See ritonavir + fluticasone.
The pharmacokinetics of fluticasone (cytochrome 3A4 metabolism, long half-life, bioavailability, volume of distribution, lipophilicity, etc.) can lead to accumulation in the presence of CYP3A4 inhibitors.
The accumulation of corticosteroids can cause Cushing's syndrome (moon face, excitation/insomnia, hypertension, increased appetite and weight, ease of doing bruising) and potentially a suppression of the hypothalamic-pituitary axis, which could lead to adrenal insufficiency. Several cases have been reported in the literature, and this in such a short time as 2 weeks.
A pharmacokinetic study demonstrated that ritonavir, a potent CYP 3A4 inhibitor, can increase fluticasone AUC up to 350-fold.
This interaction has been notably a Health Canada warning in 2004 and ritonavir monograph specifie that its association with fluticasone is a risk of serious side effects.
The safest corticosteroid is beclomethasone (Qvar) since its metabolism is mainly by an esterification mechanism.
Ref #2550 and #2551 : A cross-sectional study (n = 11 783) suggests lower prevalence of adrenal insufficiency with beclomethasone than with other corticosteroids currently available on the market. Pharmacokinetic studies with beclomethasone and ritonavir or combination darunavir/ritonavir demonstrated that there were no clinically significant pharmacokinetic interactions. No variation of blood cortisol have been observed.
Fluticasone should not be stopped without consultation with a physician. If the axis hypothalamo-hypophyseal is eliminated, stopping suddenly fluticasone can lead to signs and symptoms of adrenal incapacity. It is recommended to decrease slowly the corticosteroid to avoid the symptoms of craving (fatigue, loss of weight, intoxications, weakness, low postural blood pressure and acute adrenal crisis). Plasma cortisol and ACTH test will document the presence or absence of adrenal insufficiency.
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