Gabapentin × Morphine

Morphine and gabapentin both depress the central nervous system, and the effects add up: the risk of profound sedation, respiratory depression, coma and death rises. The kinetic effect goes one way: controlled-release morphine taken 2 hours before gabapentin raised gabapentin AUC by 44%, while gabapentin did not change morphine pharmacokinetics. In December 2019 the FDA warned about serious breathing problems when gabapentinoids are combined with opioids.

Drowsiness, slowed breathing (rate below 12/min), cyanosis of lips. Severe cases include respiratory arrest. Older patients: fall risk.

The US morphine label reserves the combination for patients whose alternative treatment options are inadequate, and the Spanish label requires limiting the dose and duration of concomitant use. Start gabapentin at a low dose. If drowsiness or slowed breathing appears, reduce the gabapentin or morphine dose per the label. Monitor respiratory rate, oxygen saturation and level of consciousness, with extra care in older adults and in patients with lung disease or renal impairment. Prescribe naloxone and teach the patient and family the signs of overdose.