considered during initiation of therapy with one selective serotonin reuptake inhibitor shortly after discontinuing the other. The potential for interaction may exist if fluoxetine is administered within approximately 2 weeks after the withdrawal of paroxetine, or if paroxetine is administered within 5 weeks after withdrawal of fluoxetine. Close monitoring is recommended for signs and symptoms of excessive serotonergic activity. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary. Moderately ill patients may also benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures.