A pharmacological rationale for improved everolimus dosing in oncology and transplant patients

Aims Everolimus is a drug from the class of mammalian target of rapamycin inhibitors used for both immunosuppressant and oncological indications. We postulate that there is room for improvement of dosing, as the optimal immunosuppressive dose in calcineurin‐free regimens is unknown and since the once daily dosing regimen for oncological indications is often associated with treatment‐limiting toxicity. Methods We developed a mechanistic population pharmacokinetic model for everolimus in cancer and transplant patients and explored alternative dosing regimens. Results We found that formulation did not influence bioavailability and that use of >20 mg prednisolone daily increased everolimus clearance. In transplant patients, the approved dose of 0.75–1 mg twice daily (BID) results in subtherapeutic trough levels (<6 μg l–1) and that a higher starting dose of 2.25–3 mg BID is required. Conclusion For oncological indications, our results encourage the investigation of dosing everolimus 3.75 mg BID in terms of superiority in safety and noninferiority in efficacy.