Maximum Dose of Gabapentin
The maximum dose of gabapentin is 3600 mg/day in adults with normal renal function, administered in three divided doses (1200 mg three times daily), with mandatory dose reduction required for any degree of renal impairment. 1
Standard Maximum Dosing in Adults
The FDA-approved maximum dose is 3600 mg/day, divided into three doses with no more than 12 hours between doses. 1
Doses of 3600 mg/day have been administered to patients for relatively short durations and have been well tolerated, though the FDA label notes these were given to only a small number of patients. 1
For postherpetic neuralgia specifically, the FDA label states that efficacy was demonstrated over a range of 1800-3600 mg/day with comparable effects across the dose range, though additional benefit of doses greater than 1800 mg/day was not demonstrated in clinical studies. 1
For epilepsy, dosages up to 2400 mg/day have been well tolerated in long-term clinical studies, with doses of 3600 mg/day also administered to a small number of patients for relatively short duration. 1
Critical Renal Dose Adjustments (Non-Negotiable)
Renal function assessment is mandatory before initiating gabapentin, as the drug is eliminated unchanged by the kidneys and requires substantial dose reduction in any degree of renal impairment. 1, 2
FDA-Approved Renal Dosing Table:
CrCl ≥60 mL/min: 900-3600 mg/day in three divided doses (maximum 1200 mg three times daily) 1
CrCl 30-59 mL/min: 400-1400 mg/day in two divided doses (maximum 700 mg twice daily) 1
CrCl 15-29 mL/min: 200-700 mg/day as a single daily dose (maximum 700 mg once daily) 1
CrCl <15 mL/min: 100-300 mg/day as a single daily dose (maximum 300 mg once daily) 1
For CrCl <15 mL/min, reduce the daily dose in proportion to creatinine clearance (e.g., patients with CrCl of 7.5 mL/min should receive one-half the daily dose that patients with CrCl of 15 mL/min receive). 1
Hemodialysis Patients:
Patients on hemodialysis should receive maintenance doses based on creatinine clearance estimates plus a supplemental post-hemodialysis dose after each 4 hours of hemodialysis. 1
Supplemental doses range from 125-350 mg depending on the maintenance dose. 1
Elderly Patients
Because elderly patients are more likely to have decreased renal function, dose selection should be based on creatinine clearance values using the Cockcroft-Gault equation, not age alone. 1
The American Academy of Neurology recommends lower starting doses (100-300 mg at bedtime) and slower titration in geriatric patients to minimize adverse effects. 2
Pharmacokinetic Rationale for Maximum Dose
Gabapentin exhibits dose-dependent, saturable absorption due to a saturable transport mechanism in the gut. 3
Plasma concentrations are essentially proportional to dosages up to 1800 mg daily, but bioavailability decreases at higher doses due to saturable absorption. 3
The elimination half-life is approximately 5-9 hours, necessitating three divided doses per day with maximum 12-hour intervals between doses. 1, 3
Evidence for Efficacy at Maximum Doses
In postherpetic neuralgia, 32% of patients achieved at least 50% pain reduction with gabapentin 1800-3600 mg/day versus 17% with placebo (NNT 6.7). 4
In painful diabetic neuropathy, 38% of patients achieved at least 50% pain reduction with gabapentin 1800-3600 mg/day versus 21% with placebo (NNT 5.9). 4
Clinical trials demonstrate that doses of 1800-3600 mg/day are effective and well tolerated, though additional benefit above 1800 mg/day was not consistently demonstrated. 1, 5
Critical Safety Considerations at Maximum Doses
Adverse event withdrawals occur in 11% of patients on gabapentin versus 8.2% with placebo (NNH 30). 4
Common dose-dependent adverse effects include dizziness (19%), somnolence (14%), peripheral edema (7%), and gait disturbance (9%). 4
These effects are typically mild to moderate and often transient, usually subsiding within approximately 10 days. 5
Serious adverse events (3%) are no more common than with placebo. 4
Critical Pitfalls to Avoid
Never exceed 3600 mg/day in adults with normal renal function—this is the absolute maximum FDA-approved dose. 1
Never use standard doses without calculating creatinine clearance first, especially in elderly patients who invariably have reduced renal function. 2, 1
Never administer gabapentin less frequently than three times daily for standard formulations—saturable absorption requires divided dosing with maximum 12-hour intervals. 1
Never abruptly discontinue gabapentin—taper gradually over a minimum of 1 week to avoid withdrawal symptoms. 1
Never assume higher doses provide better efficacy—doses above 1800 mg/day often do not provide additional benefit but increase adverse effects. 1