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【药品名称】
通用名：卡维地洛片
英文名：CarvedilolTablets
汉语拼音：Kaweidiluopian
【主要成分】
本品主要成分为卡维地洛。
【药理作用】
卡维地洛在治疗剂量范围内，兼有a1和非选择性b受体阻滞作用，无内在拟交感活性。本品阻滞突触后膜a1受体，从而扩张血管、降低外周血管阻力；阻滞b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(t1/2b)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(t1/2b)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%。
【适应证】
原发性高血压：可单独用药，也可和其它降压药合用，尤其是噻嗪类利尿剂。心功能不全：轻度或中度心功能不全(NYHA分级II或III级)，合并应用洋地黄类药物、利尿剂和血管紧张素转换酶抑制剂（ACEI）。也可用于ACEI不耐受和使用或不使用洋地黄类药物、肼屈嗪或硝酸酯类药物治疗的心功能不全者。
【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】
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；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；二度或三度房室传导阻滞；.病态窦房结综合症；心源性休克；严重心动过缓。临床严重肝功能不全患者。对本品过敏者禁用。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b-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。
16．运动员慎用。
【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。
【老人用药】
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】
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。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，。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%。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。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。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。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。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5~10mgIV，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，应给于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。
Eucardic
Main use ：Heart failure
Active ingredient：Carvedilol
Manufacturer：Roche
How does it work?
This medicine contains the active ingredient carvedilol, which is a type of medicine called a beta-blocker.
Beta-blockers block beta-receptors in the heart, lungs and other organs of the body. Blocking these receptors prevents the action of two chemicals called noradrenaline and adrenaline that occur naturally in the body. These are often referred to as the 'fight or flight' chemicals, as they are responsible for the body's reaction to stressful situations.
Carvedilol mainly blocks beta-receptors in the heart, which causes the heart to beat more slowly and with less force. This means that the heart uses less energy and so requires less oxygen from the blood. The pain of angina is caused by not enough oxygen reaching the heart when it's workload is increased, eg during exercise. Carvedilol prevents this pain by decreasing the oxygen demand of the heart, so that it always has a sufficient supply.
Due to the heart beating more slowly and with less force, the pressure at which blood is pumped out of the heart to the rest of the body is reduced. This is one way in which carvedilol reduces blood pressure.
Carvedilol also blocks receptors called alpha-receptors that are present on the walls of blood vessels. Blocking these receptors causes the blood vessels to widen, which means that there is more space and less resistance in the blood vessels. This is another mechanism by which the pressure in the blood vessels is lowered.
The widened blood vessels also allow more blood to reach the heart, which is another way in which carvedilol prevents the pain of angina.
Overall, carvedilol decreases the effort required by the heart to pump blood around the body and so can also be used to treat chronic heart failure, where the pumping action of the heart has become less effective.
Because carvedilol widens the blood vessels and maintains the blood flow to the extremities, it rarely causes the cold extremities (hands and feet) that can occur in people taking other beta-blockers.
What is it used for?
Angina pectoris
Chronic heart failure
High blood pressure (hypertension)
Warning!
This medicine may mask the symptoms of low blood sugar such as increased heart rate, tremor and nausea. People with diabetes should carefully monitor their blood sugar.
This medicine may cause fatigue and dizziness. You should take care when performing potentially hazardous activites, such as driving or operating machinery, until you know how this medicine affects you and are sure you can perform such activities safely.
This medicine may mask the symptoms of the condition caused by an excess of thyroid hormone (thyrotoxicosis).
This medicine should not be stopped abruptly, particularly in people with heart disease caused by poor blood flow to the heart (ischaemic heart disease).
Alcohol may enhance the blood pressure lowering effect of this medicine, which may result in dizziness or fainting.
This medicine may increase sensitivity to substances which cause allergy and the seriousness of severe allergic reactions (anaphylaxis). People who experience an anaphylactic reaction while taking this medicine may need larger than normal doses of adrenaline to treat the reaction. Seek further medical advice from your doctor if you have a history of allergy.
The safety of this medicine has not been established in children and adolescents under the age of 18.
Contact lens wearers should be aware that this medicine may cause dry eyes.
People with chronic heart failure should take this medicine with food.
If this medicine causes the heart rate to drop below 55 beats per minute, the dose should be reduced. Consult your doctor.
For the treatment of heart failure, treatment with carvedilol should be started and checked by a hospital specialist. Your heart failure may worsen while taking this medicine, particularly early on in your treatment. This may cause increased symptoms (eg tiredness, shortness of breath) and signs of fluid retention (eg weight gain and swelling of the legs). Consult your doctor if your symptoms or condition worsen as he may need to change the dose of carvedilol or your other medications.
Use with caution in
A severe form of angina pectoris, not caused by exertion (Prinzmetal's angina)
Decreased kidney function
Diabetes
Disease involving the blood vessels (vascular disease)
History of psoriasis associated with beta-blocker treatment
History of serious allergies
Hyperthyroidism
Narrowing of the blood vessels in the hands, causing numb and painful fingers (Raynaud's disease)
People undergoing therapy to decrease allergy (desensitisation therapy)
Tumour of the adrenal gland (phaeochromocytoma)
Not to be used in
A problem common in the elderly, related to poor control of the working of the heart (sick sinus syndrome)
Chronic obstructive pulmonary disease (COPD)
Decreased liver function
Failure of the electrical impulse that causes the heart to beat to leave the pacemaker of the heart, resulting in decreased heart function (sino-atrial heart block) Failure of the heart to maintain adequate circulation of blood (cardiogenic shock)
History of asthma
History of breathing difficulties due to a narrowing of the airways (bronchospasm)
Increased acid levels in the blood (metabolic acidosis)
Marked fluid retention requiring treatment with intravenous heart medicines (inotropes, eg digoxin)
Serious defect in the heart's electrical message pathways (2nd or 3rd degree heart block), unless an artificial pacemaker is fitted Slow heart rate of less than 50 beats per minute (bradycardia) Tumour of the adrenal gland (phaeochromocytoma), unless this is first treated with an alpha-blocker medicine Very low blood pressure (severe hypotension)
This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.
If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.
Pregnancy and Breastfeeding
Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.
This medicine should be used with caution during pregnancy, and only if the expected benefit to the mother is greater than any possible risk to the foetus. Seek medical advice from your doctor.
This medicine may pass into breast milk. For this reason it is recommended that mothers using this medicine should not breastfeed. Seek medical advice from your doctor.
Label warnings
Do not stop taking this medication except on your doctor's advice.
Side effects
Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Because a side effect is stated here, it does not mean that all people using this medicine will experience that or any side effect.
Headache
Rash
Disturbed sleep
Impotence
Fatigue
Disturbances of the gut such as diarrhoea, constipation, nausea, vomiting or abdominal pain
Weight gain
Visual disturbances
Blockade of the electrical pathways which control the pumping action of the heart (heart block)
Dizziness
Increased blood cholesterol level
Excessive fluid retention in the body tissues, resulting in swelling (oedema)
Slow heart rate (bradycardia)
A drop in blood pressure that occurs when going from lying down to sitting or standing, which results in dizziness and lightheadedness (postural hypotension)
Wheezing
Weakness or loss of strength (asthenia)
Depressed mood
The side effects listed above may not include all of the side effects reported by the drug's manufacturer.
For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.
How can this medicine affect other medicines?
If carvedilol is taken with other medicines that decrease blood pressure, either as their intended action or as a side effect, there may be a risk of a large drop in blood pressure, particularly with the first dose. Alcohol may enhance the blood pressure lowering effect of this medicine, which may result in dizziness or fainting.
In people with diabetes, carvedilol can prolong the lowering of blood sugar (hypoglycaemia) caused by insulin or other antidiabetic medicines. Individuals should monitor their blood sugar, as carvedilol can also mask the signs of hypoglycaemia.
Carvedilol may increase the blood levels of the following medicines:
- ciclosporin
- digoxin.
The blood levels of these medicines should be monitored if they are taken with carvedilol.
If carvedilol is taken with digoxin or diltiazem there may be an increased risk of slow heart rate.
If carvedilol is taken with verapamil the risk of slow heart rate and heart block may be increased.
If carvedilol is taken with medicines for abnormal heart rhythms, such as amiodarone or disopyramide, there may be an increased risk of slow heart rate or other adverse effects on the heart.
Antiarrhythmic medicines, verapamil and diltiazem should not be given intravenously (injected into a vein) to people taking this medicine.
If carvedilol is taken with nifedepine and possibly other calcium channel blockers, the risk of a large fall in blood pressure and heart failure may be increased.
The increase in blood pressure that occurs when the medicine clonidine is stopped may be worsened if carvedilol is being taken at the same time. The carvedilol should be stopped several days before slowly withdrawing the clonidine.
Non-steroidal anti-inflammatory drugs (NSAIDs) such as indometacin may reduce the blood pressure lowering effects of carvedilol.
Care should be taken when adrenaline is given with carvedilol, as this combination may cause severe high blood pressure and slow heart rate.
Rifampicin increases the removal of this medicine from the body, which may result in decreased blood levels of carvedilol . | 
