Ultracet and Paxil interaction

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Ultracet (acetaminophen-tramadol) and Paxil (paroxetine)

* The interaction is due to tramadol which is a component of Ultracet

GENERALLY AVOID: The coadministration of serotonin reuptake inhibitors

(SSRIs) and other agents with serotonergic activity, including tramadol, 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 of drugs may

also experience an increased risk of seizures. In addition, the

coadministration of certain selective SSRIs (fluoxetine, paroxetine,

sertraline) with tramadol may result in decreased plasma concentrations of

the active metabolite of tramadol. The mechanism is SSRI-induced inhibition

of CYP450 2D6 enzymatic activity, which is involved in the formation of the

tramadol metabolite. While clinical data are lacking, the possibility of

reduced therapeutic response to tramadol should be considered in patients

receiving these SSRIs. Fluvoxamine and citalopram are SSRIs with weak CYP450

2D6-inhibiting activity and may be less likely to cause this interaction.

MANAGEMENT: In general, the concomitant use of serotonin reuptake inhibitors

and tramadol should be avoided if possible, or otherwise approached with

caution if potential benefit is deemed to outweigh the risk. Close

monitoring is recommended 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.

References for Ultracet (acetaminophen-tramadol) and Paxil (paroxetine)

Drug-Drug interaction

Sternbach H. The serotonin syndrome. Am J Psychiatry 1991;148:705-13.

Mason BJ, Blackburn KH. Possible serotonin syndrome associated with tramadol

and sertraline coadministration. Ann Pharmacother 1997;31:175-7.

Anonymous. Product Information. Ultram (tramadol). McNeil Pharmaceutical,

Raritan, NJ.

Mills KC. Serotonin syndrome: A clinical update. Crit Care Clin 1997;13:763.

Egberts AC, ter Borg J, Brodie-Meijer CC. Serotonin syndroome attributed to

tramadol addition to paroxetine therapy. Int Clin Psychopharmacol

1997;12:181-2.