Review Review of drug stability in parenteral nutrition admixtures Daniel Cardona a, * , Maria Nadal b , Joan Estelrich c , M. Antònia Mangues a a Pharmacy Department, Hospital Santa Creu i Sant Pau, 167-08025 Barcelona, Spain b Primary Care Pharmacist, Catalan Health Institute, Girona, Spain c Physicochemical Department, Universitat de Barcelona, Spain article info Article history: Received 30 November 2012 Accepted 6 June 2013 Keywords: Parenteral nutrition admixtures Peripheral parenteral nutrition admixtures Drugs Incompatibility Physical emulsion stability Drug stability summary Background and aims: The addition of drugs to parenteral nutrition admixtures (PNA) or simultaneous Y- site administration is a concern in daily practice. We present a literature review studies on the physi- cochemical stability of drugs using both methods. Methods: We performed a search of electronic databases and publications about drug stability in PNA. We prioritized studies that used two methods for obtaining samples: the reproduction of clinical adminis- tration conditions or centrifugation. Results: Forty-two studies met all inclusion criteria and covered a total of 118 drugs with the following characteristics: simultaneous Y-site administration [20 studies and 115 drugs], and administration in PNA [24 studies and 13 drugs]. Eighty drugs administered in PNA via Y-site were compatible and 26 incompatible, while 9 results depended on the study conditions. Twelve out of 13 drugs included in the PNA were compatible for more than 24 h at room temperature. Conclusions: The results of drug stability tests depend on the sampling methodology. Most of the results were obtained by the centrifugation method. Although the clinical method is much more reliable and offers a higher reproducibility of physicochemical stability, we found it was used by very few studies. Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism. 1. Introduction Two methods are used to administer drugs with parenteral nutrition admixtures (PNA): simultaneous Y-site infusion or in- clusion in the PNA. The former normally consists of an intermittent infusion of drugs with PNA in simultaneous Y-site administration. The liquid content in the nutrient admixture is used as a vehicle for introducing the drugs into the patient. Once the admixture is pre- pared, the contact time between drugs and admixture can range from 10 min to 12 h. In the second method, the drug is mixed with the PNA and the period of co-infusion is the same, usually up to 24 h. However, this method is not usual in daily clinical practice due to the problems arising from a possible lack of physicochemical stability of the nutrients included in the PNA or absence of chemical stability data. Separate administration of drugs and PNA is not always possible, even though multi-lumen catheters are used, since some situations require a high number of intravenous administrations (polypharmacy). Although pharmacists are frequently consulted about the administration of drugs via PNA there is a lack of information about compatibility due to the high variability in PNA composition. Therefore, pharmacists are required to interpret the results of existing stability studies, since working conditions cannot always be guaranteed to be the same. Before adding a drug to a PNA or delivering it by simultaneous Y- site infusion, its physicochemical stability must be reviewed in order to maintain the stability of the nutritive admixture (avoiding emulsion breaking, creaming or precipitations) and the concen- tration of the drug in the mixture must be 90% of the initial concentration. 1 There are several reviews about drug compatibility with PNA and drug stability in ternary mixtures (containing amino acids, dextrose, lipids, with electrolytes, trace elements and vitamins). 2e4 The aim of the current work was to review the literature about physicochemical stability of drugs administered by simultaneous Y- site infusion or in PNA. We also focused on peripheral and central administration. Abbreviations: CC, Coulter Counter Ò ; CR, counted radioactivity recovered after 125 Iodine labelling; EMIT, enzyme multiple immunoassay; EVA, ethylene vinyl ac- etate; FACS, fluorescence activated cell sorter; FPI, Fluorescence polarization immunoassay; HPLC, high-performance liquid chromatography; LD, laser diffrac- tion; PCS, photon correlation spectroscopy; PN, parenteral nutrition; PNA, paren- teral nutrition admixtures; PPNA, peripheral parenteral nutrition admixures; PVC, polyvinyl chloride; RIA, radioimmunoassay; RT, room temperature. * Corresponding author. Tel.: þ34 93 553 74 58; fax: þ34 93 553 74 71. E-mail address: dcardona@santpau.cat (D. Cardona). Contents lists available at SciVerse ScienceDirect e-SPEN Journal journal homepage: http://www.elsevier.com/locate/clnu 2212-8263/$36.00 Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism. http://dx.doi.org/10.1016/j.clnme.2013.06.001 e-SPEN Journal 8 (2013) e135ee140