Drug Interactions between Tegretol XR and tramadol

GENERALLY AVOID: Coadministration with carbamazepine may significantly decrease the plasma concentrations of tramadol. The proposed mechanism is carbamazepine induction of CYP450 3A4, the isoenzyme partially responsible for the metabolic clearance of tramadol. Reduced analgesic efficacy, shortened duration of action, or withdrawal symptoms may occur in patients maintained on their narcotic pain regimen following the addition of carbamazepine. Conversely, discontinuation of carbamazepine may increase tramadol plasma concentrations and potentiate the risk of overdose, fatal respiratory depression, and serious adverse reactions such as seizures, serotonin syndrome, gastrointestinal obstruction, and QT interval prolongation. Because tramadol can lower seizure threshold and induce seizures, the anticonvulsant efficacy of carbamazepine may also be diminished during concomitant use. In addition, patients may experience additive central nervous system (CNS) adverse effects such as sedation, dizziness, confusion, and impairment of attention, judgment, thinking, and psychomotor skills.

MANAGEMENT: Concomitant use of tramadol and carbamazepine should generally be avoided. If coadministration is required, dosage adjustments for tramadol may be necessary, particularly following initiation, discontinuation, or change of dosage of carbamazepine. Patients receiving chronic carbamazepine dosages of up to 800 mg/day may require up to twice the recommended dosage of tramadol. Patients should be monitored closely for signs and symptoms of CNS and respiratory depression, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them. Patients should also be apprised of the epileptogenic effect of tramadol and the potential for loss of seizure control.

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