Major
Pregabalin × Tramadol
Gabapentinoids (antiepileptics)×Other opioids
Mechanism
Similar to tramadol + gabapentin: additive CNS depression, seizure risk (tramadol lowers threshold). FDA issued a 2019 warning about respiratory depression with opioid-gabapentinoid combinations.
Symptoms
Drowsiness, sedation, slowed breathing. Seizures (tramadol) and syncope from orthostatic hypotension are possible. Older patients: fall risk.
Management
The combination is possible in neuropathic pain. Keep doses minimal, start low. Warn the patient about drowsiness and ataxia. Older patients: enhanced fall monitoring. Alternative opioid for neuropathic pain: pure opioid agonist (morphine, oxycodone) without serotonergic activity.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.