英文药名: Intal CFC-free Inhaler(sodium cromoglycate） 中文药名: 色甘酸钠无氟吸入器 生产厂家：SANOFI 药品名称 中文通用名称: 色甘酸钠 英文通用名称: Sodium Cromoglicate 其 它 名 称: 咽泰,咳乐钠,色甘酸二钠,Inostral,Intal,Cromoglycate Sodium,Cromolyn,Cromolyn Sodium,色甘酸钠滴眼液,色甘酸钠气雾剂,色甘酸钠滴鼻液,Cromolyn Sodium Inhalation Aerosol Soln,Cromoglycate Disodium,Nalcrom,宁敏,衍行,Sodium Cromoglicate Aerosol,Sodium Cromoglicate Eye Drops,Sodium Cromoglicate for Inhalation,吸入用色甘酸钠,吸入用色甘酸钠胶囊,Sodium Cromoglicate Nasal Drops 产 品 分 类: 西药呼吸系统用药平喘药过敏介质阻释药 适应症 1.可用于预防各型哮喘发作。 2.可用于过敏性鼻炎、季节性花粉症、春季角膜炎、结膜炎、过敏性湿疹及某些皮肤瘙痒症。 3.可用于溃疡性结肠炎和直肠炎。 用法用量 成人 •常规剂量 •吸入给药 1.支气管哮喘： (1)干粉吸入：一次20mg，一日4次；症状减轻后，一日40-60mg；维持量，一日20mg。 (2)气雾吸入：一次3.5-7mg，一日3-4次，一日最大剂量32mg。 2.过敏性鼻炎：每侧一次10mg，一日4-6次。 •经眼给药季节性花粉症和春季过敏性角膜结膜炎：2%滴眼液，每侧一次2滴，一日4次，重症可适当增加到一日6次。在好发季节提前2-3周使用。 •外用过敏性湿疹及皮肤瘙痒症：5%-10%软膏涂患处。 •直肠给药溃疡性结肠炎、直肠炎：灌肠，一次200mg。 •肾功能不全时剂量 酌情减量。 •肝功能不全时剂量 酌情减量。 儿童 •常规剂量 •吸入给药 1.支气管哮喘： (1)干粉吸入：5岁以上儿童用成人量，不能吸粉剂的幼儿避免使用。 (2)气雾吸入： ①6岁以上儿童：一日吸2次，剂量同成人。 ②6岁以下儿童：很难做到使患儿协调吸药，故较少选用本药。 2.过敏性鼻炎：干粉吸入：6岁以上儿童，每侧一次10mg，一日2-3次。 •经眼给药结膜炎：4岁及4岁以上儿童，4%溶液，一次1-2滴，一日4-6次。 任何疑问,请遵医嘱! 给药说明 1.由于本药系预防性地阻断肥大细胞脱颗粒，而非直接舒张支气管，因此对于季节性外源性过敏原引起的支气管哮喘病例应在支气管哮喘好发时期前2-3周使用本药。运动性哮喘可在运动前15分钟给药。 2.极少数人在开始用药时出现哮喘加重，此时可先吸入少许扩张支气管的气雾剂，如异丙肾上腺素、沙丁胺醇。 3.原来用肾上腺皮质激素或其它平喘药治疗者，用本药后应继续用原药至少1周或至症状改善后，才能逐渐减量或停用原用药物。 4.获明显疗效后，可减少给药次数。如需停药，亦应逐步减量后再停，不能突然停药，以防哮喘复发。 5.本药对伴有肺气肿或慢性支气管炎的病人，疗效有限。对急性哮喘和哮喘持续状态无效。故如遇急性发作，应立即以常规方法治疗，并停用本药。 6.哮喘持续发作及严重呼吸困难者，色甘酸钠吸入不属首选治疗，应先用解痉药物或皮质激素以控制症状。 不良反应 1.偶见排尿困难、尿急、尿痛、头晕、严重或持续性头痛、喘鸣加重、关节痛或肿胀、肌痛或肌无力、恶心或呕吐、皮疹或皮肤瘙痒、口唇与眼睑肿胀、胸部紧束感、呼吸或吞咽困难等。 2.少数患者喷雾吸入干粉可出现鹗、咽喉干痒、呛咳、胸部紧迫感、鼻腔充血、支气管痉挛，甚至诱发哮喘。 3.对少数用滴鼻液、滴眼液的病人，初用时有局部刺激感。 [国外不良反应参考] 1.吸入可能导致短暂的支气管痉挛、喘鸣、咳嗽、鼻充血以及喉刺激症状。恶心、头痛、眩晕、味苦、关节疼痛和肿胀也有报道。在治疗几周或几个月后有时会出现其它一些反应，如哮喘加重、荨麻疹、肺嗜酸粒细胞浸润症、排尿困难以及尿频等。严重的反应[如显著的支气管痉挛、血管神经性水肿(如喉头水肿)以及其它过敏反应等]罕有报道，这些反应有时被称作假过敏。 2.鼻腔内使用可能导致短暂的鼻粘膜刺激症、喷嚏，偶尔出现鼻出血。 3.口服可引起恶心、皮疹和关节痛。 4.本药滴眼引起的短暂的烧灼和螫刺感也偶有报道。 注意事项 1.禁忌症: 对本药过敏者。 2.慎用肝、肾功能不全者。 3.药物对妊娠的影响孕妇慎用。美国药品和食品管理局(FDA)对本药的妊娠安全性分级为B级。 4.药物对哺乳的影响哺乳期妇女慎用。 Intal CFC-free Inhaler 5mg Pressurised Inhalation, Suspension 1. Name of the medicinal product Intal CFC-free Inhaler 5mg Pressurised Inhalation, Suspension 2. Qualitative and quantitative composition The active component of Intal CFC-free is sodium cromoglicate 3.521% w/w. Each canister provides at least 112 actuations each containing 5 mg of sodium cromoglicate. For a full list of excipients, see section 6.1. 3. Pharmaceutical form Intal CFC-free pressurised inhalation suspension is presented as a metered dose inhaler, containing sodium cromoglicate as a suspension in a new non-CFC propellant, apaflurane (HFA-227), for inhalation. The product contains no chlorofluorocarbons (CFCs). 4. Clinical particulars 4.1 Therapeutic indications Intal CFC-free is indicated for the preventative treatment of bronchial asthma, in adults and children. 4.2 Posology and method of administration Intal CFC-free is for oral inhalation use only. It is essential to instruct the patient how to use the inhaler correctly. Adults and Children The initial dose is two inhalations of the aerosol four times daily. Once adequate control of symptoms has been achieved it may be possible to reduce to a maintenance dose of one inhalation four times daily. However, the dose may be increased to two inhalations six or eight times daily in more severe cases or during periods of severe antigen challenge. An additional dose before exercise may also be taken. Elderly No current evidence for alteration of the recommended adult dose Concomitant Bronchodilator Therapy Where a concomitant aerosol bronchodilator is prescribed it is recommended that this be administered prior to Intal CFC-free. Concomitant Steroid Therapy In patients currently treated with steroids, the addition of Intal CFC-free to the regimen may make it possible to reduce the maintenance dose of steroids, or discontinue steroid therapy completely. The patient must be carefully supervised while the steroid dose is reduced; a rate of 10% weekly is suggested. If reduction of a steroid dosage has been possible, Intal CFC-free should not be withdrawn until steroid cover has been reinstituted. Method of Administration If the inhaler is new, release 4 actuations prior to inhalation. If the inhaler has not been used for more than 3 days, release 2 actuations prior to inhalation. The inhaler should be well shaken and the dustcap removed. The patient should be instructed to breathe in slowly and deeply and as inhalation begins the aerosol should be actuated by pressing the can down firmly with the first finger whilst continuing to breathe in. The breath should then be held for several seconds before exhaling into the air. To avoid condensation of moisture in the inhaler and blocking of the spray, exhalation through the inhaler should be avoided. The dustcap should be replaced following use. To prevent excessive accumulation of powder the plastic body and mouthpiece cover should be washed twice a week and then thoroughly dried. If the Fisonair holding chamber is used this should also should be washed twice a week and thoroughly dried. Children and patients with difficulty in coordinating actuation of the inhaler with inhalation of the aerosol cloud, may benefit from using a holding chamber to assist inhalation of the medication. When using a holding chamber the procedure for inhalation is different from that with the standard mouthpiece or the Syncroner spacer device (in which the aerosol cloud is inhaled directly from the mouthpiece). The medication is first released into the holding chamber from which it is subsequently inhaled (in one or more breaths) until the chamber is empty. Thus, there is no need to coordinate actuation of the inhaler with simultaneous breathing, but the medication must be inhaled slowly and deeply from the holding chamber. The standard mouthpiece, but not the Syncroner pacer device, is suitable for use with a large volume holding chamber such as Fisonair. Detailed instructions for the inhalation of Intal CFC-free from each of the three devices are provided in the respective Patient Information Leaflet supplied with each pack. 4.3 Contraindications Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Intal CFC-free is contraindicated in patients with known hypersensitivity to sodium cromoglicate or to any of the other constituents. 4.4 Special warnings and precautions for use Intal CFC-free must not be used for relief of an acute attack of bronchospasm. Since therapy is prophylactic, it is important that Intal CFC-free should be used regularly every day, in those patients who benefit, even if they become asymptomatic. The patient should also be advised that because several doses may be needed to establish benefit, relief may not be apparent immediately, but may take some weeks to develop. Patients should have relief medication, such as an inhaled short-acting bronchodilator, available to relieve symptoms of acute asthma, and must be instructed to seek medical attention if their relief medication becomes less effective, or if more inhalations than usual are required to control symptoms. In those cases where corticosteroid therapy has been reduced or discontinued, such therapy may need to be increased or reinstated if symptoms of asthma worsen - particularly during periods of stress, such as infection, illness, trauma, or severe antigen challenge. Alternative therapeutic management may also need to be considered. Intal CFC-Free should be discontinued if eosinophilic pneumonia appears. Withdrawal of INTAL CFC-free therapy If it is necessary to withdraw this treatment, it should be done progressively over a period of one week. Symptoms of asthma may recur. 4.5 Interaction with other medicinal products and other forms of interaction Sodium cromoglicate has been used for the treatment of a variety of indications in man for many years and no interactions with other drugs have been reported, nor are expected for sodium cromoglicate, due to its pharmacokinetic properties (no metabolism, moderate plasma protein binding, low plasma concentrations) and its high safety profile. 4.6 Fertility, pregnancy and lactation Pregnancy As with all medication, caution should be exercised especially during the first trimester of pregnancy. Although there is no information with the new HFA-227 formulation in human pregnancy cumulative clinical experience with sodium cromoglicate formulated with CFC propellants, suggests that the active ingredient sodium cromoglicate has no adverse effects on foetal development. In addition, both the new HFA-227 propellant and sodium cromoglicate have been separately shown to be free of adverse effects on the foetus in laboratory animals. It should only be used in pregnancy where there is a clear need. Breast-feeding It is not known whether sodium cromoglicate is excreted in human breast milk but on the basis of its physico-chemical properties this is considered unlikely. There is no evidence to suggest that the use of sodium cromoglicate has any undesirable effects on the baby, however, there is no experience to date with either the new HFA-227 propellant alone or formulated with sodium cromoglicate, during lactation in asthmatic patients. It should only be used in lactation where there is a clear need. 4.7 Effects on ability to drive and use machines Intal CFC-free has no or negligible influence on ability to drive and use machines. 4.8 Undesirable effects Mild throat irritation, coughing and transient bronchospasm may occur. Headache and rhinitis have also been reported in clinical trials of Intal CFC-free. Hypersensitivity reactions, including angioedema, bronchospasm, hypotension and collapse, have been reported extremely rarely, in patients using inhaled sodium cromoglicate. As with other inhalation therapy, paradoxical bronchospasm may occur immediately after administration: in such cases immediate treatment with a fast-acting bronchodilator is required and immediate medical attention must be sought. Therapy with Intal CFC-free should be discontinued and alternative treatment instituted. Very rare cases of eosinophilic pneumonia have been reported. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard 4.9 Overdose Animal studies have shown that sodium cromoglicate has a very low local or systemic toxicity and extended human studies have not revealed any safety hazard with products containing sodium cromoglicate. Overdosage is therefore unlikely to cause problems, but, if suspected, treatment should be supportive and directed to the control of the relevant symptoms. 5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Drugs for obstructive airway disease; Antiallergic agents, exclusive corticosteroids, ATC code: RO3BC01 Mechanism of action Sodium cromoglicate inhibits the activation of many of the cell types involved in the development and progression of asthma. Thus, sodium cromoglicate inhibits the release of inflammatory mediators including cytokines from mast cells and reduces the chemotactic activity of eosinophils and neutrophils. Activation of and mediator release from monocytes and macrophages in vitro is also reduced by sodium cromoglicate. The diverse range of activities of the drug may be explained by the ability of sodium cromoglicate to block chloride channels in different cell types which are important in cell activation. Pharmacodynamics In acute bronchial provocation tests in humans, sodium cromoglicate has been shown to inhibit or diminish the asthmatic reaction to antigen, exercise and to a range of non-specific triggers including cold air, sulphur dioxide, hypertonic saline and bradykinin. Antigen-induced increased bronchial hyperactivity to histamine is prevented and a reduction in bronchial mucus eosinophils and antigen-specific IgE occurs after 4 weeks treatment of asthmatic subjects with sodium cromoglicate. 5.2 Pharmacokinetic properties After inhalation in man via a metered dose inhaler approximately 10% of a dose of sodium cromoglicate is absorbed from the respiratory tract. The remainder is either exhaled or deposited in the oropharynx, or swallowed and eliminated via the alimentary tract, as only a small amount (1%) of the dose is absorbed from the gastrointestinal tract. The rate of absorption of sodium cromoglicate from the respiratory tract is slower than the elimination rate (t½ of 1.5-2h). Hence, the drug remains effectively in the lungs to produce its local therapeutic effect and is then cleared rapidly from the systemic circulation. No substantial increase in plasma concentration occurs during repeated dose therapy. Sodium cromoglicate is moderately and reversibly bound to plasma proteins (≈ 65%) and is not metabolised in humans. It is excreted unchanged in both urine and bile in approximately equal proportions. 5.3 Preclinical safety data Pre-clinical data reveal no special hazard for humans based on studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and toxicity to reproduction. 6. Pharmaceutical particulars 6.1 List of excipients Polyvidone K30 Polyethylene glycol (PEG) 600 Apaflurane (HFA 227 - a non ozone depleting propellant). 6.2 Incompatibilities Not applicable. 6.3 Shelf life 30 months. 6.4 Special precautions for storage Do not refrigerate or freeze. As the aerosol inhaler canister is pressurised it should be protected from heat or direct sunlight and should not be punctured or incinerated even when empty. 6.5 Nature and contents of container The aluminium can is fitted with a metering valve which delivers 112 actuations each containing 5 mg of sodium cromoglicate. Intal CFC-free Inhaler: The cartoned pack consists of an aerosol canister and a plastic adaptor with a dustcap. Intal CFC-free Fisonair: The cartoned pack consists of an aerosol canister and a plastic adaptor with a dustcap and a holding chamber. Intal CFC-free Syncroner: The cartoned pack consists of either one or two aerosol canisters, each with a spacer device and dustcap. Not all pack sizes may be marketed 6.6 Special precautions for disposal and other handling No special requirements for disposal. 7. Marketing authorisation holder Aventis Pharma Ltd One Onslow Street Guildford Surrey GU1 4YS UK Or trading as Sanofi-aventis or Sanofi One Onslow Street Guildford Surrey GU1 4YS UK 8. Marketing authorisation number(s) PL 04425/0179 9. Date of first authorisation/renewal of the authorisation Date of first authorisation: 3 November 2000 Date of latest renewal: 1 March 2006 10. Date of revision of the text 9 January 2014