Fluticasone furoate induced iatrogenic Cushing syndrome in a pediatric patient receiving anti-retroviral therapy

Berg, Sjoerd van den; Veer, Nils E van 't; Emmen, Judith M. A.; Beek, Ron H T van

doi:10.1530/edm-16-0158

Cited by 3 publications

(2 citation statements)

References 10 publications

(17 reference statements)

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“…Beclometasone and flunisolide may be safer alternatives because of their different metabolism 124125. Ritonavir has been linked to many cases of iatrogenic Cushing’s syndrome and symptomatic GI-AI when used in combination with inhaled and intranasal glucocorticoids (mostly fluticasone propionate) 52103122126. This is particularly relevant because asthma and chronic obstructive pulmonary disease are more prevalent in HIV infected populations 127…”

Section: Factors Affecting Likelihood Of Glucocorticoid Induced Adrenal Insufficiencymentioning

confidence: 99%

Glucocorticoid induced adrenal insufficiency

Prete

Bancos

2021

BMJ

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Synthetic glucocorticoids are widely used for their anti-inflammatory and immunosuppressive actions. A possible unwanted effect of glucocorticoid treatment is suppression of the hypothalamic-pituitary-adrenal axis, which can lead to adrenal insufficiency. Factors affecting the risk of glucocorticoid induced adrenal insufficiency (GI-AI) include the duration of glucocorticoid therapy, mode of administration, glucocorticoid dose and potency, concomitant drugs that interfere with glucocorticoid metabolism, and individual susceptibility. Patients with exogenous glucocorticoid use may develop features of Cushing’s syndrome and, subsequently, glucocorticoid withdrawal syndrome when the treatment is tapered down. Symptoms of glucocorticoid withdrawal can overlap with those of the underlying disorder, as well as of GI-AI. A careful approach to the glucocorticoid taper and appropriate patient counseling are needed to assure a successful taper. Glucocorticoid therapy should not be completely stopped until recovery of adrenal function is achieved. In this review, we discuss the factors affecting the risk of GI-AI, propose a regimen for the glucocorticoid taper, and make suggestions for assessment of adrenal function recovery. We also describe current gaps in the management of patients with GI-AI and make suggestions for an approach to the glucocorticoid withdrawal syndrome, chronic management of glucocorticoid therapy, and education on GI-AI for patients and providers.

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Section: Factors Affecting Likelihood Of Glucocorticoid Induced Adrenal Insufficiencymentioning

confidence: 99%

Glucocorticoid induced adrenal insufficiency

Prete

Bancos

2021

BMJ

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“…In this regard, Van der Berg et al reported a case of ICS consequent to fluticasone furoate in a paediatric patient treated for congenital HIV with a combination therapy of lopinavir/ritonavir. Pharmacogenetic analysis revealed that the patient carried the CYP3A4 *1B/*1G and CYP3A5 *3/*3 genotype, which is associated with a partial and complete loss of enzyme activity, respectively [ 54 ]. Although most reported cases of Cushing’s syndrome and AI due to associated treatment with ritonavir and exogenous GCs have been caused by inhaled fluticasone, treatment with other inhaled steroids, such as budesonide or mometasone, can also be troublesome [ 55 – 57 ].…”

Section: Introduction: Glucocorticoids Use During Critical Illnessmentioning

confidence: 99%

What we have to know about corticosteroids use during Sars-Cov-2 infection

Ferraú

Ceccato

Cannavò

et al. 2020

J Endocrinol Invest

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Purpose Glucocorticoids (GCs), alone or associated to other drugs, were widely used in the management of patients affected by severe acute respiratory syndrome caused by SARS-CoV-2 infection, during the recent COVID-19 outbreak. This review summarizes the available data on HPA axis impairment in GC-treated SARS-CoV-2 patients, focusing on the risk of adrenal insufficiency and on potential drug interactions during concomitant treatments. Methods Literature on the impact of GCs therapy on HPA axis and on the consequences of coadministration of GCs and other drugs in SARS-CoV-2 patients has been reviewed. Results GC treatment can cause symptoms of hypercortisolism, especially in patients with individual hypersensibility, or hypoadrenalism after drug withdrawal, due to hypothalamic-pituitary-adrenal (HPA) axis suppression, with consequences in terms of increased morbidity and mortality risk. On the other hand, in SARS-CoV-2-infected patient's cortisol secretion could be insufficient also due to critical illness-related corticosteroid insufficiency (CIRCI). In addition, in this clinical context, the co-administration of antiretroviral drugs and corticosteroids may trigger drug-drug interaction and enhance the exposure to the latter ones, metabolized through the CYP450 CYP3A pathway, severely impacting on HPA axis. Conclusion Physicians involved in the management of patients affected by COVID-19 should be aware of the need of an appropriate GC dose tapering, and of potential interaction of GCs with antiviral therapy and drugs used to treat associated co-morbidities.

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Complex Drug–Drug–Gene–Disease Interactions Involving Cytochromes P450: Systematic Review of Published Case Reports and Clinical Perspectives

et al. 2018

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Drug pharmacokinetics (PK) is influenced by multiple intrinsic and extrinsic factors, among which concomitant medications are responsible for drug-drug interactions (DDIs) that may have a clinical relevance, resulting in adverse drug reactions or reduced efficacy. The addition of intrinsic factors affecting cytochromes P450 (CYPs) activity and/or expression, such as genetic polymorphisms and diseases, may potentiate the impact and clinical relevance of DDIs. In addition, greater variability in drug levels and exposures has been observed when such intrinsic factors are present in addition to concomitant medications perpetrating DDIs. This variability results in poor predictability of DDIs and potentially dramatic clinical consequences. The present review illustrates the issue of complex DDIs using systematically searched published case reports of DDIs involving genetic polymorphisms, renal impairment, cirrhosis, and/or inflammation. Current knowledge on the impact of each of these factors on drug exposure and DDIs is summarized and future perspectives for the management of such complex DDIs in clinical practice are discussed, including the use of advanced Computerized Physician Order Entry (CPOE) systems, the development of model-based dose optimization strategies, and the education of healthcare professionals with respect to personalized medicine.

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Fluticasone furoate induced iatrogenic Cushing syndrome in a pediatric patient receiving anti-retroviral therapy

Cited by 3 publications

References 10 publications

Glucocorticoid induced adrenal insufficiency

Glucocorticoid induced adrenal insufficiency

What we have to know about corticosteroids use during Sars-Cov-2 infection

Complex Drug–Drug–Gene–Disease Interactions Involving Cytochromes P450: Systematic Review of Published Case Reports and Clinical Perspectives

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