Dalman Drug Interactions

Under normal conditions, very low plasma concentrations of fluticasone propionate are achieved following intranasal dosing, due to extensive first-pass metabolism in the liver and intestine and high systemic clearance mediated by cytochrome P450 3A4. Therefore, clinically significant drug interactions mediated by fluticasone propionate are not expected.
In a drug interaction study in healthy volunteers, ritonavir (a highly potent cytochrome P450 3A4 inhibitor) was shown to greatly increase the plasma concentrations of fluticasone propionate, leading to a significant decrease in serum cortisol concentrations. Clinically significant drug interactions have been reported in patients receiving intranasal or inhaled fluticasone propionate and ritonavir during post-marketing use; this has led to systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided unless the potential benefits to the patient outweigh the risk of systemic corticosteroid side effects.
Studies have shown negligible (erythromycin) and insignificant (ketoconazole) increases in systemic exposure of other cytochrome P450 3A4 inhibitors with no discernible decrease in serum cortisol concentrations of fluticasone propionate. However, caution should be exercised when co-administering potent cytochrome P450 3A4 inhibitors (eg. ketoconazole) because of the potential for increased systemic exposure to fluticasone propionate.