Iatrogenic Cushing's Syndrome in an HIV-Infected Patient Treated with Inhaled Corticosteroids (Fluticasone Propionate) and Low Dose Ritonavir Enhanced PI Containing Regimen

Clevenbergh, P.; Corcostegui, Miguel; Gérard, Danielle; Hiéronimus, S.; Mondain, V.; Chichmanian, R. M.; Sadoul, Jean‐Louis; Dellamonica, P.

doi:10.1053/jinf.2001.0928

Cited by 52 publications

(37 citation statements)

References 9 publications

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“…Interestingly, the subject had been receiving a combination of RTV, fluticasone and lopinavir for 11 months prior to the introduction of ATV without signs of Cushing Syndrome. The onset of Cushing Syndrome in patients who received RTV and fluticasone is variable (5-12 months [25][26][27]) and may be related to the frequency of use of fluticasone which we did not monitor in this study. We have reported two subjects with low ATV exposure who received either colchicine or nandrolone, two drugs that potentially interact with ATV.…”

Section: Discussionmentioning

confidence: 86%

“…A drug interaction between a metabolic inhibitor of CYP3A4 (itraconazole) and inhaled corticosteroids causing Cushing Syndrome in a patient has been described [24]. The coadministration of RTV and fluticasone is not recommended due to the ability of RTV to inhibit CYP3A4 mediated fluticasone metabolism causing iatrogenic Cushing Syndrome [25][26][27]. Furthermore, some corticosteroids are known inducers of the P-gp efflux transporter protein [28] and cytochrome metabolizing enzymes that can cause decreased exposure to drugs [29].…”

Section: Discussionmentioning

confidence: 99%

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Therapeutic drug monitoring of atazanavir: surveillance of pharmacotherapy in the clinic

Ray

Marriott

Bloch³

et al. 2005

Brit J Clinical Pharma

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BackgroundTherapeutic failure with antiretroviral therapy (ART) is a substantial issue where viral rebound, viral resistance and drug-related toxicity remain serious concerns. Drug exposure-response relationships have been described for the protease inhibitors, pharmacokinetic variability is substantial for this class of drugs and drug interactions can also alter ART exposure. Given this background we established a therapeutic drug monitoring (TDM) service to monitor atazanavir (ATV) plasma concentrations early after the therapy was made available to treatment-experienced people infected with HIV who were managed in a clinical setting. MethodsThis was a prospective observational study which evaluated plasma samples from 110 highly treatment-experienced people with HIV using TDM and applied pharmacokinetic analysis over a five month period. ResultsATV trough concentrations exhibited substantial intersubject variability ( < 25-2108 m g l -1 ). A substantial number of subjects (50%,13/26) who received ATV400 mg daily had low exposure to ATV. Serum bilirubin concentrations correlated significantly with higher ATV trough concentrations ( r = 0.803; P < 0.001) and 55% (29/53) of subjects who received ATV300/100 mg RTV daily had plasma concentrations above a proposed target concentration associated with elevated bilirubin concentrations. This study confirmed low ATV exposure in eight subjects with HIV receiving ATV 400 mg daily. Reasons for low ATV exposure in this cohort include administration of interacting drugs, including a possible interaction with ritonavir, fluticasone and ATV, impaired ATV absorption secondary to suspected achlorhydria and potential interactions with colchicine and nandrolone. Viral load remained undetectable in most of these subjects with low ATV exposure. ConclusionsTDM and targeted pharmacokinetic studies should be viewed as fundamental tools in the development and clinical application of ART, to improve pharmacotherapy for people with HIV.J. E. Ray et al. 29260 :3 Br J Clin Pharmacol

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Therapeutic drug monitoring of atazanavir: surveillance of pharmacotherapy in the clinic

Ray

Marriott

Bloch³

et al. 2005

Brit J Clinical Pharma

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“…Two series of systematic reviews were shown those effects in both adult and children [38,39]. The combination median time of treatment was 4 months and the duration for symptom correction was 3.6 months [40][41][42][43][44]. In some countries, dermatological and non-dermatological medications can be purchased without doctor's prescription at drug stores.…”

Section: Discussionmentioning

confidence: 99%

Exogenous Cushing’s syndrome due to topical corticosteroid application: case report and review literature

Tempark

Phatarakijnirund

Chatproedprai

et al. 2010

Endocr

107

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Prolonged use of topical corticosteroids causes systemic adverse effects including Cushing's syndrome and hypothalamic-pituitary-adrenal (HPA) axis suppression, which is less common than that of the oral or parenteral route. At least 43 cases with iatrogenic Cushing syndrome from very potent topical steroid usage (Clobetasol) in children and adult have been published over the last 35 years particularly in developing countries. In children group (n = 22), most are infants with diaper dermatitis and two cases who had started topical application at a very early age and died from severe disseminated CMV infection. For the adult group (n = 21), the most common purpose of steroid use was for treatment of Psoriasis. The recovery period of HPA axis suppression was 3.49 ± 2.92 and 3.84 ± 2.51 months in children and adult, respectively. We report on an 8-month-old female infant who developed Cushing's syndrome and adrenal insufficiency after diaper dermatitis treatment through the misuse of Clobetasol without doctor's prescription. Physiologic dose of hydrocortisone was prescribed to prevent an adrenal crisis for 3 months and discontinued when HPA axis recovery was confirmed by normal morning cortisol and ACTH levels.

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“…[3][4][5][6][7][8][9] In many of the cases, the presence of lipodystrophy commonly associated with long term ART treatment may have contributed to a delay in identifying Cushing syndrome. Resolution of Cushing syndrome and adrenal suppression occurred after either discontinuation or significant weaning of fluticasone, or discontinuation of RTV.…”

Section: Discussionmentioning

confidence: 99%

Cushing syndrome with secondary adrenal insufficiency from concomitant therapy with ritonavir and fluticasone

Johnson

Marion

Vrchoticky

et al. 2006

The Journal of Pediatrics

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Iatrogenic Cushing's Syndrome in an HIV-Infected Patient Treated with Inhaled Corticosteroids (Fluticasone Propionate) and Low Dose Ritonavir Enhanced PI Containing Regimen

Cited by 52 publications

References 9 publications

Therapeutic drug monitoring of atazanavir: surveillance of pharmacotherapy in the clinic

Therapeutic drug monitoring of atazanavir: surveillance of pharmacotherapy in the clinic

Exogenous Cushing’s syndrome due to topical corticosteroid application: case report and review literature

Cushing syndrome with secondary adrenal insufficiency from concomitant therapy with ritonavir and fluticasone

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