Fluticasone and Lopinavir and ritonavir interaction

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended.

Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors The use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with Fluticasone Propionate DISKUS is not recommended because increased systemic corticosteroid adverse effects…

The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with Fluticasone Propionate DISKUS is not recommended because increased systemic corticosteroid adverse effects may occur.

Ritonavir A drug interaction trial with fluticasone propionate aqueous nasal spray in healthy subjects has shown that ritonavir (a strong CYP3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations [see Clinical Pharmacology ( 12.3 )] .

During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression.

…Nasal/Ophthalmic Corticosteroids: e.g., betamethasone budesonide ciclesonide dexamethasone fluticasone methylprednisolone mometasone prednisone triamcinolone ↓ lopinavir ↑ glucocorticoids Coadministration with oral dexamethasone or other 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. * see Clinical Pharmacology ( 12.3 ) for magnitude of interaction. # refers to interaction with apalutamide.

Contraceptive: ethinyl estradiol* ↓ ethinyl estradiol Because contraceptive steroid concentrations may be altered when KALETRA is co-administered with oral contraceptives or with the contraceptive patch, alternative methods of nonhormonal contraception are recommended.