Physicochemical compatibility of pentoxifylline injection with high‐concentration parenteral medications

Pentoxifylline (PTX) is reported to provide beneficial outcomes in the treatment of neonatal sepsis and serious inflammatory conditions.1, 2 In intensive care setting, PTX administered by intravenous (IV) infusion routinely co-administered via Y-site with other parenteral medications and/or fluids. Although physicochemical compatibility a range drugs, IV fluids, lipid-free nutrition solutions has been reported, there an emerging demand for more data against previously untested (ampicillin, cloxacillin, fentanyl, fluconazole, furosemide, hydrocortisone, ibuprofen lysine) high-concentration drugs (alprostadil, dopamine, epinephrine, midazolam, milrinone, morphine, norepinephrine) which may be used fluid-restricted, vulnerable patients.3-5 order address this requirement contemporary information, we investigated physical chemical panel 20 51 PTX-drug combinations. All vials were gently mixed inspected at 5, 15, 60 min compatibility. Chemical all drug mixtures was determined on basis concentration ratio plus test reference solution. Visual observation testing also occurred hours 10 (22 combinations) highest or if prolonged mixing clinical setting plausible. The mean peak areas 95% confidence interval (CI) calculated using limits from two-sided t-test (α = 0.05; SigmaPlot v14.5; Systat Software, San Jose, CA). Further details method are provided File S1. No precipitation, color change, turbidity observed any mixtures, indicating physically compatible drugs. This finding consistent previous reports context our data, reflects importance determining both combinations, irrespective mode administration.3, 4 shown Table 1. Six not tested (cloxacillin, PTX, although results indicated it preferable dilute lysine 5% w/v glucose, rather than 0.9% sodium chloride injection. Eight higher concentrations different diluents studies (aciclovir, alprostadil, norepinephrine, phenobarbitone, piperacillin/tazobactam) PTX.3, Overall, ratios these combinations 99.0%‒100.9%, CI spanned 100%, no difference between combination One notable issue concern incompatibility two aminopenicillins injection (Table 1). Amoxicillin (100 mg/ml) incompatible PTX3; however, considered prudent compare ampicillin (hitherto untested) amoxicillin present study. We found approximately 3% 4% lower when combined 100 mg/ml mg/ml, respectively, compared control, after 1 h. further investigation cause(s) apparent beyond scope study, recommend avoiding co-administration ampicillin. Dopamine hydrochloride (1.2 injection) current findings similar dopamine 1.6 1).3 However, diluted glucose injection, (1.6 PTX. At 7.2 diluents, (99.2%) did span 100% hours, thus statistically significant controls. Nevertheless, based results, conclude clinically risk Morphine morphine sulfate 500 µg/ml 10% 200 Combined would Dilution showed modest reductions (1%‒2% control) most likely presents up h.3, A confounding result study unequivocal undiluted calcium gluconate Previously, that (50 setting); h.4 separate occasions (n 10) extended mixture time evident tight ratio. Whilst unable elucidate reasons conflicting reasonable indicate Potential limitations tests able perform conducting HPLC analysis only primary (PTX). Turbidity pH measurements commonly conducted have investigations.7-11 resource implications tests, least large sample volumes (typically > ml), problematic expensive Furthermore, intrinsic value some unclear interpretation specification inconsistent12; example, regard unit shift.9-11 quantifying concentration, assumed interaction should detected assay drug. secondary suspected, impediment developing validating assays full limitation use 1:1 ratios, well-established simulated studies.7, 8, 10, 13 By comparison, 1:4, 1:10, fluids where (1:2–1:100) simulate extremes high/low rates individual components.14-18 designed can greater rates, scenarios conventional required studies. Notwithstanding outlined above, combining visual evaluation compatibility, consider design provides acceptable evidence investigations, will help paucity data.12, 19, conclusion, pentoxifylline settings classified as incompatible. compatible, diluent morphine. studies, 40 over various diluents.3, Not required. authors gratefully acknowledge assistance Ms Claire Kendrick, Anna Dao, Mr Jack Lee (King Edward Memorial Hospital Women). work supported Women & Infants Research Foundation Department Pharmacy King Women. declare conflict interest. Please note: publisher responsible content functionality supporting information supplied authors. Any queries (other missing content) directed corresponding author article.