Concomitant use of Kaletra and fluticasone or other glucocorticoids that are metabolised by CYP3A4 is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects, including Cushing’s syndrome and adrenal suppression. Coadministration [of ritonavir (100 mg twice daily)] and fluticasone (50 µg intranasal, 4 times daily) increased fluticasone plasma levels, whereas cortisol levels decreased by 86%. Greater effects may be expected when fluticasone propionate is inhaled. Systemic corticosteroid effects including Cushing's syndrome and adrenal suppression have been reported in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate; this could also occur with other corticosteroids metabolised via the P450 3A pathway e.g. budesonide and triamcinolone. 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 have to be performed over a longer period.

Coadministration is expected to decrease lopinavir concentrations and increase concentrations of fluticasone. Coadministration with systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to lopinavir. Consider alternative corticosteroids. Coadministration with corticosteroids whose exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing’s syndrome and adrenal suppression. Alternative corticosteroids including beclomethasone and prednisolone (whose PK and/or PD are less affected by strong CYP3A inhibitors relative to other studied steroids) should be considered, particularly for long-term use.

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insufficiency and fluticasone was replaced with oral hydrocortisone (20 mg, twice daily), which was tapered off and withdrawn after one year.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.