Monitoring for valproate and phenytoin toxicity in hypoalbuminaemia: A retrospective cohort study.

AIMS

Equations to calculate albumin-adjusted total concentrations have been validated to correlate with measured free concentrations for both phenytoin and valproate, but there is a lack of data to assess correlation with clinical outcomes. We aimed to assess the association of hypoalbuminaemia and albumin-adjusted total concentrations with concentration-dependent toxicity for phenytoin and valproate and review the impact on management decisions following concentration monitoring in hypoalbuminaemia.

METHODS

Patients undergoing concentration monitoring for phenytoin or valproate between January and December 2018 were included. Patients were identified using a centralised laboratory database with data extracted from medical records.

RESULTS

Total phenytoin concentrations were measured for 144 patients, with hypoalbuminaemia (≤30 g L ) recorded in 59 (41%) patients. Albumin-adjusted phenytoin concentration >20 mg L was associated with increased neurological adverse effects (77% vs. 43%, P < .001). On logistic regression, higher albumin-adjusted phenytoin concentration was an independent risk factor for neurotoxicity (OR 1.06, 95% CI 1.01-1.12, P = .011). Total valproate concentrations were measured for 383 patients, with hypoalbuminaemia (≤30 g L ) noted in 53 (14%) patients. For the valproate cohort, hypoalbuminaemia (42% vs. 28%, P = .039) and albumin-adjusted valproate concentration >100 mg L (49% vs. 23%, P < .001) were both associated with increased neurotoxicity. On multiple logistic-regression, valproate daily dose (aOR = 1.01, 95% CI 1.00-1.02, P = .006) and albumin-adjusted valproate concentration (aOR 1.01, 95% CI 1.00-1.02, P = .033) were independent risk factors for neurotoxicity after accounting for confounders.

CONCLUSION

While measuring free drug concentrations in hypoalbuminaemia would be ideal, the adjustment equations can help identify vulnerable patients needing further assessment of potential concentration-dependent toxicity.