BERODUAL Solution

គុណភាពព្យាបាល៖

ជាប្រភេទឱសថធ្វើឱ្យទងសួតរីកធំ សម្រាប់ការពារ និងព្យាបាលវិបត្តិផ្លូវដង្ហើម៖ ហឺត រលាកទងសួតរ៉ាំរ៉ៃ ហើមសួត

កម្រិត និងរបៀបប្រើ៖ ត្រូវអនុវត្តតាមវេជ្ជបញ្ជា និងតាមសភាពជំងឺមួយៗ៖

+មនុស្សពេញវ័យ និងក្មេងអាយុលើសពី ១២ឆ្នាំ៖

 - ជំងឺដំណាក់កាលហឺតស្រួចស្រាវ៖ ប្រើ ១ម.ល (២០តំណក់) ករណីធ្ងន់ធ្ងរត្រូវប្រើកម្រិតខ្ពស់ រហូតដល់ ២.៥ម.ល (៥០តំណក់)

 - ករណីធ្ងន់ធ្ងរពិសេស ត្រូវប្រើកម្រិតខ្ពស់រហូតដល់ ៤.០ម.ល (៨០តំណក់) ក្រោមការត្រួតពិនិត្យពីគ្រូពេទ្យ

 - ការព្យាបាលឆ្លាស់គ្នា និងរយៈពេលយូរ៖ ប្រើម្តង ១ ទៅ ២ម.ល (២០ ទៅ ៤០តំណក់) ៤ដងក្នុង១ថ្ងៃ

 - ករណីការកន្ត្រាក់ជាប់ធ្វើឱ្យទងសួតរួមតូច៖ ០.៥ម.ល

+ក្មេងអាយុ ៦ ទៅ ១២ឆ្នាំ៖ ជំងឺដំណាក់កាលហឺតស្រួចស្រាវ ០.៥ម.ល ទៅ ១ម.ល (១០ ទៅ ២០តំណក់)

 - ករណីធ្ងន់ធ្ងរ ២ម.ល (៤០តំណក់) ករណីធ្ងន់ធ្ងរពិសេស ៣ម.ល (៦០តំណក់)

 - ការព្យាបាលឆ្លាស់គ្នា និងរយៈពេលយូរ៖ ប្រើម្តង ០.៥ម.ល ទៅ ១ម.ល (១០ ទៅ ២០តំណក់) ៤ដងក្នុង១ថ្ងៃ

+ក្មេងអាយុ ៦ឆ្នាំ៖ ០.៥ម.ល (១០តំណក់) ៣ដង ក្នុង១ថ្ងៃ ក្រោមការត្រួតពិនិត្យពីគ្រូពេទ្យ

 - ការព្យាបាលគួរចាប់ផ្តើមពីកម្រិតទាប ត្រូវលាយជាមួយសេរ៉ូមប្រៃពី ៣ ទៅ ៤ម.ល

 - មិនត្រូវលាយជាមួយទឹកសម្រាប់លាយ

 - កម្រិតប្រើអាចឡើងវិញ ក្រោយចន្លោះ ៤ម៉ោងយ៉ាងតិច។

BERODUAL is a bronchodilator for the prevention and treatment of symptoms in chronic obstructive airway disorders with reversible airflow limitation such as bronchial asthma and especially chronic bronchitis with or without emphysema. Concomitant anti-inflammatory therapy should be considered for patients with bronchial asthma and steroid responsive chronic obstructive pulmonary disease (COPD).

Dosage and administration and instruction for use

Dosage and administration

Treatment should be initiated and administered under medical supervision. Home based treatment can be recommended in patients when a low dose rapid acting beta-agonist bronchodilator such as Berodual pressurized inhalation, solution has been insufficient in providing relief after consultation with an experienced physician. It can also be recommended in patients who are in need for nebuliser treatment for other reasons e.g. handling issues of pressurized inhalation, solution or requirement of higher doses in experienced patients.

The treatment with the nebuliser solution should always be started with the lowest recommended dose. The dosage should be adapted to the individual requirements and tailored according to the severity of the acute episode. Administration should be stopped when sufficient symptom relief is achieved. The following dosages are recommended:

Adults (including elderly) and adolescents ≥12 years of age:

Acute episodes of bronchospasm

Depending on the severity of the acute episode doses ranging between 261mcg ipratropium bromide/500mcg fenoterol hydrobromide (i.e. 1mL=20drops) and 652.5mcg ipratropium bromide/1250mcg fenoterol hydrobromide (i.e. 2.5mL=50drops) may be used. In exceptional particular severe cases doses up to 1044mcg ipratropium bromide/2000mcg fenoterol hydrobromide (i.e. 4mL=80drops) may be used.

Children 6-12 years:

Acute asthma episodes

Depending on the severity of the acute episode and age does ranging between 130.5mcg ipratropium bromide/250mcg fenoterol hydrobromide (i.e. 0.5mL=10 drops) and 522mcg ipratropium bromide/1000mcg fenoterol hydrobromide (i.e. 2mL=40 drops) may be used.

Children < 6 years (below 22kg body weight):

Because there is limited information in this age group the following dose is recommended to be given under medical supervision only:

About 26.1mcg ipratropium bromide/50mcg fenoterol hydrobromide (i.e. 0.1mL=2 drops) /kg up to a maximum of 0.5mL(=10drops).

Instructions for use

The nebuliser solution is intended only for inhalation with suitable neblising devices and must not be taken orally.

The recommended dose is to be diluted with physiological saline to a final volume of 3-4mL and nebulised and inhaled until sufficient symptom relief is achieved.

BERODUAL nebulise solution may, however, not be diluted with distilled water.

The solution should be freshly diluted each time before use: any residual diluted solution should be discarded.

The diluted solution should be inhaled directly after preparation of the solution.

The duration of inhalation can be controlled by the dilution volume.

BERODUAL nebuliser solution can be administered using a range of commercially available neblising devices. The lung and systemic drug exposure is dependent on the nebuliser used and may be higher than with BERODUAL pressurized inhalation, solution depending on the efficiency of the device.

Where wall oxygen is available the solution is best administered at a flow rate of 6-8 litres/minute.

The instructions provided by the manufacturer of the nebulising device for proper care, maintenance and cleaning of the equipment should be followed.

អ្នកធ្លាប់ងាយមានប្រតិកម្មជាមួយសារធាតុផ្សំណាមួយជាមួយឱសថនេះ។

ការរីកសាច់ដុំបេះដូង ចង្វាក់បេះដូងដើរលឿន មិនទៀងទាត់ខុសពីធម្មតា។

In patients with known hypersensitivity to fenoterol hydrobromide or atropine-like substances or to any of the excipients of the product.

In patients with hypertrophic obstructive cardiomyopathy and tachyarrhythmia.

ញ័រសាច់ដុំ រោគសរសៃប្រសាទ ស្ងួតមាត់ជារឿយៗអាចកើតមានឈឺក្បាល វិលមុខចង្វាក់បេះដូងដើរលឿន និងញ័រទ្រូង។ បើមានផលរំខានខ្លះទៀតដែលកើតមានក្រៅពីការរៀបរាប់ខាងលើនេះត្រូវពិគ្រោះជាមួយគ្រូពេទ្យ។

ការប្រើលើសកម្រិតបណ្តាលឱ្យចង្វាក់បេះដូងដើរលឿន ញ័រទ្រូង ញ័រខ្លួន សម្ពាធឈាមឡើង សម្ពាធឈាមចុះ ចុកទ្រូង ចង្វាក់បេះដូងដើរមិនទៀងទាត់ គ្រុន រងា ស្ងួតមាត់ វិបត្តិគំហើញ។

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.

Immune system disorders: anaphylactic reaction, hypersensitivity

Metabolism and nutritional disorders: hypokalaemia

Psychiatric disorders: nervousness, agitation, mental disorder

Nervous system disorders: headache, tremor, dizziness

Eye disorders: glaucoma, intraocular pressure increased, accommodation disorder, mydriasis, vision blurred, eye pain, corneal oedema, conjunctival hyperaemia, halo vision

Cardiac disorders: tachycardia, heart rate increased, palpitations, arrhythmia, atrial fibrillation, supraventricular tachycardia, myocardial ischaemia

Respiratory, thoracic and mediastinal disorders: cough, pharyngitis, dysphonia, bronchospasm, throat irritation, pharyngeal oedema, laryngospasm, bronchospasm paradoxical, dry throat

Gastrointestinal disorders: vomiting, nausea, dry mouth, stomatitis, glossitis, gastrointestinal motility disorder, diarrhoea, constipation, oedema mouth

Skin and subcutaneous tissue disorders: urticaria, rash, pruritus, angioedema, hyperhidrosis

Musculoskeletal and connective tissue disorders: muscular weakness, muscle spasms, myalgia

Renal and urinary disorders: urinary retention

Investigations: blood pressure systolic increased, blood pressure diastolic decreased.

The chronic co-administration of BERODUAL with other anticholinergic drugs has not been studies. Therefore, the chronic co-administration of BERODUAL with other anticholinergic drugs is not recommended.

Other beta-adrenergics and anticholinergics and xanthine derivatives (e.g. theophylline) may increase the adverse reactions.

A potentially serious reduction in bronchodilatation may occur during concurrent administration of beta-blockers.

Hypokalaemia 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.

Hypokalaemia may result in an increased susceptibility to arrhythmias in patients receiving digoxin. Additionally, hypoxia may aggravate the effects of hypokalaemia on cardiac rhythm. It is recommended that serum potassium levels are 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 beta-adrenergic agonists may be enhanced.

Inhalation of halogenated hydrocarbon anaesthetics such as halothane, trichloroethylene and enflurane may increase the susceptibility on the cardiovascular effects of beta-agonists.

ស្រ្តីមានផ្ទៃពោះ និងបំបៅកូនមុនប្រើឱសថនេះត្រូវពិគ្រោះជាមួយគ្រូពេទ្យ

Pregnancy

Preclinical data, combined with available experience in humans have shown no evidence of adverse effects in pregnancy of fenoterol or ipratropium. Nonetheless, the usual precautions regarding the use of drugs during pregnancy, especially during the first trimester, should be exercised.

The inhibitory effect f fenoterol on uterine contraction should be taken into account.

Lactation

Non-clinical studies have shown that fenoterol hydrobromide, is excreted into breast milk. It is unknown 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 aerosol. However, caution should be exercised when BERODUAL is administered to a nursing woman.

- ការប្រើរយៈពេលយូរ

- ត្រូវព្យាបាលឱ្យបានទៀងទាត់ ចំពោះអ្នកជំងឺហឺត ដោយសារត្បៀតទងសួត

- ត្រូវប្រើក្រោមការត្រួតពិនិត្យរបស់គ្រូពេទ្យចំពោះ sympathomimetic bronchodilators ដទៃទៀត

- ជំងឺទងសួតរីកធំ ជំងឺទឹកនោមផ្អែម ជំងឺក្រិនសាច់ដុំបេះដូងថ្មីៗ វិបត្តិសរីរាង្គបេះដូង ឬសរសៃឈាមធ្ងន់ធ្ងរ អរម៉ូនទីរ៉ូអ៊ីត ឡើង Phaeochromocytoma

- ធ្វើឱ្យជាតិប៉ូតាស្យូមក្នុងឈាមថយចុះ

- អ្នកជំងឺរីកក្រពេញប្រូស្តាត ឬស្ទះប្លោកនោម ឬជំងឺទឹកដក់ក្នុងកែវភ្នែក

- ស្ត្រីមានផ្ទៃពោះ និងបំបៅកូន

(See the package insert about the details.)

<strong>Hypersensitivity</strong>

Paradoxical bronchospasm

Ocular complications

Systemic effects

Cardiovascular effects

Hypokalaemia

Gastro-intestinal motility disturbances

Dyspnoea

Prolonged use

Doping warning

Excipients

Pharmacotherapeutic group: Adrenergics in combination with anticholinergics for obstructive airway diseases.

BERODUAL contains two active bronchodilating ingredients: Ipratropium bromide, exhibiting an anticholinergic effect and fenoterol hydrobromide a beta-adrenergic agent.

Ipratropium bromide is a quaternary ammonium compound with anticholinergic (parasympatholytic) properties. In preclinical studies, it inhibits vagally mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released from the vagus nerve. Anticholinergics prevent the increase in intracellular concentration of Ca++ which is caused by interaction of acetylcholine with the muscarinic receptor on bronchial smooth muscle. Ca++ release is mediated by the second messenger system consisting of IP3 (inositol triphosphate) and DAG (diacylglycerol).

The bronchodilatation following inhalation of ipratropium bromide is primarily a local, site-specific effect, not a systemic one.

Non-clinical and clinical evidence suggest no deleterious effect of ipratropium bromide on airway mucous secretion, mucociliary clearance or gas exchange.

Fenoterol hydrobromide is a direct acting sympathomimetic agent, selectively stimulating beta2-receptors in the therapeutic dose range. The stimulation of beta1-receptors comes into effect at a higher dose range. Occupation of beta2- receptors activates adenyl cyclase via a stimulatory Gs-protein.

The increase in cyclic AMP activates protein kinase A which then phosphorylates target proteins in smooth muscle cells. This in turn leads to the phosphorylation of myosin light chain kinase, inhabitation of phosphoinositide hydrolysis, and the opening of large-conductance calcium-activated potassium channels.

Fenoterol hydrobromide relaxes bronchial and vascular smooth muscle and protects against bronchoconstricting and pro-inflammatory mediators from mast cells is inhibited. Further, an increase in mucociliary clearance has been demonstrated after administration of doses of fenoterol (0.6mg).

Higher plasma concentrations, which are more frequently achieved with oral, or even more so, with intravenous administration inhibit uterine motility. Also at higher doses, metabolic effects are observed: Lypolysis, glycogenolysis, hyperglycaemia and hypokalaemia, the latter caused by increased K+-uptake primarily into skeletal muscle.

Beta-adrenergic effects on the heart such as increase in heart rate and contractility are caused by the vascular effects of fenoterol, cardiac beta2- receptor stimulation, and at supratherapeutic doses, by beta1-receptor stimulation. As with other beta-adrenergic agents, QTc prolongations have been reported. For fenoterol pressurized inhalation, solutions these were discrete and observed at doses higher than recommended. However, systemic exposure after administration with nebulisers (nebuliser solution) might be higher than with recommended pressurized inhalation, solution does. The clinical significance has not been established. Tremor is a more frequently observed effect of beta-agonists, Unlike the effects on the bronchial smooth muscle, the systemic effects on skeletal muscle of beta-agonists are subject to the development of tolerance.

Concurrent use of these two active ingredients dilates the bronchi by affecting different pharmacological sites of action. The two active substances thus complement each other in their spasmolytic action on the bronchial muscles and allow a broad therapeutic use i the field of bronchopulmonary disorders associated with constriction of the respiratory tract. The complementary action is such that only a very low proportion of the beta-adrenergic component is needed to obtain the desired effect, facilitating individual dosage suited to each patient with a minimum of adverse reactions.