Gabapentin
Neurontin · Gabapentin Actavis · Gabapentin Orion · Gabapentin Accord
The same mechanism as pregabalin — binding to the α2δ subunit of voltage-gated calcium channels — but with a critical difference in kinetics: absorption occurs via a saturable amino acid transporter in the gut, so bioavailability falls as the dose rises and the dose–concentration relationship is non-linear. Hence the wide dose range and three-times-daily regimen. Used in peripheral neuropathic pain and as adjunctive treatment in focal epilepsy. Excreted unchanged renally, making renal function the single most important dosing variable.
The combination with opioids substantially increases the risk of respiratory depression and death, and the risk exists even at low doses. In renal failure gabapentin accumulates rapidly — a full dose at eGFR below 30 ml/min causes sedation, ataxia, and myoclonus that can easily be misinterpreted as progressive neurological disease.
Dosing in adults
| Indication | Regimen | Comment |
|---|---|---|
| Neuropathic pain, uptitration | Day 1: 300 mg × 1. Day 2: 300 mg × 2. Day 3: 300 mg × 3 | in the elderly or frail patient, start with 100 mg at night and titrate more slowly |
| Neuropathic pain, maintenance | 900–3 600 mg per day divided into 3 doses, maximum 3 600 mg | the interval between doses must not exceed 12 hours |
| Focal epilepsy, adjunctive treatment | Titration as above to 900–3 600 mg per day divided into 3 doses | may be titrated more rapidly when needed, 300 mg × 3 already on day 1 in adults |
| Dose increase step | Increase by 300 mg per day every 2 to 3 days until effect or adverse effect | sedation and dizziness usually resolve within one to two weeks on an unchanged dose |
| Discontinuation | Taper over at least one week, regardless of indication | abrupt discontinuation may trigger seizures in the epilepsy patient and withdrawal symptoms in others |
Dose must be guided by creatinine clearance — this is the most common dosing error. CrCl ≥ 80 ml/min: 900–3 600 mg per day in 3 doses. CrCl 50–79: 600–1 800 mg per day. CrCl 30–49: 300–900 mg per day. CrCl 15–29: 150–600 mg per day. CrCl below 15: 150–300 mg per day, and below 15 ml/min the daily dose is reduced proportionally to clearance. In haemodialysis in an anuric patient: loading dose 300–400 mg, then 200–300 mg after each four-hour dialysis session.
No dose adjustment required — gabapentin is not metabolised in the liver.
Adjunctive treatment in focal epilepsy from age 6: 25–35 mg/kg per day divided into 3 doses, titrated over at least 3 days. For children aged 3–5 years, 40 mg/kg per day. Doses up to 50 mg/kg per day have been used. Initiation via paediatric neurologist; the neuropathic pain indication is not established in children.
Do not initiate gabapentin without a current eGFR, and do not start at the target dose. The classic pitfall is the elderly patient with eGFR around 30 ml/min who receives 300 mg × 3 from the start: after just over a week the concentration has multiplied several-fold and the patient presents with gait ataxia, myoclonus, and confusion. Also accept that the effect on neuropathic pain is absent in a substantial proportion — without pain relief on an adequate dose after four weeks the drug should be tapered, not escalated.
Pharmacokinetics
- ONSET
- Pain relief after several days on an adequate dose
- Tmax
- 2–3 hours
- BIOAVAIL.
- approximately 60 % at 300 mg, falls with rising dose (saturable absorption)
- t½
- 5–7 hours at normal renal function, up to 52 hours in anuria
- PROTEIN BINDING
- Below 3 %
- METABOLISM
- None — not metabolised in the liver and does not induce enzymes
- EXCRETION
- Renal, unchanged, proportional to creatinine clearance
- DIALYSIS
- Efficiently removed by haemodialysis