Gabapentin

Gabapentin is a gabapentinoid used as adjunct therapy for focal seizures and as a first-line option for neuropathic pain. It has saturable absorption, is excreted unchanged by the kidneys, and has few drug interactions, but causes sedation and dizziness and is misused, particularly alongside opioids.

Mechanism. Binds the alpha-2-delta subunit of voltage-gated calcium channels and reduces excitatory neurotransmitter release. It has no direct action on GABA receptors.

Pharmacokinetics. Absorbed by a saturable amino acid transporter, so bioavailability falls from about 60% at 900 mg daily to about 33% at 3600 mg daily. It is not protein bound or metabolised. Half-life is 5 to 7 hours. Aluminium and magnesium antacids lower bioavailability by about 20%.

First-line use. Neuropathic pain, including painful diabetic neuropathy and post-herpetic neuralgia.

• Adults, oral gabapentin for neuropathic pain: 300 mg on day 1, 300 mg twice daily on day 2, 300 mg three times daily on day 3, then increase in steps of 300 mg every 2 to 3 days. Usual maintenance 1800 to 3600 mg daily in three divided doses. Maximum 3600 mg daily. Review after 4 to 6 weeks at the target dose; stop if no benefit.

• Older adults or frail people: start 100 mg at night and titrate slowly.

Alternative use. Adjunct for focal seizures with or without generalisation:

• Adults and children over 12 years: same titration, usual maintenance 900 to 3600 mg daily in three divided doses, with intervals between doses of no more than 12 hours. Maximum 3600 mg daily.

• Children 3 to 11 years: 10 to 15 mg/kg daily in three doses initially, titrated over about 3 days to 40 mg/kg daily at 3 to 4 years, and 25 to 35 mg/kg daily at 5 to 11 years.

Kidney function. Adult daily dose by creatinine clearance:

• Haemodialysis: give maintenance by creatinine clearance, plus a supplemental dose of 125 to 350 mg after each session.

• Liver: no adjustment.

Contraindications. Hypersensitivity.

Serious adverse effects. Respiratory depression, particularly with opioids, other sedatives, older age, chronic lung disease or renal impairment. Drug reaction with eosinophilia and systemic symptoms, suicidal ideation, withdrawal seizures if stopped abruptly, and misuse or dependence.

Common adverse effects. Dizziness, somnolence, ataxia, peripheral oedema, weight gain, blurred vision and myoclonus.

Interactions. Opioids increase sedation and respiratory depression, and morphine raises gabapentin exposure by about 44%. Other sedatives and alcohol add to central nervous system depression. Antacids lower absorption, so give gabapentin at least 2 hours after them.

Common prescribing errors. Not adjusting for kidney function. Fast titration in older adults. Co-prescribing with opioids without warning. Abrupt withdrawal.

Special groups.

• Pregnancy: limited data; use only if benefit outweighs risk.

• Breastfeeding: low infant exposure; usually acceptable with monitoring for drowsiness.

• Older adults: high risk of falls, confusion and sedation; lower starting doses.

• Regional: diversion and misuse are recognised in some settings, so limit supply and review use.

Formulations. Capsules 100, 300 and 400 mg. Tablets 600 and 800 mg. Oral solution 250 mg/5 mL. Take with or without food.

Monitoring.

• Baseline: creatinine clearance, falls risk, concurrent sedatives, mood and substance use history.

• Ongoing: pain scores, sedation, respiratory status, oedema, weight and renal function. Levels are not used.

Stopping. Taper over at least 1 week. Seizure disorders need slower tapers.

Referral and escalation. Refer neuropathic pain that fails two to three adequate drug trials to pain or neurology services. Urgent review for respiratory depression or suspected misuse.