Maximum Pregabalin Dose for Creatinine Clearance 18 mL/min
For a patient with creatinine clearance of 18 mL/min, the maximum dose of pregabalin is 75 mg per day, administered either as 25 mg three times daily or 37.5 mg twice daily. 1
Renal Dosing Algorithm
The FDA-approved dosing for severe renal impairment (CLcr 15-29 mL/min) is based on the following calculation 1:
- Step 1: Determine the normal dose for the indication (e.g., 150-600 mg/day for neuropathic pain)
- Step 2: Apply the renal adjustment factor for CLcr 15-29 mL/min, which reduces the total daily dose by approximately 75-85% 2
- Step 3: For CLcr 18 mL/min specifically, the FDA label specifies a maximum total daily dose of 75 mg/day 1
Specific Dosing Recommendations
Starting dose: Begin at 25 mg once daily, not the 75 mg/day maximum 3
Titration: Increase slowly over weeks based on response and tolerability, with the absolute ceiling at 75 mg/day 3
Dosing frequency options 1:
- 25 mg three times daily (75 mg/day total), OR
- 37.5 mg twice daily (75 mg/day total), OR
- 75 mg once daily
Critical Pharmacokinetic Rationale
Pregabalin is 85% renally excreted unchanged, making dose reduction mandatory in renal impairment 4. At CLcr 18 mL/min, the area under the curve (AUC) increases 6.3-fold compared to normal renal function, and the terminal half-life doubles to 28 hours 5, 6. This dramatic drug accumulation explains why the maximum dose is reduced from 600 mg/day (normal renal function) to just 75 mg/day 1, 6.
Hemodialysis Considerations
If this patient progresses to hemodialysis, the dosing changes 1:
- Daily dose: 25 mg once daily (or up to 75 mg once daily maximum)
- Supplemental dose: Give an additional 25-100 mg immediately after each 4-hour hemodialysis session, as pregabalin is highly dialyzable 1, 6
Common Prescribing Errors to Avoid
Never prescribe pregabalin without calculating creatinine clearance first - this is the most common error leading to toxicity, particularly in elderly patients where normal serum creatinine masks severe renal impairment due to reduced muscle mass 7, 2
Never abruptly discontinue pregabalin in renal impairment - even at low doses, sudden cessation can cause withdrawal seizures, as documented in a case report of a patient with eGFR 15 mL/min who seized 4 days after abrupt cessation of 150 mg/day 8
Do not assume therapeutic failure requires dose escalation - with CLcr 18 mL/min, 75 mg/day is the absolute maximum regardless of efficacy, as higher doses cause unacceptable toxicity 1
Monitoring Requirements
Calculate creatinine clearance using the Cockcroft-Gault equation before initiating therapy 1:
CLcr (mL/min) = [(140 - age) × weight in kg] / (72 × serum creatinine in mg/dL)
Multiply by 0.85 for females
Recheck renal function regularly during treatment, as even small declines in CLcr from 18 to <15 mL/min would require further dose reduction 2, 1
Adverse Effect Profile at Low Doses
Even at 75 mg/day maximum, expect dose-dependent adverse effects including dizziness (23-46% of patients), somnolence (15-25%), and peripheral edema (10%) 7, 2. These effects may paradoxically be more pronounced in severe renal impairment due to drug accumulation despite the reduced dose 9, 6.