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Objective To investigate the chemical and visual compatibility of dexmedetomidine injection with 44 secondary intravenous (IV) drugs and six 2-in-1 parenteral nutrition (PN) solutions used in neonatal intensive care unit settings.Methods Dexmedetomidine (1 or 4 µg/mL) was mixed 1:1 with each secondary IV drug or PN solution to simulate Y-site co-administration. Visual compatibility was evaluated for 4 hours and chemical compatibility was determined from dexmedetomidine concentrations using a validated high performance liquid chromatography (HPLC) assay. Absorption/adsorption loss of dexmedetomidine was evaluated in three syringe filters and one in-line filter.Results Dexmedetomidine injection was visually compatible with all 44 secondary IV drugs and six PN solutions tested, and chemically compatible with 42 drugs. Due to interference by nine secondary drugs in the HPLC analyses of dexmedetomidine at 1 µg/mL, compatibility tests were conducted at a higher concentration of 4 µg/mL against ampicillin, benzylpenicillin, flucloxacillin, hydrocortisone, ibuprofen, indometacin and rifampicin, and the combinations were found to be chemically compatible. However, dexmedetomidine 4 µg/mL was chemically incompatible with ibuprofen lysine injection. Results for cloxacillin were inconclusive due to unresolved interference in the HPLC assay. Modest absorption/adsorption loss of dexmedetomidine (<20%) occurred in the first millilitre of filtrate with clinically relevant filters.Conclusion Dexmedetomidine injection was chemically and visually compatible with 42 secondary IV drugs and six PN solutions for up to 4 hours. Dexmedetomidine injection should not be combined via Y-site administration with ibuprofen lysine injection. Due to inconclusive results, combining dexmedetomidine and cloxacillin injections via Y-site administration is not recommended.