英文药名: Ventolin Nebules(Salbutamol Nebulizer Solution)

中文药名: 沙丁胺醇雾化溶液

生产厂家: 葛兰素史克
药品名称
常用名: 羟甲叔丁肾上腺素, 喘乐宁, 喘特宁, 硫酸阿布叔醇, 硫酸柳丁氨醇, 舒喘灵, 沙丁胺醇, 嗽必妥, 酸嗽必妥, 硫酸索布氨, 舒喘宁, 硫酸沙丁胺醇, 全乐宁, 喘宁碟, 全特宁
英文名: Salbutamol, Albuterol sulfate, AH 3365, Broncovaleas, Ventolin, Proventil
规格　　
口服液 0.4mg/mlX250ml;
雾化溶液 0.5mg/ml，1mg/ml，2mg/1X2.5ml;
呼吸液体 0.5%X10ml;
气雾剂 100mcgX60喷；
微粉吸入剂 200mcgX60喷。
药理作用　
为选择性β2受体激动剂能选择性激动支气管平滑肌的β2受体，有较强的支气管扩张作用。于哮喘患者，其支气管扩张作用至少与异丙肾上腺素相等。抑制肥大细胞等致敏细胞释放过敏反应介质亦与其支气管平滑肌解痉作用有关。对心脏的β1受体的激动作用较弱，故其增加心率作用仅及异丙肾上腺素的1/10。 选择性激动支气管平滑肌上β2受体，松驰支气管平滑肌，解除支气管痉挛，对支气管扩张作用强，对心脏β1受体作用弱，是目前较为安全，最常用的平喘药。
药动学　
口服易吸收，但存在肝脏首过代谢，约在2．5小时血浓度达峰值，吸收药量的76%在3天内由尿排出，4%由粪便排出，半衰期为2．7-5小时。本品吸入由支气管吸收，维持3-6小时，吸收药量72%由尿排出，约10%由粪便排泄，半衰期为3．8小时左右。
适应症　
平喘，适用于防治支气管哮喘，喘息性支气管炎及肺气肿。
用法用量　　
喘息发作用雾化，注射很少用，预防发作则口服，成人口服每次2-4mg，每日3-4次，小儿每天1-2mg，分3-4次；气雾吸入，发作时1-2喷，约为0.10-0.20mg，可在4小时后反复，24小时内不超过6-8次。
任何疑问，请遵医嘱！
禁忌症　
妊娠三个月内孕妇。
不良反应　
偶有恶心，神经系统兴奋性增高，震颤，心率增快或心悸。
注意事项　　
1、久用易产生耐药性。
2、孕妇慎用。
3、心功能不全、高血压、糖尿病、甲亢患者慎用。
药物相互作用　　
不宜与肾上腺素能受体阻滞剂同时使用。

Ventolin Nebules 5mg/2.5ml Nebuliser SolutionSalbutamol
1. NAME OF THE MEDICINAL PRODUCT
Ventolin Nebules 5mg/2.5ml Nebuliser Solution
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each Nebule (2.5ml of solution) contains 5.0mg salbutamol (as sulphate).
For a full list of excipients, see section 6.1
3. PHARMACEUTICAL FORM
Nebuliser solution.
A clear, colourless to pale yellow, sterile, isotonic, aqueous solution.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Salbutamol is a selective beta-2-adrenoceptor agonist. At therapeutic doses it acts on the beta-2-adrenoceptors of bronchial muscle, with little or no action on the heart. With its fast onset of action, it is particularly suitable for the management and prevention of attacks in asthma.
Bronchodilators should not be the only or the main treatment in patients with severe or unstable asthma. Severe asthma requires regular medical assessment as death may occur. Patients with severe asthma have constant symptoms and frequent exacerbations, with limited physical capacity, and PEF values below 60% predicted at baseline with greater than 30% variability, usually not returning entirely to normal after a bronchodilator. These patients will require high dose inhaled (e.g. >1mg/day beclomethasone dipropionate) or oral corticosteroid therapy. Sudden worsening of symptoms may require increased corticosteroid dosage which should be administered under urgent medical supervision.
Ventolin Nebules 5mg are indicated for the routine management of chronic bronchospasm, unresponsive to conventional therapy.
They are also indicated in the treatment of acute severe asthma (status asthmaticus).
4.2 Posology and method of administration
Salbutamol inhaled formulations are administered by the inhaled route only, to be breathed in through the mouth.
Salbutamol has a duration of action of 4 to 6 hours in most patients.
Ventolin Nebules are intended to be used undiluted. However, if prolonged delivery time is desirable (more than 10 minutes) dilution using sterile normal saline as a diluent may be required.
Ventolin Nebules are to be used with a nebuliser, under the direction of a physician.
The solution must not be injected, or swallowed.
Increasing use of beta-2-agonists may be a sign of worsening asthma. Under these conditions a reassessment of the patient's therapy plan may be required and concomitant glucocorticosteroid therapy should be considered.
Delivery of the aerosol may be by facemask, 'T' piece or via an endotracheal tube. Intermittent positive pressure ventilation may be used but is rarely necessary. When there is a risk of anoxia through hypoventilation, oxygen should be added to the inspired air.
As there may be adverse effects associated with excessive dosing, the dosage or frequency of administration should only be increased on medical advice.
As many nebulisers operate on a continuous flow basis, it is likely that nebulised drug will be released in the local environment. Ventolin Nebules should therefore be administered in a well ventilated room, particularly in hospitals when several patients may be using nebulisers at the same time.
Adults and Children:-
A suitable starting dose of salbutamol by wet inhalation is 2.5 milligrams. This may be increased to 5 milligrams. Treatment may be repeated up to four times daily. In adults higher dosing, up to 40 milligrams per day, can be given under strict medical supervision in hospital for the treatment of severe airways obstruction.
Clinical efficacy of nebulised salbutamol in infants under 18 months is uncertain.
As transient hypoxaemia may occur, supplemental oxygen therapy should be considered.
4.3 Contraindications
Ventolin Nebules are contra-indicated in patients with a history of hypersensitivity to any of their components.
Although intravenous salbutamol and occasionally salbutamol tablets are used in the management of premature labour, uncomplicated by conditions such as placenta praevia, ante-partum haemorrhage or toxaemia of pregnancy, inhaled salbutamol preparations are not appropriate for managing premature labour. Salbutamol presentations should not be used for threatened abortion.
4.4 Special warnings and precautions for use
The management of asthma should normally follow a stepwise programme, and patient response should be monitored clinically and by lung function tests. Increasing use of short-acting inhaled beta-2-agonists to control symptoms indicates deterioration of asthma control. Under these conditions, the patient's therapy plan should be reassessed.
Sudden and progressive deterioration in asthma control is potentially life-threatening and consideration should be given to starting or increasing corticosteroid therapy. In patients considered at risk, daily peak flow monitoring may be instituted.
Patients requiring long-term management with bronchodilators should be kept under regular surveillance.
Nebules must only be used by inhalation, to be breathed in through the mouth, and must not be injected or swallowed.
Patients receiving treatment at home with Ventolin Nebules must be warned that if either the usual relief is diminished or the usual duration of action reduced, they should not increase the dose or its frequency of administration but should seek medical advice.
A responsible adult should supervise the treatment with Ventolin Nebules in children.
Ventolin Nebules should be used with caution in patients known to have received large doses of other sympathomimetic drugs.
Salbutamol should be administered cautiously to patients with thyrotoxicosis.
A small number of cases of acute angle closure glaucoma have been reported in patients treated with a combination of nebulised salbutamol and ipratropium bromide. A combination of nebulised salbutamol with nebulised anticholinergics should therefore be used cautiously. Patients should receive adequate instruction in correct administration and be warned not to let the solution or mist enter the eye.
Potentially serious hypokalaemia may result from beta-2-agonist therapy mainly from parenteral and nebulised administration. Particular caution is advised in acute severe asthma as this effect may be potentiated by concomitant treatment with xanthine derivatives, steroids, diuretics and by hypoxia. It is recommended that serum potassium levels are monitored in such situations.
In common with other beta-adrenoceptor agonists, Ventolin can induce reversible metabolic changes, for example increased blood sugar levels. The diabetic patient may be unable to compensate for this and the development of ketacidosis has been reported. Concurrent administration of corticosteroids can exaggerate this effect.
Lactic acidosis has been reported very rarely in association with high therapeutic doses of intravenous and nebulised short-acting beta-agonist therapy, mainly in patients being treated for an acute asthma exacerbation (see section 4.8, Undesirable effects). 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.
Salbutamol should not cause difficulty in micturition because unlike sympathomimetic drugs such as ephedrine, it does not stimulate alpha-adrenoceptors. However, there have been reports of difficulty in micturition in patients with prostatic enlargement. Use with caution in diabetic patients as salbutamol may cause an increase in blood sugar level.
Cardiovascular effects may be seen with sympathomimetic drugs, including salbutamol. There is some evidence from post-marketing data and published literature 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 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.
4.5 Interaction with other medicinal products and other forms of interaction
Salbutamol and non-selective beta-blocking drugs, such as propranolol, should not usually be prescribed together.
Salbutamol is not contra-indicated in patients under treatment with monoamine oxidase inhibitors (MAOIs). The effects of this product may be altered by guanethidine, reserpine, methyldopa and tricyclic antidepressants.
4.6 Pregnancy and lactation
Administration of drugs during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.
During world-wide marketing experience, rare cases of various congenital anomalies, including cleft palate and limb defects have been reported in the offspring of patients being treated with salbutamol. Some of the mothers were taking multiple medications during their pregnancies. Because no consistent pattern of defects can be discerned, and baseline rate for congenital anomalies is 2-3% a relationship with salbutamol use cannot be established.
As salbutamol is probably secreted in breast milk its use in nursing mothers is not recommended unless the expected benefits outweigh the potential risk. It is not known whether salbutamol in breast milk has a harmful effect on the neonate.
4.7 Effects on ability to drive and use machines
None reported.
4.8 Undesirable effects
Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (  1/10), common (  1/100 and < 1/10), uncommon (  1/1000 and < 1/100), rare (  1/10,000 and < 1/1000) and very rare (< 1/10,000) including isolated reports. Very common and common events were generally determined from clinical trial data. Rare and very rare events were generally determined from spontaneous data.
Immune system disorders
Very rare: Hypersensitivity reactions including angioedema and urticaria, bronchospasm, hypotension and collapse.
Metabolism and nutrition disorders
Rare: Hypokalaemia
Potentially serious hypokalaemia may result from beta-2-agonist therapy.
Very rare: Lactic acidosis.
Lactic acidosis has been reported very rarely in patients receiving intravenous and nebulised salbutamol therapy for the treatment of acute asthma exacerbation.
Nervous system disorders
Common: Tremor, headache.
Very rare: Hyperactivity
Cardiac disorders
Common: Tachycardia
Uncommon: Palpitations
Very rare: Cardiac arrhythmias including atrial fibrillation, supraventricular tachycardia and extrasystoles.
Unknown: Myocardial ischaemia* (see section 4.4, Special warnings and precautions for use).
* reported spontaneously in post-marketing data therefore frequency regarded as unknown
Vascular disorders
Rare: Peripheral vasodilatation
Respiratory, thoracic and mediastinal disorders
Very rare: Paradoxical bronchospasm
As with other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. This should be treated immediately with an alternative presentation or a different fast-acting inhaled bronchodilator. Ventolin Nebules should be discontinued immediately, the patient assessed, and if necessary alternative therapy instituted.
Gastrointestinal disorders
Uncommon: Mouth and throat irritation
Musculoskeletal and connective tissue disorders
Uncommon: Muscle cramps
4.9 Overdose
Symptoms and Signs
The most common signs and symptoms of overdose with salbutamol are transient beta agonist pharmacologically mediated events (see section 4.4, Special warnings and precautions for use and section 4.8, Undesirable effects).
Hypokalaemia may occur following overdose with salbutamol. Serum potassium levels should be monitored.
Treatment
Consideration should be given to discontinuation of treatment and appropriate symptomatic therapy such as cardioselective beta-blocking agents in patients presenting with cardiac symptoms (e.g tachycardia, palpitations).
Beta-blocking drugs should be used with caution in patients with a history of bronchospasm.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Salbutamol is a selective beta-2-adrenoceptor agonist. At therapeutic doses it acts on the beta-2-adrenoreceptors of bronchial muscle, with little or no action on the beta-1-adrenoreceptors of cardiac muscle.
5.2 Pharmacokinetic properties
Salbutamol administered intravenously has a half-life of 4-6 hours and is cleared partly renally and partly by metabolism to the inactive 4'-0- sulphate (phenolic sulphate) which is also excreted primarily in the urine. The faeces are a minor route of excretion. The majority of a dose of salbutamol given intravenously, orally or by inhalation is excreted within 72 hours. Salbutamol is bound to plasma proteins to the extent of 10%.
After administration by the inhaled route between 10 and 20% of the dose reaches the lower airways. The remainder is retained in the delivery system or is deposited in the oropharynx from where it is swallowed. The fraction deposited in the airways is absorbed into the pulmonary tissues and circulation but is not metabolised by the lung. On reaching the systemic circulation, salbutamol becomes accessible to hepatic metabolism and is excreted, primarily in the urine, as unchanged drug and as the phenolic sulphate.
The swallowed portion of an inhaled dose is absorbed from the gastrointestinal tract and undergoes considerable first-pass metabolism to the phenolic sulphate. Both unchanged drug and conjugate are excreted primarily in the urine.
5.3 Preclinical safety data
In common with other potent selective beta-2 receptor agonists, salbutamol has been shown to be teratogenic in mice when given subcutaneously. In a reproductive study, 9.3% of foetuses were found to have cleft palate, at 2.5mg/kg, 4 times the maximum human oral dose. In rats, treatment at the levels of 0.5, 2.32, 10.75 and 50mg/kg/day orally throughout pregnancy resulted in no significant foetal abnormalities. The only toxic effect was an increase in neonatal mortality at the highest dose level as a result of lack of maternal care. A reproductive study in rabbits revealed cranial malformations in 37% of foetuses at 50mg/kg/day, 78 times the maximum human oral dose.
6. PHPHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium Chloride
Dilute Sulphuric Acid (for pH adjustment)
Water for Injections
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
6.3 Shelf life
3 years.
Use nebules within three months of opening outer foil packaging. Once nebule is opened, use immediately.
6.4 Special precautions for storage
Do not store above 30°C. Store in the original container.
6.5 Nature and contents of container
The Nebules consist of low density polyethylene (LDPE) and are manufactured using blow-seal technology.
Five Nebules are linked together in a strip.
Each strip of five Nebules is packaged under nitrogen in a laminated aluminium foil blister pack consisting of a base foil bay and foil lidding material.
Twenty Nebules are packaged together in a carton.
6.6 Special precautions for disposal and other handling
Dilution: Ventolin Nebules may be diluted with sterile normal saline
Do not use the product if discoloured
Any unused solution in the chamber for the nebuliser must be discarded.
7. MARKETING AUTHORISATION HOLDER
GlaxoSmithKline (Ireland) Limited,
Stonemasons way,
Rathfarnham,
Dublin 16
Trading as: Allen & Hanburys Ltd.
8. MARKETING AUTHORISATION NUMBER(S)
PA 1077/49/9
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
17th April 1998 / 17th April 2008
10. DATE OF REVISION OF THE TEXT
January 2009