Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

Pharmacokinetic interactions
Clinical drug-drug interaction studies have not been conducted with this medicinal product, however, the potential for metabolic interactions is considered to be low based on in-vitro studies (see section 5.2).

Formoterol does not inhibit the CYP450 enzymes at therapeutically relevant concentrations (see section 5.2). Budesonide and glycopyrronium do not inhibit or induce CYP450 enzymes at therapeutically relevant concentrations.


The metabolism of budesonide is primarily mediated by CYP3A4 (see section 5.2). Co-treatment with strong CYP3A inhibitors, e.g. itraconazole, ketoconazole, HIV protease inhibitors and cobicistat- containing products, are expected to increase the risk of systemic side effects, and should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid adverse reactions, in which case patients should be monitored for systemic corticosteroid adverse reactions. This is of limited clinical importance for short-term (1-2 weeks) treatment.

Limited data about this interaction for high-dose inhaled budesonide indicates that marked increases in plasma levels (on average four-fold) may occur if itraconazole, 200 mg once daily, is administered concomitantly with inhaled budesonide (single dose of 1000 micrograms).

Since glycopyrronium is eliminated mainly by the renal route, drug interaction could potentially occur with medicinal products affecting renal excretion mechanisms. In vitro, glycopyrronium is a substrate for the renal transporters OCT2 and MATE1/2K. The effect of cimetidine, a probe inhibitor of OCT2 and MATE1, on inhaled glycopyrronium disposition showed a limited increase in its total systemic exposure (AUC0-t) by 22% and a slight decrease in renal clearance by 23% due to co-administration of cimetidine.

Pharmacodynamic interactions

Other antimuscarinics and sympathomimetics
Co-administration of this medicinal product with other anticholinergic and/or long-acting β2- adrenergic agonist containing medicinal products has not been studied and is not recommended as it may potentiate known inhaled muscarinic antagonist or β2-adrenergic agonist adverse reactions (see section 4.4 and section 4.9).

Concomitant use of other beta-adrenergic medicinal products can have potentially additive effects; therefore, caution is required when other beta-adrenergic medicinal products are prescribed concomitantly with formoterol.

Medicinal product-induced hypokalaemia
Possible initial hypokalaemia may be potentiated by concomitant medicinal products, including xanthine derivatives, steroids and non-potassium sparing diuretics (see section 4.4). Hypokalaemia may increase the disposition towards arrhythmias in patients who are treated with digitalis glycosides.

β-adrenergic blockers
β-adrenergic blockers (including eye drops) can weaken or inhibit the effect of formoterol. Concurrent use of β-adrenergic blockers should be avoided unless the expected benefit outweighs the potential risk. If β-adrenergic blockers are required, cardio-selective β-adrenergic blockers are preferred.

Other pharmacodynamic interactions
Concomitant treatment with quinidine, disopyramide, procainamide, antihistamines, monoamine oxidase inhibitors, tricyclic antidepressants and phenothiazines can prolong the QT interval and increase the risk of ventricular arrhythmias. In addition, L-dopa, L-thyroxine, oxytocin and alcohol can impair cardiac tolerance towards beta2-sympathomimetics.

Concomitant treatment with monoamine oxidase inhibitors, including medicinal products with similar properties such as furazolidone and procarbazine, may precipitate hypertensive reactions.

There is an elevated risk of arrhythmias in patients receiving concomitant anaesthesia with halogenated hydrocarbons.