Tacrolimus overdosing in lung transplant recipients: clinical manifestations and management

Tacrolimus is essential for preventing rejection after lung transplantation, but its narrow therapeutic index and interindividual variability increase the risk of overdose. Despite the frequency of overdose, the clinical impact of tacrolimus overdose remains poorly defined. This study aimed to systematically assess the frequency, severity, and clinical consequences of tacrolimus overdose in lung transplant recipients and to propose a structured management approach.

We conducted a retrospective single-center study involving 61 lung transplant recipients treated between January 2022 and December 2023. Tacrolimus overdose was defined as a trough level ≥15 µg/L, and classified as mild (15-<20 µg/L), moderate (20-<25 µg/L), or severe (≥25 µg/L). We analyzed clinical outcomes, renal function, and complications, with special attention to patients with cystic fibrosis (CF).

Tacrolimus overdose occurred in 54 patients (88.5%), with a mean peak level of 22 µg/L (range, 10-39) at a median of 81 days post-transplant. Dose normalization required a mean of 11 days (range, 0-87). Acute kidney injury occurred in 37% of patients (odds ratio: 1.14, 95% confidence interval: 0.19-6.80; P>0.99) and was not statistically associated with overdose. None progressed to end-stage renal disease. All four CF patients experienced recurrent overdoses, including moderate and severe episodes. One patient developed posterior reversible encephalopathy syndrome. C-reactive protein levels were frequently elevated, while gastrointestinal and infectious complications were uncommon.

Tacrolimus overdose is common after lung transplantation. Although acute kidney injury was frequently observed, a statistically significant association could not be established in our cohort, particularly given the small sample size. CF patients appeared more vulnerable. Although severe complications are rare, they are clinically relevant. These findings underscore the importance of individualized monitoring and support a novel classification and management algorithm to guide prevention and treatment.