How are urine pregabalin levels used to adjust therapy in patients with suspected toxicity or impaired renal function?

From the Guidelines

Urine pregabalin levels are not used to adjust therapy in patients with suspected toxicity or impaired renal function, instead, serum pregabalin concentrations and creatinine clearance are relied upon for therapeutic drug monitoring and dosing adjustments. When adjusting therapy in patients with suspected toxicity or impaired renal function, several key factors must be considered:

• Pregabalin dosing should be reduced based on creatinine clearance (CrCl) to avoid toxicity, as it is primarily eliminated unchanged in urine 1.
• For patients with CrCl >60 mL/min, standard dosing of 150-600 mg/day divided into 2-3 doses can be used.
• Those with CrCl 30-60 mL/min should receive 75-300 mg/day in 2-3 divided doses.
• Patients with CrCl 15-30 mL/min should receive 25-150 mg/day in a single or divided dose.
• For CrCl <15 mL/min, 25-75 mg once daily is recommended, and since pregabalin is efficiently removed by hemodialysis, supplemental doses may be needed after dialysis. In cases of suspected toxicity, treatment is primarily supportive, focusing on maintaining airway, breathing, and circulation, and monitoring serum pregabalin concentrations is crucial for guiding therapy adjustments. Key considerations for therapy adjustments include:
• Renal function significantly impacts pregabalin clearance, necessitating dosage adjustments in renal impairment.
• Pregabalin is efficiently removed by hemodialysis, with approximately 50% removed in a 4-hour session, which may necessitate supplemental doses after dialysis.
• Serum pregabalin concentrations should be monitored to guide therapy adjustments in patients with suspected toxicity or impaired renal function.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Urine Pregabalin Levels and Therapy Adjustment

• Urine pregabalin levels can be used to adjust therapy in patients with suspected toxicity or impaired renal function, although the evidence is limited 2, 3.
• Pregabalin is primarily cleared by the kidney, and patients with decreased kidney function may be at an increased risk of adverse effects 4, 5.
• The EXTRIP workgroup suggests that pregabalin is "dialyzable" for patients with decreased kidney function, but the clinical benefit of extracorporeal treatment is unclear 2.
• Studies have shown that higher pregabalin doses result in more severe poisonings, and patients with decreased kidney function may be more susceptible to adverse effects 6, 5.

Adjusting Therapy Based on Urine Pregabalin Levels

• There is no clear consensus on the optimal method for adjusting therapy based on urine pregabalin levels, but it is recommended to monitor patients closely for signs of toxicity or adverse effects 3, 6.
• The dose-toxicity relationship of pregabalin has been evaluated, and it has been shown that doses above 20 mg/kg can result in more severe poisonings 6.
• Patients with decreased kidney function should be prescribed gabapentinoids with caution, and the dose should be adjusted based on the patient's creatinine clearance 4, 5.

Clinical Considerations

• Clinical toxicologists should be aware of the potential for severe toxicity arising from excessive plasma pregabalin concentrations, and extra-corporeal methods such as hemodialysis may be considered in severe cases 2, 3.
• Concomitant opioid and psychiatric medications can contribute to a higher prevalence of adverse effects, regardless of kidney function 5.
• Larger, multicentre studies are needed to fully understand the relationship between gabapentinoid dosing, kidney function, and the incidence of gabapentinoid-related adverse effects 5.