Major
Morphine × Tramadol
Natural opium alkaloids×Other opioids
Mechanism
Additive CNS and respiratory centre depression. Tramadol is also serotonergic and lowers seizure threshold.
Symptoms
Drowsiness, slowed breathing (rate below 12/min), cyanosis of lips. Severe cases include respiratory arrest. Older patients: fall risk.
Management
Avoid the combination. To strengthen opioid analgesia on tramadol, switch to a pure opioid agonist (morphine, oxycodone) and stop tramadol. Dual opioid therapy is only used in palliative care with careful respiratory monitoring.