Major
Established
Description
Pregabalin combined with oxycodone produces synergistic respiratory and CNS depression, substantially elevating overdose risk.
Mechanism
Pregabalin modulates presynaptic calcium influx and GABA-ergic tone; oxycodone activates mu-opioid receptors — combined, they produce supra-additive respiratory depression.
Clinical Significance
Gabapentinoid + opioid combinations are implicated in a growing proportion of overdose deaths in multiple countries.
Management
Avoid unless no alternative exists; use minimum effective doses and consider prescribing naloxone to the patient.