Published interaction studies of itraconazole and corticosteroids

Published interaction studies of itraconazole and corticosteroids
Itraconazole is an inhibitor of cytochrome P450 3A4. It increases exposure to methylprednisolone (Varis et al, 1999; Lebrun-Vignes et al, 2001), dexamethasone (Varis et al, 2000), budesonide (Raaska et al, 2002) and probably fluticasone (Parmar et al, 2002), but not prednisolone (Variset al 2000; Lebrun-Vignes et al, 2001) or endogenous cortisol (Phillips et al, 1987; Queiroz-Telles F et al, 1997). No published study has addressed any interaction of itraconazole and beclomethasone. David W. Denning, August 2003 Varis T, Kivisto KT, Backman JT, Neuvonen PJ. The cytochrome P450 3A4 inhibitor itraconazole markedly increases the plasma concentrations of dexamethasone and enhances its adrenal-suppressant effect. Clin Pharmacol Ther 2000;68:487-94. Lebrun-Vignes B, Archer VC, Diquet B, Levron JC, Chosidow O, Puech AJ, Warot D. Effect of itraconazole on the pharmacokinetics of prednisolone and methylprednisolone and cortisol secretion in healthy subjects. Br J Clin Pharmacol 2001;51:443-50. Raaska K, Niemi M, Neuvonen M, Neuvonen PJ, Kivisto KT. Plasma concentrations of inhaled budesonide and its effects on plasma cortisol are increased by the cytochrome P4503A4 inhibitor itraconazole. Clin Pharmacol Ther 2002;72:362-9. Parmar JS, Howell T, Kelly J, Bilton D. Profound adrenal suppression secondary to treatment with low dose inhaled steroids and itraconazole in allergic bronchopulmonary aspergillosis in cystic fibrosis. Thorax. 2002;57:749-50. Varis T, Kivisto KT, Neuvonen PJ. The effect of itraconazole on the pharmacokinetics and pharmacodynamics of oral prednisolone. Eur J Clin Pharmacol 2000;56:57-60. Phillips P, Graybill JR, Fetchick R, Dunn JF. Adrenal response to corticotropin during therapy with itraconazole. Antimicrob Agents Chemother 1987;31:647-9. Queiroz-Telles F, Purim KS, Boguszewski CL, Afonso FC, Graf H. Adrenal response to corticotrophin and testosterone during long-term therapy with itraconazole in patients with chromoblastomycosis. J Antimicrob Chemother 1997;40:899-902.

Itraconazole is an inhibitor of cytochrome P450 3A4. It increases exposure to methylprednisolone (Varis et al, 1999; Lebrun-Vignes et al, 2001), dexamethasone (Varis et al, 2000), budesonide (Raaska et al, 2002) and probably fluticasone (Parmar et al, 2002), but not prednisolone (Variset al 2000; Lebrun-Vignes et al, 2001) or endogenous cortisol (Phillips et al, 1987; Queiroz-Telles F et al, 1997). No published study has addressed any interaction of itraconazole and beclomethasone.

David W. Denning, August 2003

Varis T, Kivisto KT, Backman JT, Neuvonen PJ. The cytochrome P450 3A4 inhibitor itraconazole markedly increases the plasma concentrations of dexamethasone and enhances its adrenal-suppressant effect. Clin Pharmacol Ther 2000;68:487-94.

Lebrun-Vignes B, Archer VC, Diquet B, Levron JC, Chosidow O, Puech AJ, Warot D. Effect of itraconazole on the pharmacokinetics of prednisolone and methylprednisolone and cortisol secretion in healthy subjects. Br J Clin Pharmacol 2001;51:443-50.

Raaska K, Niemi M, Neuvonen M, Neuvonen PJ, Kivisto KT. Plasma concentrations of inhaled budesonide and its effects on plasma cortisol are increased by the cytochrome P4503A4 inhibitor itraconazole. Clin Pharmacol Ther 2002;72:362-9.

Parmar JS, Howell T, Kelly J, Bilton D. Profound adrenal suppression secondary to treatment with low dose inhaled steroids and itraconazole in allergic bronchopulmonary aspergillosis in cystic fibrosis. Thorax. 2002;57:749-50.

Varis T, Kivisto KT, Neuvonen PJ. The effect of itraconazole on the pharmacokinetics and pharmacodynamics of oral prednisolone. Eur J Clin Pharmacol 2000;56:57-60.

Phillips P, Graybill JR, Fetchick R, Dunn JF. Adrenal response to corticotropin during therapy with itraconazole. Antimicrob Agents Chemother 1987;31:647-9.

Queiroz-Telles F, Purim KS, Boguszewski CL, Afonso FC, Graf H. Adrenal response to corticotrophin and testosterone during long-term therapy with itraconazole in patients with chromoblastomycosis. J Antimicrob Chemother 1997;40:899-902.