Drug Interactions between nefazodone and vilazodone

MONITOR CLOSELY: Concomitant use of vilazodone with other agents that possess serotonergic activity including nefazodone 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, hallucinations, 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.

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 including nefazodone may increase the plasma concentrations of vilazodone, which is primarily metabolized by the isoenzyme. According to the product labeling, concomitant use of vilazodone with potent CYP450 3A4 inhibitors can increase vilazodone plasma concentrations by approximately 50%.

MANAGEMENT: In general, the concomitant use of multiple serotonergic agents should be avoided if possible, or otherwise approached with caution if potential benefit is deemed to outweigh the risk. Patients should be closely monitored for symptoms of the serotonin syndrome during treatment. Particular caution is advised when increasing the dosages of these agents. The potential risk for serotonin syndrome should be considered even when administering serotonergic agents sequentially, as some agents may demonstrate a prolonged elimination half-life. 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.

MANAGEMENT: The maintenance dosage of vilazodone should be reduced to 20 mg/day when used with potent CYP450 3A4 inhibitors.