Pregabalin

Peripheral edema is a common adverse effect that may worsen fluid balance in patients with pre-existing heart failure. Dose-dependent effect.

Concurrent use of pregabalin with opioids significantly increases morbidity and mortality through additive respiratory depression. Scottish national mortality data and French addictovigilance confirm this as the highest-risk interaction.

Co-administration with benzodiazepines or Z-drugs produces additive CNS depression. A fatal case involved pregabalin with flunitrazepam and zolpidem.

Patients with prior substance use disorder — particularly opioid use disorder — have elevated risk of pregabalin misuse and dependence. Primary abuse without prior SUD has also been documented.

Dose adjustment is mandatory for CLcr <60 mL/min. Standard doses in severe renal impairment produce accumulation and increased adverse effect severity. Pregabalin is cleared by hemodialysis.

Pregabalin is contraindicated in pregnancy unless benefit clearly outweighs risk. Teratogenicity demonstrated in preclinical models; human cohort data are limited but concerning.

Alcohol consumption during pregabalin use produces additive sedation and respiratory depression. No dedicated interaction study published but clinically contraindicated.