Drug compatibility with parenteral nutrition - Recommendations for evaluation and safe coadministration

Abstract

This article, developed within the framework of the Spanish consensus on parenteral nutrition (PN) preparation, addresses key practical aspects and provides recommendations for evaluating the compatibility between PN and intravenous drugs in scenarios requiring coadministration. Simultaneous administration-though sometimes unavoidable, as in critically ill, oncologic, or catheter-limited patients-carries significant clinical risks, including precipitation, lipid emulsion destabilization, or loss of drug efficacy. Two main modalities of coadministration are analyzed: direct drug addition into the PN admixture and Y-site simultaneous infusion. Both approaches require specific data supporting physicochemical stability, and extrapolation of compatibility results between PN admixtures of different compositions is not recommended. The high methodological heterogeneity and variability in PN formulations necessitate individualized assessments, with a preference for alternative strategies such as multilumen catheters and avoidance of coadministration whenever possible. Studies combining multiple key parameters, such as pH, the percentage of lipid globules >5?µm (PFAT5), and zeta potential, are preferred. This review summarizes these critical variables and highlights complementary analytical methods for PN-drug compatibility assessment, including high-performance liquid chromatography (HPLC), visual inspection, turbidimetry, and light obscuration. The document provides technical and clinical criteria to minimize risks and support safe decision-making in clinical settings where drug-PN compatibility may impact therapeutic efficacy or patient safety.