Cushing's Syndrome Due to Antiretroviral-Budesonide Interaction

Frankel, Jonathan K.; Packer, Clifford D.

doi:10.1345/aph.1p731

Cited by 26 publications

(16 citation statements)

References 7 publications

(2 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However to our knowledge, this is only the second case in the literature where oral budesonide has been implicated-Frankel et al previously reported a HIV-positive patient on ritonavir 100 mg daily who developed CS 3 weeks after commencing budesonide 9 mg daily for lymphocytic colitis, whose CS symptoms resolved 15 days after budesonide cessation. 8 This is the also first such case in a patient being treated with ritonavir for hepatitis C, as well as the first in a patient being treated with budesonide for autoimmune hepatitis. The natural history of iatrogenic CS is reported to be reassuringly brief after cessation of either ritonavir or steroids, with normalization of laboratory tests often within 2 months 4,5 and resolution of symptoms within 4 months.…”

Section: Discussionmentioning

confidence: 87%

Iatrogenic Cushing Syndrome from Interaction Between Ritonavir and Oral Budesonide During Direct Acting Antiviral Hepatitis C Therapy

Yeoh

2016

Journal of Clinical and Experimental Hepatology

View full text Add to dashboard Cite

Direct acting antiviral (DAA) regimens containing ritonavir have been developed to treat hepatitis C, with fewer side effects than that by interferon-based regimens. However prescribers must be aware of drug-drug interactions. There are multiple reports of iatrogenic Cushing syndrome (CS) caused by ritonavir, when used to treat human immunodeficiency virus, increasing the bioavailability of exogenous steroids by inhibiting cytochrome p450 enzymes in the liver and gut wall and thus reducing steroid metabolism. We herein report a novel scenario of CS due to interaction between ritonavir for hepatitis C treatment and oral budesonide for autoimmune hepatitis. ( J CLIN EXP HEPATOL 2016;6:246-249)

show abstract

Section: Discussionmentioning

confidence: 87%

Iatrogenic Cushing Syndrome from Interaction Between Ritonavir and Oral Budesonide During Direct Acting Antiviral Hepatitis C Therapy

Yeoh

2016

Journal of Clinical and Experimental Hepatology

View full text Add to dashboard Cite

show abstract

“…17 Shortterm courses of oral steroids should be used at reduced doses, although evidence for this is lacking. If longer-term steroids are required, referral to the HIV specialist is recommended so that a switch can be made to non-ritonavir/ cobicistat ART.…”

Section: Oralmentioning

confidence: 99%

Administering steroids with HIV treatment‐boosting agents

Singh¹,

Jones²,

Shotliff³

2017

Prescriber

View full text Add to dashboard Cite

show abstract

“…18 Drug interactions are also well described between budenoside and ritonavir. 6,7,19 Conversely, there are no reported cases with beclomethasone interaction as it is predominantly metabolised by esterase hydrolysis; 20 CYP3A4 is minimally involved. In a randomised healthy volunteer study, the addition of ritonavir to inhaled beclomethasone doubled the area under the curve (AUC) for the serum concentration of the active metabolite of beclomethasone, but with no significant reduction in basal or stimulated serum cortisol levels.…”

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

View full text Add to dashboard Cite

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...

show abstract

Cushing's Syndrome Due to Antiretroviral-Budesonide Interaction

Cited by 26 publications

References 7 publications

Iatrogenic Cushing Syndrome from Interaction Between Ritonavir and Oral Budesonide During Direct Acting Antiviral Hepatitis C Therapy

Iatrogenic Cushing Syndrome from Interaction Between Ritonavir and Oral Budesonide During Direct Acting Antiviral Hepatitis C Therapy

Administering steroids with HIV treatment‐boosting agents

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

Contact Info

Product

Resources

About