Drug interactions between fluvoxamine and Ultracet

GENERALLY AVOID: The coadministration of selective serotonin reuptake inhibitors (SSRIs) with tramadol, which has weak serotonin reuptake inhibiting effect, 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. Patients receiving this combination may also have an increased risk of seizures. Pharmacokinetically, coadministration with certain SSRIs, namely fluoxetine, paroxetine and possibly sertraline, may result in decreased plasma concentrations of the active O-demethylated (M1) metabolite of tramadol due to inhibition of CYP450 2D6, the isoenyzme responsible for the formation of the metabolite. The clinical significance of this potential interaction is unknown. However, M1 is thought to possess up to 6 times the analgesic effect of tramadol, thus diminished therapeutic response to tramadol should be considered.

MANAGEMENT: In general, the concomitant use of SSRIs and tramadol should be avoided if possible, or otherwise approached with caution if potential benefit is deemed to outweigh the risk. Patients treated with the combination should be closely monitored for signs and symptoms of excessive serotonergic activity such as CNS irritability, altered consciousness, confusion, myoclonus, ataxia, abdominal cramping, hyperpyrexia, shivering, pupillary dilation, diaphoresis, hypertension, and tachycardia.