Cushing's Syndrome Due to Interaction Between Inhaled Corticosteroids and Itraconazole

Bolland, Mark J; Bagg, Warwick; Thomas, Mark G.; Lucas, Jennifer; Ticehurst, Rob; Black, Peter

doi:10.1345/aph.1d222

Cited by 88 publications

(50 citation statements)

References 15 publications

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“…Sudden, and often inadvertent, withdrawal of steroids can lead to adrenal crisis. Hence, a detailed drug history is 24 Concomitant use of steroids with itraconazole 25 or ritonavir 26 (which inhibit hepatic CYP3A metabolism of steroids) can increase this risk. Generally, longer duration, higher dosages, and oral and intraarticular preparations increase the risk of adrenal suppression.…”

Section: Risk Factorsmentioning

confidence: 99%

Adrenal Crisis: Still a Deadly Event in the 21st Century

Puar

Stikkelbroeck

Smans

et al. 2016

The American Journal of Medicine

142

140

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Adrenal crisis is a life-threatening medical emergency, associated with a high mortality unless it is appropriately recognized and early treatment is rendered. Despite it being a treatable condition for almost 70 years, failure of adequate preventive measures or delayed treatment has often led to unnecessary deaths. Gastrointestinal illness is the most common precipitant for an adrenal crisis. Although most patients are educated about "sick day rules," patients, and physicians too, are often reluctant to increase their glucocorticoid doses or switch to parenteral injections, and thereby fail to avert the rapid deterioration of the patients' condition. Therefore, more can be done to prevent an adrenal crisis, as well as to ensure that adequate acute medical care is instituted after a crisis has occurred. There is generally a paucity of studies on adrenal crisis. Hence, we will review the current literature, while also focusing on the incidence, presentation, treatment, prevention strategies, and latest recommendations in terms of steroid dosing in stress situations.

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Section: Risk Factorsmentioning

confidence: 99%

Adrenal Crisis: Still a Deadly Event in the 21st Century

Puar

Stikkelbroeck

Smans

et al. 2016

The American Journal of Medicine

142

140

View full text Add to dashboard Cite

show abstract

“…Toxicities reported in o4% of patients (peripheral neuropathy, fluid retention, gastrointestinal intolerance, elevated hepatic transaminases, rash, headache, tremor and sleep disturbance) have been found with high steady-state triazole levels in patients with chronic pulmonary aspergillosis [72,78]. In addition, an important drug-drug interaction exists between itraconazole and several corticosteroids, including oral or intravenous methylprednisolone and inhaled budesonide and fluticasone; the azole impairs metabolism of these exogenous glucocorticosteroids resulting in potential adrenal suppression, including overt Cushing syndrome [79][80][81][82][83][84][85][86][87]. It is, therefore, safer to use oral prednisone or prednisolone (neither of which has these interactions), or perhaps inhaled beclomethasone (which to date has not been shown to have an azole interaction but has also not been systematically studied in this regard), or ciclesonide (a prodrug with topical respiratory metabolism) [88], if using itraconazole or other triazoles in treating ABPA or SAFS.…”

Section: Antifungal Therapy In Abpa and Safsmentioning

confidence: 99%

Treatment options in severe fungal asthma and allergic bronchopulmonary aspergillosis

Moss

2013

European Respiratory Journal

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Severe asthma with fungal sensitisation and allergic bronchopulmonary aspergillosis encompass two closely related subgroups of patients with severe allergic asthma. Pulmonary disease is due to pronounced host inflammatory responses to noninvasive subclinical endobronchial infection with filamentous fungi, usually Aspergillus fumigatus. These patients usually do not achieve satisfactory disease control with conventional treatment of severe asthma, i.e. high-dose inhaled corticosteroids and long-acting bronchodilators. Although prolonged systemic corticosteroids are effective, they carry a substantial toxicity profile. Supplementary or alternative therapies have primarily focused on use of antifungal agents including oral triazoles and inhaled amphotericin B. Immunomodulation with omalizumab, a humanised anti-IgE monoclonal antibody, or "pulse" monthly high-dose intravenous corticosteroid, has also been employed. This article considers the experience with these approaches, with emphasis on recent clinical trials. @ERSpublications Treatment of fungal asthma includes glucocorticoids, azoles, amphotericin and anti-IgE. Trial validation is needed.

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“…In their clinical practice, clinicians should therefore be aware of the main determinants of drug interactions, such as first pass metabolism and bioavailability. Indeed, the hepatic metabolism of ICSs via cytochrome P450 (CYP3A4) is influenced by enzymatic inhibitors [64]. Therefore, the concomitant use of these drugs can be responsible for the increase in bioavailability of the ICS and risk of toxicity.…”

Section: Pneumoniamentioning

confidence: 99%

Erratum to: Safety Considerations of Inhaled Corticosteroids in the Elderly

et al. 2015

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Inhaled corticosteroids (ICSs) are widely used in the treatment of patients with chronic obstructive pulmonary diseases. However, high-dose regimens and longterm use of ICSs have the potential to cause a variety of local and systemic side effects such as candidiasis, cataracts, glaucoma, and osteoporosis. The use of ICSs can also be associated with the risk of bone fractures, diabetes mellitus and pneumonia. These ICS-related side effects are of particular importance in elderly patients due to the presence of comorbidities and age-related behavioral, cognitive, and psychological problems, which can all interact with inhaled treatment. We reviewed the available literature on the clinically relevant side effects of ICSs in the elderly to provide practical measures to properly monitor and manage the risk of ICSs in the geriatric population. Inspection of the mouth, monitoring of ocular pressure, and use of bone-protective drugs may be necessary in patients on prolonged ICS therapy. Above all, the use of the lowest possible ICS dose and a careful re-assessment of the inhalation procedure should be recommended. Taken together, these observations suggest that physicians should use ICSs appropriately for those patients in whom the benefit will outweigh the risk, especially chronic obstructive pulmonary disease (COPD) patients with previous frequent exacerbations. Given the paucity of information on the topic and the need to extrapolate the results from studies with broader age ranges, we strongly encourage the design of specifically tailored clinical studies in the elderly. Key PointsAsthma and chronic obstructive pulmonary disease (COPD) are inflammatory disorders of the airways. The pharmacological management of these chronic diseases is based on persistent and long-term use of inhaled corticosteroids (ICSs).Asthma and COPD are among the most common chronic diseases in clinical settings, and physicians are expected to diagnose and manage those diseases in the geriatric population on a daily basis. The management of chronic obstructive respiratory diseases in the geriatric population is complicated by the increased occurrence of comorbidities and associated treatment, and by age-associated physiological and structural changes of the lung.The chronic use of ICSs in the elderly is associated with the increased risk of local and systemic side effects such as candidiasis, cataract, glaucoma, diabetes mellitus, bone fractures, and pneumonia. Physicians should be aware of this in order to select those patients in whom the benefits will outweigh the risks.The online version of the original article can be found under

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Cushing's Syndrome Due to Interaction Between Inhaled Corticosteroids and Itraconazole

Abstract: The combination of itraconazole and inhaled corticosteroids is increasingly being used to treat conditions such as allergic bronchopulmonary aspergillosis. Clinicians need to be aware of the potential for an interaction between such a combination.

Cited by 88 publications

References 15 publications

Adrenal Crisis: Still a Deadly Event in the 21st Century

Adrenal Crisis: Still a Deadly Event in the 21st Century

Treatment options in severe fungal asthma and allergic bronchopulmonary aspergillosis

Erratum to: Safety Considerations of Inhaled Corticosteroids in the Elderly

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