Iatrogenic Cushing Syndrome in Patients Receiving Inhaled Budesonide and Itraconazole or Ritonavir: Two Cases and Literature Review

Blondin, M.; Beauregard, H; Serri, Omar

doi:10.4158/ep13122.cr

Cited by 36 publications

(24 citation statements)

References 14 publications

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“…Cushing's syndrome has also been reported with other routes of steroids (eg, injectable triamcinolone) 5. The same rationale can be applied for other CYP3A4 inhibitors such as cobicistat (used to boost elvitegravir in the fixed-dose combination Stribild),6 imidazoles,7 macrolides and calcium-channel blockers, among others.…”

Section: Discussionmentioning

confidence: 93%

Iatrogenic Cushing's syndrome and osteoporosis due to an interaction between fluticasone and ritonavir

et al. 2015

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The advent of highly active antiretroviral therapy for HIV infection dramatically changed the landscape of the disease. Ritonavir, a protease inhibitor (PI) frequently used in low doses to 'boost' the concentrations of other PIs, inhibits the cytochrome P450 3A4 isoenzyme, a common metabolic pathway to multiple drugs, so the potential for drug interactions is not negligible. A 39-year-old man with HIV-1 infection, treated with a ritonavir-boosted PI, was started on fluticasone/salmeterol inhaler and intranasal fluticasone, in 2009, in the setting of asthma and allergic rhinitis. In 2013, he presented with 1-year evolution of symptoms suggesting Cushing's syndrome, and was experiencing recurrent falls. A spine CT showed a vertical L3 fracture and thoracolumbar erosions; a bone density scan revealed severe osteoporosis. Hormonal assays were compatible with hypothalamic-pituitary-adrenal axis suppression, and iatrogenic Cushing's syndrome due to ritonavir-fluticasone interaction was considered. Fluticasone was suspended and oral corticosteroid replacement initiated, with a favourable outcome.

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Section: Discussionmentioning

confidence: 93%

Iatrogenic Cushing's syndrome and osteoporosis due to an interaction between fluticasone and ritonavir

et al. 2015

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“…There have been few reports of iatrogenic Cushing syndrome caused by interactions between BUD and strong inhibitors of cytochrome CYP 3A4, mainly itraconazole [54, 55]. Inhaled BUD is a potent glucocorticoid that undergoes 99% first-pass metabolism through hepatic CYP 3A4.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effects and Mechanisms of Budesonide in Combination with Fluconazole against Resistant Candida albicans

Liu

Huang

et al. 2016

PLoS ONE

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Candida albicans is an important opportunistic pathogen, causing both superficial mucosal infections and life-threatening systemic diseases in the clinic. The emergence of drug resistance in Candida albicans has become a noteworthy phenomenon due to the extensive use of antifungal agents and the development of biofilms. This study showed that budesonide potentiates the antifungal effect of fluconazole against fluconazole-resistant Candida albicans strains both in vitro and in vivo. In addition, our results demonstrated, for the first time, that the combination of fluconazole and budesonide can reverse the resistance of Candida albicans by inhibiting the function of drug transporters, reducing the formation of biofilms, promoting apoptosis and inhibiting the activity of extracellular phospholipases. This is the first study implicating the effects and mechanisms of budesonide against Candida albicans alone or in combination with fluconazole, which may ultimately lead to the identification of new potential antifungal targets.

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“…One review of the literature identified 25 cases of clinically significant adrenal suppression from fluticasone [22]. The use of both inhaled and intranasal steroids has been implicated with adrenal suppression when used in combination with ritonavir [23]. Another review identified 13 reports of Cushing's syndrome secondary to triamcinolone injection use in combination with ritonavir.…”

Section: Glucocorticoid Medicationsmentioning

confidence: 99%

A Review of the Toxicity of HIV Medications II: Interactions with Drugs and Complementary and Alternative Medicine Products

et al. 2015

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For many patients today, HIV has become a chronic disease. For those patients who have access to and adhere to lifelong antiretroviral (ARV) therapy, the potential for drugdrug interactions has become a real and life-threatening concern. It is known that most ARV drug interactions occur through the cytochrome P450 (CYP) pathway. Medications for comorbid medical conditions, holistic supplements, and illicit drugs can be affected by CYP inhibitors and inducers and have the potential to cause harm and toxicity. Protease inhibitors (PIs) tend to inhibit CYP3A4, while most nonnucleoside reverse transcriptase inhibitors (NNRTIs) tend to induce the enzyme. As such, failure to adjust the dose of coadministered medications, such as statins and steroids, may lead to serious complications including rhabdomyolysis and hypercortisolism, respectively. Similarly, gastric acid blockers can decrease several ARV absorption, and warfarin doses may need to be adjusted to maintain therapeutic concentrations. Illicit drugs such as methylenedioxymethamphetamine (MDMA, "ecstasy") in combination with PIs lead to increased toxicity, while the concomitant administration of sedative drugs such as midazolam and alprazolam in patients taking PIs can result in prolonged sedation, delayed recovery, and increased length of stay. Even supplements like St. John's Wort can alter PI concentrations. In theory, any drug that is metabolized by CYP has potential for a pharmacokinetic drug-drug interaction with all PIs, cobicistat, and most NNRTIs. When adding a new medication to an ARV regimen, use of a drug-drug interaction software and/or consultation with a clinical pharmacist/pharmacologist or HIV specialist is recommended.

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Iatrogenic Cushing Syndrome in Patients Receiving Inhaled Budesonide and Itraconazole or Ritonavir: Two Cases and Literature Review

Cited by 36 publications

References 14 publications

Iatrogenic Cushing's syndrome and osteoporosis due to an interaction between fluticasone and ritonavir

Iatrogenic Cushing's syndrome and osteoporosis due to an interaction between fluticasone and ritonavir

Synergistic Effects and Mechanisms of Budesonide in Combination with Fluconazole against Resistant Candida albicans

A Review of the Toxicity of HIV Medications II: Interactions with Drugs and Complementary and Alternative Medicine Products

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