title: [Cushing's syndrome during HIV treatment: pharmacological interaction during use of ritonavir].
abstract: Physicians are not always aware that locally administered glucocorticoids can cause systemic toxicity. This risk is greatly enhanced in the case of pharmacological interactions. We present two cases of HIV-infected patients who developed Cushing-like symptoms as a result of a pharmacological interaction. Their antiretroviral treatment regimen consisted of atazanavir, ritonavir, tenofovir and emtricitabine. One patient received salmeterol/fluticasone inhalations for asthmatic bronchitis. The other was treated with intra-articular triamcinolonacetonide injections for ongoing shoulder complaints. Ritonavir exhibits strong inhibition of hepatic enzyme CYP 3A4, which is part of the major metabolic pathway of most glucocorticoids. As a result of this interaction even locally administered glucocorticoids can cause symptoms of overdose, e.g. Cushing-like symptoms. Beclomethasone is a safe alternative for inhaled glucocorticoids as it is not metabolized by CYP 3A4. There is no substitute for intra-articular administration of triamcinolonacetonide. Depending on necessity of the administration of the drug, changing ritonavir-containing antiretroviral therapy to a non-interacting compound, e.g., an integrase inhibitor, is an option.
authors.affiliation: Onze Lieve Vrouwe Gasthuis, Afd. Interne Geneeskunde, Amsterdam, the Netherlands. j.k.schattenkerk@gmail.com
authors.forename: Jan Karel M
authors.initials: JK
authors.lastname: Eeftinck Schattenkerk
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Lager
mesh_terms: D000328:Adult; D000420:Albuterol / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use; D001249:Asthma / Q000150:complications / Q000188:drug therapy; D001993:Bronchodilator Agents / Q000009:adverse effects; D003480:Cushing Syndrome / Q000139:chemically induced*; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D004338:Drug Combinations; D004347:Drug Interactions; D000068297:Fluticasone-Salmeterol Drug Combination; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D019438:Ritonavir / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000730:Androstadienes; D001993:Bronchodilator Agents; D065692:Cytochrome P-450 CYP3A Inhibitors; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D005938:Glucocorticoids; D017320:HIV Protease Inhibitors; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D019438:Ritonavir; D000420:Albuterol