What is the recommended starting dose and titration schedule of gabapentin (Neurontin) for a patient with chronic pain, considering factors such as impaired renal function and age over 65?

Gabapentin Dosing for Chronic Pain

Start gabapentin at 100-300 mg at bedtime on day 1, increase to 300 mg three times daily by day 3, then titrate by 300 mg every 3-7 days (slower in elderly/renal impairment) to a target maintenance dose of 1800-3600 mg/day in three divided doses, with mandatory renal function assessment and dose adjustment based on creatinine clearance before initiating therapy. 1, 2, 3

Initial Dosing Strategy

• Begin with 100-300 mg at bedtime rather than the standard 300 mg dose, particularly in patients over 65 years, as lower starting doses minimize adverse effects in geriatric patients 1, 2
• Progress to 300 mg twice daily on day 2, then 300 mg three times daily (900 mg/day total) by day 3 3, 4
• The FDA-approved titration schedule allows for this rapid initial escalation in patients with normal renal function 3

Titration Schedule

• Increase by 300 mg increments every 3-7 days as tolerated until reaching the target therapeutic dose 5, 1
• For elderly or medically frail patients, use slower titration with increases every 3-7 days or longer to reduce fall risk from dizziness 5, 1, 2
• Target maintenance dose is 1800-3600 mg/day divided into three doses (e.g., 600 mg three times daily to 1200 mg three times daily) 1, 3, 6
• The minimum effective dose for most neuropathic pain conditions is 1800 mg/day (600 mg three times daily) 1
• Maximum time between doses should not exceed 12 hours 3

Critical Renal Function Assessment

Calculate creatinine clearance using the Cockcroft-Gault equation before initiating therapy, as gabapentin is renally excreted and elderly patients invariably have reduced renal function 2, 3. This is non-negotiable in patients over 65 years 2.

Renal Dose Adjustments (for patients ≥12 years):

• CrCl ≥60 mL/min: 900-3600 mg/day in three divided doses (standard dosing) 3
• CrCl 30-59 mL/min: 400-1400 mg/day in two divided doses (e.g., 200-700 mg twice daily) 3
• CrCl 15-29 mL/min: 200-700 mg/day as a single daily dose 3
• CrCl <15 mL/min: 100-300 mg/day as a single daily dose (reduce proportionally to creatinine clearance) 3
• Hemodialysis patients: Maintenance doses based on CrCl plus supplemental post-hemodialysis dose of 125-350 mg after each 4-hour dialysis session 3

For severe renal impairment (CrCl 15-29 mL/min), start at 100-200 mg once daily with a maximum of 200-700 mg/day, and use even slower titration with increases every 3-7 days or longer 2.

Expected Efficacy and Timeline

• Allow 3-8 weeks for titration plus 2 weeks at maximum tolerated dose to properly evaluate efficacy 1, 2
• An adequate trial may require 2 months or more to reach optimal effect, as efficacy develops gradually over several weeks 1, 2
• Approximately 32-38% of patients achieve at least 50% pain reduction with gabapentin 1800-3600 mg/day in validated neuropathic pain conditions (postherpetic neuralgia, diabetic neuropathy), compared to 17-21% with placebo (NNT 5.9-6.7) 1, 6
• About 46-52% achieve at least 30% pain reduction (moderate benefit) 6

Dosing Considerations by Formulation

• Standard gabapentin requires three-times-daily dosing due to saturable, nonlinear absorption pharmacokinetics 1, 2
• Do not use once-daily or twice-daily dosing for standard gabapentin, as three times daily administration is essential 1
• Gabapentin encarbil (extended-release formulation) is more efficiently absorbed and may be dosed differently, but standard gabapentin remains the most commonly prescribed formulation 5

Common Adverse Effects

Patients taking gabapentin can expect:

• At least one adverse event (62-63%) 1, 6
• Dizziness (19%) 1, 6
• Somnolence (14%) 1, 6
• Peripheral edema (7%) 1, 6
• Gait disturbance (9-14%) 1, 6
• Adverse event withdrawals (11%) versus 8.2% with placebo (NNH 30) 6

These effects are typically mild to moderate, dose-dependent, and often transient, usually subsiding within approximately 10 days 1, 4. Serious adverse events (3.2%) are no more common than placebo (2.8%) 6.

Critical Pitfalls to Avoid

• Never start at high doses (e.g., 800 mg four times daily) without gradual titration, as this dramatically increases the risk of intolerable adverse effects, particularly in elderly patients 2
• Do not fail to assess renal function before initiating therapy—this is mandatory in patients over 65 years 2
• Avoid abrupt discontinuation—taper gradually over at least 1 week (longer periods may be needed) to avoid withdrawal symptoms 1, 3
• Do not rush titration in elderly patients, as this increases fall risk from dizziness 1
• Do not assume lack of efficacy if adequate time for titration and therapeutic trial has not been allowed—allow the full 2-month trial period before declaring treatment failure 1, 2
• Do not use standard titration schedules in patients with renal impairment—slower titration with increases every 3-7 days or longer is mandatory 2

Administration Details

• 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
• Gabapentin may be used as a coanalgesic in combination with opioids, antidepressants, or topical agents for optimal pain management 5, 1