What are the indications and dosages for gabapentin (Neurontin)?

Gabapentin Indications and Dosing

Gabapentin is FDA-approved for two specific indications: management of postherpetic neuralgia in adults and adjunctive therapy for partial onset seizures (with or without secondary generalization) in adults and pediatric patients 3 years and older with epilepsy. 1

FDA-Approved Indications

Postherpetic Neuralgia

• Start gabapentin at 300 mg on Day 1, increase to 600 mg/day (300 mg twice daily) on Day 2, and 900 mg/day (300 mg three times daily) on Day 3. 1
• The target therapeutic dose is 1800 mg/day (600 mg three times daily), which demonstrates efficacy in clinical trials. 1
• Doses up to 3600 mg/day have been studied, but additional benefit beyond 1800 mg/day was not consistently demonstrated in clinical trials. 1
• Moderate-quality evidence shows 32% of patients achieve substantial benefit (≥50% pain relief) with gabapentin ≥1200 mg/day versus 17% with placebo (NNT 6.7). 2

Partial Onset Seizures (Adults and Pediatric Patients ≥12 years)

• Start at 300 mg three times daily, with a recommended maintenance dose of 300-600 mg three times daily. 1
• Dosages up to 2400 mg/day have been well tolerated in long-term studies; doses of 3600 mg/day have been administered to small numbers of patients for short durations. 1
• Maximum time between doses should not exceed 12 hours. 1

Partial Onset Seizures (Pediatric Patients Age 3-11 years)

• Starting dose range is 10-15 mg/kg/day in three divided doses, titrated over approximately 3 days. 1
• Recommended maintenance dose for ages 3-4 years: 40 mg/kg/day in three divided doses. 1
• Recommended maintenance dose for ages 5-11 years: 25-35 mg/kg/day in three divided doses. 1
• Dosages up to 50 mg/kg/day have been well tolerated in long-term studies. 1

Off-Label Use: Neuropathic Pain (Beyond Postherpetic Neuralgia)

Painful Diabetic Neuropathy

• Moderate-quality evidence shows 38% of patients achieve substantial benefit (≥50% pain relief) with gabapentin ≥1200 mg/day versus 21% with placebo (NNT 5.9). 2
• Use the same dosing schedule as postherpetic neuralgia: start 300 mg on Day 1, titrate to 900 mg/day by Day 3, then increase to target dose of 1800-3600 mg/day in three divided doses. 3, 1

HIV-Associated Neuropathic Pain

• Gabapentin is strongly recommended as first-line oral pharmacological treatment for chronic HIV-associated neuropathic pain (strong recommendation, moderate-quality evidence). 4, 5
• Titrate to a maximum of 2400 mg/day over 4 weeks in divided doses. 4
• One small trial (n=26) showed improvement in pain scores, though it had a high placebo response rate (29.8% reduction). 4

General Neuropathic Pain Syndromes

• Start at 100-300 mg at bedtime or 100-300 mg three times daily, increasing by 100-300 mg every 1-7 days as tolerated. 3
• Target therapeutic dose range is 1800-3600 mg/day in three divided doses. 3
• Allow a minimum trial duration of 3-8 weeks for titration plus 2 weeks at maximum tolerated dose (potentially 2 months total) before declaring treatment failure. 3
• Evidence from a symptom-based trial showed gabapentin reduced pain by 21% versus 14% with placebo (p=0.048) in patients with various neuropathic pain syndromes. 6

Critical Dosing Considerations

Three-Times-Daily Dosing is Essential

• Gabapentin has nonlinear, saturable absorption pharmacokinetics, making three-times-daily administration essential for standard formulations. 3
• Once-daily or twice-daily dosing should be avoided with standard gabapentin (not applicable to gabapentin encarbil extended-release). 3

Renal Impairment Requires Mandatory Dose Adjustment

• Gabapentin is eliminated unchanged by the kidneys; dose reduction is mandatory in renal impairment. 1
• CrCl ≥60 mL/min: 900-3600 mg/day in three divided doses 1
• CrCl 30-59 mL/min: 400-1400 mg/day in two divided doses 1
• CrCl 15-29 mL/min: 200-700 mg/day as single daily dose 1
• CrCl <15 mL/min: 100-300 mg/day as single daily dose 1
• Hemodialysis patients require supplemental post-dialysis doses of 125-350 mg after each 4-hour session. 1

Elderly Patients

• Start at lower doses (100 mg at bedtime) and titrate more slowly (every 3-7 days) due to increased risk of falls from dizziness. 3
• Elderly patients are more likely to have decreased renal function; adjust dose based on creatinine clearance. 1

Discontinuation

• Taper gradually over a minimum of 1 week when discontinuing to avoid withdrawal symptoms. 1, 3
• A longer taper period may be needed at prescriber's discretion. 1

Adverse Effects Profile

Common Side Effects

• Dizziness (19%), somnolence (14%), peripheral edema (7%), and gait disturbance (14%) occur significantly more often with gabapentin than placebo. 2
• Most adverse effects are mild to moderate and typically transient, occurring during the titration phase. 6
• Adverse event withdrawals occur in 11% of gabapentin patients versus 8.2% with placebo (NNH 30). 2

Serious Adverse Events

• Serious adverse events occur at similar rates with gabapentin (3.2%) and placebo (2.8%). 2
• Somnolence was reported by 80% of patients in the HIV-associated neuropathy trial at 2400 mg/day. 4

Clinical Pearls and Pitfalls

Efficacy Expectations

• Approximately 3-4 out of 10 patients achieve ≥50% pain relief with gabapentin versus 1-2 out of 10 with placebo for neuropathic pain. 2
• Over half of treated patients will not have worthwhile pain relief but may experience adverse events. 2
• Efficacy for neuropathic pain may take several weeks to achieve optimal effect. 3

Comparison with Pregabalin

• Gabapentin should be used as first-line treatment before pregabalin for neuropathic pain, as gabapentin has a stronger evidence base and is typically less expensive. 5
• Pregabalin should be considered only after inadequate response to gabapentin (weak recommendation, moderate evidence). 5
• Both medications have similar mechanisms of action (binding to α2δ subunit of voltage-gated calcium channels) but different pharmacokinetics. 5

Avoiding Common Errors

• Do not rush titration in elderly patients, as this increases fall risk from dizziness. 3
• Do not use once-daily or twice-daily dosing for standard gabapentin formulations. 3
• Do not declare treatment failure before completing a full 2-month trial period. 3
• If dividing scored 600 mg or 800 mg tablets, take the unused half-tablet as the next dose; discard unused half-tablets after 28 days. 1