A Single Centre Experience of Isavuconazole in Lung Transplant Recipients: Effects on Sirolimus and Tacrolimus Concentrations

Purpose Lung transplant (LTx) patients have increased susceptibility to fungal infections. Isavuconazole received a marketing authorisation in the UK in 2015. The use of isavuconazole has advantages over voriconazole/posaconazole as it presents a more favourable pharmacokinetic and toxicity profile. This retrospective analysis reviews the experience of isavuconazole in LTx patients in a single centre. Methods Pharmacy records were used to identify LTx patients who had received ≥14 days isavuconazole therapy since 2016 and had ≥1 serum isavuconazole level taken. Immunosuppression (sirolimus or tacrolimus) and isavuconazole serum levels were collated to calculate a concentration/dose (C/D) ratio normalised for weight and percentage time in therapeutic range (%TTR, days). All patients received a loading dose of isavuconazole 200mg three times a day for 6 doses then 200mg once daily (OD). The serum isavuconazole levels were monitored, doses were adjusted to maintain therapeutic serum levels of 1-5ng/ml. Results Forty-two courses of isavuconazole were included, in thirty-eight patients (16 CF (Cystic Fibrosis), 22 non-CF). Isavuconazole doses were adjusted in 45% (n=19) of courses. All courses achieved serum isavuconazole levels ≥ 1ng/ml at day 28 with 20 at 200mg OD (18 200mg) and had 86.95±26.5 SD% days in therapeutic range of isavuconazole treatment days. The C/D ratio increased from 72 to 134 for sirolimus and 74.5 to 116.5 for tacrolimus. Conclusion Isavuconazole demonstrated favourable pharmacokinetics and was well tolerated in LTx patients. Immunosuppressant doses should be guided by close therapeutic drug monitoring on initiating and stopping isavuconazole; also, considering isavuconazole levels. The high TTR% showed that isavuconazole serum levels maintained in therapeutic range following day 28, suggesting routine monitoring of serum levels following this may not be imperative once target range is achieved.