gabapentin
Anticonvulsant· Brands: Neurontin, Gralise, GabapinPO
Mechanism of action
Gabapentin binds to the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system. This binding reduces the release of excitatory neurotransmitters, including glutamate, and stabilises neuronal excitability. Its exact anticonvulsant mechanism is not fully understood, but it is thought to modulate calcium influx and inhibit ectopic neuronal firing.
Pharmacokinetics
Gabapentin is well absorbed after oral administration, with absorption saturable at higher doses. It is not significantly protein bound, undergoes minimal metabolism, and is excreted unchanged in the urine. The elimination half-life is approximately 5 to 7 hours in patients with normal renal function, and dosage adjustment is required in renal impairment.
Indications & dosing
Partial seizures (adjunctive therapy)
Titrate gradually; reduce in renal impairment.
- adult · PO: 300–1200 mg TID · Titrate gradually; reduce in renal impairment.
Postherpetic neuralgia
Start at 300 mg at night, then titrate up to 600 mg TID.
- adult · PO: 300–600 mg TID · Start at 300 mg at night, then titrate up to 600 mg TID.
Painful diabetic neuropathyoff-label
Off-label; similar dosing to postherpetic neuralgia.
- adult · PO: 300–600 mg TID · Off-label; similar dosing to postherpetic neuralgia.
Contraindications & precautions
- Known hypersensitivity to gabapentin or any excipient · May present as rash, fever, or eosinophilia with prior use.
- Acute pancreatitis · Gabapentin may cause or exacerbate pancreatitis; use with caution.
- Avoid abrupt withdrawal; taper gradually over at least one week to prevent rebound seizures.
- Dose adjustment is required in renal impairment; consult local guidance.
- Concomitant use with opioids or other CNS depressants increases risk of respiratory depression and sedation; monitor closely.
- May impair driving ability; advise patients not to drive until effects are known.
- Has abuse potential; use with caution in patients with a history of substance misuse.
- Monitor for signs of suicidal ideation or changes in behaviour.
Adverse effects
- Dizziness
- Somnolence
- Ataxia
- Peripheral oedema
- Angioedemaserious
- Stevens-Johnson syndromeserious
- Respiratory depression (especially with opioids or CNS depressants)serious
- Suicidal ideation or behaviourserious
Renal & hepatic adjustment
- eGFR 60+: No adjustment required; usual dose. For neuropathic pain, usual dose up to 3600 mg daily in 3 divided doses.
- eGFR 30–59: Reduce dose; e.g., 400-1400 mg daily in 2 divided doses.
- eGFR 15–29: Reduce dose; e.g., 200-700 mg once daily.
- eGFR 0–14: Reduce dose; e.g., 100-300 mg once daily. Consider supplemental dose after haemodialysis.
Monitoring, pregnancy & toxicity
- CNS effects (drowsiness, dizziness, ataxia) · At each review
- Seizure frequency (when used for epilepsy) · Regularly
- Mood and behaviour (risk of suicidal ideation) · At each review
- Signs of misuse or dependence · At each review
- Pregnancy: Not recommended during pregnancy unless clearly necessary; seek specialist advice.
- Toxicity: Drowsiness, dizziness, ataxia, nystagmus, tremors, hypotension, coma · Supportive care; consider activated charcoal if recent ingestion; haemodialysis may be helpful in severe cases or renal impairment.
- Toxicity: Seizures (in overdose, paradoxical effect possible) · Standard anticonvulsant management; monitor and support.
Clinical notes
Gabapentin is used as adjunctive therapy for focal seizures and for the management of neuropathic pain, such as postherpetic neuralgia. Treatment should be initiated at a low dose and titrated gradually to minimise adverse effects, which include somnolence, dizziness, and peripheral oedema. Abrupt withdrawal should be avoided, as it may precipitate seizures or rebound pain. Caution is needed in patients with renal impairment, and doses should be adjusted according to creatinine clearance.
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BNF; local formulary; manufacturer's prescribing information