部份中文达沙替尼处方资料（仅供参考） 中文名：达沙替尼片 商品名：Sprycel(Dasatinib Tablets) 通用名：Dasatinib 生产厂家：百时美施贵宝 作用机制 达沙替尼，在纳克分子浓度抑制下列激酶：BCR-ABL，SRC家族(SRC，LCK，YES，FYN)，c-KIT，EPHA2,和PDGFRβ。根据模型研究，预计达沙替尼与ABL激酶的多种构象结合。 在体外，达沙替尼在甲磺酸伊马替尼敏感和耐药病的血病细胞株代表变种有活性。达沙替尼抑制过表达BCR-ABL的慢性粒性白血病(CML)和急性淋巴细胞白血病(ALL)细胞株的生长。在分析条件下，达沙替尼能克服来自BCR-ABL激酶结构区突变导致伊马替尼耐药性，激活SRC家族激酶(LYN, HCK)另外涉及信号通路，和多药抗药基因过表达。 适应证和用途 SPRYCEL是一种激酶抑制剂适用于下列治疗 （1）新诊断的有费城染色体-阳性(Ph+)慢性期慢性粒细胞白血病(CML)成年。将需要正进行试验和进一步资料确定长期结局。 （2）有慢性，加速，或粒性或淋巴原始细胞期Ph+CML对既往治疗包括伊马替尼[imatinib]有耐药或不能耐受的成年。 （3）有费城染色体-阳性急性淋巴细胞白血病(Ph+ALL)对既往治疗耐药或不能耐受的成年。 剂量和给药方法 （1）慢性期CML：100mg每天1次。 （2）加速期CML，粒性或淋巴原始细胞期CML，或Ph+ALL：140 mg每天1次。 口服给药，有或无进餐。不要弄碎或切片。 剂型和规格 片剂：20mg，50mg，70mg，80mg，100mg，和140mg。 禁忌证 无。 警告和注意事项 骨髓抑制：可能发生严重血小板减少，中性粒细胞减少，和贫血和需要中断给药或减量。定期监测完全血细胞计数。 出血相关事件(大多数伴随严重血小板减少)：曾发生CNS和胃肠道出血，包括死亡。严重出血可能需要中断治疗和输血。在需要抑制血小板功能或抗凝剂药物患者中慎用SPRYCEL。 液体潴留：SPRYCEL伴随液体潴留，有时严重，包括腹水，水肿，和胸和心包积液。用适当支持治疗措施处理。 QT延长：在已经或可能发生QT间隔延长患者中慎用SPRYCEL。 充血性心衰，左室功能不全和心肌梗死：监查患者对与心功能不全一致征象和症状和适当治疗。 当给予妊娠妇女可能危害胎儿，应忠告妇女对胎儿潜在危害和避免成为怀孕。 不良反应 有新诊断的慢性期CML患者中最常见不良反应(≥10%)包括骨髓抑制，液体潴留，腹泻，头痛，肌肉骨骼痛，和皮疹。在有耐药或不能耐受对既往伊马替尼治疗患者中最常见不良反应(≥20%)包括骨髓抑制，液体潴留事件，腹泻，头痛，呼吸困难，皮疹，疲劳，恶心，和出血。 药物不良反应 （1）CYP3A4抑制剂：可能增加达沙替尼药物水平和应避免。如不能避免同时给药，严密监视和考虑减低SPRYCEL剂量。 （2）CYP3A4诱导剂：可能减低达沙替尼药物水平。如不能避免同时给药, 考虑增加SPRYCEL剂量。 （3）抗酸药：可能减低达沙替尼药物水平。避免同时给药，如需要，SPRYCEL给药前至少2小时或后2小时给予抗酸药. （4）H2拮抗剂/质子泵抑制剂：可能减低达沙替尼药物水平，考虑抗酸药代替H2拮抗剂或质子泵抑制剂。 在特殊人群中使用 • 肝损伤：在有肝损伤患者中慎用SPRYCEL。 注：本栏英国药品，采购者以咨询为准。 Sprycel 20mg 50mg 80mg 100mg 140mg Film Coated Tablets Bristol-Myers Squibb Pharmaceuticals Limited The product code(s) for this leaflet are: EU/1/06/363/008, EU/1/06/363/002, EU/1/06/363/011, EU/1/06/363/015, EU/1/06/363/001, EU/1/06/363/012, EU/1/06/363/014, EU/1/06/363/007, EU/1/06/363/005, EU/1/06/363/010, EU/1/06/363/013, EU/1/06/363/004. Sprycel 20mg 50mg 80mg 100mg 140mg Film Coated Tablets Package leaflet: Information for the user SPRYCEL 20 mg film-coated tablets SPRYCEL 50 mg film-coated tablets SPRYCEL 70 mg film-coated tablets SPRYCEL 80 mg film-coated tablets SPRYCEL 100 mg film-coated tablets SPRYCEL 140 mg film-coated tablets dasatinib Read all of this leaflet carefully before you start taking this medicine because it contains important information for you. •Keep this leaflet. You may need to read it again. •If you have any further questions, ask your doctor or pharmacist. •This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. •If you get any side effects , talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4. What is in this leaflet 1. What SPRYCEL is and what it is used for 2. What you need to know before you take SPRYCEL 3. How to take SPRYCEL 4. Possible side effects 5. How to store SPRYCEL 6. Contents of the pack and other information 1. What SPRYCEL is and what it is used for SPRYCEL contains the active substance dasatinib. This medicine is used to treat chronic myeloid leukaemia (CML) in adults. Leukaemia is a cancer of white blood cells. These white cells usually help the body to fight infection. In people with CML, white cells called granulocytes start growing out of control. SPRYCEL inhibits the growth of these leukaemic cells. SPRYCEL is also used to treat Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia (ALL), and lymphoid blast CML in adults who are not benefiting from prior therapies. In people with ALL, white cells called lymphocytes multiply too quickly and live too long. SPRYCEL inhibits the growth of these leukaemic cells. If you have any questions about how SPRYCEL works or why this medicine has been prescribed for you, ask your doctor. 2. What you need to know before you take SPRYCEL Do not take SPRYCEL •if you are allergic to dasatinib or any of the other ingredients of this medicine (listed in section 6). If you could be allergic, ask your doctor for advice. Warnings and precautions Talk to your doctor or pharmacist before using SPRYCEL •if you are taking medicines to thin the blood or prevent clots (see "Other medicines and SPRYCEL") •if you have a liver or heart problem, or used to have one •if you start having difficulty breathing, chest pain, or a cough when taking SPRYCEL: this may be a sign of fluid retention in the lungs or chest (which can be more common in patients aged 65 years and older), or due to changes in the blood vessels supplying the lungs •if you have ever had or might now have a hepatitis B infection. This is because SPRYCEL could cause hepatitis B to become active again, which can be fatal in some cases. Patients will be carefully checked by their doctor for signs of this infection before treatment is started. Your doctor will regularly monitor your condition to check whether SPRYCEL is having the desired effect. You will also have blood tests regularly while you are taking SPRYCEL. Children and adolescents SPRYCEL is not recommended for patients below 18 years of age. There is limited experience with the use of SPRYCEL in this age group. Other medicines and SPRYCEL Tell your doctor if you are taking, have recently taken or might take any other medicines. SPRYCEL is mainly handled by the liver. Certain medicines may interfere with the effect of SPRYCEL when taken together. These medicines are not to be used with SPRYCEL: •ketoconazole, itraconazole - these are antifungal medicines •erythromycin, clarithromycin, telithromycin - these are antibiotics •ritonavir - this is an antiviral medicine •dexamethasone - this is a corticosteroid •phenytoin, carbamazepine, phenobarbital - these are treaments for epilepsy •rifampicin - this is a treatment for tuberculosis •famotidine, omeprazole - these are medicines that block stomach acids •St. John’s wort - a herbal preparation obtained without a prescription, used to treat depression and other conditions (also known as Hypericum perforatum) Do not take medicines that neutralise stomach acids (antacids such as aluminium hydroxide or magnesium hydroxide) in the 2 hours before or 2 hours after taking SPRYCEL. Tell your doctor if you are taking medicines to thin the blood or prevent clots. SPRYCEL with food and drink Do not take SPRYCEL with grapefruit or grapefruit juice. Pregnancy and breast-feeding If you are pregnant or think you may be pregnant, tell your doctor immediately. SPRYCEL is not to be used during pregnancy unless clearly necessary. Your doctor will discuss with you the potential risk of taking SPRYCEL during pregnancy. Both men and women taking SPRYCEL will be advised to use effective contraception during treatment. If you are breast-feeding, tell your doctor. You should stop breast-feeding while you are taking SPRYCEL. Driving and using machines Take special care when driving or using machines in case you experience side effects such as dizziness and blurred vision. It is not known if SPRYCEL will affect your ability to drive or use machines. SPRYCEL contains lactose If you have been told by your doctor that you have an intolerance to some sugars, talk to your doctor before taking this medicine. 3. How to take SPRYCEL SPRYCEL will only be prescribed to you by a doctor with experience in treating leukaemia. Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure. SPRYCEL is prescribed for adults. The starting dose recommended for patients with chronic phase CML is 100 mg once a day. The starting dose recommended for patients with accelerated or blast crisis CML or Ph+ ALL is 140 mg once a day. Take your tablets at the same time every day. Depending on how you respond to the treatment, your doctor may suggest a higher or lower dose, or even stopping treatment briefly. For higher or lower doses, you may need to take combinations of the different tablet strengths. The tablets may come in packs with calendar blisters. These are blisters showing the days of the week. There are arrows to show the next tablet to be taken according to your treatment schedule. How to take SPRYCEL Swallow the tablets whole. Do not crush them. They can be taken with or without a meal. Special handling instructions for SPRYCEL It is unlikely that the SPRYCEL tablets will get broken. But if they do, persons other than the patient should use gloves when handling SPRYCEL. How long to take SPRYCEL Take SPRYCEL daily until your doctor tells you to stop. Make sure you take SPRYCEL for as long as it is prescribed. If you take more SPRYCEL than you should If you have accidentally taken too many tablets, talk to your doctor immediately. You may require medical attention. If you forget to take SPRYCEL Do not take a double dose to make up for a forgotten tablet. Take the next scheduled dose at the regular time. If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 4. Possible side effects Like all medicines, this medicine can cause side effects, although not everybody gets them. The following can all be signs of serious side effects: •if you have chest pain, difficulty breathing, coughing and fainting •if you experience unexpected bleeding or bruising without having an injury •if you find blood in your vomit, stools or urine, or have black stools •if you get signs of infections such as fever, severe chills •if you get fever, sore mouth or throat, blistering or peeling of your skin and/or mucous membranes Contact your doctor immediately if you notice any of the above. Very common side effects (may affect more than 1 in 10 people) •Infections (including bacterial, viral and fungal) •Heart and lungs: shortness of breath •Digestive problems: diarrhoea, feeling or being sick (nausea, vomiting) •Skin, hair, eye, general: skin rash, fever, swelling around the face, hands and feet, headache, feeling tired or weak, bleeding •Pain: pain in the muscles, tummy (abdominal) pain •Tests may show: low blood platelet count, low white blood cells count (neutropaenia), anaemia, fluid around the lungs Common side effects (may affect up to 1 in 10 people) •Infections: pneumonia, herpes virus infection, upper respiratory tract infection, serious infection of the blood or tissues (including uncommon cases with fatal outcomes) •Heart and lungs: palpitations, irregular heartbeat, congestive heart failure, weak heart muscle, high blood pressure, increased blood pressure in the lungs, cough •Digestive problems: appetite disturbances, taste disturbance, bloated or distended tummy (abdomen), inflammation of the colon, constipation, heartburn, mouth ulceration, weight increase, weight decrease, gastritis •Skin, hair, eye, general: skin tingling, itching, dry skin, acne, inflammation of the skin, persistent noise in ears, hair loss, excessive perspiration, visual disorder (including blurred vision and disturbed vision), dry eye, bruise, depression, insomnia, flushing, dizziness, contusion (bruising), anorexia, somnolence, generalised oedema •Pain: pain in joints, muscular weakness, chest pain, pain around hands and feet, chills, stiffness in muscles and joints, muscle spasm •Tests may show: fluid around the heart, fluid in the lungs, arrhythmia, febrile neutropaenia, gastrointestinal bleeding, high uric acid levels in the blood Uncommon side effects (may affect up to 1 in 100 people) •Heart and lungs: heart attack (including fatal outcome), inflammation of the lining (fibrous sack) surrounding the heart, irregular heartbeat, chest pain due to lack of blood supply to the heart (angina), low blood pressure, narrowing of airway that may cause breathing difficulties, asthma, increased blood pressure in the arteries (blood vessels) of the lungs •Digestive problems: inflammation of the pancreas, peptic ulcer, inflammation of the food pipe, swollen tummy (abdomen), tear in the skin of the anal canal, difficulty in swallowing, inflammation of the gallbladder, blockage of bile ducts, gastro-oesophageal reflux (a condition where acid and other stomach contents come back up into the throat) •Skin, hair, eye, general: allergic reaction including tender, red lumps on the skin (erythema nodosum), anxiety, confusion, mood swings, lower sexual drive, fainting, tremor, inflammation of the eye which causes redness or pain, a skin disease characterized by tender, red, well-defined blotches with the sudden onset of fever and raised white blood cell count (neutrophilic dermatosis), loss of hearing, sensitivity to light, visual impairment, increased eye tearing, disturbance in skin colour, inflammation of fatty tissue under the skin, skin ulcer, blistering of the skin, nail disorder, hair disorder, hand-foot disorder, renal failure, urinary frequency, breast enlargement in men, menstrual disorder, general weakness and discomfort, low thyroid function, losing balance while walking, osteonecrosis (a disease of reduced blood flow to the bones, which can cause bone loss and bone death), arthritis, skin swelling anywhere in the body •Pain: inflammation of vein which can cause redness, tenderness and swelling, inflammation of the tendon •Brain: loss of memory •Tests may show: abnormal blood test results and possibly impaired kidney function caused by the waste products of the dying tumour (tumour lysis syndrome), low levels of albumin in the blood, low levels of lymphocytes (a type of white blood cell) in the blood, high level of cholesterol in the blood, swollen lymph nodes, bleeding in the brain, irregularity of the electrical activity of the heart, enlarged heart, inflammation of the liver, protein in the urine, raised creatine phosphokinase (an enzyme mainly found in the heart, brain and skeletal muscles), raised troponin (an enzyme mainly found in the heart and skeletal muscles), raised gamma-glutamyltransferase (an enzyme mainly found in the liver) Rare side effects (may affect up to 1 in 1,000 people) •Heart and lungs: enlargement of the right ventricle in the heart, inflammation of the heart muscle, collection of conditions resulting from blockage of blood supply to the heart muscle (acute coronary syndrome), cardiac arrest (stopping of blood flow from the heart), coronary (heart) artery disease, inflammation of the tissue covering the heart and lungs, blood clots, blood clots in the lungs •Digestive problems: loss of vital nutrients such as protein from your digestive tract, bowel obstruction, anal fistula (an abnormal opening from the anus to the skin around the anus), impairment of kidney function, diabetes •Skin, hair, eye, general: convulsion, inflammation of the optic nerve that may cause a complete or partial loss of vision, blue-purple mottling of the skin, abnormally high thyroid function, inflammation of the thyroid gland, ataxia (a condition associated with lack of muscular coordination), difficulty walking, miscarriage, inflammation of the skin blood vessels, skin fibrosis •Brain: stroke, temporary episode of neurologic dysfunction caused by loss of blood flow, facial nerve paralysis, dementia Other side effects that have been reported (frequency not known) include: •Inflammation of the lungs •Bleeding in the stomach or bowels that can cause death •Recurrence (reactivation) of hepatitis B infection when you have had hepatitis B in the past (a liver infection) •A reaction with fever, blisters on the skin, and ulceration of the mucous membranes •Disease of the kidneys with symptoms including oedema and abnormal laboratory test results such as protein in the urine and low protein level in the blood Your doctor will check for some of these effects during your treatment. Reporting of side effects If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly (see details below). By reporting side effects you can help provide more information on the safety of this medicine.