Maximum Gabapentin Dose Per Day
The maximum recommended daily dose of gabapentin is 3600 mg/day, divided into three doses (1200 mg three times daily), though doses up to this maximum must be adjusted downward in patients with renal impairment. 1
Standard Maximum Dosing for Adults
The FDA-approved maximum dose is 3600 mg/day for both postherpetic neuralgia and epilepsy, administered as three divided doses with no more than 12 hours between doses 1
For postherpetic neuralgia specifically, efficacy was demonstrated across doses from 1800-3600 mg/day with comparable effects, though additional benefit beyond 1800 mg/day was not clearly demonstrated in pivotal trials 1
For neuropathic pain conditions, the target therapeutic range is 1800-3600 mg/day in three divided doses, with 1800 mg/day considered the minimum effective dose for most patients 2, 3
Clinical studies have shown that 32-38% of patients achieve at least 50% pain reduction at therapeutic doses of 1800-3600 mg/day, compared to 17-21% with placebo 4
Critical Dosing Considerations Due to Nonlinear Pharmacokinetics
Gabapentin has saturable, dose-dependent absorption that becomes less efficient at higher doses, requiring three-times-daily administration to maximize bioavailability 2, 5
At 3600 mg/day given three times daily, mean bioavailability is approximately 39%, but this drops to 29% at 4800 mg/day with the same dosing frequency 5
Switching from three-times-daily to four-times-daily dosing at 4800 mg/day increases bioavailability by 22% (from 29% to 36%), though this must be weighed against the inconvenience of more frequent dosing 5
The maximum interval between doses should not exceed 12 hours to maintain therapeutic levels 1
Mandatory Dose Reductions in Renal Impairment
Dose adjustment is absolutely required in patients with compromised renal function, as gabapentin is eliminated unchanged by the kidneys 1
Renal Dosing Algorithm (for patients ≥12 years):
CrCl ≥60 mL/min: 900-3600 mg/day in three divided doses (no adjustment needed) 1
CrCl 30-59 mL/min: Maximum 1400 mg/day in two divided doses (reduce by ~50-60%) 1
CrCl 15-29 mL/min: Maximum 700 mg/day as a single daily dose (reduce by ~75-80%) 1
CrCl <15 mL/min: Maximum 300 mg/day as a single daily dose (reduce by ~85-90%) 1
Hemodialysis patients: Maintenance dose based on CrCl as above, PLUS supplemental post-hemodialysis dose of 125-350 mg after each 4-hour dialysis session 1
Critical Pitfall in Renal Dosing:
In patients with acute renal failure, standard gabapentin doses can cause severe toxicity including hearing loss, myoclonus, confusion, hallucinations, and coma 6
Gabapentin concentrations of 17.6 mcg/mL (compared to therapeutic range of 2-20 mcg/mL) were associated with severe toxicity that resolved rapidly after hemodialysis 6
The half-life of gabapentin increases from 6.5 hours in normal renal function to 52 hours when CrCl <30 mL/min, and up to 132 hours in anuric patients 1
Special Population Considerations
Elderly Patients:
Elderly patients require dose adjustment based on creatinine clearance, as age-related decline in renal function is often masked by normal serum creatinine due to reduced muscle mass 2, 1
Apparent oral clearance decreases from ~225 mL/min in patients under 30 years to ~125 mL/min in those over 70 years 1
Always calculate creatinine clearance using the Cockcroft-Gault equation rather than relying on serum creatinine alone in elderly patients 1
Pediatric Patients (3-11 years):
Maximum doses up to 50 mg/kg/day have been well tolerated in long-term clinical studies, though the recommended maintenance dose is 25-35 mg/kg/day for ages 5-11 years and 40 mg/kg/day for ages 3-4 years 1
Pediatric patients with renal insufficiency have not been studied, so use in this population requires extreme caution 1
Practical Titration to Maximum Dose
Standard titration schedule: Start 300 mg on day 1, increase to 600 mg/day (300 mg twice daily) on day 2, then 900 mg/day (300 mg three times daily) on day 3 1
Continue increasing by 300 mg every 3-7 days as tolerated until reaching target dose of 1800-3600 mg/day 2, 3
Slower titration (increases every 3-7 days or longer) is recommended for elderly or medically frail patients to reduce fall risk from dizziness 2
The minimum trial duration is 3-8 weeks for titration plus 2 weeks at maximum tolerated dose before declaring treatment failure 2
Common Adverse Effects at Maximum Doses
At doses of 1800-3600 mg/day, adverse event withdrawals occur in 11% of patients versus 8.2% with placebo (NNH 30) 4
Most common dose-dependent side effects: dizziness (19%), somnolence (14%), peripheral edema (7%), and gait disturbance (14%) 4
Side effects typically occur around onset of dosing and are often transient, subsiding within approximately 10 days 3, 7