Source: Z-Index G-Standaard (NL) Revision Year: 2022 Publisher: Boehringer Ingelheim International GmbH, Binger Straße 173, D-55216 Ingelheim am Rhein, Germany
Hypersensitivity to the active substances, to any of the excipients listed in section 6.1, or to other atropine like substances.
Hypertrophic obstructive cardiomyopathy or tachyarrhythmia.
Immediate hypersensitivity reactions may occur after administration of Berodual Respimat, as demonstrated by rare cases of urticaria, angio-oedema, rash, bronchospasm, oropharyngeal oedema and anaphylaxis.
As with other inhaled medicines Berodual Respimat may result in paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs Berodual Respimat should be discontinued immediately and alternative therapy substituted.
Berodual Respimat, like other medicinal products containing anticholinergic active substances, should be used with caution in patients predisposed to narrow-angle glaucoma.
There have been isolated reports of ocular complications (i.e. mydriasis, increased intraocular pressure, narrow-angle glaucoma and eye pain) when aerosolised ipratropium bromide either alone or in combination with an adrenergic beta2-agonist, has come into contact with the eyes. Eye pain or discomfort, blurred vision, visual halos or coloured images in association with red eyes from conjunctival congestion and corneal oedema may be signs of acute narrow-angle glaucoma. Should any combination of these symptoms develop, treatment with miotic eye drops should be initiated and specialist advice should be sought immediately.
Thus patients must be instructed in the correct administration of Berodual Respimat. Care must be taken not to allow the product to enter the eyes.
In the following conditions Berodual Respimat should only be used after careful risk/benefit assessment, especially when doses higher than recommended are used: in insufficiently controlled diabetes mellitus, recent myocardial infarction, severe organic heart or vascular disorders, hyperthyroidism, and pheochromocytoma or with pre-existing urinary outflow tract obstruction (e.g. prostatic hyperplasia or bladder-neck obstruction).
Cardiovascular effects may be seen with sympathicomimetic drugs, including Berodual Respimat. There is some evidence from post-marketing data and published literature of rare occurrences of myocardial ischaemia associated with beta-agonists. Patients with underlying severe heart disease (e.g. ischaemic heart disease, arrhythmia or severe heart failure) who are receiving Berodual Respimat, should be warned to seek medical advice if they experience chest pain or other symptoms of worsening heart disease. Attention should be paid to assessment of symptoms such as dyspnoea and chest pain, as they may be of either respiratory or cardiac origin.
Potentially serious hypokalemia may result from beta2-agonist therapy (see also section 4.9).
Patients with cystic fibrosis may be more prone to gastro-intestinal motility disturbances when treated with inhaled anticholinergics.
In the case of acute, rapidly worsening of dyspnoea patients should be advised to consult a doctor immediately.
In asthmatic patients, the use of increasing amounts of beta2-agonist containing medicinal products, such as Berodual Respimat, on a regular basis to control symptoms of bronchial obstruction may suggest declining disease control.
If bronchial obstruction deteriorates it is inappropriate and possibly hazardous to simply increase the use of beta2-agonist containing medicinal products, beyond the recommended dose over extended periods of time. In this situation the patient’s therapy plan, and in particular the adequacy of antiinflammatory therapy with inhaled corticosteroids, should be reviewed to prevent potentially lifethreatening deterioration of disease control.
Other sympathomimetic bronchodilators should only be used in combination with Berodual Respimat under medical supervision (see section 4.5).
Benzalkonium chloride may cause wheezing and breathing difficulties. Patients with asthma are at an increased risk for these adverse events.
The chronic co-administration of Berodual Respimat with other anticholinergic drugs has not been studied. Therefore, the chronic co-administration of Berodual Respimat with other anticholinergic drugs is not recommended.
Other beta-adrenergics, anticholinergics and xanthine derivatives (such as theophylline) may enhance the bronchodilatory effect. The concurrent administration of other beta-mimetics, systemically available anticholinergics and xanthine derivatives may increase the adverse reactions.
A potentially serious reduction in bronchodilatation may occur during concurrent administration of beta-blockers.
Hypokalemia induced by beta2-agonist may be increased by concomitant treatment with xanthine derivatives, corticosteroids and diuretics. This should be taken into account, particularly in patients with severe airway obstruction.
Hypokalemia may result in an increased susceptibility to arrhythmias in patients receiving digoxin. Additionally, hypoxia may aggravate the effects of hypokalemia on cardiac rhythm. It is recommended that serum potassium levels be monitored in such situations.
Beta2-agonist containing medicinal products should be administered with caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, since the action of betaadrenergic agonists may be enhanced. Inhalation of halogenated hydrocarbon anaesthetics (e.g. halothane, trichloroethylene and enflurane) can increase the susceptibility on the cardiovascular effects of beta2-agonists.
The risk of acute glaucoma (see section 4.4) may be increased when nebulised ipratropium bromide and beta2-agonists come into contact with the eyes simultaneously.
There are no sufficient data from the use of Berodual Respimat in pregnant women. Animal studies do not indicate direct or indirect harmful effect with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). The potential risk for humans is unknown. Caution should be exercised when prescribing to pregnant women. The potential of beta2-agonists to inhibit uterine contraction should be taken into account.
Use of ß-2 sympathomimetics in the end of the pregnancy or in high doses may cause negative effects in the newborn baby (tremor, tachycardia, blood glucose fluctuations, hypokalaemia).
Non-clinical studies have shown that fenoterol hydrobromide is excreted into breast milk. It is not known whether ipratropium is excreted into breast milk. But it is unlikely that ipratropium would reach the infant to an important extent, especially when taken by inhalation. However, because many active substances are excreted into breast milk, caution should be exercised when Berodual Respimat is administered to nursing mothers.
Clinical data on fertility are neither available for the combination of ipratropium bromide and fenoterol hydrobromide nor for each of the two components of the combination. Non-clinical studies performed with the individual components ipratropium bromide and fenoterol hydrobromide showed no adverse effect on fertility (see section 5.3).
No studies on the effects on the ability to drive and use machines have been performed.
However, patients should be advised that they may experience undesirable effects such as dizziness, tremor, accomodation disorder, mydriasis and blurred vision during treatment with Berodual Respimat. Therefore, caution should be recommended when driving a car or operating machinery. If patients experience the above mentioned side effects they should avoid potentially hazardous tasks such as driving or operating machinery.
Many of the listed undesirable effects can be assigned to the anticholinergic and beta-adrenergic properties of Berodual Respimat. As with all inhalation therapy Berodual Respimat may show symptoms of local irritation. Adverse drug reactions were identified from data obtained in clinical trials and pharmacovigilance during post approval use of the drug.
The most frequent side effects reported in clinical trials were cough, dry mouth, headache, tremor, pharyngitis, nausea, dizziness, dysphonia, tachycardia, palpitations, vomiting, blood pressure systolic increased and nervousness.
Adverse reactions have been ranked 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); not known (cannot be estimated from the available data)
The reported incidences of adverse reactions to Berodual Respimat are based on three multiple-dose clinical trials [mean duration of treatment was 62 days and maximum was 107 days] and one phase IIIb trial comparing Berodual Respimat with Berodual HFA MDI involving 802 patients. Furthermore two phase III studies with Berodual HFA MDI are included resulting in a total of 2009 patients. Most adverse reactions are uncommon (<1/100) or rare (<1/1,000) and are mainly due to the pharmacological effects of the medicinal product. Cough and pharyngitis fall under the category common as local side effects.
| System Organ Class | Frequency |
|---|---|
| Immune System Disorders | |
| Anaphylactic reaction | Rare* |
| Hypersensitivity | Rare* |
| Metabolism and nutricional disorders | |
| Hypokalemia | Rare* |
| Psychiatric Disorders | |
| Nervousness | Uncommon |
| Agitation | Rare |
| Mental disorder | Rare |
| Nervous System Disorders | |
| Headache | Uncommon |
| Tremor | Uncommon |
| Dizziness | Uncommon |
| Hyperactivity | Not known |
| Eye Disorders | |
| Glaucoma | Rare* |
| Intraocular pressure increased | Rare* |
| Accommodation disorder | Rare* |
| Mydriasis | Rare* |
| Vision blurred | Rare* |
| Eye pain | Rare* |
| Corneal oedema | Rare* |
| Conjunctival hyperaemia | Rare* |
| Halo vision | Rare* |
| Cardiac disorders | |
| Tachycardia, heart rate increased | Uncommon |
| Palpitations | Uncommon |
| Arrhythmia | Rare |
| Atrial fibrillation | Rare |
| Supraventricular tachycardia | Rare* |
| Myocardial ischaemia | Rare* |
| Respiratory, Thoracic and Mediastinal Disorders | |
| Cough | Common |
| Pharyngitis | Uncommon |
| Dysphonia | Uncommon |
| Bronchospasm | Rare |
| Throat irritation | Rare |
| Pharyngeal oedema | Rare |
| Laryngospasm | Rare* |
| Bronchospasm paradoxical | Rare* |
| Dry throat | Rare* |
| Gastro-intestinal Disorders | |
| Vomiting | Uncommon |
| Nausea | Uncommon |
| Dry mouth | Uncommon |
| Stomatitis | Rare |
| Glossitis | Rare |
| Gastrointestinal motility disorder | Rare |
| Diarrhoeia | Rare |
| Constipation | Rare* |
| Oedema mouth | Rare* |
| Skin and Subcutaneous Disorders | |
| Urticaria | Rare |
| Rash | Rare |
| Pruritus | Rare |
| Angioedema | Rare* |
| Hyperhidrosis | Rare* |
| Musculoskeletal and connective Tissue Disorders | |
| Myalgia | Rare |
| Muscle spasms | Rare |
| Muscular weakness | Rare |
| Renal and Urinary Disorders | |
| Urinary retention | Rare |
| Investigations | |
| Blood pressure systolic increased | Uncommon |
| Blood pressure diastolic decreased | Rare |
* Side effect has not been observed in any of the selected BERODUAL clinical trials. The estimate is based on the upper limit of its 95% confidence interval, calculated from the totality of treated patients in accordance with the EU SmPC guideline (3/4968 = 0.00060 which relates to “rare”).
Coughing, pharyngitis, throat irritation, hoarseness, taste perversion, glossitis and stomatitis are being considered as local irritation phenomena, mainly due to the inhaled route of administration.
The following reactions were not observed in clinical trials but are known to be associated with medicinal products in the same pharmacological class as the components of Berodual Respimat.
Beta2-agonists: sweating and weakness (muscle) may occur. In rare cases decreased diastolic blood pressure, increased systolic blood pressure, particularly after higher doses, have been observed. Potentially serious hypokalemia and myocardial ischaemia may result from beta2-agonist therapy.
Anticholinergic active substances: supraventricular tachycardia, gastro intestinal motility disturbances and urinary retention may occur. Ocular adverse reactions like visual accommodation disturbances, mydriasis, increased intraocular pressure and eye pain have been reported (see section 4.4).
Hypersensitivity reactions such as angio-oedema of the tongue, lips and face may occur.
As with other inhalation therapy, inhalation induced bronchospasm may occur immediately after dosing.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
Not applicable.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
