Effects of High-Dose Inhaled Corticosteroids on Plasma Cortisol Concentrations in Healthy Adults

Brus, R

doi:10.1001/archinte.159.16.1903

Cited by 38 publications

(25 citation statements)

References 23 publications

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“…A larger study also documented significantly greater (p<0.05) suppression of plasma and urinary cortisol after inhaled FP compared with BDP in adult healthy volunteers [87].However, a recent Cochrane Collaboration systematic review comparing FP with BDP or BUD for chronic asthma in adults and children was unable to calculate an overall pooled treatment effect for the effects of FP and BDP/BUD in suppressing plasma or urinary cortisol levels because of limitations in data reported from randomized controlled trials, although there was some indication that FP is more potent in suppressing 24-hour urinary cortisol levels than BDP/BUD [88].…”

Section: A C C E P T E D Article In Pressmentioning

confidence: 77%

Inhaled corticosteroid therapy with nebulized beclometasone dipropionate

Nicolini

Cremonesi

Melani

2010

Pulmonary Pharmacology & Therapeutics

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Inhaled corticosteroids (ICS) are the most effective anti-inflammatory agents for the management of chronic persistent asthma, and are therefore recommended as first-line antiasthmatic therapy in children and adults. In various settings, the administration of ICS via nebulizer rather than hand-held inhaler (HHI) may have certain advantages, as many patients with HHI fail to use these devices properly or efficiently. In particular, young children, the elderly, the acutely ill, and those with restricted dexterity may be unable to coordinate inhalation with actuation of the device or to generate sufficient inspiratory flow to operate breath-actuated devices effectively. Compliance with nebulized therapy may also be better than that with a pressurized metered-dose inhaler (pMDI) plus spacer. Systematic reviews conclude that there is no significant difference in clinical effects between nebulizers and HHI. Performance and clinical effect of nebulization are influenced by several technical aspects such as the nebulizer-drug combination, nebulizer type, output and lung deposition. Among the currently available ICS, nebulized beclometasone dipropionate (BDP) has been in clinical use for more than 35 years, and has demonstrated marked clinical efficacy and a favorable tolerability profile in children and adults with chronic persistent asthma. The clinical efficacy of nebulized beclometasone is discussed in the present review using data from 13 published studies, which included a total of 1250 patients. Three multicenter, randomized, double-blind studies showed that nebulized BDP is as effective as BDP via pMDI plus spacer in a 2:1 dose ratio. Controlled trials involving 497 adults and children demonstrated similar clinical efficacy between nebulized BDP and either nebulized fluticasone propionate or nebulized budesonide. In all these trials, treatment-related adverse effects were generally uncommon, most were mild to moderate in severity, and most were associated with the respiratory system. Metaanalyses show that BDP, like other inhaled corticosteroids, has no major influence on patient height, urinary cortisol concentration, or bone metabolism, thus suggesting the absence of growth retardation or any marked effect on adrenal function or the hypothalamic-pituitaryadrenal axis when used in the approved dose range. M A N U S C R I P T A C C E P T E D ARTICLE IN PRESSOverall, nebulized BDP appears to have a particularly important place in asthma therapy: as a general alternative to HHIs (e.g. in patients with poor HHI compliance); when patients such as children or the elderly are unable to operate HHIs because of poor hand-lung coordination, lack of cooperation, or low inspiratory flow rate; and when high dosages of ICS are required, such as in adults with severe, corticosteroid-dependent asthma.

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Section: A C C E P T E D Article In Pressmentioning

confidence: 77%

Inhaled corticosteroid therapy with nebulized beclometasone dipropionate

Nicolini

Cremonesi

Melani

2010

Pulmonary Pharmacology & Therapeutics

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“…17 Manufacturers of fluticasone specifically warn of co-administration with ritonavir. 18 Drug interactions are also well described between budenoside and ritonavir.…”

Section: Current Evidence On Individual Glucocorticoids By Route Inhaledmentioning

confidence: 99%

Iatrogenic Cushing’s syndrome due to drug interaction between glucocorticoids and the ritonavir or cobicistat containing HIV therapies

et al. 2016

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Ritonavir and cobicistat, used as pharmacokinetic enhancers in combination with some antiretrovirals (ARVs) for the treatment of HIV, are potent inhibitors of the CYP3A4 isoenzyme. Most glucocorticoids are metabolised via the CYP3A4 pathway and iatrogenic Cushing's syndrome (ICS), with possible secondary adrenal insufficiency (SAI), is a recognised complication following co-administration with ritonavir or cobicistat. A structured approach for identifying and managing potentially affected individuals has not been established. We systematically identified patients with ICS/SAI and found substantial heterogeneity in clinical practice across three large London HIV centres. While this significant drug interaction and its complications are now well-recognised, it is apparent that there is no standardised approach to management or guidance for the general physician. Here we describe the management of ICS/SAI in our current practice, review the available evidence and suggest practice recommendations. KEYWORDS : Adrenal insuffi ciency , cobicistat , Cushing's syndrome , HIV , ritonavir IntroductionRitonavir and cobicistat are pharmacokinetic enhancers used in the treatment of HIV infection. They are extremely potent inhibitors of cytochrome P450 3A4 (CYP3A4) activity. Ritonavir, originally developed as an antiretroviral, is used ABSTRACT Iatrogenic Cushing's syndrome due to drug interaction between glucocorticoids and the ritonavir or cobicistat containing HIV therapies at sub-therapeutic doses, in combination with HIV protease inhibitors (PIs), to significantly increase their concentrations and allow less frequent and lower dosing.1 Cobicistat was developed more recently and is similar in structure. It is used in combination with PIs or elvitegravir (an integrase inhibitor) 2 but has no antiretroviral activity itself. 3 The downside of this pharmacokinetic manipulation is the significant potential for interactions with CYP3A4 substrates, leading to side effects. CYP3A4 is the dominant isoenzyme of the hepatic cytochrome P450 system and is the primary metabolic step for the degradation of endogenous and most prescribed corticosteroids. The metabolism of these can therefore be decreased by inhibitors such as ritonavir/cobicistat. 4 Subsequent increases in exogenous corticosteroid plasma concentrations and half-life can lead to iatrogenic Cushing's syndrome (ICS) 5 and, at supraphysiological levels, to suppression of adrenocorticotropic hormone (ACTH) and endogenous corticosteroid secretion, potentially resulting in secondary adrenal insufficiency (SAI). There is abundant evidence highlighting this issue. 1,[6][7][8][9][10][11] However, a structured approach to identify and manage potentially affected individuals has not been established. We aim to summarise the current management of ICS/SAI in three large HIV patient cohorts, review the available literature and develop practice recommendations. Of note, cobicistat became available after the evaluation period covered; however, all advice for ritonavir is applicable to i...

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“…25 In a prospective study, fluticasone was significantly more suppressive on the 24-hour serum cortisol values than beclomethasone, budesonide, flunisolide and triamcinolone. 26 Significant serum concentrations could occur as a result concomitant administration of any drugs that affect hepatic metabolism. In our cases, evidence of Cushing syndrome developed after patients were given age-appropriate fluticasone dosages and ritonavir.…”

Section: Arrington-sanders Et Almentioning

confidence: 99%

Ritonavir–Fluticasone Interaction Causing Cushing Syndrome in HIV-Infected Children and Adolescents

Arrington‐Sanders¹,

Hutton²,

Siberry³

2006

Pediatric Infectious Disease Journal

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Effects of High-Dose Inhaled Corticosteroids on Plasma Cortisol Concentrations in Healthy Adults

Abstract: These results indicate that there are differences in the systemic effects of inhaled corticosteroids when used in high doses and emphasize the importance of using the minimum dose of inhaled corticosteroids required to maintain control of asthma symptoms.

Cited by 38 publications

References 23 publications

Inhaled corticosteroid therapy with nebulized beclometasone dipropionate

Inhaled corticosteroid therapy with nebulized beclometasone dipropionate

Iatrogenic Cushing’s syndrome due to drug interaction between glucocorticoids and the ritonavir or cobicistat containing HIV therapies

Ritonavir–Fluticasone Interaction Causing Cushing Syndrome in HIV-Infected Children and Adolescents

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