Ritonavir × Tacrolimus

Tacrolimus is almost entirely cleared via hepatic CYP3A4. Ritonavir is the strongest CYP3A4 inhibitor available. Tacrolimus plasma levels can rise 50-fold or more. Acute nephrotoxicity and neurotoxicity with encephalopathy have been reported.

Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Tremor, headache, hypertension, hyperglycaemia, hyperkalaemia. In transplant patients, accelerated graft function decline.

Avoid the combination where possible, as the tacrolimus SmPC states. If ritonavir cannot be avoided, the SmPC advises considering omitting the tacrolimus dose on the day ritonavir starts. Tacrolimus is restarted the next day at a reduced dose guided by blood levels. Trough levels (C0) are checked often from the first days and again after ritonavir is stopped, and the dose follows them. Renal function and the QT interval on ECG are monitored as well. Transplant patients are managed jointly by transplant and infectious diseases teams. Where possible, switch to a ritonavir-free antiretroviral regimen, for example one based on dolutegravir or bictegravir.