Gabapentin Dosing in Acute Kidney Injury
In patients with acute kidney injury, gabapentin dosing must be reduced based on creatinine clearance to prevent severe neurotoxicity—for CrCl 30-59 mL/min reduce to 200-700 mg twice daily, for CrCl 15-29 mL/min reduce to 100-300 mg once daily, and for CrCl <15 mL/min reduce to 100-300 mg once daily with supplemental post-hemodialysis dosing if applicable. 1
Critical Dosing Algorithm Based on Renal Function
The FDA-approved dosing adjustments for gabapentin in renal impairment are mandatory and non-negotiable 1:
- CrCl ≥60 mL/min: 900-3600 mg/day divided three times daily (300-1200 mg TID) 1
- CrCl 30-59 mL/min: 400-1400 mg/day divided twice daily (200-700 mg BID) 1
- CrCl 15-29 mL/min: 200-700 mg/day given once daily (200-700 mg QD) 1
- CrCl <15 mL/min: 100-300 mg/day given once daily (100-300 mg QD) 1
- Hemodialysis patients: Maintenance dose based on residual CrCl plus supplemental post-hemodialysis dose of 125-350 mg after each 4-hour dialysis session 1
Why Dose Adjustment is Critical in AKI
Gabapentin is eliminated entirely unchanged by renal excretion with no hepatic metabolism 2. The elimination half-life increases dramatically from 5-9 hours in normal renal function to 132 hours in anuric patients 3. Plasma clearance and renal clearance of gabapentin correlate linearly with creatinine clearance 2. Failure to adjust dosing causes preventable toxicity including altered mental status, confusion with hallucinations, myoclonus, tremulousness, hearing loss, dizziness, somnolence, falls, fractures, and coma 4, 5.
Common Pitfalls and How to Avoid Them
Never rely on serum creatinine alone—this is the most common error leading to toxicity 4. Serum creatinine significantly underestimates renal impairment in elderly patients with reduced muscle mass 4, 6. Always calculate creatinine clearance using the Cockcroft-Gault equation 1:
- For males: CrCl = [(140 - age) × weight in kg] / (72 × serum creatinine in mg/dL)
- For females: multiply result by 0.85
Do not continue pre-AKI doses during acute illness—gabapentin accumulation during acute renal failure has caused severe neurological deterioration requiring extensive diagnostic workup including brain CT scans, when the underlying cause was simply drug overdose 5, 7. Symptoms resolve with drug discontinuation 5.
Initiation and Titration in AKI
For patients with moderate renal impairment (CrCl 30-59 mL/min), start with 100-200 mg/day and titrate cautiously over weeks rather than days 4. The American Geriatrics Society recommends starting at 100 mg at bedtime for 3-7 days, then increasing by 100-300 mg every 3-7 days as tolerated 4. Monitor closely for dose-dependent adverse effects during titration, particularly dizziness and sedation 6.
Special Considerations for Hemodialysis
Hemodialysis removes approximately 35% of gabapentin dose, with a hemodialysis clearance of 142 mL/min (93% of dialyzer creatinine clearance) 3. The elimination half-life during hemodialysis is approximately 4 hours 3. Patients require both maintenance dosing based on residual renal function and supplemental post-dialysis doses 6, 1. Plasma gabapentin concentrations increase approximately 30% during the first 2 hours after hemodialysis due to drug redistribution 3.
For end-stage renal disease patients on hemodialysis, give an initial loading dose of 300-400 mg, then maintain plasma concentrations by giving 200-300 mg after every 4 hours of hemodialysis 3.
Monitoring Requirements
The maximum time between doses should not exceed 12 hours 1. If gabapentin is reduced, discontinued, or substituted, taper gradually over a minimum of 1 week 1. In patients with CrCl <30 mL/min receiving dalteparin (unrelated to gabapentin but illustrating monitoring principles for renally cleared drugs), monitoring of peak anti-Xa levels is recommended 8—similarly, therapeutic drug monitoring may be useful for gabapentin in severe renal impairment 9.
Pharmacokinetic Changes in AKI
Beyond simple renal excretion changes, AKI causes decreased activity of hepatic and gastrointestinal drug-metabolizing enzymes and transporters, significant changes in protein binding, and altered serum amino acid levels 9. However, gabapentin is not protein-bound and undergoes no metabolism, making dose adjustment based solely on creatinine clearance appropriate 2.