Trimbow · 4.5 Interaction with other medicinal products and other forms of interaction · 3

HOS-217477 · has-adverse-reaction-information · PDF-Seite 9

Summary of the safety profile The most frequently reported adverse reactions in patients with COPD or asthma are respectively: dysphonia (0.3% and 1.5%) and oral candidiasis (0.8% and 0.3%), which are normally associated with inhaled corticosteroids; muscle spasms (0.4% and 0.2%), which can be attributed to the long-acting beta2-agonist component; and dry mouth (0.4% and 0.5%), which is a typical anticholinergic effect. In asthmatic patients, adverse reactions tend to cluster during the first 3 months following initiation of therapy and become less frequent with longer-term use (after 6 months of treatment). Tabulated list of adverse reactions Adverse reactions associated to beclometasone dipropionate/formoterol/glycopyrronium occurred during clinical studies and post-marketing experience as well as adverse reactions listed for the marketed individual components are provided below, listed by system organ class and frequency. Frequencies are defined as: 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). 9  MedDRA system Adverse reaction Frequency organ class Pneumonia (in COPD patients), pharyngitis, oral Common candidiasis, urinary tract infection1, nasopharyngitis1 Influenza1, oral fungal infection, oropharyngeal Infections and candidiasis, oesophageal candidiasis, fungal infestations Uncommon (oro)pharyngitis, sinusitis1, rhinitis1, gastroenteritis1, vulvovaginal candidiasis1 Lower respiratory tract infection (fungal) Rare Blood and lymphatic Granulocytopenia1 Uncommon system disorders Thrombocytopenia1 Very rare Dermatitis allergic1 Uncommon Immune system Hypersensitivity reactions, including erythema, lips, disorders

Auszug; vollständigen Abschnitt im Original lesen.

HOS-217489 · has-adverse-reaction-information · PDF-Seite 47

Summary of the safety profile In a 4-week study, the safety profile of Trimbow inhalation powder was similar to the one observed for Trimbow pressurised solution. The most frequently reported adverse reactions in patients with COPD or asthma with Trimbow pressurised solution are respectively dysphonia (0.3% and 1.5%) and oral candidiasis (0.8% and 0.3%), which are normally associated with inhaled corticosteroids; muscle spasms (0.4% and 0.2%), which can be attributed to the long-acting beta2-agonist component; and dry mouth (0.4% and 0.5%), which is a typical anticholinergic effect. Similarly, dry mouth was reported in 2 patients (0.6%) with Trimbow inhalation powder. In asthmatic patients, adverse reactions tend to cluster during the first 3 months following initiation of therapy and become less frequent with longer-term use (after 6 months of treatment). 47 Tabulated list of adverse reactions Adverse reactions, associated to beclometasone dipropionate/formoterol/glycopyrronium, occurred during clinical studies and post-marketing experience as well as adverse reactions listed for the marketed individual components are provided below, listed by system organ class and frequency. Frequencies are defined as: 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). MedDRA system Adverse reaction Frequency organ class Pneumonia (in COPD patients), pharyngitis, oral candidiasis, Common urinary tract infection1, nasopharyngitis1 Infections and Influenza1, oral fungal infection, oropharyngeal candidiasis, infestations oesophageal candidiasis, fungal (oro)pharyngitis, sinusitis1, Uncommon rhinitis1, gastroenteritis1, vulvovaginal candidiasis1 Lower respiratory tract infection (fungal) Rare Blood and lymphatic Granulocytopenia1 Uncommon system disorders Thrombocytopenia1 Very rare Dermatitis allergic1

Auszug; vollständigen Abschnitt im Original lesen.

HOS-217483 · has-adverse-reaction-information · PDF-Seite 29

Summary of the safety profile The most frequently reported adverse reactions in patients with COPD or asthma are respectively: dysphonia (0.3% and 1.5%) and oral candidiasis (0.8% and 0.3%), which are normally associated with inhaled corticosteroids; muscle spasms (0.4% and 0.2%), which can be attributed to the long-acting beta2-agonist component; and dry mouth (0.4% and 0.5%), which is a typical anticholinergic effect. In asthmatic patients, adverse reactions tend to cluster during the first 3 months following initiation of therapy and become less frequent with longer-term use (after 6 months of treatment). Tabulated list of adverse reactions Adverse reactions associated to beclometasone dipropionate/formoterol/glycopyrronium occurred during clinical studies and post-marketing experience as well as adverse reactions listed for the marketed individual components are provided below, listed by system organ class and frequency. Frequencies are defined as: 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). MedDRA system Adverse reaction Frequency organ class Pneumonia (in COPD patients), pharyngitis, oral Common candidiasis, urinary tract infection1, nasopharyngitis1 Influenza1, oral fungal infection, oropharyngeal Infections and candidiasis, oesophageal candidiasis, fungal infestations Uncommon (oro)pharyngitis, sinusitis1, rhinitis1, gastroenteritis1, vulvovaginal candidiasis1 Lower respiratory tract infection (fungal) Rare Blood and lymphatic Granulocytopenia1 Uncommon system disorders Thrombocytopenia1 Very rare Dermatitis allergic1 Uncommon Immune system Hypersensitivity reactions, including erythema, lips, disorders

Auszug; vollständigen Abschnitt im Original lesen.

HOS-217479 · has-contraindication-information · PDF-Seite 25

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

HOS-217473 · has-contraindication-information · PDF-Seite 5

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

HOS-217485 · has-contraindication-information · PDF-Seite 43

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

HOS-217484 · has-indication-information · PDF-Seite 40

Chronic obstructive pulmonary disease (COPD) Maintenance treatment in adult patients with moderate to severe chronic obstructive pulmonary disease (COPD) who are not adequately treated by a combination of an inhaled corticosteroid and a long-acting beta2-agonist or a combination of a long-acting beta2-agonist and a long-acting muscarinic antagonist (for effects on symptoms control and prevention of exacerbations see section 5.1). Asthma Maintenance treatment of asthma, in adults not adequately controlled with a maintenance combination of a long-acting beta2-agonist and medium dose of inhaled corticosteroid, and who experienced one or more asthma exacerbations in the previous year.

HOS-217478 · has-indication-information · PDF-Seite 22

Maintenance treatment of asthma, in adults not adequately controlled with a maintenance combination of a long-acting beta2-agonist and high dose of inhaled corticosteroid, and who experienced one or more asthma exacerbations in the previous year.

HOS-217472 · has-indication-information · PDF-Seite 2

Chronic obstructive pulmonary disease (COPD) Maintenance treatment in adult patients with moderate to severe COPD who are not adequately treated by a combination of an inhaled corticosteroid and a long-acting beta2-agonist or a combination of a long-acting beta2-agonist and a long-acting muscarinic antagonist (for effects on symptoms control and prevention of exacerbations see section 5.1). Asthma Maintenance treatment of asthma, in adults not adequately controlled with a maintenance combination of a long-acting beta2-agonist and medium dose of inhaled corticosteroid, and who experienced one or more asthma exacerbations in the previous year.

HOS-217487 · has-interaction-information · PDF-Seite 46

Pharmacokinetic interactions Since glycopyrronium is eliminated mainly by the renal route, interaction could potentially occur with medicinal products affecting renal excretion mechanisms (see section 5.2). The effect of organic cation transport inhibition (using cimetidine as a probe inhibitor of OCT2 and MATE1 transporters) in the kidneys on inhaled glycopyrronium disposition showed a limited increase in its total systemic exposure (AUC0-t) by 16% and a slight decrease in renal clearance by 20% due to co-administration of cimetidine. Beclometasone is less dependent on CYP3A metabolism than some other corticosteroids, and in general interactions are unlikely; however, the possibility of systemic effects with concomitant use of strong CYP3A inhibitors (e.g. ritonavir, cobicistat) cannot be excluded, and therefore caution and appropriate monitoring is advised with the use of such medicinal products. Pharmacodynamic interactions Related to formoterol Non-cardioselective beta-blockers (including eye drops) should be avoided in patients taking inhaled formoterol. If they are administered for compelling reasons, the effect of formoterol will be reduced or abolished. 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. 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. Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate a possible hypokalaemic effect of beta2-agonists (see section 4.4). Hypokalaemia may increase the disposition towards arrhythmias in patients who are treated with digitalis glycosides. Related to glycopyrronium The long-term co-administration of Trimbow with other anticholinergic-containing medicinal products has not been studied and is ther

Auszug; vollständigen Abschnitt im Original lesen.

HOS-217475 · has-interaction-information · PDF-Seite 8

Pharmacokinetic interactions Since glycopyrronium is eliminated mainly by the renal route, interaction could potentially occur with medicinal products affecting renal excretion mechanisms (see section 5.2). The effect of organic cation transport inhibition (using cimetidine as a probe inhibitor of OCT2 and MATE1 transporters) in the kidneys on inhaled glycopyrronium disposition showed a limited increase in its total systemic exposure (AUC0-t) by 16% and a slight decrease in renal clearance by 20% due to co administration of cimetidine. Beclometasone is less dependent on CYP3A metabolism than some other corticosteroids, and in general interactions are unlikely; however, the possibility of systemic effects with concomitant use of strong CYP3A inhibitors (e.g. ritonavir, cobicistat) cannot be excluded, and therefore caution and appropriate monitoring is advised with the use of such medicinal products. Pharmacodynamic interactions Related to formoterol Non-cardioselective beta-blockers (including eye drops) should be avoided in patients taking inhaled formoterol. If they are administered for compelling reasons, the effect of formoterol will be reduced or abolished. 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. 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. Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate a possible hypokalaemic effect of beta2-agonists (see section 4.4). Hypokalaemia may increase the disposition towards arrhythmias in patients who are treated with digitalis glycosides. Related to glycopyrronium The long-term co-administration of Trimbow with other anticholinergic-containing medicinal products has not been studied and is ther

Auszug; vollständigen Abschnitt im Original lesen.

HOS-217481 · has-interaction-information · PDF-Seite 27

Pharmacokinetic interactions Since glycopyrronium is eliminated mainly by the renal route, interaction could potentially occur with medicinal products affecting renal excretion mechanisms (see section 5.2). The effect of organic cation transport inhibition (using cimetidine as a probe inhibitor of OCT2 and MATE1 transporters) in the kidneys on inhaled glycopyrronium disposition showed a limited increase in its total systemic exposure (AUC0-t) by 16% and a slight decrease in renal clearance by 20% due to co administration of cimetidine. Beclometasone is less dependent on CYP3A metabolism than some other corticosteroids, and in general interactions are unlikely; however, the possibility of systemic effects with concomitant use of strong CYP3A inhibitors (e.g. ritonavir, cobicistat) cannot be excluded, and therefore caution and appropriate monitoring is advised with the use of such medicinal products. Pharmacodynamic interactions Related to formoterol Non-cardioselective beta-blockers (including eye drops) should be avoided in patients taking inhaled formoterol. If they are administered for compelling reasons, the effect of formoterol will be reduced or abolished. 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. 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. 27 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. Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate a possible hypokalaemic effect of beta2-agonists (see section 4.4). Hypokalaemia may increase the disposition towards arrhythmias in patients who are treated with digitalis glycosides. Related to glycopyrronium The long-term co-administration of Trimbow with other anticholinergic-contain

Auszug; vollständigen Abschnitt im Original lesen.

HOS-217476 · has-pregnancy-information · PDF-Seite 8

There is no experience with or evidence of safety issues on the use of the propellant norflurane (HFA134a) during human pregnancy or lactation. However, studies on the effect of HFA134a on the reproductive function and embryofoetal development in animals revealed no clinically relevant adverse effects. 8 Pregnancy There are no or limited amount of data from the use of Trimbow in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Glucocorticoids are known to cause effects in the early gestation phase, while beta2-sympathomimetics like formoterol have tocolytic effects. Therefore, as a precautionary measure, it is preferable to avoid the use of Trimbow during pregnancy and during labour. Trimbow should only be used during pregnancy if the expected benefit to the patient outweighs the potential risk to the foetus. Infants and neonates born to mothers receiving substantial doses should be observed for adrenal suppression. Breast-feeding There are no relevant clinical data on the use of Trimbow during breast-feeding in humans. Glucocorticoids are excreted in human milk. It is reasonable to assume that beclometasone dipropionate and its metabolites are also excreted in human milk. It is unknown whether formoterol or glycopyrronium (including their metabolites) are excreted in human milk but they have been detected in the milk of lactating animals. Anticholinergics like glycopyrronium could suppress lactation. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Trimbow therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility No specific studies have been performed with Trimbow with regard to the safety in human fertility. Animal studies have shown impairment of fertility (see section 5.3).

HOS-217482 · has-pregnancy-information · PDF-Seite 28

There is no experience with or evidence of safety issues on the use of the propellant norflurane (HFA134a) during human pregnancy or lactation. However, studies on the effect of HFA134a on the reproductive function and embryofoetal development in animals revealed no clinically relevant adverse effects. Pregnancy There are no or limited amount of data from the use of Trimbow in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Glucocorticoids are known to cause effects in the early gestation phase, while beta2-sympathomimetics like formoterol have tocolytic effects. Therefore, as a precautionary measure, it is preferable to avoid the use of Trimbow during pregnancy and during labour. Trimbow should only be used during pregnancy if the expected benefit to the patient outweighs the potential risk to the foetus. Infants and neonates born to mothers receiving substantial doses should be observed for adrenal suppression. If treatment during pregnancy is necessary, the lowest effective dose should be used (see section 4.2). Breast-feeding There are no relevant clinical data on the use of Trimbow during breast-feeding in humans. Glucocorticoids are excreted in human milk. It is reasonable to assume that beclometasone dipropionate and its metabolites are also excreted in human milk. It is unknown whether formoterol or glycopyrronium (including their metabolites) are excreted in human milk but they have been detected in the milk of lactating animals. Anticholinergics like glycopyrronium could suppress lactation. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Trimbow therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility No specific studies have been performed with Trimbow with regard to the safety in human fertility. Animal studies have shown impairment of fertility (see section 5.3).

HOS-217488 · has-pregnancy-information · PDF-Seite 47

Pregnancy There are no or limited amount of data from the use of Trimbow in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Glucocorticoids are known to cause effects in the early gestation phase, while beta2-sympathomimetics like formoterol have tocolytic effects. Therefore, as a precautionary measure, it is preferable to avoid the use of Trimbow during pregnancy and during labour. Trimbow should only be used during pregnancy if the expected benefit to the patient outweighs the potential risk to the foetus. Infants and neonates born to mothers receiving substantial doses should be observed for adrenal suppression. Breast-feeding There are no relevant clinical data on the use of Trimbow during breast-feeding in humans. Glucocorticoids are excreted in human milk. It is reasonable to assume that beclometasone dipropionate and its metabolites are also excreted in human milk. It is unknown whether formoterol or glycopyrronium (including their metabolites) are excreted in human milk but they have been detected in the milk of lactating animals. Anticholinergics like glycopyrronium could suppress lactation. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Trimbow therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the women. Fertility No specific studies have been performed with Trimbow with regard to the safety in human fertility. Animal studies have shown impairment of fertility (see section 5.3).

HOS-217474 · has-warning-information · PDF-Seite 5

Not for acute use This medicinal product is not indicated for the treatment of acute episodes of bronchospasm, or to treat an acute disease exacerbation (i.e. as a rescue therapy). Hypersensitivity Immediate hypersensitivity reactions have been reported after administration. If signs suggesting allergic reactions occur, in particular, angioedema (including difficulties in breathing or swallowing, swelling of the tongue, lips and face), urticaria or skin rash, treatment should be discontinued immediately and alternative therapy instituted. Paradoxical bronchospasm Paradoxical bronchospasm may occur with an immediate increase in wheezing and shortness of breath after dosing. This should be treated immediately with a fast-acting inhaled bronchodilator (reliever). Treatment should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary. Deterioration of disease It is recommended that treatment should not be stopped abruptly. If patients find the treatment ineffective, they should continue treatment but medical attention must be sought. Increasing use of reliever bronchodilators indicates a worsening of the underlying condition and warrants a reassessment of the therapy. Sudden or progressive deterioration in symptoms is potentially life-threatening and the patient should undergo urgent medical assessment. Cardiovascular effects Due to the presence of a long-acting beta2-agonist and a long-acting muscarinic antagonist, Trimbow should be used with caution in patients with cardiac arrhythmias, especially third degree atrioventricular block and tachyarrhythmias (accelerated and/or irregular heartbeat, including atrial fibrillation), idiopathic subvalvular aortic stenosis, hypertrophic obstructive cardiomyopathy, severe heart disease (particularly acute myocardial infarction, ischaemic heart disease, congestive heart failure), occlusive vascular diseases (particularly arteriosclerosis), arterial hypertension and aneurysm. 5 Caution should also be exercised when treating patients with known or suspected prolongation of the QTc interval (QTc > 450 milliseconds for males, or > 470 milliseconds for females), either congenital or induced by medicinal products. Patients diagnosed with the described cardiovascular conditions were excluded from clinical studies with Trimbow. Limited data in asthmatic patients with cardiovascular co-morbidities or risk-factors suggest

Auszug; vollständigen Abschnitt im Original lesen.

HOS-217486 · has-warning-information · PDF-Seite 43

Not for acute use This medicinal product is not indicated for the treatment of acute episodes of bronchospasm, or to treat an acute disease exacerbation (i.e. as a rescue therapy). Hypersensitivity Immediate hypersensitivity reactions have been reported after administration. If signs suggesting allergic reactions occur, in particular, angioedema (including difficulties in breathing or swallowing, swelling of the tongue, lips and face), urticaria or skin rash, treatment should be discontinued immediately and alternative therapy instituted. Paradoxical bronchospasm Paradoxical bronchospasm may occur with an immediate increase in wheezing and shortness of breath after dosing. This should be treated immediately with a fast-acting inhaled bronchodilator (reliever). Treatment should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary. Deterioration of disease It is recommended that treatment should not be stopped abruptly. If patients find the treatment ineffective, they should continue treatment but medical attention must be sought. Increasing use of reliever bronchodilators indicates a worsening of the underlying condition and warrants a reassessment of the therapy. Sudden or progressive deterioration in symptoms is potentially life-threatening and the patient should undergo urgent medical assessment. 43 Cardiovascular effects Due to the presence of a long-acting beta2-agonist and a long-acting muscarinic antagonist, Trimbow should be used with caution in patients with cardiac arrhythmias, especially third degree atrioventricular block and tachyarrhythmias (accelerated and/or irregular heartbeat, including atrial fibrillation), idiopathic subvalvular aortic stenosis, hypertrophic obstructive cardiomyopathy, severe heart disease (particularly acute myocardial infarction, ischaemic heart disease, congestive heart failure), occlusive vascular diseases (particularly arteriosclerosis), arterial hypertension and aneurysm. Caution should also be exercised when treating patients with known or suspected prolongation of the QTc interval (QTc > 450 milliseconds for males, or > 470 milliseconds for females), either congenital or induced by medicinal products. Patients diagnosed with the described cardiovascular conditions were excluded from clinical studies with Trimbow. Limited data in asthmatic patients with cardiovascular co-morbidities or risk-factors suggest th

Auszug; vollständigen Abschnitt im Original lesen.

HOS-217480 · has-warning-information · PDF-Seite 25

Not for acute use This medicinal product is not indicated for the treatment of acute episodes of bronchospasm, or to treat an acute disease exacerbation (i.e. as a rescue therapy). Hypersensitivity Immediate hypersensitivity reactions have been reported after administration. If signs suggesting allergic reactions occur, in particular, angioedema (including difficulties in breathing or swallowing, swelling of the tongue, lips and face), urticaria or skin rash, treatment should be discontinued immediately and alternative therapy instituted. Paradoxical bronchospasm Paradoxical bronchospasm may occur with an immediate increase in wheezing and shortness of breath after dosing. This should be treated immediately with a fast-acting inhaled bronchodilator (reliever). Treatment should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary. Deterioration of disease It is recommended that treatment should not be stopped abruptly. If patients find the treatment ineffective, they should continue treatment but medical attention must be sought. Increasing use of reliever bronchodilators indicates a worsening of the underlying condition and warrants a reassessment of the therapy. Sudden or progressive deterioration in symptoms is potentially life-threatening and the patient should undergo urgent medical assessment. Cardiovascular effects Due to the presence of a long-acting beta2-agonist and a long-acting muscarinic antagonist, Trimbow should be used with caution in patients with cardiac arrhythmias, especially third degree atrioventricular block and tachyarrhythmias (accelerated and/or irregular heartbeat, including atrial fibrillation), idiopathic subvalvular aortic stenosis, hypertrophic obstructive cardiomyopathy, severe heart disease (particularly acute myocardial infarction, ischaemic heart disease, congestive heart failure), occlusive vascular diseases (particularly arteriosclerosis), arterial hypertension and aneurysm. Caution should also be exercised when treating patients with known or suspected prolongation of the QTc interval (QTc > 450 milliseconds for males, or > 470 milliseconds for females), either congenital or induced by medicinal products. Patients diagnosed with the described cardiovascular conditions were excluded from clinical studies with Trimbow. Limited data in asthmatic patients with cardiovascular co-morbidities or risk-factors suggest that these patients are also at higher risk of adverse rea

Auszug; vollständigen Abschnitt im Original lesen.