In a patient with focal (partial‑onset) epilepsy refractory to first‑line agents, can gabapentin be used, and what are the recommended dosing, renal dose adjustments, and common adverse effects?

Gabapentin for Focal (Partial-Onset) Epilepsy

Role as Adjunctive Therapy

Gabapentin is an effective adjunctive (add-on) agent for patients with refractory focal seizures, reducing seizure frequency by ≥50% in 18–28% of patients when added to existing antiepileptic regimens. 1, 2

• Gabapentin is specifically indicated as adjunctive therapy for partial-onset seizures with or without secondary generalization in patients ≥12 years of age who have failed first-line agents 3
• Three large randomized, placebo-controlled trials established that gabapentin 600–1800 mg/day provides notable benefit in refractory partial epilepsy, with overall seizure frequency reductions of 18–32% during 3-month treatment periods 2, 4
• Patients with complex partial seizures and partial seizures with secondary generalization are particularly likely to respond 2

Recommended Dosing

Adults and Adolescents ≥12 Years

Initiate gabapentin at 300 mg three times daily (900 mg/day total) and titrate upward to a maintenance dose of 1800–3600 mg/day divided three times daily. 3, 5

• Starting dose: 300 mg three times daily 3
• Maintenance dose: 300–600 mg three times daily (900–1800 mg/day total) 3
• Maximum studied dose: 3600 mg/day, which has been well tolerated and may provide superior seizure control compared to lower doses 3, 5
• The maximum interval between doses should not exceed 12 hours 3
• Recent evidence suggests improved seizure control at maintenance dosages ≥3600 mg/day without increased adverse effects, though most clinical practice uses 1800 mg/day 5

Pediatric Patients (3–11 Years)

Begin with 10–15 mg/kg/day divided three times daily, then titrate over approximately 3 days to age-specific maintenance doses. 3

• Ages 3–4 years: Maintenance dose of 40 mg/kg/day divided three times daily 3
• Ages 5–11 years: Maintenance dose of 25–35 mg/kg/day divided three times daily 3
• Dosages up to 50 mg/kg/day have been well tolerated in long-term studies 3
• Maximum interval between doses should not exceed 12 hours 3

Titration Strategy

• Most adult patients tolerate initiation at 900 mg/day with rapid titration to ≥3600 mg/day if necessary 5
• Adverse effects typically occur at treatment onset and are often transient 5
• Optimal seizure control may require months to achieve despite rapid titration 5

Renal Dose Adjustments

Gabapentin requires mandatory dose reduction in any degree of renal impairment because it is eliminated unchanged in urine. 3, 6

Dosing by Creatinine Clearance (Adults ≥12 Years)

CrCl (mL/min)	Total Daily Dose	Regimen
≥60	900–3600 mg/day	300–1200 mg TID
30–59	400–1400 mg/day	200–700 mg BID
15–29	200–700 mg/day	200–700 mg once daily
<15	100–300 mg/day	100–300 mg once daily*

*For CrCl <15 mL/min, reduce the daily dose in proportion to creatinine clearance (e.g., patients with CrCl 7.5 mL/min receive half the dose of those with CrCl 15 mL/min) 3

Hemodialysis Patients

• Administer maintenance doses based on creatinine clearance as above 3
• Post-dialysis supplemental dose: 125–350 mg after each 4-hour hemodialysis session 3

Estimating Creatinine Clearance

Use the Cockcroft-Gault equation in patients with stable renal function to estimate creatinine clearance 3

Critical caveat: Gabapentin use in pediatric patients <12 years with renal impairment has not been studied 3

Common Adverse Effects

Most Frequent Reactions (Postherpetic Neuralgia Trials)

The most common adverse effects in adults are dizziness (28%), somnolence (21%), and peripheral edema (8%), which occur at substantially higher rates than placebo 3

• Dizziness: 28% vs 8% placebo 3
• Somnolence: 21% vs 5% placebo 3
• Peripheral edema: 8% vs 2% placebo 3
• Ataxia: 3% vs 0% placebo 3
• Dry mouth: 5% vs 1% placebo 3
• Weight gain: 2% vs 0% placebo 3

Epilepsy Adjunctive Therapy (Adults >12 Years)

• Somnolence: 19% vs 9% placebo 3
• Dizziness: 17% vs 7% placebo 3
• Ataxia: 13% vs 6% placebo 3
• Nystagmus: 8% vs 4% placebo 3
• Fatigue: 11% vs 5% placebo 3
• Tremor: 7% vs 3% placebo 3

Somnolence and ataxia exhibit a positive dose-response relationship 3

Pediatric Patients (3–12 Years)

• Viral infection: 11% vs 3% placebo 3
• Fever: 10% vs 3% placebo 3
• Somnolence: 8% vs 5% placebo 3
• Hostility: 8% vs 2% placebo 3
• Emotional lability: 4% vs 2% placebo 3

Neuropsychiatric adverse reactions (hostility, emotional lability, hyperkinesia) are particularly concerning in pediatric patients aged 3–12 years 3

Discontinuation Rates

• Approximately 16% of adults with postherpetic neuralgia discontinued gabapentin due to adverse effects (vs 9% placebo), most commonly dizziness, somnolence, and nausea 3
• Approximately 7% of epilepsy patients >12 years discontinued due to adverse effects, most commonly somnolence (1.2%), ataxia (0.8%), and fatigue (0.6%) 3
• In pediatric epilepsy patients, 7% discontinued, most commonly due to emotional lability (1.6%), hostility (1.3%), and hyperkinesia (1.1%) 3

Critical Safety Warnings

Serious Adverse Reactions

• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity 3
• Anaphylaxis and angioedema 3
• Withdrawal-precipitated seizures and status epilepticus: Discontinue gradually over a minimum of 1 week (longer periods may be needed) 3
• Suicidal behavior and ideation: Monitor all patients for emergence of suicidal thoughts 3
• Sudden unexplained death in epilepsy (SUDEP) 3

Special Population Considerations

• Elderly patients: More likely to have decreased renal function; adjust dose based on creatinine clearance 3
• Pediatric behavioral effects: Hostility, emotional lability, and hyperkinesia are more common in children 3–12 years 3
• Pregnancy: Gabapentin is not mentioned as a preferred agent in women of childbearing potential, unlike levetiracetam 7

Pharmacokinetic Advantages

Gabapentin has a uniquely favorable drug-interaction profile because it is not protein-bound, is not metabolized, and does not induce liver enzymes. 2, 8

• No cytochrome P450 interactions, minimizing risk of interactions with other antiepileptics and oral contraceptives 2, 8
• Eliminated unchanged in urine 6, 2
• Does not require therapeutic drug monitoring 8
• Limited effects on cognition compared to traditional antiepileptics 8

Limitations and Clinical Context

• Gabapentin is not recommended as monotherapy for newly diagnosed epilepsy; carbamazepine is the preferred first-line agent for partial-onset seizures 6
• Evidence for gabapentin monotherapy efficacy is limited, particularly in pediatric patients 8
• The drug has not been compared head-to-head with other second-line antiepileptics in refractory epilepsy 6
• Gabapentin is not mentioned in status epilepticus treatment algorithms; benzodiazepines, valproate, levetiracetam, and fosphenytoin are the recommended agents 9, 10

Administration Guidance

• Administer orally with or without food 3
• If dividing scored 600 mg or 800 mg tablets, take the unused half-tablet as the next dose within 28 days 3
• When discontinuing or substituting, taper gradually over a minimum of 1 week to prevent withdrawal seizures 3