Abstract and Introduction
As a consequence of inhibition of the hepatic cytochrome P450 3A4 isozyme, treatment with HIV protease inhibitors can result in significant drug–drug interactions. One noteworthy interaction is between protease inhibitors and inhaled or intranasal corticosteroids. This interaction can result in adrenal insufficiency and iatrogenic Cushing's syndrome (with symptoms such as rapid weight gain, obesity, facial hirsutism and swelling), as well as hypertension, osteoporosis and decreased CD4 cell count. In this paper, we review and unite pharmacokinetic data, case reports and current research regarding this drug–drug interaction in order to suggest options for the clinical management of HIV-positive patients requiring treatment with protease inhibitors and inhaled or intranasal corticosteroids.
Ritonavir is a potent inhibitor of the hepatic cytochrome P450 3A4 (CYP3A4) isozyme and is used at low doses to boost the levels of other protease inhibitors (PIs) for the treatment of HIV infection. As a consequence of this property, the use of ritonavir and other PIs can result in numerous drug–drug interactions. Inhaled and intranasal corticosteroids, such as beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, mometasone and triamcinolone, are mostly substrates of hepatic CYP3A4 and have the potential to interact with ritonavir. These interactions can result in steroid accumulation, adrenal suppression and Cushing's syndrome. Given the widespread use of intranasal and inhaled corticosteroids for allergic rhinitis, asthma and chronic obstructive pulmonary disease, there is a potential for the erroneous prescription and use of these medications in HIV-positive adult and paediatric patients on a PI-containing antiretroviral regimen. The purpose of this article is to review the literature on the pharmacokinetics of inhaled and intranasal corticosteroids and case reports regarding this drug–drug interaction and to suggest options for the clinical management of HIV-positive patients requiring treatment with PIs and inhaled or intranasal corticosteroids.
HIV Medicine. 2013;14(9):519-529. © 2013 Blackwell Publishing