Drug-Drug Interaction


TRICYCLIC COMPOUNDS; CARBAMAZEPINE/TRAMADOL

MECHANISM OF ACTION
Tramadol and tricyclic compounds, including carbamazepine, may lower the seizure threshold.(1) Carbamazepine may also induce the metabolism of tramadol.(1)

DISCUSSION
The use of tramadol in patients treated with tricyclic compounds may increase the risk of seizures.(1) A review of 124 reports of seizures following tramadol therapy received by the FDA through July 31, 1996 revealed that 23% of the patients were also taking tricyclic antidepressants.(3) Therefore, the manufacturer of tramadol states that tramadol should be used with caution in patients treated with tricyclic compounds.(1) The manufacturer of tramadol also states that the use of tramadol with carbamazepine is not recommended.(1)

CLINICAL EFFECTS
Concurrent use of tramadol and a tricyclic compound may result in seizures(1) or serotonin syndrome.(2) Concurrent use of tramadol and carbamazepine may result in seizures and decreased efficacy of tramadol. (1)

SEVERITY LEVEL
2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

PATIENT MANAGEMENT
Tramadol should be used with caution in patients taking tricyclic compounds.(1) The use of tramadol and carbamazepine is not recommended.(1)

PREDISPOSING FACTORS
Risk of seizures may be increased in patients with epilepsy, a history of seizures, head trauma, metabolic disorders, alcohol or drug withdrawal, or infections of the central nervous system.(1)

REFERENCES

  1. Ultram (tramadol) US prescribing information. Ortho-McNeil Pharmaceutical, .Ultram (tramadol) US prescribing information. Ortho-McNeil Pharmaceutical, Inc. May, 2004.
  2. Kitson R, Carr B. Tramadol and severe serotonin syndrome. Anaesthesia 2005 .Kitson R, Carr B. Tramadol and severe serotonin syndrome. Anaesthesia 2005 Sep;60(9):934-5.
  3. Kahn LH, Alderfer RJ, Graham DJ. Seizures reported with tramadol. JAMA .Kahn LH, Alderfer RJ, Graham DJ. Seizures reported with tramadol. JAMA 1997 Nov 26;278(20):1661.