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.

Reduce tacrolimus dose 10- to 20-fold from day 1 and check daily trough (C0) levels. Post-transplant patients require joint management by transplant and infectious diseases teams. Where possible, switch antiretroviral therapy to a ritonavir-free regimen (dolutegravir + bictegravir-based).