tramadol and linezolid

Pharmacodynamic interaction: both drugs increase serotonergic activity in the CNS. Tramadol inhibits serotonin reuptake and promotes serotonin release; linezolid inhibits monoamine oxidase, reducing the breakdown of serotonin. Combined effects can lead to excessive serotonin accumulation.

Patients are at risk of serotonin syndrome, which may present as agitation, confusion, tachycardia, hyperthermia, myoclonus, and in severe cases, seizures, rhabdomyolysis, and death. Tramadol also lowers the seizure threshold, which may be further reduced by linezolid.

Avoid co-prescription. If co-administration is considered essential, use the lowest possible doses and monitor frequently for early signs of serotonin syndrome. Consider alternative analgesic agents with no serotonergic activity. If serotonin syndrome is suspected, stop both drugs immediately and provide supportive care.

Well documented in case reports and pharmacovigilance data; recognised as a clinically important interaction. Many formularies recommend avoiding the combination.