What percentage of Lyrica (pregabalin) is removed through renal excretion in a patient with severe impaired renal function?

Pregabalin Elimination in Dialysis Patients with Severe Renal Impairment

In a patient with GFR of 8 requiring dialysis, approximately 90% of a single 50mg pregabalin dose would be removed from renal excretion, necessitating significant dose adjustment and careful timing around dialysis sessions. 1

Pregabalin Pharmacokinetics in Severe Renal Impairment

• Pregabalin is primarily eliminated through renal excretion with approximately 90% of the drug excreted unchanged in the urine 1
• Total and renal pregabalin clearance are directly proportional to creatinine clearance (approximately 56-58% proportional to CrCl) 1
• In patients with severe renal impairment (GFR <15 mL/min), pregabalin clearance is dramatically reduced, leading to drug accumulation and increased risk of toxicity 1, 2

Hemodialysis Effects on Pregabalin

• Pregabalin is highly dialyzable with approximately 50% removed during a standard 4-hour hemodialysis session 3
• Hemodialysis clearance of pregabalin has been measured at 88.8 mL/min in case reports 4
• The drug's properties that make it amenable to removal by hemodialysis include:
  • Low molecular weight (159.23 Da)
  • Relatively low volume of distribution (0.5 L/kg)
  • Lack of plasma protein binding 4

Dosing Recommendations for Dialysis Patients

• For patients with CrCl <15 mL/min (including those on hemodialysis), the pregabalin dose should be significantly reduced compared to patients with normal renal function 1
• Daily doses should be reduced by approximately 50% for each 50% decrease in CrCl below 60 mL/min 1
• Supplemental doses may be required after each hemodialysis session to maintain therapeutic levels 1
• Medication administration should be scheduled after hemodialysis to avoid premature removal of the drug 5

Risks of Inappropriate Dosing in Renal Failure

• Pregabalin toxicity in renal failure can manifest as:
  • Myoclonus
  • Encephalopathy
  • Reduced consciousness
  • Confusion
  • Agitation 3, 6, 4
• Abrupt discontinuation of pregabalin in patients with renal impairment can lead to withdrawal symptoms including seizures 7

Clinical Implications

• For a patient with GFR of 8 requiring dialysis, a single 50mg dose would have significantly altered pharmacokinetics:
  • Elimination half-life would be substantially prolonged (normal t1/2 is 6.3 hours) 2
  • Area under the curve (AUC) would be markedly increased 1
  • Approximately 50% of the drug would be removed during a standard hemodialysis session 3
• Regular medication reconciliation at each transition of care is essential to prevent inappropriate dosing in dialysis patients 5

Management of Pregabalin Toxicity

• There is no specific antidote for pregabalin overdose 3
• Hemodialysis is an effective method for removing pregabalin in cases of toxicity 3, 4
• Supportive care with monitoring of vital signs and clinical status is recommended 3