制造商
勃林格殷格翰

性状
本品为复方制剂,其组分如下 :异丙托溴铵-水合物,其化学名称为:(8γ-3α-羟基-8-异丙基-1αh,5αh-溴化托品(±)-托品酸盐-水合物,分子式为C20h30BrNO3·h2O,分子量 为430.4 ;硫酸沙丁胺醇,其化学名称为:(RS)-2-叔-丁基氨基-1-[4-羟基]-3(羟甲基)苯基]-乙醇硫酸盐,分子式为C26h44N2O10S,分子量为576.7。本品气雾剂在耐压容器中的药液为乳白色混悬液 ;揿压阀门,药液即呈雾粒喷出。雾化吸入剂为无色或几乎无色的澄清液体。

药理作用 
异丙托溴铵是一种具有抗胆碱能(副交感)特性的四价铵化合物。临床前试验显示其通过拮抗迷走神经释放的递质乙酰胆碱而抑制迷走神经的反射。抗胆碱能药物可阻止乙酰胆碱和支气管平滑肌上的毒蕈碱受体相互作用引起的细胞内一磷酸环鸟苷酸的增高。吸入异丙托溴铵后,其作用只局限于肺部而扩张支气管,并不作用于全身。沙丁胺醇为β2-肾上腺素能受体激动剂,其作用为舒张呼吸道平滑肌。它作用于从主气管至终末细支气管的所有平滑肌,并有拮抗支气管收缩的作用。本品中的异丙托溴铵及沙丁胺醇叠加作用于肺部毒蕈碱及β2-肾上腺素能受体而产生支气管扩张作用,疗效优于单一给药。对中重度慢性阻塞性肺病患者的对照试验显示,本药的支气管扩张效应优于其单一成分的使用,并且无潜在不良反应。

药代动力学 
异丙托溴铵吸入后可很快被吸收,估计吸入后的全身生物利用度低于用药量的10%。静脉给药后,异丙托溴铵的肾脏排泄为46%,静脉用药终末清除期的半衰期约为1.6小时。由放射标记法测定的清除药物及其代谢产物的半衰期是3.6小时。异丙托溴铵不通过血脑屏障。经口吸入或经胃肠道口服,沙丁胺醇可快速完全地在体内吸收,3小时内达血浆最高浓度,24小时后经尿以原形排出,消除半衰期为4小时。沙丁胺醇可通过血脑屏障,其浓度为血浆浓度的5%。已证明异丙托溴铵和沙丁胺醇共同雾化治疗时,不增加单独使用其中任一药物的全身吸收,其药效增强是由于吸入后局限于肺部的联合作用所致。

毒理研究 
已对大鼠和狗进行本药雾化吸入剂的急性毒性试验。异丙托溴铵/沙丁胺醇之比使用技术上可测的最高剂量,即大鼠887/5397微克/公斤体重,狗165/862微克/公斤体重时,未出现全身毒性的征象,本化合物局部耐受性很好。根据受试种属(小鼠、大鼠和狗)计算静脉给予异丙托溴铵的LD50约为12-20
毫克/公斤体重,沙丁胺醇为60-70毫克/公斤体重。对鼠和狗分2组进行了合用异丙托溴铵和沙丁胺醇的13周吸入毒性试验。在此试验中,证明心脏为靶器官。对大鼠使用剂量为31.3/183.4到375.5/2188.4微克/公斤体重/天的异丙托溴铵/沙丁胺醇,观察到非剂量依赖性心脏重量增加,但无任何可检测出的组织病理学改变。对狗使用剂量32.3/197.6到129.2/790.4微克/公斤体重/天时,异丙托溴铵/沙丁胺醇可轻度增加心率,使用更高剂量时,可观察到左心室乳头肌出现组织病理学瘢痕和/或纤维化,有时伴有钙化作用。以上试验中得到的结果是沙丁胺醇β肾上腺素能共知的作用结果。另一种成分(异丙托溴铵)的毒理学特性已多年为人所知,其具有典型抗胆碱能作用,诸如头部粘膜干燥,瞳孔放大,只出现于犬类的干燥性角膜结膜炎(干眼)和出现于大鼠的声调降低、胃肠道动力受抑制。已有关于本药两种成分生殖毒性的试验研究,较大剂量沙丁胺醇可引起小鼠腭裂。这种现象已为人所知并可发生于使用其它β肾上腺素能药物时,目前推测此种反应是由于母体皮质类固醇水平增加所致,并被视为与其它种属无关的应激结果。另外,临床前资料表明的沙丁胺醇有致畸可能性的特性已被予以考虑,已限制妇女使用。除了这些发现,对沙丁胺醇和异丙托溴铵试验显示,对胚胎、胎儿和幼畜只有轻微影响,而这些均在母体毒性范围之内。对沙丁胺醇和异丙托溴铵均进行了大量体内体外试验,两者均无致突变作用。分别对沙丁胺醇和异丙托溴铵进行了几项体内致癌试验以研究其肿瘤特性。小鼠口服沙丁胺醇后,在比人吸入治疗剂量高100倍时,卵巢系膜平滑肌瘤发生率增加,对于大鼠和狗无此发现。同时服用β受体阻滞剂可防止平滑肌瘤的发生。这些结果被推测为种属特异性,无临床相关性,因此不必限制临床使用。小鼠和大鼠口服异丙托溴铵无潜在致癌性。无本药或其有效成份引起免疫毒性的报道。

适应症  
适用于需要多种支气管扩张剂联合应用的病人,用于治疗气道阻塞性疾病有关的可逆性支气管痉挛。

用法用量 
气雾剂
成人
2喷/次,每日4次,必要时可用至最大剂量,即12喷/24小时。若发生迅速且追加给药不能改善的呼吸困难时,应立即给予急救处理。
雾化吸入剂成人(包括老年人)及12岁以上儿童急性发作期
通常1个小瓶的治疗剂量即可缓解症状,对于严重的病例,可增加到2个小瓶。维持治疗期 每次使用1个小瓶,每日3-4次。雾化吸入剂必须通过合适的雾化器或间歇正压通气机给药,不能口服。

不良反应 
与其它β受体激动剂一样,本药常见不良反应包括头疼、口干、发声困难、眩晕、焦虑、心动过速、骨骼肌的细颤和心悸,尤其是对易感患者。应用β-受体激动剂可导致潜在的严重低钾血症。同其它吸入治疗一样,可出现咳嗽、局部刺激感,吸入性气管痉挛较少见。同其它拟β类药物一样,用药后可出现恶心、呕吐、出汗、肌肉无力和肌痛/肌肉痉挛,极少数病例出现舒张压下降、收缩压上升、心律失常,尤其是使用较大剂量药物后。极少数病例出现皮肤反应或过敏反应,尤其是高敏患者。少数报道使用拟β类药物吸入治疗后出现心理上的改变。最常见的与抗胆碱能药物有关的非呼吸道不良反应有口干和发音困难。散在报道单独使用异丙托溴铵或与肾上腺素能β2受体激动剂同时使用时,雾化剂进入眼睛后出现眼部并发症(如瞳孔散大、眼内压增高、闭角型青光眼、眼痛)。眼部不良反应、胃肠动力障碍和尿潴留仅出现于少数病例,并且可完全恢复正常。(见注意事项)过敏样反应如皮疹及舌、唇、脸部血管性水肿、荨麻疹(包括巨型荨麻疹)、喉痉挛和过敏反应均有报告。在一些病例中,存在阳性再激发免疫反应。这些患者中有许多人对药物和/或食物包括大豆有过敏史。

禁忌症 
对本品任何成分或对阿托品及其衍生物过敏者禁用。肥厚梗阻型心肌病、快速型心律失常、对大豆卵磷酯或有关的食品如大豆或花生过敏者禁用气雾剂,但可使用本品的雾化吸入剂。
 
注意事项 
极少数病例报道,使用雾化吸入剂后迅速发生过敏反应,如荨麻疹、血管神经性水肿、皮疹、支气管痉挛和口咽部水肿。眼部并发症
当雾化的异丙托溴铵单独或与肾上腺素β2受体激动剂合用雾化剂进入眼睛时,有个别报告出现眼部并发症(如瞳孔散大、眼内压增高、闭角型青光眼、眼痛)。眼睛疼痛或不适、视物模糊、结膜充血和角膜水肿所导致的红眼,视物有光晕或有色成像可能是急性闭角型青光眼的征象。如果出现某些上述症状,应首先使用缩瞳药并请眼科医生会诊。指导患者正确使用本药,应注意避免使眼睛接触到药液或气雾。建议患者通过口件吸入雾化剂,如果没有该装置,可使用合适的雾化面罩。有青光眼倾向的患者应注意保护眼睛。
有以下疾患,特别是用药剂量超过推荐剂量时,应在权衡利弊后,慎重使用本药:尚未有效控制的糖尿病、近期心肌梗塞、严重的器质性心血管疾病、甲亢、嗜铬细胞瘤、闭角型青光眼高危者、前列腺肥大或膀胱癌颈部阻塞的患者。应用β2受体兴奋剂可导致潜在的严重低血钾,另外缺氧可加重低血钾对心律的影响。有囊性纤维变性的病人更易于出现胃肠动力障碍。进行雾化吸入治疗时,若出现急剧加重的呼吸困难,应及时处理。若需要使用超过本药的推荐剂量来控制症状时,应在医生指导下制定治疗方案。

孕妇及哺乳期妇女用药 
在人类妊娠期的本药安全性尚未确定,妊娠期尤其是前3月应常规慎重用药。本药对子宫收缩的抑制作用应予以考虑。硫酸沙丁胺醇和异丙托溴铵可从乳汁中排泄,尚不知对新生儿有何影响,尽管非脂溶性四价铵化合物可进入乳汁,异丙托溴铵不太可能较大程度地进入婴儿体内,特别是在吸入用药时。但是,由于许多药物从乳汁中排泄,因此对哺乳妇女应特别谨慎用药。

儿童用药 
尚无12岁以下儿童使用本品的临床经验。

老年患者用药 
本产品用法和用量中已包括老年患者用药。参见“用法用量”。

药物相互作用 
同时使用黄嘌呤衍生物、β-肾上腺素能类和抗胆碱能类药物可增加副作用。黄嘌呤衍生物、皮质类固醇和利尿剂可增强β-受体激动剂引起的低钾血症。对有严重气道阻塞的患者要特别重视,低钾血症可增加服用地高辛患者出现心律失常的危险,建议在此种情况时监测血钾水平。同时使用β-受体阻滞剂可使支气管扩张效果显著降低。单胺氧化酶抑制剂或三环类抗抑郁药可增强β-肾上腺素能激动剂的作用,合用时应谨慎。吸入卤化羟类麻醉剂如卤烷、三氯乙烯和安氟醚可以增加β受体激动剂对心血管作用的易感性。

药物过量 
症状
过量时的不良反应主要是由于沙丁胺醇的作用所致。β-肾上腺素能过度刺激,最明显的表现为心动过速、心悸、震颤、高血压、低血压、脉压增宽、咽痛、心律失常和面色潮红。鉴于长时间治疗和局部用药,异丙托溴铵过量的症状(如口干、视力调节障碍)实际上是很轻微而短暂的。治疗严重病例可使用镇静剂、安定药。β-受体阻滞剂,尤其是选择性β-1受体阻滞剂是合适的特异性解毒剂,但是必须考虑使用这类药物时,有可能加重支气管阻塞,对支气管哮喘患者应仔细调整剂量。

用药须知 
气雾剂
正确使用气雾剂才能获得满意疗效。首次使用气雾器前应先将气雾液摇匀,并按压2次气雾器活瓣。
每次使用遵循以下的规则:打开保护盖。每次使用前摇匀。深呼气。手持气雾器,嘴唇合拢咬住喷嘴,箭头及气雾器底部指向上方。尽量深吸气,同时用力按压气雾器的基底部,这样就释放1喷,屏住呼吸数秒,然后将气雾器喷嘴从口中取出,缓慢呼气。接着重复进行第2喷吸入过程。重新盖上保护盖。容器内部有压力,请勿用暴力打开容器或将其暴露于50°C以上温度。由于容器不透明,所以不能看到药物是否用完,但振摇液体可显示容器内是否有残存液体。喷嘴应一直保持清洁并可用温水清洗。如用肥皂或清洁剂,喷嘴应用清水彻底冲洗干净。雾化吸入剂只能通过合适的雾化器或间歇正压通气机给药,不能口服。每次吸入治疗时应重新开启1小瓶新药,已开瓶的或药瓶有破损的药物应丢弃,不宜使用。不要把本雾化吸入剂和其它药品混在同一雾化器中使用。

贮藏/有效期 
30°C以下避光保存。
有效期3年。

注：本栏药品是在美国本地上市，购买时请以电话咨询为准！
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原产地英文商品名:
COMBIVENT INHALER 15g/box
原产地英文药品名:
IPRATROPIUM BROMIDE/ALBUTEROL SULFATE
中文参考商品译名:
可必特吸入剂 15克/盒
中文参考药品译名:
异丙托溴铵/硫酸沙丁胺醇
生产厂家中文参考译名:
勃林格殷格翰
生产厂家英文名:
BOEHRINGER INGELHEIM

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GENERIC NAME: IPRATROPIUM/ALBUTEROL (SALBUTAMOL) - INHALATION (IP-ra-TROE-pee-um/al-BUE-ter-ol) (sal-BUE-tah-mol)

BRAND NAME(S): Combivent

USES: This product is a combination of 2 medications: albuterol (also known as salbutamol) and ipratropium. It is used to treat or prevent wheezing and shortness of breath caused by ongoing breathing problems (e.g., chronic obstructive pulmonary disease-COPD, emphysema, chronic bronchitis). It works in the airways by opening breathing passages and relaxing muscles. Controlling symptoms of breathing problems can decrease time lost from work or school.

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start using this product and each time you get a refill. Refer to the illustrated directions provided by the manufacturer for directions on how to use this device. If any of the information is unclear, consult your doctor or pharmacist.Follow the instructions for test sprays in the air (priming) if you are using a new canister or if you have not used it for more than 24 hours. Avoid spraying the medication in your eyes.Before each dose, shake the inhaler well for at least 10 seconds. Inhale this medication by mouth, usually 4 times daily or as directed by your doctor. You may use more doses if you have wheezing and shortness of breath between your prescribed doses. However, the manufacturer recommends that you do not use more than 12 inhalations in a 24-hour period. Doing so may increase the risk of serious side effects. Use this medication regularly to receive the most benefit from it. To help you remember, use it at the same times each day.If you find it difficult to use this inhaler correctly, it may help to use a spacer device with this inhaler. Ask your doctor or pharmacist for more information.Keep track of the number of inhalations you use, and discard the inhaler after you have used the labeled number of inhalations on the product package. Test sprays used to prime the inhaler should also be counted.If this medication stops working well or your breathing symptoms become worse, seek immediate medical attention.

SIDE EFFECTS: Headache, nausea, nervousness, trouble sleeping, dizziness, dry mouth/throat, coughing, or runny nose may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor immediately if any of these unlikely but serious side effects occur: eye pain, fast/pounding heartbeat, muscle cramps, trouble urinating, vision changes, weakness.Seek immediate medical attention if any of these rare but very serious side effects occur: chest pain, irregular heartbeat.Rarely, this medication has caused severe (rarely fatal), sudden worsening of breathing problems/asthma (paradoxical bronchospasm). If you have trouble breathing or experience sudden wheezing, seek immediate medical attention.A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects.

PRECAUTIONS: Before using this product, tell your doctor or pharmacist if you are allergic to albuterol (salbutamol) or ipratropium; or to peanuts, soybeans, soy lecithin, atropine, or other belladonna-type drugs; or if you have any other allergies.Before using this product, tell your doctor your medical history, especially of: diabetes, heart disease (e.g., irregular heartbeat, coronary insufficiency), high blood pressure, glaucoma, low potassium blood level (hypokalemia), seizure, overactive thyroid (hyperthyroidism), urination problems (e.g., due to enlarged prostate, urinary retention).This drug may make you dizzy. If accidentally sprayed into your eyes, it may also cause temporary blurred vision. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely. Limit alcoholic beverages.Before having surgery, tell your doctor or dentist that you are using this medication.During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.Avoid taking MAO inhibitors (e.g., furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine) within 2 weeks before, during, and after treatment with this medication. In some cases a serious, possibly fatal drug interaction may occur.Before using this product, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: anticholinergic drugs (e.g., benztropine, trihexyphenidyl), anti-spasmodic drugs (e.g., dicyclomine, hyoscyamine), adrenaline-like drugs (e.g., ephedrine, pseudoephedrine), asthma drugs (e.g., salmeterol, formoterol), some beta blockers (such as propranolol), pramlintide, tricyclic antidepressants (e.g., amitriptyline, nortriptyline), "water pills"/diuretics (e.g., furosemide, hydrochlorothiazide).Check the labels on all your medicines (e.g., cough-and-cold products, diet aids) because they may contain ingredients that could increase your heart rate or blood pressure. Ask your pharmacist about the safe use of these products.This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: chest pain, fast/pounding/irregular heartbeat, shaking (tremors).

NOTES: Do not share this medication with others.Laboratory and/or medical tests (e.g., pulmonary function tests, blood pressure, potassium blood levels) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.Learn to use a peak flow meter, use it daily, and promptly report worsening breathing problems (such as readings in the yellow/red range, increased use of quick-relief inhalers).Avoid allergens/irritants such as smoke, pollen, pet dander, dust, or molds that may worsen breathing problems.Ask your doctor or pharmacist whether you should have an annual flu shot.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Do not puncture the canister or expose it to high heat or open flame. Keep all medicines away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.MEDICAL ALERT: Your condition can cause complications in a medical emergency.