Pregabalin Dosing in Moderate Renal Impairment
No, 25mg twice daily (bid) of pregabalin is not safe in a patient with moderate impaired renal function. The dose should be reduced to 25-50mg once daily based on the FDA-approved dosing guidelines for renal impairment. 1
Renal Adjustment Guidelines for Pregabalin
Pregabalin is primarily eliminated by renal excretion, making dose adjustment essential in patients with reduced renal function. According to the FDA drug label:
| Creatinine Clearance (CLcr) (mL/min) | Total Pregabalin Daily Dose (mg/day) | Dose Regimen |
|---|---|---|
| ≥60 | 150-600 | BID or TID |
| 30-60 | 75-300 | BID or QD |
| 15-30 | 25-150 | QD or BID |
| <15 | 25-75 | QD |
Pharmacokinetic Considerations
Pregabalin's pharmacokinetics are significantly affected by renal function:
- Total and renal pregabalin clearance are directly proportional (56% and 58%, respectively) to creatinine clearance 2
- In moderate renal impairment (CrCl 30-60 mL/min), the drug's half-life is prolonged and AUC (area under the curve) increases
- A 50% reduction in daily dose is recommended for patients with CrCl between 30-60 mL/min compared to those with normal renal function 2
Risks of Inappropriate Dosing
Improper dosing in renal impairment can lead to serious adverse effects:
- Myoclonic encephalopathy - even without evidence of drug accumulation in acute renal failure 3
- Negative myoclonus - can occur even in patients with normal renal function but risk increases with impaired renal function 4
- Seizures upon sudden discontinuation - documented in patients with chronic kidney disease who had pregabalin abruptly stopped 5
Recommended Approach
- Calculate creatinine clearance using the Cockcroft-Gault equation to determine degree of renal impairment
- For moderate renal impairment (CrCl 30-60 mL/min):
- Reduce total daily dose to 75-300 mg/day
- Consider once daily dosing or divided BID dosing
- Start at the lower end of the dosing range (25-50mg daily) and titrate slowly
- Monitor for adverse effects including:
- Neurological symptoms (dizziness, somnolence, confusion)
- Myoclonus or other movement disorders
- Edema or weight gain
Conclusion
For a patient with moderate renal impairment, pregabalin 25mg once daily would be a more appropriate starting dose than 25mg twice daily. The dose can be cautiously titrated based on clinical response and tolerability, but should generally not exceed 300mg total daily dose in this population 1.