英文药名: Atrovent(Ipratropium Bromide Inhaler) 中文药名: 异丙托溴胺气雾剂 生产厂家: Boehringer Ingelheim 药品名称 中文药名: 异丙托溴胺 爱全乐(Atrovent)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而引起的细胞内环一磷酸鸟苷酸(cGMP)浓度的增高。 药物活性成份异丙托溴铵口服后吸收很快。药物吸入后仅几分钟,血浆浓度就达到峰值。异丙托溴铵静脉给药后通过计算血浆水平数据可得到基本的药代动力学参数。血浆中异丙托溴铵快速双相减退。终点清除期的半衰期约为1.6小时。药物和代谢产物清除的半衰期是3.6小时,与放射性标记检测的结果一样。在尿中发现主要代谢产物很少与毒蕈碱受体结合。活性成份异丙托溴铵的清除率是2.3升/分钟。大约40%通过肾脏清除(0.9升/分钟),60%不通过肾脏而主要通过肝脏代谢。分布容积(Vz)是338升(即4.6升/公斤)。46%静脉给药剂量的活性成份通过肾脏排泄,8%气雾剂剂量的活性成份通过肾脏排泄。药物与血浆蛋白的结合率低于20%。由于其四价铵离子的分子结构特点,异丙托溴铵不能通过血脑屏障。 爱全乐 (Atrovent) 为支气管痉挛维持期治疗的支气管扩张剂,适用于慢性支气管炎、肺气肿、哮喘等慢性阻塞性肺疾病。 剂量应根据个体需要加以调整。除非医生特别处方,以下为成人及学龄儿童推荐剂量:2喷/次,每日4次。需要增加药物剂量者,一般每天的剂量不宜超过12喷。如果药物治疗不能产生明显的病情改善或患者的状况恶化,应就诊以寻求新的治疗计划。若发生急性呼吸困难或呼吸困难迅速恶化,应立即就诊。 在临床试验中最常见的非呼吸道的不良事件是头痛、恶心和口干。 由于爱全乐(Atrovent)全身吸收很少,其抗胆碱能副作用如心率增加和心悸、眼部调节障碍、胃肠道蠕动紊乱、尿潴留是很少见的,并且是可逆性的,但对已有尿道梗阻的患者来讲可能增加其尿潴留的危险性。 对大豆卵磷脂或有关的食品如大豆和花生过敏者禁用爱全乐(Atrovent)气雾剂。这些患者可以使用不含大豆卵磷脂的爱全乐(Atrovent)的其它剂型如爱全乐(Atrovent)雾化吸入剂。对阿托品或其衍生物或本品其它成份过敏者禁用。 临床前试验未显示对妊娠有不良反应,但怀孕期间用药的安全性尚未被确证。怀孕期间尤其是前三个月用药必须谨慎。爱全乐(Atrovent)是否会进入乳汁目前尚不清楚。尽管非脂溶性的四价铵可进入乳汁,但进入婴儿体内的药物量不会很多,特别在吸入给药时。但是,因为很多药物可进入乳汁,哺乳期妇女使用爱全乐(Atrovent)亦应特别注意。 儿童使用爱全乐(Atrovent)气雾剂应遵医嘱并在成人监护下进行。 请参见成人用药,目前尚无老年患者用药的特殊注意事项。 同其它吸入治疗一样,可观察到支气管扩张性咳嗽、局部刺激,而吸入刺激所产生的支气管收缩较少出现。 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。(见慎用于有闭角型青光眼倾向的患者或有前列腺肥大或膀胱颈梗阻的患者。患有纤维囊泡症的患者可能会引起胃肠道蠕动的紊乱。有极少病例报道,使用爱全乐(Atrovent)后可能会立即发生过敏反应,如出现荨麻疹、血管性水肿、皮疹、支气管痉挛和咽喉部水肿。 眼部并发症有个别病例报告异丙托溴铵单用或与b2受体激动剂合用药物喷到眼内时,可发生眼部并发症(如瞳孔散大、眼内压增加、闭角型青光眼、眼痛)。 使用b-肾上腺素能兴奋剂或黄嘌呤类制剂可加强本品的支气管扩张作用。 爱全乐(Atrovent)与其它治疗慢性阻塞性肺疾病的常用药物包括拟交感神经性支气管扩张剂、甲基黄嘌呤、类固醇、色甘酸二钠等合用,药物间无不良相互作用。 尚未发现特异性过量症状。基于爱全乐(Atrovent)气雾剂宽广的治疗范围和使用局部给药方法,不会发生严重的抗胆碱能症状。轻微的抗胆碱能全身表现如口干、视力调节障碍、心率增加等可能发生。 贮存于30℃ 以下环境。请存放于儿童伸手不及处。 DESCRIPTION Ipratropium bromide is a white to off-white, crystalline substance. It is freely soluble in lower alcohols and water, existing in an ionized state in aqueous solutions, and relatively insoluble in non-polar media. ATROVENT(ipratropium bromide) Nasal Spray 0.06% is a metered-dose, manual pump spray unit which delivers 42 mcg ipratropium bromide (on an anhydrous basis) per spray (70µL) in an isotonic, aqueous solution with pH-adjusted to 4.7. It also contains benzalkonium chloride, edetate disodium, sodium chloride, sodium hydroxide, hydrochloric acid, and purified water. Each bottle contains 165 sprays. CLINICAL PHARMACOLOGY Pharmacokinetics Distribution: Ipratropium bromide is minimally bound (0 to 9% in vitro ) to plasma albumin and (alpha) 1 -acid glycoprotein. Its blood/plasma concentration ratio was estimated to be about 0.89. Studies in rats have shown that ipratropium bromide does not penetrate the blood-brain barrier. Metabolism: Ipratropium bromide is partially metabolized to ester hydrolysis products, tropic acid, and tropane. These metabolites appear to be inactive based on in vitro receptor affinity studies using rat brain tissue homogenates. Elimination: After intravenous administration of 2 mg ipratropium bromide to 10 healthy volunteers, the terminal half-life of ipratropium bromide was approximately 1.6 hours. The total body clearance and renal clearance were estimated to be 2,505 and 1,019 mL/min, respectively. The amount of the total dose excreted unchanged in the urine (Ae) within 24 hours was approximately one-half of the administered dose. Pediatrics: Following administration of 84 mcg of ipratropium bromide per nostril three times a day in patients 5-18 years old (n=42) with a naturally acquired common cold, the mean amount of the total dose excreted unchanged in the urine of 7.8% was comparable to 84 mcg per nostril four times a day in an adult induced common cold population (n=22) of 7.3 to 8.1%. Plasma ipratropium concentrations were relatively low (ranging from undetectable up to 0.62 ng/mL). No correlation of the amount of the total dose excreted unchanged in the urine (Ae) with age or gender was observed in the pediatric population. Special Populations: Gender does not appear to influence the absorption or excretion of nasally administered ipratropium bromide. The pharmacokinetics of ipratropium bromide have not been studied in patients with hepatic or renal insufficiency or in the elderly. Drug-Drug Interactions: No specific pharmacokinetic studies were conducted to evaluate potential drug-drug interactions. Pharmacodynamics: In two single dose trials (n=17), doses up to 336 mcg of ipratropium bromide did not significantly affect pupillary diameter, heart rate, or systolic/diastolic blood pressure. Similarly, ATROVENT Nasal Spray 0.06% in adult patients (n=22) with induced-colds (84 mcg/nostril four times a day) and in pediatric patients (n=45) with naturally acquired common cold (84 mcg/nostril three times a day) had no significant effects on pupillary diameter, heart rate, or systolic/diastolic blood pressure. Controlled clinical trials demonstrated that intranasal fluorocarbon-propelled ipratropium bromide does not alter physiologic nasal functions (e.g., sense of smell, ciliary beat frequency, mucociliary clearance, or the air conditioning capacity of the nose). Clinical Trials One clinical trial was conducted with ATROVENT Nasal Spray 0.06%, administered four times daily for three weeks, in 218 patients with rhinorrhea associated with Seasonal Allergic Rhinitis (SAR), compared to its vehicle in 211 patients. Patients in this trial were adults and adolescents 12 years of age and above. ATROVENT (ipratropium bromide) Nasal Spray 0.06% was significantly more effective in reducing the severity and duration of rhinorrhea over the three weeks of the study, as measured by daily patient symptom scores. There was no difference between treatment groups in the effect on nasal congestion, sneezing or itching eyes. INDICATIONS AND USAGE The safety and effectiveness of the use of ATROVENT (ipratropium bromide) Nasal Spray 0.06% beyond four days in patients with the common cold or beyond three weeks in patients with seasonal allergic rhinitis has not been established. CONTRAINDICATIONS WARNINGS PRECAUTIONS Information for Patients Drug Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Oral reproduction studies were performed at doses of 10 mg/kg in mice, 1,000 mg/kg in rats and 125 mg/kg in rabbits. These doses correspond, in each species respectively, to approximately 60, 12,000, and 3,000 times the maximum recommended daily intranasal dose in adults on a mg/m 2 basis. Inhalation reproduction studies were conducted in rats and rabbits at doses of 1.5 and 1.8 mg/kg, respectively, (approximately 20 and 45 times, respectively, the maximum recommended daily intranasal dose in adults on a mg/m 2 basis). These studies demonstrated no evidence of teratogenic effects as a result of ipratropium bromide. At oral doses above 90 mg/kg in rats (approximately 1,100 times the maximum recommended daily intranasal dose in adults on a mg/m 2 basis) embryotoxicity was observed as increased resorption. This effect is not considered relevant to human use due to the large doses at which it was observed and the difference in route of administration. However, no adequate or well controlled studies have been conducted in pregnant women. Because animal reproduction studies are not always predictive of human response, ipratropium bromide should be used during pregnancy only if clearly needed. Nursing Mothers Pediatric Use ADVERSE REACTIONS Table 1 shows adverse events reported for patients who received ATROVENT (ipratropium bromide) Nasal Spray 0.06% at the recommended dose of 84 mcg per nostril, or vehicle, administered three or four times daily, where the incidence is 1% or greater in the ATROVENT group and higher in the ATROVENT ® group than in the vehicle group.
ATROVENT (ipratropium bromide) Nasal Spray 0.06% was well tolerated by most patients. The most frequently reported adverse events were transient episodes of nasal dryness or epistaxis. The majority of these adverse events (96%) were mild or moderate in nature, none was considered serious, and none resulted in hospitalization. No patient required treatment for nasal dryness, and only three patients (<1%) required treatment for epistaxis, which consisted of local application of pressure or a moisturizing agent (e.g., petroleum jelly). No patient receiving ATROVENT (ipratropium bromide) Nasal Spray 0.06% was discontinued from the trial due to either nasal dryness or bleeding. Adverse events reported by less than 1% of the patients receiving ATROVENT (ipratropium bromide) Nasal Spray 0.06% during the controlled clinical trials that are potentially related to ATROVENT's local effects or systemic anticholinergic effects include: taste perversion, nasal burning, conjunctivitis, coughing, dizziness, hoarseness, palpitation, pharyngitis, tachycardia, thirst, tinnitus, and blurred vision. No controlled trial was conducted to address the relative incidence of adverse events for three times daily versus four times daily therapy. Nasal adverse events seen in the clinical trial with seasonal allergic rhinitis (SAR) patients (see Table 2) were similar to those seen in the common cold trials. Additional events were reported at a higher rate in the SAR trial due in part to the longer duration of the trial and the inclusion of upper respiratory tract infection (URI) as an adverse event. In common cold trials, URI was the disease under study and not an adverse event.
Additional anticholinergic effects noted with other ATROVENT dosage forms (ATROVENT Inhalation Solution, ATROVENT Inhalation Aerosol and ATROVENT Nasal Spray 0.03%) include: precipitation or worsening of narrow-angle glaucoma, urinary retention, prostate disorders, constipation, and bowel obstruction. There were no reports of allergic-type reactions in the controlled clinical trials. Allergic-type reactions such as skin rash, angioedema of the throat, tongue, lips and face, generalized urticaria, laryngospasm and anaphylactic reactions have been reported with ATROVENT Nasal Spray 0.06% and other ipratropium bromide products. OVERDOSAGE Oral median lethal doses of ipratropium bromide were greater than 1,000 mg/kg in mice (approximately 6,000 and 3,800 times the maximum recommended daily intranasal dose in adults and children, respectively, on a mg/m 2 basis), 1,700 mg/kg in rats (approximately 21,000 and 13,000 times the maximum recommended daily intranasal dose in adults and children, respectively, on a mg/m 2 basis) and 400 mg/kg in dogs (approximately 16,000 and 10,000 times the maximum recommended daily intranasal dose in adults and children, respectively, on a mg/m 2 basis). DOSAGE AND ADMINISTRATION The recommended dose of ATROVENT ® (ipratropium bromide) Nasal Spray 0.06% is two sprays (84 mcg) per nostril three or four times daily (total dose 504 to 672 mcg/day) in adults and children age 12 years and older. Optimum dosage varies with response of the individual patient. The recommended dose of ATROVENT (ipratropium bromide) Nasal Spray 0.06% for children age 5-11 years is two sprays (84 mcg) per nostril three times daily (total dose of 504 mcg/day). The safety and effectiveness of the use of ATROVENT (ipratropium bromide) Nasal Spray 0.06% beyond four days in patients with the common cold have not been established. For Symptomatic Relief of Rhinorrhea Associated with Seasonal Allergic Rhinitis The recommended dose of ATROVENT (ipratropium bromide) Nasal Spray 0.06% is two sprays (84 mcg) per nostril four times daily (total dose 672 mcg/day) in adults and children age 5 years and older. The safety and effectiveness of the use of ATROVENT (ipratropium bromide) Nasal Spray 0.06% beyond three weeks in patients with seasonal allergic rhinitis have not been established. Initial pump priming requires seven sprays of the pump. If used regularly as recommended, no further priming is required. If not used for more than 24 hours, the pump will require two sprays, or if not used for more than seven days, the pump will require seven sprays to reprime. HOW SUPPLIED Store tightly closed between 59°F (15°C) and 86°F (30°C). Avoid freezing. Keep out of reach of children. Do not spray in the eyes. Patients should be reminded to read and follow the accompanying Patient's Instructions for Use, which should be dispensed with the product. Rx only Boehringer Ingelheim Pharmaceuticals, Inc. |
异丙托溴胺气雾剂|Atrovent(Ipratropium Bromide Inhaler)简介:
英文药名: Atrovent(Ipratropium Bromide Inhaler)
中文药名: 异丙托溴胺气雾剂
生产厂家: Boehringer Ingelheim
药品名称
中文药名: 异丙托溴胺 药理作用
爱全乐(Atrovent)是一种具有抗胆碱能 ... 责任编辑:admin |
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