Major
Established
Description
Gabapentin and oxycodone together produce enhanced CNS and respiratory depression beyond what either drug causes alone, with risk of fatal overdose.
Mechanism
Gabapentin inhibits voltage-gated calcium channels and enhances GABA-ergic inhibition; opioids suppress brainstem respiratory centers via mu receptors — synergistic CNS depression results.
Clinical Significance
Epidemiological data from Canada and the UK show a significant increase in opioid-related overdose deaths when gabapentinoids are co-prescribed.
Management
Avoid combination unless clearly indicated; use lowest effective doses, monitor respiratory rate and sedation level.