Iatrogenic Cushing syndrome and multifocal osteonecrosis caused by the interaction between inhaled fluticasone and ritonavir

BMJ Case Rep. 2020 May 27;13(5):e233712. doi: 10.1136/bcr-2019-233712.

Abstract

Inhaled corticosteroids are generally considered safe and do not usually lead to systemic adverse events since their plasma concentrations are low due to hepatic metabolism by the cytochrome P450 3A4. However, when associated with inhibitors of this cytochrome, such as ritonavir, they may lead to iatrogenic Cushing syndrome by the systemic accumulation of corticosteroids and consequent suppression of the hypothalamic-pituitary-adrenal axis. We present a case of iatrogenic Cushing syndrome complicated by multifocal osteonecrosis in a patient with HIV infection on antiretroviral therapy with protease inhibitors boosted with ritonavir, after the association of inhaled fluticasone. This clinical case highlights a relevant interaction between corticosteroids and inhibitors of the cytochrome P450 and the severe consequences that may occur.

Keywords: HIV / AIDS; adrenal disorders; drug interactions; drugs: musculoskeletal and joint diseases; unwanted effects / adverse reactions.

Publication types

  • Case Reports

MeSH terms

  • Administration, Inhalation
  • Adult
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / adverse effects*
  • Cushing Syndrome / chemically induced*
  • Drug Interactions
  • Fluticasone / administration & dosage
  • Fluticasone / adverse effects*
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / adverse effects*
  • Humans
  • Iatrogenic Disease
  • Male
  • Osteonecrosis / chemically induced*
  • Pulmonary Disease, Chronic Obstructive / complications
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Ritonavir / administration & dosage
  • Ritonavir / adverse effects*

Substances

  • Bronchodilator Agents
  • HIV Protease Inhibitors
  • Fluticasone
  • Ritonavir