Conversion from Compounded Liquid Prograf to Prograf Granules - Lessons Learned from Our Early Experience

Purpose In June 2018, the US Food and Drug Administration approved Prograf granules for pediatric solid-organ heart transplant without a US trial. This was due to concerns over compounding errors associated with pharmacy preparation of Prograf suspension for children who cannot swallow capsules. We reviewed our early experience converting children from Prograf suspension to granules to ensure safe transition practices. Methods All children transitioned from Prograf suspension to Prograf granules at a single center in 2019 were identified using pharmacy records. The starting dose for the transition from compounded liquid to granules was determined by using a one to one dosing conversion. The steady dose of Prograf pre and post conversion were compared, as was the time to reach a therapeutic level. Patients with modified target goals (e.g. secondary to infection) before or after conversion were excluded. Results Between January and September 2019, a total of 12 children were converted from Prograf suspension to Prograf granules of whom 9 met the inclusion criteria. Of these, the median age was 6.25 (IQR 4, 8) years, the median weight was 17 (15, 21) kg; 56% were female and 67% had prior congenital heart disease. Prior to conversion, the mean daily dose was 0.106 (SD 0.07) mg/kg. Following conversion, the mean daily dose was 0.112 (SD 0.08) mg/kg, a 15% increase on average. On average, 3 levels were obtained before a goal target level was achieved at a mean of 34 days after conversion. Conclusion Children transitioned from Prograf suspension to granules often required a dosing change to achieve the same target level on Prograf granules. The number of dose increases outnumbered dose decreases. Increasing the frequency of monitoring tacrolimus levels after conversion may help to foreshorten the period of time outside the goal range.