Aim Off-label use of IV sildenafil (Revatio) is one of the limited treatment options available in the treatment of Pulmonary Hypertension in the paediatric and neonatal population. The lack of compatibility data on the co-administration of IV sildenafil with other drugs in critical care means a dedicated line is required for sildenafil. However, in critically unwell patients multiple drug infusions are commonly administered and the dedication of an IV line for sildenafil could be problematic and can further increase the risks of adverse events.^1,2 Our Lady’s Children’s Hospital Crumlin in Dublin Ireland, identified the following five drugs as critical and commonly encountered in PICU; Adrenaline, Noradrenaline, Vasopressin, Milrinone and Heparin. The aim of this study is to determine the physical and chemical compatibility of Noradrenaline and Vasopressin in combination with Sildenafil.

Method To simulate Y-site conditions the drugs were mixed in a 1:1 ratio as previously demonstrated by Allen et al. ³ Clear glass tubes as specified by the EP, were used to allow for the investigation of compatibility at specific time-points across a 24 hour period at room temperature. Drugs were prepared in accordance with clinical practice; Noradrenaline 60 micrograms/ml, vasopressin 0.4 units/ml and sildenafil 800 micrograms/ml. Different diluents: NaCl 0.9% w/v, Glucose 5% w/v and Glucose 10% w/v were examined. Chemical compatibility was assessed using HPLC and physical by pH determination and visual inspection of contents. Drugs were deemed compatible if concentrations of both remained between 90% and 110% of the original concentration³ and if no signs of physical incompatibility was noted (i.e. pH change, haze or cloudiness).

Results No physical incompatibility was noted between the compounds with stable pH and no visual changes. Concentrations of vasopressin, noradrenaline and sildenafil were all within concentration limits indicating chemical compatibility.

Conclusion The limited and incomplete data presented in the literature for the compatibility of drugs administered via Y-site in combination with sildenafil, makes studies such as this one invaluable to clinicians. The overall aim of this work is to provide a complete compatibility chart of all five drugs identified as critical in combination with Sildenafil at RT and at 37°C. This preliminary data provides a starting point in the investigation of the compatibility of Sildenafil in combination with commonly used ICU drug infusions.

References

1. Fender RA, Hasselman TE, Wang Y, Harthan AA. Evaluation of the tolerability of intermittent intravenous sildenafil in paediatric patients with pulmonary hypertension. JPPT2016;21(5):419–25.

2. Kelly LK, Porta NFM, Goodman DM, Carroll CL, Steinhorn RH. Inhaled prostacyclin for term infants with persistent pulmonary hypertension refractory to inhaled nitric oxide. JPeds2002;141(6):830–2.

3. Allen LV, Jr., Levinson RS, Phisutsinthop D. Compatibility of various admixtures with secondary additives at Y-injection sites of intravenous administration sets. Am J Hosp Pharm1977;34(9):939–43.