Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

Concomitant administration of orally inhaled indacaterol and glycopyrronium, under steady-state conditions of both active substances, did not affect the pharmacokinetics of either active substance.

No specific interaction studies were conducted with Ultibro Breezhaler. Information on the potential for interactions is based on the potential for each of its two active substances.

Concomitant use not recommended

Beta-adrenergic blockers
Beta-adrenergic blockers may weaken or antagonise the effect of beta2-adrenergic agonists. Therefore Ultibro Breezhaler 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.

Anticholinergics
The co-administration of Ultibro Breezhaler with other anticholinergic-containing medicinal products has not been studied and is therefore not recommended (see section 4.4).

Sympathomimetics
Concomitant administration of other sympathomimetics (alone or as part of combination therapy) may potentiate the adverse events of indacaterol (see section 4.4).

Caution required with concomitant use

Hypokalaemic treatment
Concomitant hypokalaemic treatment with methylxanthine derivatives, steroids, or non-potassium- sparing diuretics may potentiate the possible hypokalaemic effect of beta2-adrenergic agonists, therefore use with caution (see section 4.4).


ULT API MAY23 V 2.1                                                      REF EU SmPC 18Nov2020 To be taken into account with concomitant use

Metabolic and transporter based interactions
Inhibition of the key contributors of indacaterol clearance, CYP3A4 and P-glycoprotein (P-gp), raises the systemic exposure of indacaterol up to two-fold. The magnitude of exposure increases due to interactions does not raise any safety concerns given the safety experience of treatment with indacaterol in clinical studies of up to one year at doses up to twice the maximum recommended indacaterol dose.


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.