Glycoair Breezhaler Drug Interactions

Interactions linked to the indacaterol/glycopyrronium: Concomitant administration of orally inhaled indacaterol and glycopyrronium under steady‑state conditions of both drugs did not affect the pharmacokinetics (PK) of either drug.
No specific drug-drug interaction studies were conducted. Information on the potential for interactions is based on the potential for each of its two monotherapy components.
Interactions linked to indacaterol: In vitro investigations have indicated that indacaterol has negligible potential to cause metabolic interactions with medications at the systemic exposure levels achieved in clinical practice (see Pharmacology: Pharmacokinetics: Biotransformation/metabolism and elimination under Actions).
Beta-adrenergic blockers: Beta-adrenergic blockers may weaken or antagonize the effect of beta₂-adrenergic agonists.
Therefore it should not be given together with beta-adrenergic blockers (including eye drops) unless there are compelling reasons for their use. Where required, cardioselective beta-adrenergic blockers should be preferred, although they should be administered with caution.
Drugs known to prolong QTc interval: As with other beta₂-adrenergic agonist-containing drugs, it should be administered with caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QT interval, as any effect of these on the QT interval may be potentiated. Drugs known to prolong the QT-interval may increase the risk of ventricular arrhythmia (see Precautions).
Sympathomimetic agents: Concomitant administration of other sympathomimetic agents (alone or as part of combination therapy) may potentiate the undesirable effects of indacaterol (see Precautions).
Hypokalemia: Concomitant treatment with methylxanthine derivatives, steroids, or non-potassium-sparing diuretics may potentiate the possible hypokalemic effect of beta₂-adrenergic agonists (see Precautions).
Metabolic and transporter based drug interaction: Inhibition of the key contributors of indacaterol clearance, CYP3A4 and P-gp, has no impact on safety of therapeutic doses of indacaterol. Drug interaction studies were carried out using potent and specific inhibitors of CYP3A4 and P-gp (i.e., ketoconazole, erythromycin, verapamil and ritonavir). Verapamil was used as the prototypic inhibitor of P-gp and resulted in 1.4- to two-fold increase in AUC and 1.5-fold increase in C_max. Co-administration of erythromycin with indacaterol resulted in an increase of 1.4- to 1.6-fold for AUC and 1.2 fold for C_max. Combined inhibition of P-gp and CYP3A4 by the very strong dual inhibitor ketoconazole caused a 2-fold and 1.4-fold increase in AUC and C_max, respectively. Concomitant treatment with ritonavir, another dual inhibitor of CYP3A4 and P-gp, resulted in a 1.6- to 1.8-fold increase in AUC whereas C_max was unaffected. Taken together, the data suggest that systemic clearance is influenced by modulation of both P-gp and CYP3A4 activities and that the 2-fold AUC increase caused by the strong dual inhibitor ketoconazole reflects the impact of maximal combined inhibition. The magnitude of exposure increases due to drug interactions does not raise any safety concerns given the safety experience of treatment with indacaterol in clinical trials of up to one year at doses of 600 microgram.
Interactions linked to glycopyrronium: In vitro studies showed that glycopyrronium is not likely to inhibit or induce the metabolism of other drugs, nor processes involving drug transporters. Metabolism in which multiple enzymes are involved, plays a secondary role in the elimination of glycopyrronium (see Pharmacology: Pharmacokinetics: Biotransformation/metabolism and elimination under Actions). Inhibition or induction of metabolism of glycopyrronium is unlikely to result in a relevant change of systemic exposure to the drug.
Anticholinergics: The co-administration of indacaterol/glycopyrronium with inhaled anticholinergic-containing drugs has not been studied and is therefore, like for other anticholinergic containing drugs, not recommended.
Cimetidine or other inhibitors of organic cation transport: In a clinical study in healthy volunteers, cimetidine, an inhibitor of organic cation transport which is thought to contribute to the renal excretion of glycopyrronium, increased total exposure (AUC) to glycopyrronium by 22% and decreased renal clearance by 23%. Based on the magnitude of these changes, no clinically relevant drug interaction is expected when glycopyrronium is co-administered with cimetidine or other inhibitors of the organic cation transport.