Understanding the Risk of Drug Interactions Between Ritonavir-Containing COVID-19 Therapies and Small-Molecule Kinase Inhibitors in Patients With Cancer.

PURPOSE: The introduction of COVID-19 therapies containing ritonavir has markedly expanded the scope of use for this medicine. As a strong cytochrome P450 3A4 inhibitor, the use of ritonavir is associated with a high drug interaction risk. There are currently no data to inform clinician regarding the likely magnitude and duration of interaction between ritonavir-containing COVID-19 therapies and small-molecule kinase inhibitors (KIs) in patients with cancer. METHODS: Physiologically based pharmacokinetic modeling was used to conduct virtual clinical trials with a parallel group study design in the presence and absence of ritonavir (100 mg twice daily for 5 days). The magnitude and time course of changes in KI exposure when coadministered with ritonavir was evaluated as the primary outcome. RESULTS: Dosing of ritonavir resulted in a > 2-fold increase in steady-state area under the plasma concentration-time curve and maximal concentration for six of the 10 KIs. When the KI was coadministered with ritonavir, dose reductions to between 10% and 75% of the original dose were required to achieve an area under the plasma concentration-time curve within 1.25-fold of the value in the absence of ritonavir. CONCLUSION: To our knowledge, this study provides the first data to assist clinicians' understanding of the drug interaction risk associated with administering ritonavir-containing COVID-19 therapies to patients with cancer who are currently being treated with KIs. These data may support clinicians to make more informed dosing decisions for patients with cancer undergoing treatment with KIs who require treatment with ritonavir-containing COVID-19 antiviral therapies.

Ten minutes with Professor Andrew Rowland, Lead Employer Medical Director of St Helens and Knowsley Teaching Hospitals NHS Trust, Honorary Professor at the University of Salford, Chair of SicKids children's charity, Non-Executive Director of M’Lop Tapang, and Consultant in Children’s Emergency Medicine

Lead Employer Medical Director for over 10000 doctors and dentists, and non-medically qualified public health trainees, in training in England;Honorary Professor (Paediatrics) at the University of Salford with research leadership roles in individual research studies;Consultant in Children’s Emergency Medicine with the senior leadership activities that this entails;Non-Executive member of the Board of Directors of M’Lop Tapang;and Chair of a children’s charity (SicKids—1164131). [...]book some days off work (either as leave or time off in lieu) regularly—and have proper days away from work, even if this just involves a walk, a TV day, a socially distant catch up from family or friends (when the rules permit) or some time doing something one enjoys such as a hobby. [...]book some annual leave to look forward to. Are there any ideas or readings that you find helpful, for inspiration and support, which you would recommend to others? Since 2014 I’ve been proud to be a Fellow of the Winston Churchill Memorial Trust and I try to lead my life (both at home and at work) with one of Sir Winston’s quotes at the forefront of everything I do: