What are the considerations for using pregablin (lyrica) in a pediatric patient under 18 years with impaired renal function?

Pregabalin Use in Pediatric Patients Under 18 Years with Renal Impairment

Pregabalin is not FDA-approved for use in patients under 17 years of age, and its use in pediatric patients with renal impairment requires extreme caution with substantial dose reductions based on creatinine clearance and body weight. 1

FDA-Approved Age Restrictions

• The FDA label explicitly states that pregabalin is approved only for patients 17 years and older, with a recommended initial dose of 150 mg/day and maximum of 600 mg/day for this age group 1
• Pediatric dosing information exists for Pfizer's branded product but is not included in generic labeling due to marketing exclusivity rights, creating a significant knowledge gap for prescribers 1

Critical Dosing Adjustments for Renal Impairment

In Adolescents 17+ Years (Per FDA Label)

• For creatinine clearance 30-60 mL/min: reduce total daily dose to 75-300 mg/day divided into 2-3 doses 1
• For creatinine clearance 15-30 mL/min: reduce to 25-150 mg/day, given once or twice daily 1
• For creatinine clearance <15 mL/min: reduce to 25-75 mg/day as a single daily dose 1
• Hemodialysis patients: require supplemental dosing of 25-150 mg immediately after each 4-hour dialysis session 1

In Pediatric Patients Under 17 Years (Based on PBPK Modeling)

• For moderate renal impairment: maximum dose should not exceed 7 mg/kg/day in children <30 kg or 5 mg/kg/day in children >30 kg 2
• For severe renal impairment: maximum dose should not exceed 3.5 mg/kg/day in children <30 kg or 2.5 mg/kg/day in children >30 kg 2
• For end-stage renal disease: maximum dose should not exceed 1.4 mg/kg/day in children <30 kg or 1 mg/kg/day in children >30 kg 2
• Drug exposure (AUC) increases 1.23-fold in mild RI, 2.02-fold in moderate RI, 3.86-fold in severe RI, and 9.92-fold in end-stage RI compared to normal renal function 2

Pharmacokinetic Considerations

• Pregabalin is 95% renally eliminated unchanged, making dose adjustment essential in any degree of renal impairment 3
• The elimination half-life is approximately 6 hours in normal renal function but extends to 11.5 hours in acute renal failure 4
• Pregabalin exhibits 90% oral bioavailability, is not protein-bound, and undergoes negligible hepatic metabolism 3

Serious Adverse Events in Renal Impairment

• Myoclonic encephalopathy can occur even with therapeutic plasma levels (3.42 μg/mL) in patients with acute renal failure, suggesting a threshold phenomenon rather than simple drug accumulation 4
• Neurological symptoms including altered consciousness, myoclonus, and encephalopathy may develop rapidly and require immediate drug discontinuation 4
• Rare but serious reactions include neutropenia and urticarial rash, particularly concerning in immunosuppressed patients such as transplant recipients 5

Monitoring Requirements

• Calculate creatinine clearance using the Cockcroft-Gault equation before initiating therapy and monitor renal function regularly 1
• In pediatric patients with renal impairment, close monitoring for dose-dependent adverse reactions (dizziness, somnolence, peripheral edema) is essential 1, 2
• Monitor for neurological symptoms including myoclonus, altered mental status, and encephalopathy, which may occur even at therapeutic levels 4
• In urine drug testing scenarios, pregabalin remains detectable for 56-64 hours after single doses in patients with normal renal function, but this window extends significantly with renal impairment 6

Critical Clinical Pitfalls

• Never use adult dosing recommendations in pediatric patients under 17 years, as drug exposure increases disproportionately with renal impairment in this population 2
• Do not assume that therapeutic plasma levels exclude toxicity in renal failure—myoclonic encephalopathy can occur within the therapeutic range 4
• Avoid initiating pregabalin in patients with unstable or rapidly declining renal function without appropriate dose reduction 1
• In transplant recipients or immunosuppressed patients, monitor complete blood counts as neutropenia may be mistakenly attributed to immunosuppressive medications rather than pregabalin 5