What are the guidelines for prescribing gabapentinoid (Gabapentin or Pregabalin) SR to an elderly patient with impaired renal function?

Gabapentinoid Dosing in Elderly Patients with Renal Impairment

For elderly patients with impaired renal function, you must calculate creatinine clearance using the Cockcroft-Gault equation before prescribing any gabapentinoid, then reduce the starting dose by at least 50% for moderate impairment (CrCl 30-59 mL/min) and implement slow weekly titration to avoid preventable toxicity including altered mental status, falls, and fractures. 1

Critical First Step: Accurate Renal Function Assessment

• Never rely on serum creatinine alone in elderly patients, as it significantly underestimates renal impairment in those with reduced muscle mass 1
• Calculate creatinine clearance using the Cockcroft-Gault equation: CLcr (mL/min) = [(140 - age) × weight in kg] / (72 × serum creatinine in mg/dL), multiplied by 0.85 for females 2
• The most common prescribing error is failing to calculate creatinine clearance accurately, which leads directly to toxicity 1
• Age-related decline in renal function is often masked by normal serum creatinine due to reduced muscle mass 2

Gabapentin Dosing Algorithm by Renal Function

For CrCl 30-59 mL/min (Moderate Impairment):

• Start at 100-200 mg/day (or 100 mg at bedtime for 3-7 days) 1
• Maximum total daily dose: 400-1400 mg/day divided twice daily 1
• Increase by 100-300 mg every 3-7 days as tolerated 1
• This represents at least a 50% reduction from standard dosing 1

For CrCl 15-30 mL/min (Severe Impairment):

• Start at 100 mg at bedtime 1
• Maximum dose: 700 mg/day 1
• Titrate every 3-7 days with close monitoring 1

For CrCl <15 mL/min:

• Start at 100 mg at bedtime 1
• Maximum dose: 300 mg/day 1
• For hemodialysis patients: loading dose 300-400 mg, then 200-300 mg after each 4-hour hemodialysis session 1, 3

Pregabalin Dosing Algorithm by Renal Function

For CrCl 30-60 mL/min (Moderate Impairment):

• Start at 25-75 mg/day (25 mg at bedtime or 50 mg twice daily) 2
• Reduce total daily dose by approximately 50% from standard dosing 2
• Maximum dose: 150-300 mg/day in divided doses 2
• Titrate weekly as tolerated 2

For CrCl 15-30 mL/min (Severe Impairment):

• Start at 25 mg once daily or every other day 2
• Reduce total daily dose by approximately 75% 2
• Maximum dose: 75-150 mg/day 2

For CrCl <15 mL/min:

• Start at 25 mg once daily 2
• Reduce total daily dose by 85-90% 2
• Maximum dose: 25-75 mg/day 2
• At CrCl 18 mL/min, pregabalin AUC increases 6.3-fold with half-life doubling to 28 hours 2

Critical Pharmacokinetic Differences

Pregabalin has significant advantages over gabapentin in elderly patients with renal impairment:

• Pregabalin exhibits linear pharmacokinetics with >90% oral bioavailability that is dose-independent, making titration more predictable 2, 4
• Gabapentin has nonlinear, saturable absorption that becomes less efficient at higher doses, requiring more complex titration 5, 6
• Both drugs are eliminated unchanged by the kidneys (95% pregabalin, similar for gabapentin), requiring mandatory dose reduction in renal impairment 2, 4, 6
• Pregabalin achieves pain relief within 1.5-3.5 days versus gabapentin requiring 2+ months for adequate trial 2

Toxicity Recognition and Monitoring

Common manifestations of gabapentinoid toxicity in renal impairment include: 1

• Altered mental status and confusion with hallucinations
• Myoclonus and tremulousness
• Dizziness and somnolence (most common, occurring in 23-46% with pregabalin) 2
• Falls and balance disturbances
• Hearing loss
• Coma in severe cases

Monitor closely during titration for: 1, 2

• Dose-dependent adverse effects, particularly dizziness and sedation
• Falls risk, especially in first 4-8 weeks
• Peripheral edema (occurs in 10% with pregabalin) 2

Critical Drug Interaction Warning

Avoid concurrent use of gabapentinoids with opioids or benzodiazepines except when transitioning from the former to the latter, as this combination increases risk of respiratory depression, sedation, and falls 7

The 2019 AGS Beers Criteria specifically added avoiding concurrent opioid and gabapentinoid use to their drug-drug interaction recommendations 7

Special Considerations for Elderly Patients

• Elderly patients often achieve pain relief at lower doses than the typical 900-3600 mg/day gabapentin or 300-600 mg/day pregabalin required in younger adults 1, 2
• Pregabalin oral clearance decreases with increasing age, consistent with age-related decreases in creatinine clearance 4
• Gabapentin apparent oral clearance decreased from about 225 mL/min in those under 30 years to about 125 mL/min in those over 70 years 6
• Higher doses of gabapentinoids in patients with CrCl <60 mL/min were associated with increased falls (p=0.029) 8

Common Prescribing Errors to Avoid

1. Do not assume normal renal function based on serum creatinine alone - always calculate CrCl 1
2. Do not use standard doses in renal impairment - both medications require mandatory dose reduction 1, 2
3. Do not rush titration - increases fall risk from dizziness, particularly in elderly patients 1, 5
4. Do not abruptly discontinue - taper gradually over minimum of 1 week to avoid withdrawal symptoms 2, 5
5. Do not combine gabapentin and pregabalin - no evidence supports this, and it creates unacceptable additive sedative burden 2

Evidence on Inappropriate Dosing Frequency

Recent studies demonstrate widespread inappropriate dosing in clinical practice:

• 34% of patients with CrCl <60 mL/min were prescribed inappropriately high gabapentin doses 8
• 48.8% of patients with CrCl 15-29 mL/min received inappropriately high gabapentin doses 8
• 45% of patients with CrCl <15 mL/min received inappropriately high pregabalin doses 8
• Higher-dose gabapentinoids (gabapentin >300 mg/day or pregabalin >75 mg/day) in patients with CKD were associated with 27% increased risk of hospital visits for encephalopathy, falls, fractures, or respiratory depression (weighted RR 1.27,95% CI 1.13-1.42) 9