Iatrogenic Cushing’s syndrome due to drug interaction between glucocorticoids and the ritonavir or cobicistat containing HIV therapies

• Published in: Clinical medicine (London, England) Vol. 16; no. 5; pp. 412 - 418
• Main Authors: Elliot, Emilie R, Theodoraki, Aikaterini, Jain, Lakshmi R, Marshall, Neal J, Boffito, Marta, Baldeweg, Stephanie E, Waters, Laura J
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2016; Royal College of Physicians
• Subjects: Adrenal insufficiency; Adult; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Audit; cobicistat; Cobicistat - adverse effects; Cobicistat - therapeutic use; Cushing Syndrome - chemically induced; Cushing’s syndrome; Drug Interactions; Female; Glucocorticoids - adverse effects; Glucocorticoids - therapeutic use; HIV; HIV Infections - drug therapy; Humans; Iatrogenic Disease; Male; Medical Audit; Middle Aged; Retrospective Studies; ritonavir; Ritonavir - adverse effects; Ritonavir - therapeutic use; Cushing’s syndrome; Adrenal insufficiency; HIV; cobicistat; ritonavir
• ISSN: 1470-2118; 1473-4893
• DOI: 10.7861/clinmedicine.16-5-412

Ritonavir and cobicistat, used as pharmacokinetic enhancers in combination with some antiretrovirals (ARVs) for the treatment of HIV, are potent inhibitors of the CYP3A4 isoenzyme. Most glucocorticoids are metabolised via the CYP3A4 pathway and iatrogenic Cushing’s syndrome (ICS), with possible secondary adrenal insufficiency (SAI), is a recognised complication following co-administration with ritonavir or cobicistat. A structured approach for identifying and managing potentially affected individuals has not been established. We systematically identified patients with ICS/SAI and found substantial heterogeneity in clinical practice across three large London HIV centres. While this significant drug interaction and its complications are now well-recognised, it is apparent that there is no standardised approach to management or guidance for the general physician. Here we describe the management of ICS/SAI in our current practice, review the available evidence and suggest practice recommendations.