Hypersensitivity: Immediate hypersensitivity reactions may occur after administration of COMBIVENT, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm and oropharyngeal oedema.
Paradoxical bronchospasm: As with other inhaled medicines COMBIVENT may result in paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs, COMBIVENT should be discontinued immediately and substituted with an alternative therapy.
Ocular complications: There have been isolated cases of ocular complications (i.e. mydriasis, increased intraocular pressure, narrow-angle glaucoma, eye pain) when aerosolised ipratropium bromide either alone or in combination with an adrenergic beta2- agonist, has come in contact with the eyes.
Eye pain or discomfort, blurred vision, visual halos or colored 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 drops should be initiated and specialist advice sought immediately.
Patients must be instructed in the correct administration of COMBIVENT. Care must be taken not to allow the solution or mist to enter into the eyes. Patients who may be predisposed to glaucoma should be warned specifically to protect their eyes.
It is recommended that COMBIVENT nebuliser solution in unit dose vials (UDV) be administered via a mouth piece. If this is not available and a nebuliser mask is used, it must fit properly.
Systemic effects: In the following conditions COMBIVENT should only be used after careful risk/benefit assessment, especially when doses higher than recommended are used: insufficiently controlled diabetes mellitus, recent myocardial infarction, severe organic heart or vascular disorders, hyperthyroidism, phaeochromocytoma, risk of narrow-angle glaucoma, prostatic hypertrophy or bladder-neck obstruction.
Cardiovascular effects: Cardiovascular effects may be seen with sympathomimetic drugs, including COMBIVENT. There is some evidence from post-marketing data and published literature of rare occurrences of myocardial ischaemia associated with salbutamol. Patients with underlying severe heart disease (e.g.ischaemic heart disease, arrhythmia or severe heart failure) who are receiving salbutamol for respiratory disease, 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 as dyspnoea and chest pain, as they may be of either respiratory or cardiac origin.
Hypokalaemia: Potentially serious hypokalaemia may result from beta2-agonist therapy. Additionally, hypoxia may aggravate the effects of hypokalaemia on cardiac rhythm. In such situations, monitoring of serum potassium levels is recommended.
Gastro-intestinal motility disturbances: Patients with cystic fibrosis may be more prone to gastro-intestinal motility disturbances.
Dyspnoea: In the case of acute, rapidly worsening dyspnoea patients should be advised to consult a physician immediately.
Interference with laboratory tests or other diagnostic measures: The use of COMBIVENT may lead to positive results with regards to salbutamol in tests for nonclinical substance abuse, e.g. in the context of athletic performance enhancement (doping).
Effects on ability to drive and use machines: 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, accommodation disorder, mydriasis and blurred vision during treatment with COMBIVENT. Therefore, caution should be recommended when driving a car or operating machinery.