Ciclosporin × Ritonavir

Ritonavir strongly inhibits CYP3A4, which is why it is used as a pharmacokinetic booster in HIV regimens. Cyclosporine is cleared through CYP3A4 and P-glycoprotein, so its blood level rises on ritonavir. Both labels expect the rise: the ritonavir SmPC names cyclosporine, and the cyclosporine SmPC lists protease inhibitors among drugs that raise its levels. The size of the rise is not known in advance: the FDA cyclosporine label notes that no formal studies of this pair are available. Excess cyclosporine damages the kidneys and raises blood pressure.

Sharp creatinine rise, hypertension.

The combination is possible only with cyclosporine level monitoring: the FDA ritonavir label recommends therapeutic concentration monitoring of the immunosuppressant, and the ritonavir SmPC asks for careful monitoring of effect and adverse reactions. Cyclosporine trough levels are measured before ritonavir starts, frequently in the first days and after any change of the antiretroviral regimen, and the cyclosporine dose follows the result. Creatinine, potassium and blood pressure are watched in parallel. When ritonavir stops, cyclosporine levels fall and the dose is reviewed again by level. The transplant team and the HIV specialist agree on the plan together.