Gabapentin
First line gabapentinoid
Mechanism of action: Gabapentin displays high affinity binding to the alpha2-delta subunits of voltage-gated calcium channels in central nervous system neurones, thus reducing the release of neurotransmitters. It is a chemical analogue of GABA but has no activity in GABAergic neuronal systems.
Presentation: capsule (which can be opened, and the contents sprinkled onto food or dissolved in water if needed). Tablets are not available in the OUH.
Suggested initial dose: 300mg once, then twice, then three times a day on sequential days for adults over 50kg with normal hepatic and renal function; reduce in frailty to 100mg per dose. Maximum 3600mg per day in divided doses.
Avoid abrupt withdrawal.
It usually takes up to 7 days for the analgesic effect to become clinically beneficial.
Oral absorption: Bioavailability of 60% at a dose of 900mg/day, reducing to 33% at 3600mg/day. Peak plasma concentrations are reached at 3-4 hours. Gabapentin exhibits saturable absorption – a zero order process - such that its pharmacokinetics are less predictable and plasma concentrations do not increase proportionally with increasing dose. It is absorbed mainly in the small intestine with minimal absorption in the colon.
Protein binding: Gabapentin does not bind to plasma proteins
Metabolism: not appreciably metabolized
Elimination: renal excretion as unchanged drug.
Reduce dose in renal failure, e.g. 100mg once a day.
Half-life: 6 hours
Common side effects include: sedation, dizziness, weakness, weight gain, peripheral oedema.
Further prescribing information (side effects, contraindications, interactions):
For frail patients Principles of Prescribing for the Older Person, or those with renal dysfunction Oral Analgesic Dose Adjustments in Renal Impairment, start at doses of 100mg.