【药理毒理】：卡维地洛在治疗剂量范围内，兼有?1和非选择性? 受体阻滞作用，无内在拟交感活性。本品阻滞突触后膜?1受体，从而扩张血管、降低外周血管阻力；阻滞?受体，抑制肾脏分泌肾素，阻断肾素-血管紧张素-醛固酮系统，产生降压作用。卡维地洛降压迅速，可长时间维持降压作用。对左室射血分数、心功能、肾功能、肾血流灌注、外周血流量、血浆电解质和血脂水平没有影响，不影响心率或使其稍微减慢，极少产生水钠潴留。
药代动力学： 卡维地洛口服后易于吸收，绝对生物利用度(F)约为25%～35％，有明显的首过效应，消除相半衰期(t1/2?)约为7～10小时。与食物一起服用时，其吸收减慢，但对生物利用度没有明显影响，且可减少引起体位性低血压的危险性。卡维地洛为碱性亲脂化合物，与血浆蛋白结合率大于98%。其稳态分布容积大约为1.5L，血浆清除率为500～700ml/min。卡维地洛代谢完全，其代谢产物先经胆汁再通过粪便排出，不到2％以原形随尿液排出。8名健康受试者单次服用本品30mg，进行药代动力学测定，血药浓度峰(Cmax)为89.89ng/ml，消除相半衰期(t1/2?)为2.01小时，曲线下面积(AUC)为 233.1(ng·h)/ml。本品口服吸收迅速、完全，食物可减慢吸收，使达峰时间延迟。因显著的首过代谢，绝对生物利用度为25%~35%。血浆蛋白结合率约98%。大约在1小时可达到最大血清浓度。表观分布容积稳定，约为115L。终末消除T1/27~10小时。本品口服后经过立体选择性首过代谢，健康受试者体内卡维地洛右旋体的血浆水平是左旋体的2~3倍，右旋体终末消除T1/2为5~9h，左旋体为7~11h。药物在肝脏广泛代谢，主要参加的P450酶是CYP2D6 和CYP2C9，其它有CYP3A4、2C19、1A2和2E1。其苯环的去甲基化和羟基化产生3种具有β受体阻滞活性的代谢产物，但扩张血管活性微弱，血浆浓度约是卡维地洛的1/10，药代动力学与原药相似。卡维地洛<2%以原型经尿排出，血浆清除率为500~700ml/min，代谢产物主要通过胆汁排入粪便。心功能不全患者的稳态血药浓度随剂量的增加而成比例的增加，平均AUC和Cmax增高，终末消除T1/2与健康者相似。肝肾功能不全的患者，卡维地洛的血浆浓度增加。老年人卡维地洛的血浆水平比年轻人大约高50%。

【用法用量】：剂量必须个体化，需在医师的密切监测下加量。
1. 高血压推荐起始剂量6.25mg/次，一日二次口服，如果可耐受，以服药后1小时的立位收缩压作为指导，维持该剂量7~14天，然后根据谷浓度时的血压，在需要的情况下增至 12.5mg/次，一日二次。同样，剂量可增至25mg/次，一日二次。一般在7~14天内达到完全的降压作用。总量不得超过50mg/日。本品须和食物一起服用，以减慢吸收，降低体位性低血压的发生。在本品的基础上加用利尿剂或在利尿剂的基础上加用本品，预计可产生累加作用，扩大本品的体位性作用。
2．心功能不全：在使用本品之前，洋地黄类药物、利尿剂和ACEI(如果应用)的剂量必须稳定。推荐起始剂量3.125mg/次，一日二次口服2周，如果可耐受，可增至6.25mg/次，一日二次。此后可每隔2周剂量加倍至患者可耐受的最大剂量。每次应用新剂量时，需观察患者有无眩晕或轻度头痛1小时。推荐最大剂量：<85kg者，25mg/次，一日二次；≥85kg者， 50mg/次，一日二次。本品须和食物一起服用，以减慢吸收，降低体位性低血压的发生。每次增加剂量前，经评估心功能不全情况，如心功能恶化、血管扩张(眩晕、轻度头痛、症状性低血压)或心动过缓症状，以确定对卡维地洛的耐受性。一过性心功能不全恶化可通过增加利尿剂剂量治疗，偶尔需要卡维地洛减量或暂时停药。血管扩张的症状对利尿剂或ACEI减量治疗有反应，如果症状不能缓解，可能需卡维地洛减量。心功能不全恶化或血管扩张的症状稳定后，才可增加本品剂量。如果心功能不全患者发生心动过缓(脉搏<55次/分)，必须减量。

【不良反应】：
1. 高血压：发生率≥1%，不考虑因果关系的不良事件：乏力，心动过缓，体位性低血压，体位依赖性水肿，下肢水肿，眩晕，失眠，嗜睡，腹痛，腹泻，血小板减少，高脂血症，背痛，病毒感染，鼻炎，咽炎，呼吸困难，泌尿道感染。发生率>0.1%，<1%：四肢缺血，心动过速，运动功能减退，胆红素尿，转氨酶增高，胸骨下疼痛，水肿，焦虑，睡眠紊乱，抑郁加重，注意力不集中，思维异常，情绪不稳定，哮喘，男性性欲下降，瘙痒，红斑，斑丘疹，光过敏反应，耳鸣，尿频，口干，多汗，低钾，糖尿病，高脂血症，贫血，白细胞减少。发生率≤0.1%，但很重要：三度房室传导阻滞，束支传导阻滞，心肌缺血，脑血管障碍，惊厥，偏头痛，神经痛，脱发,剥脱性皮炎，健忘症，胃肠道出血，气管痉挛，肺水肿，听力下降，呼吸性碱中毒，尿素氮增高，高密度脂蛋白下降，全血细胞减少。
2. 心功能不全：发生率>2%，不考虑因果关系的不良事件：多汗，乏力，胸痛，疼痛，水肿，发热，下肢水肿，心动过缓，低血压，晕厥，房室传导阻滞，心绞痛恶化，眩晕，头痛，腹泻，恶心，腹痛，呕吐，血小板减少，体重增加，痛风，尿素氮增加，高脂血症，脱水，高血容量，背痛，关节痛，肌痛，上呼吸道感染，感染，鼻窦炎，气管炎，咽炎，泌尿道感染，血尿，视觉异常。发生率>1%，<2%：过敏，突然死亡，不适，低血容量，体位性低血压，感觉减退, 眩晕，黑便，牙周炎，谷丙转氨酶、谷草转氨酶升高，高尿酸尿，低血糖，低血钠，碱性磷酸酶增加，尿糖呈阳性，紫癜，嗜睡，肾功能异常，白蛋白尿。罕见再生障碍性贫血的报道，并仅在合用与该事件有关的其它药物时发生。

【禁忌症】：
1．NYHA分级IV级失代偿性心功能不全，需要静脉使用正性肌力药物患者；
2.气管痉挛(2例报道持续性哮喘患者服用单剂卡维地洛死亡)或相关的气管痉挛状态；
3．二度或三度房室传导阻滞；
4．病态窦房结综合症；
5．心源性休克；
6．严重心动过缓。
7． 临床严重肝功能不全患者。
8． 对本品过敏者禁用。
9． 糖尿病酮症酸中毒、代谢性酸中毒。

【注意事项】：
1．肝损害 卡维地洛治疗罕见轻度肝细胞损害。当出现肝功能障碍的首发症状（如瘙痒、尿色加深、持续食欲缺乏、黄疸、右上腹部压痛、不能解释的“流感样”症状) 时，必须进行实验室检查。如果实验室检查证实存在肝损害或黄疸，必须立即停药，不可重复使用。
2．外周血管疾病 β受体阻滞剂诱发或加重外周血管疾病患者的动脉血流不足症状。此类患者需小心使用。
3．麻醉和重大手术 如果周期性长期使用卡维地洛，当使用对心脏有抑制作用的麻醉剂如乙醚、三甲烯和三氯乙烯时，须加倍小心。 4．糖尿病和低血糖 β受体阻滞剂可能掩盖低血糖症状，尤其是心动过速。非选择性β受体阻滞剂可能增强胰岛素引起的低血糖，延迟血糖水平的恢复。易自发性低血糖者或接受胰岛素或口服降糖药的糖尿病患者使用卡维地洛时须小心谨慎。
5．甲状腺功能亢进中毒症状 β受体阻滞剂可能掩盖甲状腺功能亢进的症状，如心动过速。突然停用?-受体阻滞剂可能加重甲状腺功能亢进的症状或诱发甲状腺危象。
6．因卡维地洛具有β受体阻滞活性，不能突然停药，尤其是缺血性心脏病患者。必须1~2周以上逐渐停药。
7．临床试验中卡维地洛可导致心动过缓，当脉搏<55次/分，必须减量。
8．低血压、体位性低血压和晕厥在首次服药30天内发生的危险最高，为减少这些事件的发生，心功能不全患者的开始治疗剂量为3.125mg/次，一日二次；高血压患者为 6. 25mg/次，一日二次；缓慢加量，并且与食物同时服用。起始治疗期，患者必须小心避免如驾驶或危险操作等情况。
9．罕见心功能不全患者肾功能恶化，尤其是低血压(收缩压<100mmHg)、缺血性心脏病和弥漫性血管疾病、和/或潜在肾功能不全者。停药后肾功能恢复至基线水平。此类患者在加量时建议监测肾功能，如肾功能恶化，停药或减量。
10．卡维地洛加量期可能出现心功能不全恶化或体液潴留，必须增加利尿剂，卡维地洛不加量直到临床稳定。偶尔需要卡维地洛减量或暂时停药。
11．嗜铬细胞瘤患者在使用β受体阻滞剂之前应先使用α受体阻滞剂。虽然卡维地洛具有β受体和α受体阻滞活性，但尚无在这类患者中使用的临床经验。因此，怀疑嗜铬细胞瘤的患者使用卡维地洛时须小心。
12．变异性心绞痛患者使用非选择性β受体阻滞剂时可能诱发胸痛。虽然卡维地洛的α受体阻滞活性可能预防心绞痛的发生，但尚无在这类患者中使用的临床经验。因此，怀疑变异性心绞痛的患者使用卡维地洛时须小心。
13．过敏反应的危险：对许多过敏原有严重过敏病史的患者对重复使用可能发应更强烈，此类患者可能对治疗过敏的常规剂量肾上腺素无反应。
14．非过敏性气管痉挛（如慢性支气管炎和肺气肿）支气管痉挛疾病的患者一般禁止使用β受体阻滞剂。对其他降压药物无反应或不能耐受者可小心使用卡维地洛，应用最小的有效剂量，尽量减少对内源性或外源性β激动剂的抑制。
15．患者须知： ①无医师的同意下不得突然停药； ②充血性心力衰竭患者如果出现体重增加或呼吸困难增加等心功能恶化的症状时，必须向医师请教。 ③站位时血压可能下降，导致眩晕，罕见昏晕，这时坐下或躺下。 ④如果患者出现眩晕或昏晕，必须避免驾驶或危险工作。 ⑤当剂量必须调整时出现眩晕或昏晕，必须向医师请教。 ⑥必须和食物同时服用。 ⑦糖尿病患者必须向医师报告任何血糖水平的变化。 ⑧戴隐形眼镜者可能会出现流泪。
 
【孕妇及哺乳期妇女用药】：人体研究尚不充分，只有卡维地洛对胎儿的有益性大于危险性时，方可用于孕妇。是否分泌入人类的乳汁不清楚。许多其它β受体阻滞剂可分泌入乳汁，以及潜在的严重不良反应，如心动过缓，因此通过衡量药物对母亲的重要性，确定哺乳妇女应停药或停止哺乳。
儿童用药： 年龄<18岁者的安全性和疗效尚不明确。

【老年患者用药】：老年与年轻心功能不全患者、高血压之间的疗效和不良事件的发生率无不同。

【药物相互作用】：
1. CYP2D6抑制剂 无卡维地洛与CYP2D6抑制剂(如奎尼丁、氟西汀、帕罗西汀) 相互作用的研究，但预计该类药物将提高卡维地洛右旋体的浓度。回顾性分析表明，2D6 代谢不良者在加量期眩晕的发生率高，推测可能是由于浓度增高的具有α阻滞活性的右旋体的血管扩张作用。
2. 耗竭儿茶酚胺的药物 卡维地洛与可耗竭儿茶酚胺药物(如利血平、单氨氧化酶抑制剂) 同时服用，必须密切观察患者的低血压和/或严重心动过缓症状，。
3. 地高辛 卡维地洛和地高辛同时服用，可增加血地高辛浓度15%。
4. 可乐定 与卡维地洛同时服用，可能增强降低血压和减慢心率的作用。在停用可乐定前几天应先停用卡维地洛，然后可乐定逐渐减量至停药。
5. 环胞素 增加环胞素的血谷浓度，环胞素需要减量以维持在治疗浓度之内。建议开始卡维地洛的治疗后密切监测环胞素浓度，适当调整环胞素剂量。
6. 肝代谢诱导剂和抑制剂 雷米封减少70%的卡维地洛血浆浓度。西米替丁使卡维地洛的AUC 增加30%，但Cmax无变化。
7. 钙拮抗剂 有报道与地尔硫卓合用发生传导障碍。建议与其它β受体阻滞剂一样，与维拉帕米或地尔硫卓类钙拮抗剂合用时，需监测心电图和血压。
8. 胰岛素或口服降糖药 具有β受体阻滞活性的药物可能增强胰岛素或口服降糖药降低血糖的作用，因此需监测血糖。

【药物过量】：药物过量可能导致严重低血压、心动过缓、心功能不全、心源性休克和心跳骤停，也可能出现呼吸系统问题、气管痉挛、呕吐、神志丧失和抽搐。患者应平卧位，如果需要可重病特别护理。可能使用洗胃和催吐剂。可能使用下列药物：
1．严重心动过缓：阿托品2mg 静脉注射。
2．支持心血管功能：每隔30秒胰高血糖素5~10mg IV，随后5mg/h静脉点滴。应及时给予心血管支持治疗，包括心肺监测、抬高下肢、注意循环血容量和尿量。根据体重和疗效使用拟交感神经药(如多巴胺、异丙肾、肾上腺素)。
3．如果外周血管扩张明显，在持续循环监测的条件下，可能需要使用异丙肾、肾上腺素。对于药物治疗无效的心动过缓，应安装起搏器。对于气管痉挛，应给予β拟交感神经药(气雾剂或静脉用药)或静脉用氨茶碱。抽搐时，缓慢静推安定或氯硝安定。
4．严重药物过量致休克时，解救药物过量的治疗药物必须持续使用至卡维地洛的 7~10个半衰期。
贮藏： 遮光、密封保存。

COREG CR是β-阻滞剂类药品中的一款心脏药物，每日服用一次。COREG CR主要治疗患有及曾患下列一种或多种症状的人群：高血压、心力衰竭、并发/或导致心供血不足的心脏病发作。如果您曾被确诊患有心力衰竭，或曾有导致心供血不足的心脏病发作经历，COREG CR可以加强您的心脏机能并为您提供日常心脏养护。

【原产地英文商品名】COREG 25mg/tab 100tabs/bottle
【原产地英文药品名】CARVEDILOL
【中文参考商品译名】
注：以下产品不同规格和不同价格，购买时请以电话咨询为准！
•络德 25毫克/片 100片/瓶
•络德 6.25毫克/片 100片/瓶
•络德 3.125毫克/片 100片/瓶
【中文参考药品译名】卡维地洛片
【生产厂家中文参考译名】葛兰素史克
【生产厂家英文名】SMITHKLINE BEECHAM

Coreg

Generic Name: carvedilol (KAR ve dil ole)
Brand Names: Coreg, Coreg CR

Coreg Oral Warnings
Do not stop using this drug without first consulting your doctor. Your condition may become worse when the drug is suddenly stopped, especially if you have chest pain (angina) or heart disease (e.g., coronary artery disease, ischemic heart disease, heart failure, high blood pressure). If your doctor decides you should no longer use this drug, you must gradually decrease your dose according to your doctor's instructions.

When gradually stopping this medication, it is recommended that you temporarily limit physical activity to decrease strain on the heart. Seek immediate medical attention if you develop: worsening chest pain, tightness/pressure in the chest, chest pain spreading to the jaw/neck/arm, unusual sweating, trouble breathing, or fast/irregular heartbeat.

Coreg Oral Uses
This medication is an alpha and beta blocker used to treat high blood pressure and heart failure. It is also used after a heart attack to improve the chance of survival. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems.

This drug works by blocking the action of certain natural chemicals in your body (such as epinephrine) that affect the heart and blood vessels. This effect lowers heart rate, blood pressure, and strain on the heart.

How to use Coreg Oral
See also Warning section.

Read the Patient Information Leaflet provided by your pharmacist before you start using carvedilol and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

Take this medication by mouth with food, usually twice daily or as directed by your doctor. Dosage is based on your medical condition and response to treatment.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day. Do not suddenly stop taking this medication without consulting your doctor. Your condition may become worse when the drug is suddenly stopped. Your dose should be gradually decreased.

For the treatment of high blood pressure, it may take 1 to 2 weeks before you get the full benefit of this drug. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick.

Tell your doctor if your condition worsens (e.g., your routine blood pressure readings increase).

Coreg Oral Side Effects
See also Warning and Precautions sections.

Dizziness, lightheadedness, drowsiness, diarrhea, or tiredness may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To lower your risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position. The risk of dizziness is highest within 1 hour after you take your dose. Dizziness is most common when you first start using this drug or any time your doctor increases your dose.

This drug may reduce blood flow to your hands and feet, causing them to feel cold. Smoking may worsen this effect. Dress warmly and avoid tobacco use.

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: very slow heartbeat, severe dizziness, fainting, unusual weakness, new or increased shortness of breath, sudden weight gain, swelling hands/ankles/feet, increased thirst/urination, numbness/tingling of the hands/feet, bluish fingers/toes.

Tell your doctor immediately if any of these rare but very serious side effects occur: change in the amount of urine, easy bruising/bleeding, mental/mood changes (e.g., depression, nervousness), seizures.

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.

Coreg Oral Precautions
Before taking carvedilol, tell your doctor or pharmacist if you are allergic to it; or if you have had a serious reaction to other beta blockers (e.g., propranolol); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: asthma, certain types of heart rhythm problems (sinus bradycardia, sick sinus syndrome, second- or third-degree atrioventricular block), severe heart failure.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, serious reaction/allergy needing treatment with epinephrine, other breathing problems (e.g., bronchitis, emphysema), other heart problems (e.g., Prinzmetal's variant angina), diabetes, overactive thyroid disease (hyperthyroidism), kidney disease, blood circulation problems (e.g., Raynaud's disease, peripheral vascular disease), a certain type of tumor (pheochromocytoma), mental/mood disorders (e.g., depression), a certain muscle disease (myasthenia gravis).

Before having surgery (including cataract eye surgery), tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

This drug may make you dizzy or drowsy or cause you to faint. This is most likely to occur within 1 hour after taking your dose or any time your doctor increases your dose. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

If you have diabetes, this product may prevent the fast/pounding heartbeat you would usually feel when your blood sugar level falls too low (hypoglycemia). Other symptoms of a low blood sugar level, such as dizziness and sweating, are unaffected by this drug. This product also may make it harder to control your blood sugar levels. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor immediately if you have symptoms of high blood sugar such as increased thirst, hunger, and urination. Your anti-diabetic medication or diet may need to be adjusted.

Caution is advised when using this drug in older adults because they may be more sensitive to its effects, especially dizziness and lightheadedness.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

Based on information from related drugs, this medication may pass into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

Coreg Oral 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.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: calcium channel blockers (e.g., diltiazem, verapamil), cyclosporine, digoxin, drugs affecting liver enzymes that remove carvedilol from your body (such as cimetidine, certain heart medications including amiodarone/quinidine/propafenone, rifamycins including rifabutin, certain SSRI antidepressants including fluoxetine/paroxetine), drugs for diabetes (e.g., insulin, sulfonylureas such as glipizide/glyburide), epinephrine, MAO inhibitors (e.g., furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine), other drugs to treat high blood pressure (e.g., clonidine, hydralazine, methyldopa, reserpine), theophylline.

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 using these products safely.

This medication may interfere with certain medical/laboratory tests (including cardiovascular stress testing using arbutamine), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

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.

Coreg Oral Overdose
If overdose is suspected, contact your local poison control center or emergency room immediately. Canada residents can call a provincial poison control center. Symptoms of overdose may include: very slow heartbeat, severe dizziness, fainting, slow/shallow breathing, seizures.

NOTES:
Do not share this medication with others.

Talk with your doctor about making changes to your lifestyle that may increase the effectiveness of this medication (e.g., stress reduction programs, exercise, and dietary changes).

Have your blood pressure and pulse (heart rate) checked regularly while taking this medication. Learn how to monitor your own blood pressure and pulse at home, and share the results with your doctor.

Laboratory and/or medical tests (e.g., kidney function test, liver function test) should be performed regularly to monitor your progress or check for side effects. Consult your doctor for more details.

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 away from light and moisture. Different brands/strengths of this medication may have different storage requirements. Read the package labeling or ask your pharmacist for the storage requirements for the product you are using. Protect from light. Do not store in the bathroom. 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.