rritability, have been reported very rarely and primarily in children.
Reproductive System and Breast Disorders: Dysmenorrhea.
Respiratory, Thoracic, and Mediastinal Disorders: Chest congestion; chest tightness, dyspnea;facial and oropharyngeal edema, immediate bronchospasm; paradoxical bronchospasm;tracheitis; wheezing; reports of upper respiratory symptoms of laryngeal spasm, irritation, orswelling such as stridor or choking.
Skin and Subcutaneous Tissue Disorders: Ecchymoses, photodermatitis.
Vascular Disorders: Pallor.
7 DRUG INTERACTIONS
Fluticasone propionate/salmeterol MDPI has been used concomitantly with other drugs,including short-acting beta2-agonists, and intranasal corticosteroids, commonly used in patientswith asthma without adverse drug reactions [see Clinical Pharmacology (12.2)]. No formal druginteraction trials have been performed with AirDuo Digihaler.
7.1 Inhibitors of Cytochrome P450 3A4
Fluticasone propionate and salmeterol, the individual components of AirDuo Digihaler, aresubstrates of CYP3A4. The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir,clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with AirDuo Digihaler is not recommended because increased systemic
corticosteroid and increased cardiovascular adverse effects may occur.
Ritonavir: Fluticasone Propionate: A drug interaction trial with fluticasone propionate aqueousnasal spray in healthy subjects has shown that ritonavir (a strong CYP3A4 inhibitor) cansignificantly increase plasma fluticasone propionate exposure, resulting in significantly reducedserum cortisol concentrations [see Clinical Pharmacology (12.3)]. During postmarketing use,there have been reports of clinically significant drug interactions in patients receiving fluticasonepropionate and ritonavir, resulting in systemic corticosteroid effects including Cushing’ssyndrome and adrenal suppression.
Ketoconazole: Fluticasone Propionate: Coadministration of orally inhaled fluticasonepropionate (1,000 mcg) and ketoconazole (200 mg once daily) resulted in a 1.9-fold increase inplasma fluticasone propionate exposure and a 45% decrease in plasma cortisol area under thecurve (AUC) but had no effect on urinary excretion of cortisol.
Salmeterol: In a drug interaction trial in 20 healthy subjects, coadministration of inhaledsalmeterol (50 mcg twice daily) and oral ketoconazole (400 mg once daily) for 7 days resulted ingreater systemic exposure to salmeterol (AUC increased 16-fold and Cmax increased 1.4-fold).
Three (3) subjects were withdrawn due to beta2-agonist side effects (2 with prolonged QTc and1 with palpitations and sinus tachycardia). Although there was no statistical effect on the meanQTc, coadministration of salmeterol and ketoconazole was associated with more frequentincreases in QTc duration compared with salmeterol and placebo administration [see ClinicalPharmacology (12.3)].
7.2 Monoamine Oxidase Inhibitors and Tricyclic Antidepressants
AirDuo Digihaler should be administered with extreme caution to patients being treated withmonoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuationof such agents, because the action of salmeterol, a component of AirDuo Digihaler, on thevascular system may be potentiated by these agents.
7.3 Beta-Adrenergic Rece |
