Gabapentin

Co-administration of gabapentin with opioids (prescription or illicit) is contraindicated due to compounded respiratory depression risk. A population-based nested case-control study demonstrated significantly increased risk of opioid-related death with gabapentin co-prescription. Gabapentinoid use by heroin users substantially increases overdose risk.

Co-administration with benzodiazepines or other CNS depressants requires caution due to additive sedation and respiratory depression. Risk increases with higher doses of either agent and in the presence of additional CNS depressants.

Concurrent recreational alcohol use amplifies sedation and respiratory depression risk. While gabapentin is used therapeutically for alcohol withdrawal under medical supervision, unsupervised co-use carries additive CNS depressant risk.

Patients with depression or history of suicidal ideation require monitoring during gabapentin therapy per the FDA class-wide AED warning. The magnitude of risk specific to gabapentin (vs the AED class as a whole) is debated.

Dose reduction is mandatory in patients with reduced renal function. Standard dosing in renal impairment produces drug accumulation due to gabapentin's exclusive renal elimination pathway. Hemodialysis effectively removes gabapentin.

Human pregnancy registry data are limited. No adverse fetal effects in mice (up to 3,000 mg/kg) or rats (up to 1,500 mg/kg). Rabbit data show maternal toxicity at 1,500 mg/kg. Benefits must outweigh potential risks.

Elderly patients have reduced gabapentin clearance due to age-related renal function decline. Dose adjustment based on creatinine clearance is necessary. Falls risk is elevated due to ataxia and dizziness.

Prescribing gabapentin to individuals with active or past substance use disorder — particularly opioid use disorder — requires careful risk-benefit assessment and monitoring. Misuse prevalence is approximately 26% in OUD populations vs 4% in non-OUD populations.