Duolin Respules 0,5 mg/2,5 mg in 2,5 mL Solution.

DUOLIN RESPULES is indicated for the treatment of reversible bronchospasm associated with obstructive pulmonary disease.

Posology
Do not exceed recommended doses. In the case of acute or rapidly worsening dyspnoea, a medical practitioner should be consulted immediately (see section 4.4).
Adults (including elderly patients) and children over the age of 12 years
Treatment of acute symptoms
One unit dose (one respule) provides prompt relief in most cases. In severe cases, if an attack has not been relieved by one respule, two respules may be required. In this situation, the patient should seek prompt medical attention.
Maintenance treatment
One respule three or four times a day.
Paediatric population
Children under the age of 12 years
There is no experience in the use of DUOLIN RESPULES in children under the age of 12 years (see section 4.3).
Method of administration
Oral inhalation. DUOLIN RESPULES solution for inhalation may be administered via a suitable nebuliser or an intermittent positive pressure ventilator. The respules should not be taken orally (swallowed) or administered parenterally (see 'Instructions for use').
Instructions for use
1. Prepare the nebuliser according to the instructions of the manufacturer or medical practitioner.
2. Tear one respule from the strip.
3. Open the respule by twisting the top.
4. Squeeze the contents into the nebuliser reservoir.
5. Assemble the nebuliser and use as directed.
6. Discard any solution left in the nebuliser, as well as any partly used, opened respules.
7. Clean the nebuliser according to the manufactureru2019s instructions. Since DUOLIN RESPULES contains no preservatives, it is important that the contents are used immediately after opening and that a fresh respule is used for each administration to avoid microbial contamination. Partly used, open or damaged respules should be discarded. DUOLIN RESPULES should be used undiluted. It is strongly recommended that DUOLIN RESPULES solution for inhalation should not be mixed with other medicines in the same nebuliser reservoir.

DUOLIN RESPULES is contraindicated in:
u2022 Patients with known hypersensitivity to salbutamol sulphate, ipratropium bromide, atropine or its derivatives, or to any of the excipients in DUOLIN RESPULES (see section 6.1),
u2022 Patients with tachydysrhythmias,
u2022 Patients with hypertrophic obstructive cardiomyopathy,
u2022 Children under 12 years, as safety has not been established (see section 4.2).

Do not exceed the recommended maximum doses. Following administration of DUOLIN RESPULES solution for inhalation, immediate hypersensitivity reactions may occur, as demonstrated by less frequent cases of urticaria, rash, angioedema, oropharyngeal oedema and bronchospasm (see section 4.8). There have been reports of ocular complications (i.e. blurring of vision, mydriasis, increased intraocular pressure, narrow-angle glaucoma and eye pain) (see section 4.8) when aerosolised ipratropium bromide, either alone, or in combination with a u03b22-agonist, as in DUOLIN RESPULES, has escaped into the eyes. DUOLIN RESPULES must be used correctly, by giving proper instruction to patients. Care must be taken to avoid eye exposure to DUOLIN RESPULES solution or mist. It is recommended that administration of the nebulised solution be done via a mouthpiece. A nebuliser mask that fits properly should be used if a mouthpiece is not available. Patients who may be susceptible to glaucoma should be warned specifically to protect their eyes. Signs of acute narrow-angle glaucoma, in association with red eyes from conjunctival congestion and corneal oedema, may include eye pain or discomfort, blurred vision, visual halos or coloured images. Treatment should be commenced with miotic drops and specialist advice should be obtained immediately if any combination of these ocular symptoms develop. Fatalities have been reported following excessive use of inhaled u03b22-agonists. DUOLIN RESPULES should be given with caution in patients with:
u2022 Recent myocardial infarction.
u2022 Cardiovascular disorders, such as ischaemic heart disease, severe cardiac decompensation, dysrhythmias, severe hypertension, since these patients may require special care and supervision, with particular emphasis on dosage limits.
u2022 Hyperthyroidism, since patients with uncontrolled hyperthyroidism are usually more sensitive to u03b22-agonists, as contained in DUOLIN RESPULES.
u2022 Diabetes mellitus, since close blood glucose monitoring is recommended due to the increased risk of hyperglycaemia (see section 4.8). In common with other u03b2-adrenoceptor agonists, salbutamol, as contained in DUOLIN RESPULES, can induce reversible metabolic changes such as increased blood glucose levels. Diabetic patients may be unable to compensate for the increase in blood glucose, and the development of ketoacidosis has been reported. Concurrent administration of corticosteroids can exaggerate this effect.
u2022 Phaeochromocytoma. Due to its ipratropium bromide content, DUOLIN RESPULES should be administered with caution in patients with:
u2022 Urinary retention, bladder-neck obstruction and prostatic hypertrophy (see section 4.8).
u2022 Glaucoma (narrow-angle) u2013 an acute attack may be precipitated if the inhalation is inadvertently sprayed into the eyes. From post-marketing data and published literature, there is some evidence of incidences of myocardial ischaemia associated with salbutamol, as contained in DUOLIN RESPULES. Patients receiving salbutamol for respiratory disease, who also suffer from severe underlying heart disease (e.g. ischaemic heart disease, severe heart failure or arrhythmia), should be warned to seek medical advice if chest pain or other symptoms of worsening heart disease are experienced. Attention should be paid to assessment of symptoms, such as chest pain and dyspnoea, as they may be of either cardiac or respiratory origin. The u03b22-agonist in DUOLIN RESPULES may lead to potentially serious hypokalaemia. In severe airway obstruction, particular caution is advised, as the hypokalaemic effect may be potentiated by simultaneous treatment with xanthine derivatives, diuretics and steroids (see section 4.5). Additionally, the effects of hypokalaemia on cardiac rhythm may be aggravated by hypoxia and acidosis. Hypokalaemia may result in an increased susceptibility to dysrhythmias in patients receiving digoxin (see section 4.5 and section 4.8). It is recommended that serum potassium levels are monitored in such situations. Patients with cystic fibrosis may be more prone to gastrointestinal motility disturbances (see section 4.8). A medical practitioner should be consulted immediately in the case of acute, rapidly worsening dyspnoea. In addition, if a reduced response becomes obvious, the patient should be warned to seek medical advice. The patientu2019s therapy plan should be reviewed by a medical practitioner, if higher than recommended doses of DUOLIN RESPULES are required to control symptoms. Paradoxical bronchospasm has been reported following bronchodilator therapy with an immediate increase in wheezing and shortness of breath after dosing (see section 4.8). In addition, regular use of inhaled, short-acting u03b22-agonists, such as salbutamol (as opposed to on an as-needed basis), has been demonstrated to increase airway hyperresponsiveness to various stimuli and to lead to the possible development of tolerance to the bronchoprotective effect. Paradoxical bronchospasm responds to a rapid-acting inhaled bronchodilator and should be treated promptly. DUOLIN RESPULES should be stopped immediately, the patient should be assessed and alternative treatment instituted if necessary. Lactic acidosis has been reported in association with high therapeutic doses of intravenous and nebulised short-acting beta-agonist therapy, mainly in patients being treated for an acute exacerbation of bronchospasm in severe asthma or chronic obstructive pulmonary disease (see section 4.8 and section 4.9). Increase in lactate levels may lead to dyspnoea and compensatory hyperventilation, which could be misinterpreted as a sign of asthma treatment failure and lead to inappropriate intensification of short-acting beta-agonist treatment. It is therefore recommended that patients are monitored for the development of elevated serum lactate and consequent metabolic acidosis in this setting (see section 4.9). When testing for non-clinical substance abuse, e.g. in the context of athletic performance enhancement (doping), the use of salbutamol as in DUOLIN RESPULES, may lead to positive results. Porphyria Safety has not been established in porphyria.

u2022 Concurrent use of other anticholinergics or other medicines with anticholinergic effects may potentiate the effects of ipratropium bromide in DUOLIN RESPULES or vice versa.
u2022 Concurrent use of u03b2-blockers may result in mutual inhibition of therapeutic effects.
u2022 The use of additional beta-agonists, xanthine derivatives and corticosteroids may enhance the effect of DUOLIN RESPULES. The concurrent use of xanthine derivatives (e.g. theophylline) with u03b2-adrenergic agonists as well as systemically absorbed anticholinergics, may increase the severity of the side-effects due to DUOLIN RESPULES (see section 4.4).
u2022 Diuretics (non-potassium sparing), digitalis glycosides (digoxin), methylxanthines and corticosteroids may increase the hypokalaemic effect of u03b22-agonists, as contained in DUOLIN RESPULES, and lead to an increased disposition to dysrhythmias in patients treated with digitalis glycosides (digoxin). Monitor serum potassium levels. Potentiation of u03b2-agonist induced hypokalaemia should be taken into consideration, particularly in patients with severe airway obstruction (see section 4.4).
u2022 Since the action of the u03b22-adrenergic agonist in DUOLIN RESPULES may be enhanced in patients taking monoamine oxidase inhibitors or tricyclic antidepressants, DUOLIN RESPULES should be administered with caution.
u2022 An increase in susceptibility to the cardiovascular effects of the u03b2-agonist in DUOLIN RESPULES may be caused by inhalation of halogenated hydrocarbon anaesthetics, such as halothane, trichloroethylene and enflurane.

Pregnancy
Safety in pregnancy has not been established.
Breastfeeding
Safety in breastfeeding has not been established.
Fertility
No data available.

No studies have been performed on the effects on the ability to drive and the use of machines. However, during treatment with DUOLIN RESPULES, patients should be advised that they may experience undesirable effects such as accommodation disorder, dizziness, blurred vision and mydriasis (see section 4.8). If patients experience any of these side-effects, potentially hazardous tasks, such as driving or operating machines, should be avoided.

Summary of the safety profile
The anticholinergic and u03b22-sympathomimetic properties of DUOLIN RESPULES are responsible for several of the listed undesirable effects. DUOLIN RESPULES may show symptoms of local irritation. The most frequent side-effects reported were headache, throat irritation, cough, dry mouth, gastrointestinal motility disorders (including constipation, diarrhoea and vomiting), nausea and dizziness.
Tabulated list of adverse reactions
MedDRA system organ class
Frequency
Side effects
Infections and infestations
Frequency unknown
Infection and inflammation in children including viral infection, rhinitis, tonsillitis and gastroenteritis.
Immune system disorders
Less frequent
Hypersensitivity reactions (see section 4.4) including paradoxical bronchospasm, angioedema of the tongue, lips and face, oropharyngeal oedema, urticaria, rash, hypotension and collapse, anaphylactic reaction.
Metabolism and nutritional disorders
Less frequent
Hyperglycaemia (with large doses), hypokalaemia (after large doses) leading to dysrhythmias (see 'Cardiac disorders' and section 4.4).
Frequency unknown
Lactic acidosis (see section 4.4).
Psychiatric disorders
Less frequent
Agitation, restlessness, anxiety, sleep disturbances, nervousness, mental disorder.
Nervous system disorders
Less frequent
Tremor.
Frequent
Dizziness, headache.
Eye disorders
Less frequent
Mydriasis, increased intraocular pressure, narrow-angle glaucoma, eye pain, blurred vision, visual halos or coloured images when solution for inhalation has escaped into eyes in patients with narrow-angle glaucoma (see section 4.4), accommodation disorder, corneal oedema, conjunctival hyperaemia.
Cardiac disorders
Less frequent
Palpitations, tachycardia, dysrhythmias, atrial fibrillation, myocardial ischaemia, supraventricular tachycardia.
Vascular disorders
Less frequent
Increases in blood pressure, increased systolic blood pressure, decreased diastolic blood pressure (see section 4.4).
Respiratory, thoracic and mediastinal disorders
Frequent
Dysphonia, throat irritation.
Less frequent
Bronchospasm (cough, shortness of breath, chest tightness, wheezing) (see section 4.4), laryngospasm, pharyngeal oedema (see 'Immune system disorders'), paradoxical bronchospasm (see section 4.4), dry throat.
Gastrointestinal disorders
Frequent
Dry mouth, nausea, vomiting, constipation, gastrointestinal motility disorder (e.g. diarrhoea).
Less frequent
Dyspepsia, abdominal pain, mouth oedema (see 'Immune system disorders'), stomatitis.
Skin and subcutaneous tissue disorders
Less frequent
Rash, urticaria, pruritus, sweating/hyperhidrosis, skin reactions.
Musculoskeletal and connective tissue disorders
Frequent
Skeletal muscle tremor.
Less frequent
Muscle cramps, muscle spasms, muscular weakness, myalgia.
Renal and urinary disorders
Less frequent
Urinary retention (see section 4.4).
General disorders and administrative site conditions
Less frequent
Asthenia.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on the SAHPRA website, or to Cipla Medpro (Pty) Ltd. by email: [email protected] or telephone: 080 222 6662 (toll free).

Symptoms
Expected symptoms of overdose are primarily related to salbutamol and are those of excessive u03b2-adrenergic stimulation. The most prominent effects are headache, hyperglycaemia (blurred vision, increased hunger or thirst, increased urination), hypotension, hypertension, metabolic acidosis (shortness of breath), hypokalaemia, skeletal muscle tremor, tachycardia, palpitations, widening of the pulse pressure, anginal pain, dysrhythmias, and flushing (see section 4.4 and section 4.8). Metabolic acidosis has been observed with an overdose of salbutamol, including lactic acidosis, which has been reported in association with high therapeutic doses as well as overdoses of short-acting beta-agonist therapy, therefore monitoring for elevated serum lactate and consequent metabolic acidosis (particularly if there is persistence or worsening of tachypnoea despite resolution of other signs of bronchospasm, such as wheezing) may be indicated in the setting of overdose. (see section 4.4 and section 4.8). Expected symptoms of overdose with ipratropium bromide (such as visual accommodation disorders/disturbances and dry mouth) are mild and transient in nature, in view of the wide therapeutic range and due to its poor systemic absorption after either inhalation, topical or oral administration. Effects of overdose are therefore likely to be related to the salbutamol component of DUOLIN RESPULES.
Treatment of overdosage
Treatment with DUOLIN RESPULES should be discontinued. Acid base and electrolyte monitoring should be considered. Administration of sedatives, tranquillisers and in severe cases, intensive therapy. Specific antidotes are u03b2-receptor blockers, preferably u03b21-selective (cardio selective u03b2-blocking medicines). However, the possibility of an increased risk of bronchial obstruction must be taken into consideration. The dose should therefore be carefully adjusted in patients suffering from bronchial asthma or with a history of bronchospasm. Further treatment is symptomatic and supportive.