Bevespi Aerosphere · 4.8 Undesirable effects · 1

HOS-217431 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile The safety profile is characterised by anticholinergic and β2-adrenergic class effects related to the individual components of the combination. The most commonly reported adverse reactions in patients receiving Bevespi Aerosphere were headache (1.9%), nausea (1.4%), muscle spasms (1.4%), and dizziness (1.3%). Tabulated list of adverse reactions The tabulated list of adverse reactions is based on clinical trials and post-approval experience with Bevespi Aerosphere as well as experience with the individual components and related products. The frequency of adverse reactions is defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000) and not known (cannot be estimated from available data). Table 1 Adverse reactions by frequency and system organ class (SOC) System Organ Class Preferred term Frequency Immune system disorders Hypersensitivity reactions including rash and Uncommon pruritus Metabolism and nutrition Hyperglycaemia1 Uncommon disorders Psychiatric disorders Anxiety Common Agitation Uncommon Restlessness Insomnia Headache1 Nervous system disorders Common Dizziness Tremor1 Uncommon Tachycardia Uncommon Palpitations Cardiac disorders Cardiac arrhythmias (atrial fibrillation, supraventricular tachycardia, and extrasystoles) Gastrointestinal Dry mouth2, Nausea Common disorders Musculoskeletal and Muscle spasms1 Common connective tissue disorders Renal and urinary Urinary tract infection Common

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HOS-217427 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substances or any of the excipients listed in section 6.1.

HOS-217426 · has-indication-information · PDF-Seite 2

Bevespi Aerosphere is indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD) (see section 5.1).

HOS-217429 · has-interaction-information · PDF-Seite 4

Pharmacokinetic interactions No interaction studies have been performed with Bevespi Aerosphere; however, the potential for metabolic interactions is considered to be low based on in-vitro studies (see section 5.2). Since glycopyrronium is eliminated mainly by the renal route, interactions 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 4 Other antimuscarinics and sympathomimetics Co-administration of Bevespi Aerosphere 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 sections 4.4 and 4.9). Although no formal in-vivo interaction studies have been performed with Bevespi Aerosphere, studies indicate no clinical evidence of interactions when used concomitantly with other COPD medicinal products including short-acting β2-adrenergic bronchodilators, methylxanthines, and oral and inhaled steroids. Drug-induced hypokalaemia Concomitant treatment with methylxanthine derivatives, steroids, or non-potassium sparing diuretics may potentiate the possible initial hypokalaemic effect of β2-adrenergic agonists, therefore, caution is advised in their concomitant use (see section 4.4). β-adrenergic blockers β-adrenergic blockers (including eye drops) can weaken or inhibit the effect of β2-adrenergic agonists, such as formoterol. Concurrent use of either non-selective or selective β-adrenergic blockers should be avoided unless there are compelling reasons for their use. If β-adrenergic blockers are required (including eye drops), cardioselective β-adrenergic blockers are preferred, although they should also be administered with caution. Other pharmacodynamic interactions Bevespi Aerosphere should be administered with caution to patients being treated with medicinal products known to prolong the QTc interval (see section 4.4).

HOS-217430 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are no data on the use of Bevespi Aerosphere in pregnant women. Single-dose studies in humans found that very small amounts of glycopyrronium passed the placental barrier. In animal studies, formoterol and glycopyrronium, individually, have caused adverse effects in reproduction studies at very high doses/systemic exposure levels (see section 5.3). Bevespi Aerosphere should only be used during pregnancy if the expected benefits outweigh the potential risks. Breast-feeding It is not known whether glycopyrronium or formoterol are excreted in human milk. Evidence of transfer of glycopyrronium and formoterol into maternal milk in rats has been reported. Administration of Bevespi Aerosphere to women who are breast-feeding should only be considered if the expected benefit to the mother is greater than any possible risk to the infant (see section 5.3). Fertility Studies in rats have shown adverse effects on fertility only at dose levels higher than the maximum human exposure to formoterol (see section 5.3). Glycopyrronium did not cause any adverse effects on fertility in rats. It is unlikely that Bevespi Aerosphere administered at the recommended dose will affect fertility in humans.

HOS-217428 · has-warning-information · PDF-Seite 3

Not for acute use Bevespi Aerosphere is not indicated for the treatment of acute episodes of bronchospasm, i.e. as a rescue therapy. Asthma Bevespi Aerosphere should not be used to treat asthma. Paradoxical bronchospasm As with other inhalation therapy, administration of this medicinal product may result in paradoxical bronchospasm, which can be life-threatening. If paradoxical bronchospasm does occur, treatment with the medicinal product should be stopped and other treatments considered. 3 Cardiovascular effects Cardiovascular effects, such as cardiac arrhythmias e.g. atrial fibrillation and tachycardia, may be seen after the administration of muscarinic receptor antagonists and sympathomimetics, including glycopyrronium or formoterol. Patients with clinically significant uncontrolled cardiovascular disease were excluded from clinical studies. Bevespi Aerosphere should be used with caution in patients with severe cardiovascular disorders, such as ischaemic heart disease, tachyarrhythmias or severe heart failure. Caution should also be exercised in patients with thyrotoxicosis or known or suspected prolongation of the QTc interval (see section 4.5). Hypokalaemia β2-adrenergic agonists may produce significant hypokalaemia, which may increase the susceptibility to cardiac arrhythmias. The decrease in serum potassium is usually transient, not requiring supplementation. In patients with severe COPD, hypokalaemia may be potentiated by hypoxia and concomitant treatment (see section 4.5). Hyperglycaemia Inhalation of high doses of β2-adrenergic agonists may produce increases in plasma glucose. Anticholinergic activity Due to its anticholinergic activity, Bevespi Aerosphere should be used with caution in patients with symptomatic prostatic hyperplasia, urinary retention or with narrow-angle glaucoma (see section 4.8). Patients with severe renal impairment As glycopyrronium is predominantly renally excreted, patients with severe renal impairment (creatinine clearance of < 30 mL/min), including those with end-stage renal disease requiring dialysis, should only be treated with Bevespi Aerosphere if the expected benefit outweighs the potential risk (see section 5.2). Patients with severe hepatic impairment In patients with severe hepatic impairment, Bevespi Aerosphere should be used only if the expected benefit outweighs the potential risk (see section 5.2). These patients should be monitored for

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