Stability of levosimendan during simulated y-site administration

Purpose:   Limited information currently exists regarding the compatibility of the calcium sensitizer/inodilator levosimendan.  The intent of this study was to evaluate the stability of levosimendan during simulated y-site administration with common infusions used in a critical care setting.

Methods: Levosimendan 50 mcg/mL in D5W was incubated at 25 ^oC for 24 hours in a Waters® high performance liquid chromatography (HPLC) carousel.  Samples were separated on a Novapak® C18 column and levosimendan was monitored and quantified by ultra-violet absorbance at 380 nm.  Stability of levosimendan was measured after mixing with dobutamine, dopamine, epinephrine, esmolol, fentanyl, midazolam, milrinone, norepinephrine, remifentanil, rocuronium, sodium nitroprusside/sodium thiosulfate, vasopressin, and vecuronium.  Stability was defined as ≥ 90% of the initial drug concentration remaining in the admixtures at 24h. Visual inspection was performed to assess physical compatibility.

Results: Levosimendan was stable for 24 h with all the tested compounds.  In the presence of sodium nitroprusside/sodium thiosulfate, a new peak was detected that eluted from the HPLC column prior to levosimendan.  This peak increased linearly with time such that at 24h, ~ 7% of the original drug was depleted.  This new peak did not appear when levosimendan was mixed with nitroprusside alone but a similar time-dependent increase was seen on incubation with thiosulfate alone. Visual inspection determined the solutions studied were physically compatible.

Conclusions: Levosimendan was compatible for 24 hours during simulated y-site testing with all of the drugs tested. Levosimendan does interact with sodium thiosulfate in a time-dependent manner.  The new reaction product absorbs at 380 nm but the structure of the new compound has not yet been determined.