Drug interactions between Cymbalta and fluvoxamine

GENERALLY AVOID: Coadministration with fluvoxamine may significantly increase the plasma concentrations of duloxetine. The mechanism is fluvoxamine inhibition of duloxetine metabolism via CYP450 1A2. In 14 male study subjects, fluvoxamine caused a 2.5-fold increase in duloxetine peak plasma concentration (Cmax), a nearly 6-fold increase in duloxetine systemic exposure (AUC), and an approximately 3-fold increase in duloxetine half-life. High plasma levels of duloxetine may increase the risk of serious cardiovascular effects such as hypertension, hypertensive crisis, increased heart rate, orthostatic hypotension, and syncope. In addition, the risk of serotonin syndrome may be potentiated, not just due to elevated levels of duloxetine but also because of additive serotonergic effects from coadministration with fluvoxamine, an SSRI. Serotonin syndrome is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms 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, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MANAGEMENT: Concomitant use of duloxetine with fluvoxamine should be avoided.