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Pharmacogenomic response of low dose haloperidol in critically ill adults with delirium. | LitMetric

Pharmacogenomic response of low dose haloperidol in critically ill adults with delirium.

J Crit Care

Department of Intensive Care Adults, Erasmus MC University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands; Department of Hospital Pharmacy, Erasmus MC University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic address:

Published: June 2020

Purpose: To characterize the pharmacogenomic response of low-dose haloperidol for delirium treatment in critically ill adults.

Materials And Methods: Single-center, pilot study of a convenience sample of ICU adults with delirium treated with low-dose IV haloperidol. Patients were evaluated for delirium with the ICDSC every 8 h. Serum haloperidol concentrations were collected on ICU days 2-6, CYP2D6 and CYP3A4 genotypes were characterized and patients were categorized as extensive (EM), intermediate (IM) or poor metabolizers (PM).

Results: The 22 patients (median age 67 [IQR 48,77] years; median APACHE III 81[IQR 54,181]; CYP2D6 [EM = 12, IM = 7, PM = 3], CYP3A [EM = 18, IM = 4]) received a median [IQR] daily haloperidol dose of 3.0 [2.4, 4.5] mg. After adjusting for age, SOFA, and ICU day, neither an association between CYP2D6 (IM p = .67/PM p = .25) or CYP3A4 (IM p = .44) metabolizer status and serum haloperidol concentrations was found. After adjusting for age, SOFA, and ICU day, neither an association between daily haloperidol dose (p = .77) or ICDSC score (p = .13) and serum haloperidol concentrations was found. No patient experienced QTc interval prolongation (≥500 ms).

Conclusions: This pilot study, the first to evaluate the pharmacogenomic response of low-dose haloperidol when used to treat delirium in the ICU, suggests CYP2D6/CYP3A4 metabolizer status does not affect the serum haloperidol concentrations.

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http://dx.doi.org/10.1016/j.jcrc.2020.03.001DOI Listing

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