The cytochrome P450 3A4 inhibitor itraconazole markedly increases the plasma concentrations of dexamethasone and enhances its adrenal-suppressant effect

Varis, Tiina

doi:10.1067/mcp.2000.110772

Cited by 114 publications

(62 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…163 No inhibition of NTCP or BSEP. 170 CYP3A4 inhibition will affect metabolism of a variety of drugs to increase their levels (e.g., BU, 171 dexamethasone, 172 midazolam, 173 ciclosporin, 174 tacrolimus, 174 methyl-prednisolone 175 ) or the levels of their metabolites. (e.g., CY 47 ).…”

Section: Interaction Commentsmentioning

confidence: 99%

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

Ashbee

Gilleece

2011

Bone Marrow Transplant

View full text Add to dashboard Cite

Section: Interaction Commentsmentioning

confidence: 99%

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

Ashbee

Gilleece

2011

Bone Marrow Transplant

View full text Add to dashboard Cite

“…High-dose budesonide was primarily recommended to CF patients chronically infected with Pseudomonas aeruginosa [14], but has since been extended to include CF patients with other bacterial infections. Azoles such as ketoconazole and itraconazole are strong inhibitors of cytochrome P450 dependent CYP3A4, which is involved in the metabolism of budesonide [15][16][17]. Ketoconazole has an inhibitory effect on other cytochrome P450-dependent enzymes such as 17,20 desmolase, 16a-hydroxylase, 17a-hydroxylase, 18 hydroxylase and 11b-hydroxylase enzymes (listed with decreasing activity), thus potentially compromising steroidogenesis in the adrenals and gonads [18,19].…”

mentioning

confidence: 99%

Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide

Skov¹,

Main²,

Sillesen³

et al. 2002

Eur Respir J

132

View full text Add to dashboard Cite

A recent case of iatrogenic Cushing's syndrome and complete suppression of the pituitary-adrenal-axis in a patient with cystic fibrosis (CF) and allergic bronchopulmonary aspergillosis treated with itraconazole as an antifungal agent, and budesonide as an anti-inflammatory agent led to a systematic assessment of this axis and gonadal function in all patients treated with itraconazole in the authors' CF centre. Itraconazole can inhibit CYP3A, thus interfering with synthesis of gluco- and mineralocorticoids, androgens and oestradiol as well as the metabolism of budesonide. The aim of this study was to evaluate adrenal and gonadal function in patients treated with itraconazole with or without budesonide.An adrenocorticotrophic hormone (ACTH) test (250 µg tetracosactid) was performed in 25 CF patients treated with both itraconazole and budesonide, and in 12 patients treated with itraconazole alone (six patients with CF and six with chronic granulomateous disease). Mineralocorticoid and gonadal steroid function were evaluated by measurements of plasma-renin, follicle stimulating hormone, luteinising hormone, progesterone, oestradiol, testosterone, serum-inhibin A and B. ACTH tests performed as part of a pretransplantation programme in an additional 30 CF patients were used as controls.Eleven of the 25 patients treated with both itraconazole and budesonide had adrenal insufficiency. None of the patients on itraconazole therapy alone nor the control CF patients had a pathological ACTH test. Mineralocorticoid and gonadal insufficiency was not observed in any of the patients. Only one patient with an initial pathological ACTH-test subsequently normalised, the other 10 patients improved but had not achieved normalised adrenal function 2–10 months after itraconazole treatment had been discontinued.Suppression of the adrenal glucocorticoid synthesis was observed in 11 of 25 cystic fibrosis patients treated with both itraconazole and budesonide. The pathogenesis is most likely an itraconazole caused increase in systemic budesonide concentration through a reduced/inhibited metabolism leading to inhibition of adrenocorticotrophic hormone secretion along with a direct inhibition of steroidogenesis. In patients treated with this combination, screening for adrenal insufficiency at regular intervals is suggested.

show abstract

“…They have moderate protein binding and a moderate apparent volume of distribution (Derendorf et al, 1991;Varis et al, 2000). Over 90% of circulating plasma corticosteroids attached to two types of proteins: (1) a non-specific albumin, and (2) a high affinity transcortin, an -2-globulin important in regulating corticosteroid flowing freely, as allows greater freedom in tissues with an inflammatory response.…”

Section: Absorption and Distributionmentioning

confidence: 99%

Clinical Pharmacokinetics of Triple Immunosuppression Scheme in Kidney Transplant (Tacrolimus, Mycophenolate Mofetil and Corticosteroids)

Luisa¹,

Alejandro²

2011

Understanding the Complexities of Kidney Transplantation

View full text Add to dashboard Cite

The cytochrome P450 3A4 inhibitor itraconazole markedly increases the plasma concentrations of dexamethasone and enhances its adrenal-suppressant effect

Abstract: Itraconazole markedly increases the systemic exposure to and effects of dexamethasone. A careful follow-up is recommended when itraconazole or other potent inhibitors of the cytochrome P450 3A4 are added to the drug regimen of patients receiving dexamethasone.

Cited by 114 publications

References 0 publications

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide

Clinical Pharmacokinetics of Triple Immunosuppression Scheme in Kidney Transplant (Tacrolimus, Mycophenolate Mofetil and Corticosteroids)

Contact Info

Product

Resources

About