Adco-Combineb Inhalant Solution

ADCO-COMBINEB is indicated for the treatment of reversible bronchospasm associated with obstructive pulmonary disease.

Hypersensitivity to any of the ingredients.
Hypersensitivity to atropine or its derivatives.
Tachyarrhythmias.
Hypertrophic Obstructive Cardiomyopathy.
Safety in children under 12 years has not been established (see DOSAGE AND DIRECTION FOR USE).

Do not exceed the recommended maximum doses.
Fatalities have been reported following excessive use of inhaled u00df 2 agonists.
u00df 2 agonists should be given with caution in patients with:-
u2022 Cardiovascular disorders - such as ischaemic heart disease, severe cardiac decompensation, arrhythmias, severe hypertension - may require special care and supervision, with particular emphasis on dosage limits.
u2022 Hyperthyroidism - patients with uncontrolled hyperthyroidism are unusually more sensitive to beta-2-agonists.
u2022 Diabetes mellitus u2013 close blood glucose monitoring may be required.

Ipratropium bromide should be administered with caution in patients with:-
u2022 Urinary retention, bladder neck obstruction and prostatic hypertrophy
u2022 Glaucoma (narrow angle) u2013 An acute attack may be precipitated if the inhalation is inadvertently sprayed into the eyes.
Porphyria: Safety has not been established.
Immediate hypersensitivity reactions may occur after administration of ADCO-COMBINEB solution for inhalation (see Side u2013 effects).
Paradoxical bronchospasm has been reported following bronchodilator therapy. In addition, regular use of inhaled, short-acting u00df 2 agonists such as salbutamol (as opposed to on an as-needed basis) has been shown to increase airway hyperresponsiveness to various stimuli and leads to the possible development of tolerance to the bronchoprotective effect.
There have been reports of ocular complications (see Side- effects), when aerosolised ipratropium bromide either alone, or in conjunction with a u00df 2-receptor agonist has escaped into 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 u2013 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 use of ADCO-COMBINEB. Care must be taken not to expose the eyes to the solution or mist of ADCO-COMBINEB. It is recommended that the nebulised solution be administered via a mouth u2013 piece. If this is not available and a nebuliser mask is used, it must fit properly. Patients who may be predisposed to glaucoma should be warned specifically to protect their eyes.
In the following conditions ADCO-COMBINEB should only be used after careful risk/benefit assessment, especially where doses higher than recommended are used: Insufficiently controlled diabetes mellitus, recent myocardial infarction and/or severe organic heart vascular disorders, hyperthyroidism, phaeochromocytoma, risk of narrow-angle glaucoma, prostatic hypertrophy or bladder-neck obstruction. In the case of acute, rapidly worsening dyspnoea a medical practitioner should be consulted immediately. If higher than recommended doses of ADCO-COMBINEB are required to control symptoms, the patientu2019s therapy plan should be reviewed by a medical practitioner.
Potentially serious hypokalaemia may result from u00df 2 -receptor agonist therapy. Particular caution is advised in severe airway obstruction, as the hypokalaemic effect may be potentiated by concomitant treatment with xanthine derivatives, steroids and diuretics. Additionally, hypoxia and acidosis may aggravate the effects of hypokalaemia on cardiac rhythm. Hypokalaemia may result in an increased susceptibility to arrhythmias in patients receiving digoxin.
Patients with cystic fibrosis may be prone to gastro-intestinal motility disturbances.

u2022 Concurrent use of other anticholinergics or other medicines with anticholinergic effects may potentiate the effects of ipratropium bromide or vice-versa.
u2022 Concurrent use of beta u2013 blockers may result in mutual inhibition of therapeutic effects.
u2022 Diuretics (non-potassium sparing), digitalis glycosides, methylxanthines, corticosteriods u2013 may increase the hypokalaemic effect of u00df 2 agonists and lead to an increased disposition to arrhythmias in patients treated with digitalis glycosides. Monitor serum potassium levels.
u2022 Beta u2013 adrenergic agonists should be administered with caution in patients taking monoamine oxidase inhibitor or tricyclic antidepressants.
u2022 Inhalation of halogenated hydrocarbon anaesthetics such as halothane, trichloroethylene and enflurane may increase the susceptibility to cardiovascular effects of beta-agonists.

Safety in pregnancy and lactation has not been established.

Dizziness, tremor or agitation may affect the ability to drive a vehicle or to operate machinery.

Gastro u2013 intestinal system: Frequent: Dry mouth. Less Frequent: Nausea, vomiting, dyspepsia, abdominal pain, constipation.
Skin and appendages: Less Frequent: Rash, urticaria, pruritus.
Respiratory system: Less Frequent: Bronchospasm (cough, shortness of breath, chest tightness, wheezing).
Central Nervous System: Less Frequent: Dizziness, headache, agitation, restlessness, anxiety, sleep disturbances, nervousness.
Musculoskeletal system: Frequent: Skeletal muscle tremor. Less Frequent: Muscle cramps.
Cardiovascular system: Less Frequent: Palpitations, tachycardia, arrhythmias, increases in blood pressure.
Genitourinary system: Less Frequent: Urinary retention.
Metabolic system: Less Frequent: Hyperglycaemia (with large doses). Potentially serious hypokalaemia has been reported after large doses. Hypokalaemia may lead to arrhythmias.
Vision: Less Frequent: Mydriasis, increased intraocular pressure, narrow u2013 angle glaucoma, eye pain, blurred vision, visual halos or coloured images when solution for inhalation has escaped into the eyes in patients with narrow-angle glaucoma.
Hypersensitivity reaction: Less Frequent: Hypersensitivity reactions have occurred, including paradoxical bronchospasm, angioedema, oropharyngeal oedema, urticaria, rash, hypotension and collapse.
Other: Frequent: Dysphonia. Less Frequent: Sweating. Infection and inflammation have been reported to occur in children and includes viral infection, rhinitis, tonsillitis and gastroenteritis.

Expected symptoms of overdose are primarily related to salbutamol and are those of excessive beta-adrenergic stimulation. The most prominent effects are headache, hyperglycaemia (blurred vision, increased hunger or thirst, increased urination), hypotension, hypertension, metabolic acidosis (shortness of breath), skeletal muscle tremor, tachycardia, palpitation, anginal pain, arrhythmias and flushing. Expected symptoms of overdose with ipratropium bromide (such as dry mouth and visual accommodation disturbances) are mild and transient.
Treatment of overdose: Administration of sedatives, tranquillizers. Beta-receptor blockers, preferably beta 1-selective, are suitable as specific antidotes. However, a possible increase in bronchial obstruction must be taken into account and the dose should be adjusted carefully in patients suffering from bronchial asthma. FURTHER TREATMENT IS SYMPTOMATIC AND SUPPORTIVE.