英文药名: Clozaril(Clozapine Tablets)

中文药名: 氯氮平片

药品名称
通用名称：氯氮平片
英文名称：Clozapine Tablets，Leponex，Clozaril，Clozapine
成份：氯氮平
性状：本品为淡黄色片。
此药也称为: FazaClo.
规格
(1)25mg (2)100mg
药理毒理
本品系苯氮类抗精神病药。对脑内5-羟色胺(5-HT2A)受体和多巴胺(DA1)受体的阻滞作用较强，对多巴胺(DA4)受体的也有阻滞作用，对多巴胺(DA2)受体的阻滞作用较弱，此外还有抗胆碱(M1)，抗组胺(H1)及抗α-肾上腺素受体作用，极少见锥体外系反应，一般不引起血中泌乳素增高。能直接抑制脑干网状结构上行激活系统，具有强大镇静催眠作用。
药代动力学
口服吸收快而完全，食物对其吸收速率和程度无影响，吸收后迅速广泛分布到各组织，生物利用度个体差异较大，平均约50%～60%，有肝脏首过效应。服药后3.2小时(1～4小时)达血浆峰浓度，消除半衰期(t1/2β)平均9小时(3.6～14.3小时)，表观分布容积(Vd)4.04～13.78L/kg，组织结合率高。经肝脏代谢，80%以代谢物形式出现在尿和粪中，主要代谢产物有N-去甲基氯氮平、氯氮平的N-氧化物等。在同等剂量与体重一定的情况下，女性病人的血清药物浓度明显高于男性病人，吸烟可加速本品的代谢，肾清除率及代谢在老年人中明显减低。本品可从乳汁中分泌且可通过血脑屏障。
适应症
本品不仅对精神病阳性症状有效，对阴性症状也有一定效果。适用于急性与慢性精神分裂症的各个亚型，对幻觉妄想型、青春型效果好。也可以减轻与精神分裂症有关的情感症状(如：抑郁、负罪感、焦虑)。对一些用传统抗精神病药治疗无效或疗效不好的病人，改用本品可能有效。
本品也用于治疗躁狂症或其他精神病性障碍的兴奋躁动和幻觉妄想。因导致粒细胞减少症，一般不宜作为首选药。
用法用量
(1)治疗精神分裂症：口服开始剂量为每日50～100mg，分2～3次，以后视病人耐受情况逐渐递增，一般有效剂量为每日 0.4～0.6g，分次服用，待病情缓解后渐减至每日0.1g作为维持量。肌注每次50～100mg，每日2次。一般在用药1周后可见效。
(2)治疗躁狂症：一般多采用注射给药，每次肌注50～100mg，每日3次，疗程1～2周。维持治疗可采用口服给药。
(3)治疗其他疾病的用法从小剂量开始，根据临床效果调整药量。
任何疑问，请遵医嘱！
不良反应
1．血液系统反应
这是氯氮平最易发生的严重不良反应。主要表现为白细胞减少甚至粒细胞缺乏，偶可出现白细胞增多，部分病人可引起血小板减少。由氯氮平引起的粒细胞缺乏多发生在用药后的1～6个月内，但也有在用药后1～2天内突然发生者，早期症状与上呼吸道感染的症状相似。所以治疗过程中及停药后4周内均应严密观察血象变化。一般应每周进行一次白细胞检测，如白细胞数低于3×109／L，或粒细胞数低于15×109／L，则应立即停药，停药后一般在2周内白细胞数可基本恢复正常。
2．心血管系统反应
较常见的有心悸(16％)、心动过速(25％)、低血压(90％)和直立性低血压(3％～4％)、心律不齐(2％)、高血压(4％)等。氯氮平所致的低血压多在服药初期发生，多数是一过性低血压至直立性虚脱，但持续用药血压可趋稳定。服药期间，心电图异常的发生率可达7％以上，主要表现为频率改变、ST段下降、QRS及Q-T间期延长，传导阻滞等。
3．消化系统反应
较常见的有食欲减退、恶心、呕吐、腹痛、腹胀、腹泻或便秘，偶可发生肠麻痹、胃出血和一过性肝损害。引起肠麻痹的原因可能是氯氮平对肠运动神经的作用，进而影响体液调节而致的动力性肠麻痹。
4．自主神经系统反应
最常见为流涎(31％)和便秘(14％)，其次为出汗、视力模糊和口干，个别病人可出现神经阻滞恶性综合征(NMS)，主要表现为肌强直、意识障碍以及发热、心动过速、血压异常、大汗、流涎、呼吸急促等自主神经功能紊乱。
禁忌
严重心、肝、肾疾患、昏迷、谵妄、低血压、癫痫、青光眼、骨髓抑制或白细胞减少者禁用。对本品过敏者禁用。
注意事项
1．出现过敏性皮疹及恶性综合征应立即停药并进行相应的处理。
2．中枢神经抑制状态者慎用。尿潴留患者慎用。
3．治疗头3个月内应坚持每1～2周检查白细胞计数及分类，以后定期检查。
4．定期检查肝功能与心电图。
5．定期检查血糖，避免发生糖尿病或酮症酸中毒。
6．用药期间不宜驾驶车辆、操作机械或高空作业。
7．用药期间出现不明原因发热，应暂停用药。
孕妇及哺乳期妇女用药
孕妇禁用。哺乳期妇女使用本品期间应停止哺乳。
儿童用药
12岁以下儿童不宜使用。
老年患者用药
慎用或使用低剂量。
药物相互作用
1．本品与乙醇或与其他中枢神经系统抑制药合用可增加中枢抑制作用。
2．本品与抗高血压药合用有增加体位性低血压的危险。
3．本品与抗胆碱药合用可增加抗胆碱作用。
4．本品与地高辛、肝素、苯妥英、华法令合用，可加重骨髓抑制作用。
5．本品与碳酸锂合用，有增加惊厥、恶性综合征、精神错乱与肌张力障碍的危险。
6．本品与氟伏沙明、氟西汀、帕罗西汀、舍曲林等抗抑郁药合用可升高血浆氯氮平与去甲氯氮平水平。
7．本品与大环内酯类抗生素合用可使血浆氯氮平浓度显著升高，并有报道诱发癫痫发作。
药物过量
中毒症状：最常见的症状和包括谵妄、昏迷、心动过速、低血压、呼吸抑制或衰竭、唾液分泌过多等，也有发生癫痫的报道。
处理：建立和维持呼吸道通畅，及时催吐和洗胃，并依病情给予对症治疗及支持疗法。

tablet form 25mg, 50mg and 100mg.
Commonly used brand name(s):
In the U.S., India and rest of the world:
•Clozapine
•Fazaclo
•Zaponex
•Clopine
•Generic Clozaril
•Generic Clozapine
•Sizopine
Available Dosage Forms:
•Tablet, Disintegrating
•Tablet
Therapeutic Class: Antipsychotic
Chemical Class: Dibenzodiazepine
Uses For Clozaril
Clozapine is used to treat schizophrenia in patients who have not been helped by or are unable to take other medicines. This medicine should NOT be used to treat behavioral problems in older adult patients who have dementia.
Clozapine is available only from pharmacies that agree to participate with your doctor in a plan to monitor your blood tests. You will need to have blood tests done every week for at least 6 months. After that, your doctor will decide if it is safe for you to have blood tests every other week. You will receive enough clozapine to last until your next blood test, but only if the results of your blood tests show that it is safe for you to take this medicine. If any of your blood tests are not normal, you may need to have blood tests more often than every week until they return to normal.
Before Using Clozaril
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:
Allergies
Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Pediatric
Appropriate studies have not been performed on the relationship of age to the effects of clozapine in the pediatric population. Safety and efficacy have not been established.
Geriatric
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of clozapine in the elderly. However, elderly patients are more likely to have constipation or age-related liver, kidney, or heart problems, which may require caution in patients receiving clozapine. This medicine should not be used for behavioral problems in older adults with dementia.
Pregnancy
Pregnancy - Trimesters - B: Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.
Breast Feeding
There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.
Interactions with Medicines
Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
•Droperidol
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
•Buspirone
•Carbamazepine
•Lithium
•Mate
•Tramadol
•Zotepine
Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
•Aprindine
•Cimetidine
•Ciprofloxacin
•Citalopram
•Encainide
•Erythromycin
•Flecainide
•Fluoxetine
•Fluvoxamine
•Lorcainide
•Nefazodone
•Nicotine
•Paroxetine
•Perphenazine
•Phenobarbital
•Phenytoin
•Propafenone
•Quinidine
•Rifampin
•Ritonavir
•Sertraline
•Thioridazine
•Venlafaxine
Interactions with Food/Tobacco/Alcohol
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.
Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.
•Caffeine
Other Medical Problems
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:
•Blood diseases (e.g., agranulocytosis, granulocytopenia), history of or
•Bone marrow disorder or
•Central nervous system depression (not fully awake), severe or
•Intestinal blockage or
•Seizures, uncontrolled—Should not be used in patients with these conditions.
•Blood vessel problems (poor circulation) or
•Heart attack, history of or
•Heart failure or
•Heart rhythm problems or
•Hypotension (low blood pressure) or
•Lung problems or
•Stroke, history of—May cause side effects to become worse.
•Constipation or
•Diabetes or
•Difficult urination or
•Enlarged prostate or
•Glaucoma, narrow angle or
•Liver disease (e.g., hepatitis) or
•Neuroleptic malignant syndrome, history of or
•Seizures, history of—Use with caution. May make these conditions worse.
•Kidney disease or
•Liver disease—Higher blood levels of clozapine may occur, increasing the chance that unwanted effects will occur.
Proper Use of clozapine
This section provides information on the proper use of a number of products that contain clozapine. It may not be specific to Clozaril. Please read with care.
Take this medicine exactly as directed. Do not take more of it and do not take it more often than your doctor ordered. Do not miss any doses.
This medicine has been prescribed for your current medical condition only. It must not be given to other people or used for other conditions. Talk to your doctor if you have questions.
Take the tablets with or without food.
Dosing
The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
•For oral dosage form (tablets):
◦For schizophrenia:
■+ Adults—At first, 12.5 milligrams (mg) (one half of a 25-mg tablet) once or twice a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 900 mg a day.
■+ Children—Use and dose must be determined by your doctor.
Missed Dose
If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
If you miss 2 or more days of clozapine doses, talk to your doctor before you start taking it again. You may need to restart this medicine at a lower dose than you were taking before.
Storage
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
Precautions While Using Clozaril
It is important that you have your blood tests done when they are scheduled, and that your doctor check your progress at regular visits. Clozapine can cause some very serious blood problems that you may not be able to feel or see. The pharmacy will give you this medicine only if your blood tests show that it is safe for you to take clozapine. Also, your doctor will make sure the medicine is working properly and change the dosage if needed.
If you have been using this medicine regularly, do not stop taking it without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are taking before stopping it completely. This is to help prevent the illness from suddenly returning and to decrease the chance of having symptoms such as headache, nausea, vomiting or diarrhea.
This medicine will add to the effects of alcohol and other central nervous system (CNS) depressants, which are medicines that slow down the nervous system and possibly cause drowsiness. Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; barbiturates; medicine for seizures; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using this medicine.
Clozapine can temporarily lower the number of white blood cells in your blood, which increases the chance of getting an infection. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection:
•If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
•Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
•Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
Contact your doctor as soon as possible if you have chest pain or discomfort, a fast heartbeat, trouble breathing, or fever and chills. These can be symptoms of a very serious problem with your heart.
Clozapine may cause drowsiness, blurred vision or convulsions (seizures). Do not drive, climb, swim, operate machines or do anything else that could be dangerous while you are taking this medicine.
Dizziness, lightheadedness, or fainting may occur, especially when you get up from a lying or sitting position suddenly. Getting up slowly may help. If this problem continues or gets worse, check with your doctor.
This medicine may increase the amount of sugar in your blood. Check with your doctor right away if you have increased thirst or urination. Diabetic patients should check their blood and urine sugar levels more often while taking this medicine. The dose of diabetic medicines may need to be changed.
In some patients, clozapine may cause increased watering of the mouth. Other patients, however, may get dryness of the mouth. For temporary relief of mouth dryness, use sugarless gum or candy, melt bits of ice in your mouth, or use a saliva substitute. However, if your mouth continues to feel dry for more than 2 weeks, check with your medical doctor or dentist. Continuing dryness of the mouth may increase the chance of dental disease, including tooth decay, gum disease, and fungus infections.
Check with your doctor right away if you are having convulsions (seizures); difficulty with breathing; fast heartbeat; high fever; high or low blood pressure; increased sweating; loss of bladder control; severe muscle stiffness; unusually pale skin; or tiredness. These could be symptoms of a serious condition called neuroleptic malignant syndrome (NMS).
This medicine may cause tardive dyskinesia (a movement disorder) among the elderly, especially elderly women. Check with your doctor right away if you have any of the following symptoms while taking this medicine: lip smacking or puckering, puffing of the cheeks, rapid or worm-like movements of the tongue, uncontrolled chewing movements, or uncontrolled movements of the arms and legs.
Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine several days before having surgery or medical tests.
Clozaril Side Effects
Along with its needed effects, a medicine may cause some unwanted effects. Some side effects may not have signs or symptoms that you can see or feel. Clozapine can cause some very serious blood problems. Your doctor will watch for these by doing blood tests every week or two for as long as you are taking clozapine and for 4 weeks after you stop taking it. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
More common
•Blurred vision
•confusion
•dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
•fainting
•fast, pounding, or irregular heartbeat or pulse
•fever
•low blood pressure
•shakiness in legs, arms, hands, or feet
•sleepiness or unusual drowsiness
•sweating
•trembling or shaking of hands or feet
•unusual tiredness or weakness
Less common
•Anxiety
•black, tarry stools
•chest pain
•chills
•convulsions
•cough or hoarseness
•decrease in frequency of urination
•decrease in urine volume
•difficult or labored breathing
•difficulty in passing urine (dribbling)
•discouragement
•dry mouth
•fear or nervousness
•feeling sad or empty
•fever with or without chills
•frequent strong or increased urge to urinate
•general feeling of tiredness or weakness
•headache
•hyperventilation
•irritability
•lack of appetite
•loss of bladder control
•loss of interest or pleasure
•lower back or side pain
•mood or mental changes
•muscle spasm or jerking of all extremities
•painful or difficult urination
•pounding in the ears
•restlessness or need to keep moving
•severe or continuing headache
•shakiness and unsteady walk
•shortness of breath
•slurred speech
•sore throat
•sores, ulcers, or white spots on lips or in mouth
•sudden jerky movements of body
•sudden loss of consciousness
•swollen glands
•throat discomfort
•tightness in chest
•trouble concentrating
•trouble sleeping
•unsteadiness, trembling, or other problems with muscle control or coordination
•wheezing
Rare
•Absence of or decrease in movement
•dark urine
•decreased appetite
•decreased sexual ability
•difficult or fast breathing or sudden shortness of breath
•increased appetite
•increased sweating
•increased thirst
•increased urination
•lip smacking or puckering
•loss of bladder control
•mental depression
•muscle stiffness (severe)
•nausea
•puffing of the cheeks
•rapid or worm-like movements of the tongue
•swelling or pain in leg
•trouble breathing
•trouble in urinating
•uncontrolled chewing movements
•uncontrolled movements of the arms and legs
•unusual bleeding or bruising
•unusually pale skin
•vomiting
•weakness
•yellow eyes or skin
Incidence not known
•Abdominal or stomach pain
•bloating
•burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
•clay-colored stools
•confusion as to time, place, or person
•constipation
•darkened urine
•diarrhea
•epileptic seizure that will not stop
•feeling that others are watching you or controlling your behavior
•feeling that others can hear your thoughts
•feeling, seeing, or hearing things that are not there
•holding false beliefs that cannot be changed by fact
•inability to move eyes
•increased blinking or spasms of eyelid
•indigestion
•itching
•joint pain
•light-colored stools
•muscle twitching
•pains in stomach, side, or abdomen, possibly radiating to the back
•rhythmic movement of muscles
•severe mood or mental changes
•skin rash
•sticking out of tongue
•swelling around the eyes
•swelling of body or feet and ankles
•trouble in breathing, speaking, or swallowing
•uncontrolled twisting movements of neck, trunk, arms, or legs
•unpleasant breath odor
•unusual behavior
•unusual excitement, nervousness, or restlessness
•unusual facial expressions
•unusual weight gain
•upper right abdominal pain
•vomiting of blood
•yellow eyes or skin
Get emergency help immediately if any of the following symptoms of overdose occur:
Symptoms of overdose
•Change in consciousness
•drowsiness
•increased watering of mouth (severe)
•irregular, fast or slow, or shallow breathing
•loss of consciousness
•pale or blue lips, fingernails, or skin
•pounding or rapid pulse
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common
•Acid or sour stomach
•belching
•feeling of constant movement of self or surroundings
•heartburn
•relaxed and calm sensation of spinning
•sleepiness
•sleeplessness
•unable to sleep
Less common
•Blurred or loss of vision
•change or problem with discharge of semen
•disturbed color perception
•double vision
•halos around lights
•inability to sit still
•increase in body movements
•muscle pain or ache
•muscle weakness
•night blindness
•nightmares
•overbright appearance of lights
•pain in the back, neck, or legs
•pain in the chest below the breastbone
•severe muscle stiffness
•sore tongue
•stuffy nose
•tunnel vision
•unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
Incidence not known
•Blistering, peeling, or loosening of skin
•difficulty swallowing
•hives
•increased sensitivity of skin to sunlight
•painful or prolonged erection of the penis
•red, irritated eyes
•red skin lesions, often with a purple center
•reddening of the skin, especially around ears
•severe stomach pain
•severe sunburn
•sores, welting, or blisters
•swelling of eyes, face, or inside of nose
•swelling of salivary glands
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
完整说明阅览：http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=16164