Coadministration of fluticasone propionate aqueous nasal spray (200 µg once daily) and ritonavir (100 mg twice daily) increased fluticasone AUC by ~350-fold and Cmin by ~25-fold. Systemic corticosteroid effects including Cushing's syndrome and adrenal suppression (plasma cortisol levels were noted to be decreased 86% in the above study) have been reported in patients receiving ritonavir and inhaled or intranasal fluticasone propionate; similar effects could also occur with other corticosteroids metabolised by CYP3A e.g., budesonide. Consequently, concomitant administration of ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer and these glucocorticoids is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects. A dose reduction of the glucocorticoid should be considered with close monitoring of local and systemic effects or a switch to a glucocorticoid, which is not a substrate for CYP3A4 (e.g., beclomethasone). Moreover, in case of withdrawal of glucocorticoids progressive dose reduction may be required over a longer period.

Cushing's syndrome and adrenal suppression have been reported when ritonavir has been coadministered with fluticasone propionate. Concomitant use of fluticasone propionate and ritonavir is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid side effects. Concomitant use may result in increased fluticasone concentrations and reduced serum cortisol concentrations. Systemic corticosteroid effects including Cushing's syndrome and adrenal suppression have been reported during postmarketing use in patients when ritonavir has been coadministered with fluticasone propionate. Coadministration of fluticasone proprionate aqueous nasal spray (200 µg once daily for 7 days) and ritonavir (100 mg twice daily for 7 days) to 18 healthy subjects increased fluticasone AUC by approximately 350-fold and increased Cmax by approximately 25-fold. This significant increase in plasma fluticasone propionate exposure resulted in a significant decrease (86%) in plasma cortisol AUC.

A case was reported of a 48-year-old asthmatic HIV positive man treated with lamivudine (150 mg), abacavir (300 mg) and lopinavir/ritonavir (400/100 mg), all twice daily. He also took salbutamol (200 µg, as needed) and fluticasone (250 µg, twice daily). He presented with a two-month history of weight loss, weakness and fatigue. He was diagnosed with secondary adrenal insufficiency and fluticasone was replaced with oral hydrocortisone (20 mg, twice daily), which was tapered off and withdrawn after one year. His cortisol and ACTH levels returned to normal levels. The authors hypothesise a drug-drug interaction occurred via inhibition of CYP3A4 by ritonavir.

Two cases in 66 year old HIV+ men have been reported of an interaction with fluticasone and ritonavir (100 mg twice daily). The first case had been receiving fluticasone for 12 months prior to presentation and indinavir/ritonavir for 4 months prior to presentation. A good recovery was made with i.v. gamma globulin and the initial fluticasone dose of 500 µg twice daily was halved. The second case had been receiving fluticasone for 12 months prior to presentation and amprenavir/ritonavir for 6 months prior to presentation. Budesonide/efomoterol was substituted for fluticasone and his Cushingoid features gradually improved over 6-12 months. However, ~1 year later he presented with a fractured neck of the femur; investigations revealed avascular necrosis, osteoporosis and a subnormal cortisol level. A possible cause maybe the augmentation of budesonide concentrations by ritonavir.