fluticasone/salmeterol

• Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with ADVAIR DISKUS is not recommended because increased systemic corticosteroid and increased cardiovascular adverse effects may occur. Ketoconazole Fluticasone Propionate: Coadministration of orally inhaled fluticasone propionate (1,000 mcg) and ketoconazole (200 mg once daily) resulted in a 1.9-fold increase in plasma fluticaso...

Mechanism: Ketoconazole stops your body from clearing the medicine in the inhaler. This can lead to higher levels of the steroid in your body and may cause heart-related side effects.

What to do: This combination is not recommended. Your doctor may need to change your medication to avoid serious side effects.

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

Mechanism: Clarithromycin blocks the enzyme that breaks down the ingredients in your inhaler. This can cause the medicine to build up in your body and increase the risk of side effects.

What to do: Using these two drugs together is not recommended. Your doctor may need to choose a different antibiotic or a different inhaler.

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

Mechanism: Itraconazole stops the body from breaking down the inhaler medicine, which can lead to higher levels in your blood and more side effects.

What to do: This combination is not recommended. Talk to your doctor about safer alternatives to avoid heart or hormone problems.

( 7.4 ) 7.1 Inhibitors of Cytochrome P450 3A4 Fluticasone propionate and salmeterol, the individual components of ADVAIR DISKUS, are substrates of CYP3A4. Ritonavir Fluticasone Propionate: 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 interactio...

Mechanism: Both of these products contain the same steroid medicine. Taking them together increases the amount of medicine in your body, which can lower your natural hormone levels.

What to do: Your doctor should check your total dose to ensure you are not taking too much steroid medication.

May potentiate effect of salmeterol on vascular system. ( 7.4 ) 7.1 Inhibitors of Cytochrome P450 3A4 Fluticasone propionate and salmeterol, the individual components of ADVAIR DISKUS, are substrates of CYP3A4. Salmeterol: In a drug interaction trial in 20 healthy subjects, coadministration of inhaled salmeterol (50 mcg twice daily) and oral ketoconazole (400 mg once daily) for 7 days resulted in greater systemic exposure to salmeterol (AUC increased 16-fold and C max increased 1.4-fold).

Mechanism: These two products contain the same active ingredient. Taking both at once can lead to an overdose, which may cause heart or blood pressure problems.

What to do: You should not use both of these medications together unless your doctor tells you to.