{
  "abstract": "Background and Importance Sirolimus, a CYP3A4 substrate, is commonly used as an immunosuppressant after liver transplantation. Co-administration with voriconazole, a potent CYP3A4 inhibitor, markedly increases sirolimus plasma concentration, predisposing to toxicity. In hypoalbuminemia, the free (unbound) drug fraction rises due to reduced protein binding, resulting in exaggerated pharmacologic effects even within the normal therapeutic range. The complex interplay between metabolic inhibition and protein binding necessitates close monitoring. This report highlights the pharmacist’s role in identifying and managing this interaction to prevent toxicity while maintaining therapeutic efficacy.Aim and Objectives To describe the clinical pharmacist’s intervention in managing sirolimus–voriconazole interaction in a paediatric liver transplant patient with hypoalbuminemia, emphasising therapeutic drug monitoring (TDM) and individualised dose adjustment.Material and Methods A 12-year-old girl (38 kg), 8 years post–liver transplantation, was admitted with suspected graft rejection. She received tacrolimus 0.25 mg/day (level 4.8 ng/mL) and voriconazole 100 mg twice daily (level 1.56 mg/L). Laboratory results showed albumin 14.9 g/L, elevated bilirubin, and liver enzyme abnormalities. Sirolimus 1 mg daily was initiated. After 5 days, the sirolimus trough level rose to 21.93 ng/mL, platelets decreased to 100,000/mm 3, and albumin was 19.6 g/L. The pharmacist identified a CYP3A4-mediated interaction exacerbated by hypoalbuminemia and recommended holding sirolimus for 7 days, monitoring levels every 2–3 days. Once the trough decreased to 8.49 ng/mL, sirolimus was restarted at 0.5 mg every other day.Results Sirolimus levels stabilised at 6.99 ng/mL (therapeutic range) by day 11, platelet count recovered, and no further adverse effects were observed. The pharmacist’s proactive intervention prevented sirolimus toxicity and ensured effective immunosuppression.Conclusion and Relevance This case underscores the importance of pharmacist-led TDM in managing CYP3A4-mediated drug interactions, particularly in hypoalbuminemic paediatric transplant patients. Dose reduction of sirolimus by approximately 75% should be considered when co-administered with voriconazole. Continuous collaboration between pharmacists and physicians is crucial for optimising safety and therapeutic outcomes.References and/or Acknowledgements 1. Staatz CE, Tett SE. Sirolimus PK/PD in transplant. Clin Pharmacokinet 2014;53(10):849–72.2. Neely M, et al. Voriconazole–immunosuppressant interaction in paediatrics. Ther Drug Monit 2015;37(6):822–8.3. KDIGO Work Group. Kidney transplant guideline. Am J Transplant 2009;9(Suppl 3):S1–57.4. PKP-013. Drug interactions with azole antifungals in transplants. Eur J Hosp Pharm. 2014;21(Suppl 1):A141.2.Conflict of Interest No conflict of interest",
  "authors": [
    {
      "affiliations": [
        "Ramathibodi Hospital, Department of Pharmacy Paediatric Ward, Bangkok, Thailand"
      ],
      "name": "A Suppasittikulchai"
    }
  ],
  "title": "4CPS-088 Pharmacist-led management of sirolimus–voriconazole interaction in a hypoalbuminemic paediatric liver transplant patient: a case report",
  "uid": "9fc334f0-8c55-5ebf-a49b-7e7599f93414"
}