Unmasking Tacrolimus Toxicity due to the Hacked Liver System

Fluconazole-tacrolimus interactions occur, but the additional effect of ritonavir is emphasized here, underscoring the need for careful prescription reconciliation in renal transplant recipients living with HIV-AIDS to prevent accidental ritonavir coadministration and inadvertent tacrolimus toxicity. The findings provide valuable insight for therapeutic drug monitoring (TDM) specialists. Patient informed consent was obtained for publication of the anonymized data.

A 52-year-old male kidney transplant recipient presented to the emergency department with difficulty walking, myalgia, trouble swallowing, weakness, altered mental state, headache, loss of appetite, drowsiness, and painful oral ulcers. Laboratory results indicated an exceptionally high tacrolimus C 0 (139 ng/mL), elevated serum creatinine (3.08 mg/dL), electrolyte imbalances, and hyperglycemia. The medical team discontinued immunosuppressants, antimicrobials, and initiated supportive care. Recent use of fluconazole for the treatment of oral candidiasis was noted in medical history. Despite preemptively reducing the tacrolimus dose by nearly 57% of the original dose (1.75-1 mg BD), the C 0 remained dangerously high. On examining the pill box, the TDM physicians discovered that antiretroviral therapy had been mistakenly switched from Abacavir plus lamivudine to atazanavir plus ritonavir (a potent CYP3A inhibitor), which significantly increased tacrolimus exposure due to dual inhibition of tacrolimus metabolism by ritonavir and fluconazole. The C 0 began to decline 5 days after tacrolimus discontinuation. Complete uneventful clinical recovery was observed once C 0 dropped to 13 ng/mL, with serum creatinine reaching a baseline of 2.1 mg/dL. Tacrolimus was reintroduced at a starting dose of 0.25 mg BD 10 days after admission.

This case highlights the importance of reviewing potential drug interactions before prescribing or dispensing drugs.