Drug interactions between Advair Diskus and Reyataz

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the systemic levels and pharmacologic effects of salmeterol, which is primarily metabolized by the isoenzyme. Because salmeterol prolongs the QT interval in a dose-dependent manner, high systemic levels of salmeterol may increase the risk of ventricular arrhythmias such as ventricular tachycardia, ventricular fibrillation, and torsade de pointes. In a placebo-controlled, crossover drug interaction study consisting of 20 healthy subjects, coadministration of salmeterol (50 mcg twice daily) and the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily) for 7 days resulted in a 16-fold increase in plasma salmeterol exposure (AUC) mainly due to increased bioavailability of the swallowed portion of the dose. Peak plasma salmeterol concentrations (Cmax) were increased by 1.4-fold, and three out of 20 subjects (15%) were withdrawn from the combination due to salmeterol-mediated systemic effects (two with QTc prolongation and one with palpitations and sinus tachycardia). Coadministration of salmeterol and ketoconazole did not result in a clinically significant effect on mean heart rate, blood potassium, or blood glucose. Although there was no statistical effect on the mean QTc, the combination was associated with more frequent increases in QTc duration than salmeterol and placebo.

MANAGEMENT: The use of salmeterol in combination with potent CYP450 3A4 inhibitors such as itraconazole, ketoconazole, voriconazole, nefazodone, delavirdine, protease inhibitors, and ketolide and certain macrolide antibiotics is not recommended.

GENERALLY AVOID: Coadministration with protease inhibitors, particularly ritonavir, may increase the systemic exposure of fluticasone propionate administered intranasally or by oral inhalation. The mechanism is inhibition of fluticasone metabolism via CYP450 3A4. In 18 healthy subjects, coadministration of fluticasone propionate nasal spray (200 mcg once daily) and ritonavir (100 mg twice daily) for 7 days resulted in dramatic increases in fluticasone propionate plasma levels accompanied by an 86% decrease in mean plasma cortisol AUC compared to administration of the nasal spray alone. Systemic corticosteroid effects such as adrenal suppression, Cushing's syndrome, osteoporosis, and exacerbation of diabetes mellitus have been reported during postmarketing use in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate.

MANAGEMENT: The use of intranasal or orally inhaled fluticasone in combination with ritonavir is not recommended unless the potential benefit outweighs the risk of systemic side effects. Caution is advised if fluticasone is prescribed with other protease inhibitors (without ritonavir). Alternatives to fluticasone should be considered, particularly for long-term use.