Comparative evaluation of amiodarone and furosemide compatibility under different mixing conditions

Amiodarone and furosemide are frequently administered together in the intensive care unit, and their co-administration poses a risk of precipitation and catheter occlusion due to incompatibility. Thus, compatibility should be evaluated under clinically relevant conditions to ensure safe drug administration. This study investigated the impact of different mixing procedures on the physical compatibility of amiodarone and furosemide by employing two clinically relevant approaches: simulated mixing (SM) and route mixing (RM). Mixtures were prepared at therapeutic concentrations and evaluated by visual inspection, absorbance measurement, powder X-ray diffraction (PXRD), pH analysis, and particle size assessment. Although the drug ratios were identical, the RM samples displayed greater turbidity than the SM samples. The PXRD analysis showed no formation of new crystalline substances, and the precipitates consisted of known furosemide and amiodarone hydrochloride polymorphs. The pH shifted toward the alkaline range as the injection volume increased with furosemide dose. Importantly, differences in particle growth behavior were noted between SM and RM, with larger particles observed in the RM samples. In conclusion, mixing route significantly affects drug compatibility, with RM presenting a higher risk of precipitation. Assessing drug compatibility under clinically relevant conditions may help prevent catheter-related complications and improve the safety of intravenous pharmacotherapy.