Iatrogenic Cushing’s syndrome due to drug interaction between glucocorticoids and the ritonavir or cobicistat containing HIV therapies
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 seco...
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| Published in | Clinical medicine (London, England) Vol. 16; no. 5; pp. 412 - 418 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Elsevier Ltd
01.10.2016
Royal College of Physicians |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1470-2118 1473-4893 |
| DOI | 10.7861/clinmedicine.16-5-412 |
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| Abstract | 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. |
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| AbstractList | 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. 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. |
| Author | Boffito, Marta Jain, Lakshmi R Theodoraki, Aikaterini Waters, Laura J Elliot, Emilie R Marshall, Neal J Baldeweg, Stephanie E |
| Author_xml | – sequence: 1 givenname: Emilie R surname: Elliot fullname: Elliot, Emilie R email: emilieelliot@doctors.net.uk organization: Chelsea and Westminster Hospital, London, UK – sequence: 2 givenname: Aikaterini surname: Theodoraki fullname: Theodoraki, Aikaterini organization: University College London Hospitals Foundation Trust, London, UK – sequence: 3 givenname: Lakshmi R surname: Jain fullname: Jain, Lakshmi R organization: Mortimer Market Centre, London, UK – sequence: 4 givenname: Neal J surname: Marshall fullname: Marshall, Neal J organization: Ian Charleson Centre for HIV Medicine, Royal Free London NHS Foundation Trust, London, UK – sequence: 5 givenname: Marta surname: Boffito fullname: Boffito, Marta organization: Chelsea and Westminster Hospital, London, UK – sequence: 6 givenname: Stephanie E surname: Baldeweg fullname: Baldeweg, Stephanie E organization: University College London Hospitals Foundation Trust, London, UK – sequence: 7 givenname: Laura J surname: Waters fullname: Waters, Laura J organization: Mortimer Market Centre, London, UK |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27697800$$D View this record in MEDLINE/PubMed |
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| Keywords | Cushing’s syndrome Adrenal insufficiency HIV cobicistat ritonavir |
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| SubjectTerms | 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 |
| Title | Iatrogenic Cushing’s syndrome due to drug interaction between glucocorticoids and the ritonavir or cobicistat containing HIV therapies |
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