Generic Name

Neurontin (gabapentin)

Mechanism

Neurontin (gabapentin) is a structural analogue of the neurotransmitter gamma‑aminobutyric acid (GABA) but does not bind GABA receptors.
• Selective binding to the α₂δ subunit of voltage‑gated calcium channels (VGCCs) in dorsal root ganglion and spinal cord neurons.
• *Inhibition of calcium influx* ↓ excitatory neurotransmitter release (glutamate, norepinephrine, substance P).
• *Reduction in neuronal hyperexcitability* leads to its anticonvulsant, neuropathic pain, and anxiolytic effects.

Pharmacokinetics

• Absorption: Rapid, linear uptake; bioavailability ≈ 60 % (decreases with higher doses).
• Distribution: Moderate protein binding (< 10 %). Volume of distribution ≈ 0.4 L/kg.
• Metabolism: Minimal hepatic metabolism – largely unchanged. Cleared unchanged by the kidneys.
• Elimination: 60–70 % excreted unchanged in urine; terminal half‑life ≈ 5–7 h (dose‑dependent).
• Renal dosing: Adjust dose proportional to creatinine clearance.

Indications

• Partial‑onset seizures (adjunctive therapy in adults and children > 12 yrs).
• Peripheral neuropathic pain secondary to diabetic neuropathy, post‑herpetic neuralgia, or spinal cord injury.
• Tic disorders (as adjunct in Tourette’s).
• Off‑label uses: Restless legs syndrome, fibromyalgia, chronic migraine prophylaxis, and certain anxiety disorders.

Contraindications

• Contraindications:
• Hypersensitivity to gabapentin or components.
• Warnings:
• *Renal impairment*: Accumulation → CNS toxicity.
• *Drug interactions*: Avoid concomitant use with opioids or other CNS depressants.
• *Pregnancy*: Category C – use only if benefits outweigh risks.
• *Abrupt discontinuation*: Can precipitate withdrawal seizures or rebound pain.

Dosing

• Adults (partial seizures):
• Initiate 300 mg/day → titrate 300 mg qid as needed.
• Target therapeutic range: 900–3600 mg/day.
• Neuropathic pain:
• Start 300 mg/day → typically 900–1800 mg/day divided qtid.
• Renal adjustment:
• eGFR 30‑60 mL/min: reduce dose by half.
• eGFR  1200 mg/day.
• Route: Oral capsules or solution.
• Administration tip: Allow patient to split dose to mitigate dizziness or somnolence.

Adverse Effects

• Common (≥ 5 %)
• Somnolence, dizziness, ataxia, peripheral edema, blurred vision.
• Gastrointestinal: nausea, vomiting, constipation.
• Serious (≤ 1 %)
• Seizure recurrence or breakthrough seizures (if dose inadequate).
• Severe hypersensitivity reactions: rash, angioedema, anaphylaxis.
• Psychiatric: agitation, anxiety, suicidal ideation.
• Renal crystal precipitation (rare, high doses).

Monitoring

• Baseline: Renal function (serum creatinine, eGFR), weight, CBC if long‑term.
• Follow‑up: Weight, renal function every 3–4 weeks for 3 months, then annually.
• Clinical: Seizure frequency, pain score, cognitive function, signs of drug accumulation.
• Lab: Not routinely required unless renal dysfunction or suspected toxicity.

Clinical Pearls

• Titrate cautiously: Sudden dose escalation can provoke dizziness, sedation, and ataxia – start low and go slow.
• Renal dosing: Calculate adjusted dose = (Target daily dose) × (Patient CrCl / 120 mL/min) to avoid toxicity.
• Drug interactions: Gabapentin competes for urinary excretion; co‑administration with other renally cleared agents may elevate levels.
• Seizure vs. pain: Use efficacy data from appropriate trials; neuropathic pain thresholds differ from seizure control doses.
• Patient education: Emphasize not to abruptly stop; taper over weeks to prevent rebound seizures or withdrawal.
• Mood monitoring: Screen for depression or suicidal ideation in patients on long‑term gabapentin, especially with epilepsy.

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• References

1. Katz IR, et al. *Epilepsia.* 2006.

2. McCall WA, et al. *Neurology.* 2016.

3. American Academy of Neurology Practice Guidelines, 2023.