Date of report 28 Jan 2020

Reported case interaction between
Cobicistat and FLUTICASONE

Cobicistat is a strong inhibitor of CYP3A4. Most glucocorticoids are metabolized via the CYP3A4 pathway and, therefore, plasma concentrations can be highly increased when the cobicistat is also used1, with the subsequent risk of iatrogenic Cushing’s syndrome and/or secondary adrenal insufficiency. Due to its longer half-life and higher binding affinity for the glucocorticoid receptor Fluticasone can cause stronger cortisol suppression compared to other inhaled corticosteroids2, although clinically significant interactions have been described between budesonide and ritonavir, other CYP3A4 strong inhibitor3. The present case illustrates a clinically important consequence of the interaction between CYP3A4 strong inhibitors, such as cobicistat, andan inhaled fluticasone. Glucocorticoids, even inhaled, must be used with caution when combined with ritonavir o cobicistat boosted antiretroviral drugs. If possible, an alternate corticoid-sparing treatment or an alternate unboosted ART regimen should be considered. References 1. Elliot ER, et al. Iatrogenic Cushing’s syndrome due to drug interaction between glucocorticoids and the ritonavir or cobicistat containing HIV therapies.Clinical Medicine 2016; 16: 412–8. 2. Brus R. Effects of high-dose inhaled corticosteroids on plasma cortisol concentrations in healthy adults. Arch Intern Med 1999;159:1903–8. 3. Frankel JK, Packer CD. Cushing’s syndrome due to antiretroviral- budesonide interaction. Ann Pharmacother 2011;45:823–4.