部份中文Levact處方資料（僅供參考） 英文名: Levact(Bendamustine) 中文名: 鹽酸苯達莫司汀 生產廠家: Mundipharma GmbH 適應症： 1.慢性淋巴細胞白血病（CLL）。不同於苯丁酸氮芥的一線療法的療效尚未確立。 2.在利妥昔單抗（rituximab，美羅華）或含利妥昔單抗方案治療過程中，或者治療6個月內，病情仍然進展的惰性B細胞非霍奇金淋巴瘤（NHL）患者。 作用機理 本品是一種雙功能基烷化劑，可以導致DNA單鍊和雙鏈通過烷化作用交聯，打亂DNA 的功能和DNA的合成，使DNA和蛋白之間，以及蛋白和蛋白之間產生交聯，從而發揮抗腫瘤作用。 用法用量： 劑量及用藥 該藥儲存溫度不應超過30℃，避光保存，使用前臨時配製。 配製流程：該藥每100mg須先溶於20ml無菌注射用水，充分振搖直到完全溶解成澄清、無色或淡黃色溶液，溶解時間一般不超過5分鐘，溶解後濃度為5mg/ml。在溶解後30分鐘之內，根據需要抽取適量苯達莫司汀水溶液，轉移至500ml氯化鈉注射液（0.9%）或葡萄糖氯化鈉注射液（2.5%/0.45%）中，並確保苯達莫司汀在註射液中的最終濃度在0.2～0.6mg/ml之間。配製好的注射液可在2～8℃冷藏保存24小時，或在室溫及自然光下保存3小時。 苯達莫司汀治療CLL時，以28天為一個治療週期，一般需要6個治療週期。在每個治療週期的第一天和第二天給藥，推薦劑量為100mg/m2。該藥經靜脈滴注給藥，每次給藥時間不應少於30分鐘。 苯達莫司汀治療NHL時，以21天為一個治療週期，一般需要8個治療週期。在每個治療週期的第一天和第二天給藥，推薦劑量為120mg/m2。每次給藥時間不應少於60分鐘。 禁忌症 對鹽酸苯達莫司汀及甘露醇過敏者禁用。 藥物相互作用 與CYP1A2抑製劑（如氟伏沙明，環丙沙星等）合用時，有可能會升高苯達莫司汀血濃度，並使其代謝物M3和M4濃度降低；與CYP1A2誘導劑（如奧美拉唑，抽煙等）合用時，有可能會降低苯達莫司汀血濃度，並使其代謝物M3和M4濃度升高。 不良反應 苯達莫司汀常見不良反應包括噁心、嘔吐、腹瀉、疲乏、虛弱、皮疹、搔癢、一些感染症狀和體徵（如持續咽喉疼痛、發熱和寒戰）、容易碰傷/出血以及口腔潰瘍等；嚴重不良反應可能還有骨髓抑制、腫瘤溶解綜合徵等。苯達莫司汀可能引起輕微或嚴重過敏反應，患者在給藥過程中或給藥後初期可能出現皮疹、面部腫脹、呼吸困難等過敏症狀。苯達莫司汀可能對胎兒造成影響，因此，女性治療過程中及治療後3個月內，應採取適當避孕措施及停止哺乳。 產品特點 ①療效確切，能明顯降低復發率與死亡率，且不良反應小，安全性好，起效迅速，作用持久； ②本品在31至84歲人群中的藥代動力學指標（AUC和Cmax）顯示：65周歲以上或以下患者之間沒有明顯區別； ③在兒童患者上的有效性雖尚未建立。但通過白血病兒童患者的I、II期臨床試驗評估，其安全性與成人體內基本相似； ④隨著深入臨床研究，未來可能擴大到兒童用藥； ⑤R-CHOP方案（環磷酰胺、多柔比星、長春新鹼、潑尼松加利妥昔單抗）是目前晚期惰性淋巴瘤和套細胞淋巴瘤老年患者的一線標準治療。苯達莫司汀單藥治療利妥昔單抗耐藥的B細胞惰性淋巴瘤可提高療效,且耐受性良好。研究發現苯達莫司汀聯合利妥昔單抗較之傳統R-CHOP更有效且毒性更小，耐受性更好。 《柳葉刀》雜誌的一項研究，苯達莫司汀聯合利妥昔單抗治療方案可以替代標準治療，用於新診斷的惰性非霍奇金淋巴瘤(NHL)和套細胞淋巴瘤( MCL)患者。 ------------------------------------------- 提示：本品德国上市产品，有现货，需要者请赶快采购。 ------------------------------------------- 产地国家: 德国 原产地英文商品名: Levact 100mg/vial 5injectable solution 原产地英文药品名: BENDAMUSTINE HCL 中文参考商品译名: Levact 100毫克/瓶 5支装 中文参考药品译名: 盐酸苯达莫司汀 生产厂家中文参考译名: Mundipharma GmbH. 生产厂家英文名: Mundipharma GmbH --------------------------------------------------------------- 产地国家: 德国 原产地英文商品名: Levact 25mg/vial 20injectable solution 原产地英文药品名: BENDAMUSTINE HCL 中文参考商品译名: Levact 25毫克/瓶 20支装 中文参考药品译名: 盐酸苯达莫司汀 生产厂家中文参考译名: Mundipharma GmbH. 生产厂家英文名: Mundipharma GmbH --------------------------------------------------------------- 产地国家: 德国 原产地英文商品名: Levact 25mg/vial 10injectable solution 原产地英文药品名: BENDAMUSTINE HCL 中文参考商品译名: Levact 25毫克/瓶 10支装 中文参考药品译名: 盐酸苯达莫司汀 生产厂家中文参考译名: Mundipharma GmbH. 生产厂家英文名: Mundipharma GmbH --------------------------------------------------------------- 产地国家: 德国 原产地英文商品名: Levact 25mg/vial 5injectable solution 原产地英文药品名: BENDAMUSTINE HCL 中文参考商品译名: Levact 25毫克/瓶 5支装 中文参考药品译名: 盐酸苯达莫司汀 生产厂家中文参考译名: Mundipharma GmbH. 生产厂家英文名: Mundipharma GmbH Levact 2.5 mg/ml powder for concentrate for solution for infusion Read all of this leaflet carefully before you start using this medicine. 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. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. In this leaflet: 1. What Levact is and what it is used for 2. Before you use Levact 3. How to use Levact 4. Possible side effects 5. How to store Levact 6. Further information What Levact Is And What It Is Used For Levact is a medicine which is used for the treatment of certain types of cancer (cytotoxic medicine). Levact is used alone (monotherapy) or in combination with other medicines for the treatment of the following forms of cancer: chronic lymphocytic leukaemia in cases where fludarabine combination chemotherapy is not appropriate for you, non-Hodgkin’s lymphomas, which had not, or only shortly, responded to prior rituximab treatment, Multiple myeloma in cases where high-dose chemotherapy with autologous stem cell transplantation, thalidomide or bortezomib containing therapy is not appropriate for you. Before You Use Levact Do not use Levact if you are hypersensitive (allergic) to the active substance bendamustine hydrochloride or any of the other ingredients of Levact; while breastfeeding; if you have severe liver dysfunction (damage to the functional cells of the liver); if you have yellowing of the skin or whites of the eyes caused by liver or blood problems (jaundice); if you have severely disturbed bone marrow function (bone marrow depression) and serious changes in your number of white blood cells and platelets in the blood (white blood cells and/or thrombocyte values drop to < 3,000/?l or < 75,000/?l, respectively.); if you have had major surgical operations less than 30 days before starting treatment; if you have an infection, especially one accompanied by a reduction in white blood cells (leucocytopenia); in combination with yellow fever vaccines. Take special care with Levact in case of reduced capability of the bone marrow to replace blood cells. You should have your number of white blood cells and platelets in the blood checked before starting treatment with Levact, before each subsequent course of treatment and in the intervals between courses of treatment. in case of infections. You should contact your doctor if you have signs of infection, including fever or lung symptoms. in case of reactions on your skin during treatment with Levact. The reactions may increase in severity. in cases of existing heart disease (e.g. heart attack, chest pain, severely disturbed heart rhythms). in case you notice any pain in your side, blood in your urine or reduced amount of urine. When your disease is very severe, your body may not be able to clear all the waste products from the dying cancer cells. This is called tumour lysis syndrome and can cause kidney failure and heart problems within 48 hours of the first dose of Levact. Your doctor will be aware of this and may give you other medicines to help prevent it. in case of severe allergic or hypersensitivity reactions. You should pay attention to infusion reactions after your first cycle of therapy. Men receiving treatment with Levact are advised not to conceive a child during treatment and for up to 6 months afterwards. Before starting treatment, you should seek advice on storing sperm because of the possibility of permanent infertility. Unintentional injection into the tissue outside blood vessels (extravasal injection) should be stopped immediately. The needle should be removed after a short aspiration. Thereafter the affected area of tissue should be cooled. The arm should be elevated. Additional treatments like the use of corticosteroids are not of clear benefit (see section 4). Using other medicines Please tell your doctor or pharmacist if you are taking or have recently taken other medicines, including medicines obtained without a prescription. If Levact is used in combination with medicines which inhibit the formation of blood in the bone marrow, the effect on the bone marrow may be intensified. If Levact is used in combination with medicines which alter your immune response, this effect may be intensified. Cytostatic medicines may diminish the effectiveness of live-virus vaccination. Additionally cytostatic medicines increase the risk of an infection after vaccination with live vaccines (e.g. viral vaccination). Pregnancy and breastfeeding Pregnancy Levact can cause genetic damage and has caused malformations in animal studies. You should not use Levact during pregnancy unless certainly indicated by your doctor. In case of treatment you should use medical consultation about the risk of potential adverse effects of your therapy for the unborn child and genetic consultation is recommended. If you are a woman of childbearing potential you must use an effective method of contraception both before and during treatment with Levact. If pregnancy occurs during your treatment with Levact you must immediately inform your doctor and should use genetic consultation. If you are a man, you should avoid fathering a child during treatment with Levact and for up to 6 months after treatment has stopped. There is a risk that treatment with Levact will lead to infertility and you may wish to seek advice on conservation of sperm before treatment starts. Breastfeeding Levact must not be administered during breastfeeding. If treatment with Levact is necessary during lactation you must discontinue breastfeeding. Ask your doctor or pharmacist for advice before taking any medicine. Driving and using machines No studies on the effects on the ability to drive and to use machines have been performed. Do not drive or operate machines if you experience side effects, such as dizziness or lack of coordination. How To Use Levact Levact is administered into a vein over 30-60 minutes in various dosages, either alone (monotherapy) or in combination with other medicines. Treatment should not be started if your white blood cells (leukocytes) have fallen to counts below 3,000 cells/?l and/or your blood platelets have fallen to counts below 75,000 cells/l. Your doctor will determine these values at regular intervals. Chronic lymphocytic leukaemia Levact 100 mg per square metre of your body surface area (based on your height and weight) on Days 1+2 Repeat the cycle after 4 weeks up to 6 times Non-Hodgkin’s lymphomas Levact 120 mg per square metre of your body surface area (based on your height and weight) on Days 1 + 2 Repeat the cycle after 3 weeks at least 6 times Multiple myeloma Levact 120 - 150 mg per square metre of your body surface area (based on your height and weight) on Days 1+2 Prednisone 60 mg per square metre of your body surface area (based on your height and weight) i.v. on Days 1 - 4 Repeat the cycle after 4 weeks at least 3 times Treatment should be terminated if white blood cell (leukocyte) and/or platelet values drop to < 3,000/?l or < 75,000/?l, respectively. Treatment can be continued after white blood cell values have increased to > 4,000/?l and platelet values to > 100,000/?l. Impaired liver or kidney function Dependent on the degree of impairment of your liver function it may be necessary to adjust your dose (by 30% in case of moderate liver dysfunction). No dose adjustment is necessary in case of impairment of kidney function. Your attending doctor will decide whether a dosage adjustment is necessary. How it is administered Treatment with Levact should be undertaken only by doctors experienced in tumour therapy. Your doctor will give you the exact dose of Levact and use the necessary precautions. Your attending doctor will administer the solution for infusion after preparation as prescribed. The solution is administered into a vein as a short-term infusion over 30 – 60 minutes. Duration of use There is no time limit laid down as a general rule for treatment with Levact. Duration of treatment depends on disease and response to treatment. If you are at all worried or have any questions regarding treatment with Levact, please speak to your doctor or nurse. If you forget to use Levact If a dose of Levact has been forgotten, your doctor will usually retain the normal dosage schedule. If you stop using Levact The doctor treating you will decide whether to interrupt the treatment or to change over to a different preparation. If you have any further questions on the use of this product, ask your doctor or pharmacist. Possible Side Ffects Like all medicines, Levact can cause side-effects, although not everybody gets them. The following definitions of frequency are used when assessing side-effects: Very common: affects more than 1 user in 10 Common: affects 1 to 10 users in 100 Uncommon: affects 1 to 10 users in 1,000 Rare: affects 1 to 10 users in 10,000 Very rare: affects less than 1 user in 10,000 Not known: frequency cannot be estimated from the available data Tissue changes (necrosis) have been observed very rarely following unintentional injection into the tissue outside blood vessels (extravascular). A burning sensation where the infusion needle is inserted may be a sign for administration outside the blood vessels. The consequence of administration in this way can be pain and poorly healing skin defects. The dose-limiting side-effect of Levact is impaired bone-marrow function, which usually returns to normal after treatment. Suppressed bone marrow function increases the risk of infection. Very common: Low counts of white blood cells (leukocytopenia) Decrease in the red pigment of the blood (haemoglobin) Low counts of platelets (thrombocytopenia) Infections Feeling sick (nausea) Vomiting Mucosal inflammation Increased blood level of creatinine Increased blood level of urea Fever Fatigue Common: Bleeding (haemorrhage) Disturbed metabolism caused by dying cancer cells releasing their contents into the blood stream Reduction in red blood cells which can make the skin pale and cause weakness or breathlessness (anaemia) Low counts of neutrophils (neutropenia) Hypersensitivity reactions such as allergic inflammation of the skin (dermatitis), nettle rash (urticaria) A rise in liver enzymes AST/ALT A rise in the enzyme alkaline phosphatase A rise in bile pigment Low potassium blood levels Disturbed function (dysfunction) of the heart Disturbed heart rhythms (arrhythmia) Low or high blood pressure (hypotension or hypertension) Disturbed lung function Diarrhoea Constipation Sore mouth (Stomatitis) Loss of appetite Hair loss Skin changes Missed periods (amenorrhoea) Pain Insomnia Chills Dehydration Uncommon: Accumulation of fluid in the heart sac (escape of fluid into the pericardial space) Rare: Infection of the blood (sepsis) Severe allergic hypersensitivity reactions (anaphylactic reactions) Signs similar to anaphylactic reactions (anaphylactoid reactions) Drowsiness Loss of voice (aphonia) Acute circulatory collapse Reddening of the skin (erythema) Inflammation of the skin (dermatitis) Itching (pruritus) Skin rash (macular exanthema) Excessive sweating (hyperhidrosis) Very rare: Primary atypical inflammation of the lungs (pneumonia) Break-down of red blood cells Rapid decrease in blood pressure sometimes with skin reactions or rash (anaphylactic shock) Disturbed sense of taste Altered sensations (paraesthesia) Malaise and pain in the limbs (peripheral neuropathy) Disease of the nervous system (anticholinergic syndrome) Neurological disorders Lack of coordination (ataxia) Inflammation of the brain (encephalitis) Increased heart rate (tachycardia) Heart attack, chest pain (myocardial infarct) Heart failure Inflammation of the veins (phlebitis) Formation of tissue in the lungs (fibrosis of the lungs) Bleeding inflammation of the gullet (haemorrhagic oesophagitis) Bleeding of stomach or gut Infertility Multiple organ failure There have been reports of secondary tumours (myelodysplastic syndrome, AML, bronchial carcinoma) following treatment with Levact. No clear relationship with Levact could be determined. A small number of cases of severe skin reactions (Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis) have been reported. The relationship with Levact is unclear. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor. How To Store Levact Keep out of the reach and sight of children. Do not use Levact after the expiry date which is stated on the label and the carton. The expiry date refers to the last day of that month. Keep the container in the outer carton to protect the content from light. Note on shelf-life after opening or preparing the solution Solutions for infusions prepared according to the directions listed at the end of this leaflet are stable in polyethylene bags at room temperature / 60% relative humidity for 3.5 hours, and in a refrigerator they are stable for 2 days. Levact contains no preservatives. The solutions should not therefore be used after these lengths of time. It is the responsibility of the user to maintain aseptic conditions. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment. Further Information What Levact contains The active substance is bendamustine hydrochloride. 1 vial contains 25 mg of bendamustine hydrochloride 1 vial contains 100 mg of bendamustine hydrochloride After reconstitution 1 ml of the concentrate contains 2.5 mg bendamustine hydrochloride. The other ingredient is Mannitol. What Levact looks like and contents of the pack Brown glass vials with rubber stopper and an aluminium flip-off cap. The powder appears white and crystalline. Levact is available in packs containing 5 and 20 injection vials with 25 mg of bendamustine hydrochloride and 5 injection vials with 100 mg of bendamustine hydrochloride. Marketing Authorisation Holder Astellas Pharma GmbH Postfach 50 01 66 80971 Munich Germany