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 详细处方信息以本药内容附件PDF文件（201182818434834.pdf）的“原文Priscribing Information”为准
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部分中文Ontak处方资料（仅供参考）

Denileukin diftitox
【一】其他名:Ontak。

【二】来源：利用基因重组把白喉毒素A和B段基因与白介素-2基因连接，转染大肠杆菌产生白介素-2和免疫毒素复合物。
 
【三】作用机制：本品是白介素-2和免疫毒素的融合剂，可以介导白喉毒素的细胞毒作用，杀伤表达IL-2受体的细胞。人类IL-2受体有三种形式，低亲和力（CD25），和亲和力（CD122/CD132),高亲和力于活化T细胞，活化B细胞，活化巨噬细胞。包括皮肤T细胞淋巴瘤在内的某些白血病和淋巴瘤细胞表达一种以上IL-2受体亚单位。体外实验发现本品与细胞表面高亲和性IL-2受体结合，通过白喉毒素作用，抑制细胞蛋白合成，导致细胞几小时内死亡。

【四】药代动力学：在小鼠体内进了放射性标记药物48小时内生物分布与排泄的研究。肝、肾是血管外药物分布与聚集的首要部位。本品通过蛋白降解代谢。淋巴瘤患者静脉输入本品3～31mg/ml(kg/d)。
首次给药后，本品呈两室分布相（半衰期2～5分钟）和终末相（半衰期70～80分钟）。清除率为1.5～2ml/(min.kg),分布容积相当于循环血（0.06～0.08L/kg).第一次和第五次用药之间没有明显药物聚集。

【五】药物间相互作用：尚无相关研究。

【六】适应症：表达CD25（白细胞介素2受体，IL-2R）的难治性、复发性皮肤T细胞淋巴瘤。

【七】单药有效率：治疗皮肤T细胞淋巴瘤单药有效率为30%～38%，完全缓解率为10%～16%。

【八】剂型：针剂，每支300mg/2ml冷冻溶液。

【九】剂量：推荐方案：9mg/(kg.d)或18mg(kg.d)，静脉用药，连用5天，21天为一个疗程。输液时间15分钟以上。对于输液时间过长，如超过80分钟，尚无相关研究，尚未确定最佳疗程数，但是研究表明治疗4个疗程后，只有2%（1/51）的患者肿瘤负荷降低∠25%。

【十】给药途径：静脉给药。

【十一】配伍：不能与其他药品混合使用。

【十二】禁忌症：对本品和白喉毒素、IL-2过敏的患者禁用。老年患者、孕妇慎用，哺乳期妇女治疗期间应停止哺乳。

【十三】不良反应：1.全身症状：发热、寒战、感染、头痛。2.呼吸系统：呼吸急促、咳嗽、声音嘶哑。3.循环系统：心率加快、心律失常。4.消化系统：吞咽困难、腹痛、消化不良、在老年患者更易于发生。5.皮肤病变：皮疹、皮肤发热、潮红、皮肤红斑、注射部位肿瘤。6.肌肉骨骼：背痛、胸痛、肘部疼痛、腹股沟疼痛、腿痛、足部或下肢肿胀、面部肿胀。7.神经精神：睡眠障碍、眩晕、晕厥、共济失调、视力突然改变、手足无力、指（趾）尖麻木。8.泌尿系统：絮状尿、血尿、尿痛、排尿困难、尿少。

【十四】临床应用规程：1.用药前检测血常规、心电图、血压。2.用药后定期检测血常规、心电图、血压、神经系统检查。3.稀释和配制时需要无菌操作，用塑料注射器和配液袋，不能使用玻璃容器，因为药品会吸附在玻璃上，影响药品浓度。4.配掖过程中药物浓度至少15mg/ml，最好吸出所需要的药品，注入空的静脉输液袋内。每1ml药品加入不超过9ml的不含防腐剂的无菌盐水。5.输液前30分钟给予抗组胺药、解热镇痛药、密切观察输液反应和过敏反应，并予相应处理。6.输液时间不短于15分钟。7.本品不能一次冲式给药。应该使用输液泵或者静脉输液袋。

Ontak ®
Generic name: Denileukin Diftitox

Chemocare.com uses generic names in all descriptions of drugs. Ontak is the trade name for Denileukin Diftitox. In some cases, health care professionals may use the trade name Ontak when referring to the generic drug name Denileukin Diftitox.

Drug type:  Ontak is a targeted therapy.  This medication is classified as an "biologic response modifier agent."  (For more detail, see "How this drug works" section below).

What this drug is used for:
•Denileukin diftitox is used to treat patients with persistent or recurrent cutaneous T-cell lymphoma.  The patient's lymphoma cells need to be a specific type -- they must have the high affinity component of the IL-2 receptor -- to be treated with this drug.  This is generally confirmed by testing the lymphoma tissue before the drug is given.

Note:  If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful. 

How this drug is given:
•This medication is given by intravenous injection (IV), through a vein.  The infusion will take 15 minutes or longer.
•The amount of denileukin diftitox that you will receive depends on many factors, including your height and weight, your general health or other health problems, and the type of cancer or condition being treated.  Your doctor will determine your dose and schedule.

Side effects: Important things to remember about the side effects of denileukin diftitox:
•Most people do not experience all of the side effects listed.
•Side effects are often predictable in terms of their onset and duration.
•Side effects are almost always reversible and will go away after treatment is complete.
•There are many options to help minimize or prevent side effects.
•There is no relationship between the presence or severity of side effects and the effectiveness of the medication

The following side effects are common (occurring in greater than 30%) for patients taking denileukin diftitox:
•Hypersensitivity reaction during the infusion with symptoms such as low blood pressure, back pain, shortness of breath (see allergic reactions).
•Fever/Chills (usually occurs during or soon after the infusion).
•Nausea and vomiting.
•Blood test abnormalities (low albumin level, hypoalbuminemia).
•Liver problems (elevated liver enzymes; transaminase).
•Weakness.
•Swelling (usually of hands and feet).
•Infection.
•Pain.
•Low blood pressure (hypotension).
•Poor appetite.
•Rash.

These side effects are less common side effects (occurring in about 10-29%) of patients receiving denileukin diftitox:
•Diarrhea
•Shortness of breath
•Headache
•Chest pain
•Cough
•Dizziness
•Itching
•Pharyngitis or Rhinitis (inflammation of the throat or nose) (see cold symptoms).
•Low Red blood cell count. Your red blood cells may temporarily decrease.  This can put you at increased risk for anemia.
•Numbness and tingling of hands and feet.
•Blood test abnormalities (low calcium level, low albumin level).
•Muscle pain
•Weight loss
•Rapid heart rate (see heart problems)
•Anxiety or nervousness
•Sweating (see skin problems)
•Blood in the urine (see bladder problems)
•Cloudy urine (see kidney problems)
•A serious side effect of denileukin diftitox  is "capillary leak syndrome" or "vascular leak syndrome."  Capillary leak syndrome is a potentially serious disease in which fluids within the vascular system (veins and capillaries) leaks into the tissue outside the bloodstream.  This results in low blood pressure and poor blood flow to the internal organs.  Capillary leak syndrome is characterized by the presence of 2 or more of the following 3 symptoms; low blood pressure, swelling, and low levels of protein in the blood.  Your doctor will monitor these things carefully while you are taking denileukin diftitox.   You should notify your doctor immediately if you notice dizziness (especially when changing position), sudden swelling or rapid weight gain, little or no urine output (for 8-12 hours), shortness of breath, difficulty breathing, irregular heart beats, or chest pain.  If this syndrome occurs, it will likely be delayed, within about 2 weeks of treatment.

Not all side effects are listed above. Some that are rare (occurring in less than 10% of patients) are not listed here.  However, you should always inform your health care provider if you experience any unusual symptoms.

When to contact your doctor or health care provider:
Contact your health care provider immediately, day or night, if you should experience any of the following symptoms:
•Dizziness (especially when changing position), sudden swelling or rapid weight gain, little or no urine output (for 8-12 hours), shortness of breath, difficulty breathing, irregular heart beats, or chest pain.

The following symptoms require medical attention, but are not an emergency.  Contact your health care provider within 24 hours of noticing any of the following:
•Fever of 100.5o F (38o C) or higher, chills occurring 1-2 days after infusion or later (possible signs of infection).
•Nausea (interferes with ability to eat and unrelieved with prescribed medication)
•Vomiting (vomiting more than 4-5 times in a 24 hour period)
•Diarrhea (4-6 episodes in a 24-hour period)
•Unusual bleeding or bruising
•Blood in the urine
•Cloudy urine
•Pain or burning with urination
•Extreme fatigue or weakness (unable to carry on self-care activities)
•Anxiety or nervousness that interferes with your ability to function
•Yellowing of the skin or eyes

Note:  Notify your health care provider of any symptoms that get worse or do not go away.

Always inform your health care provider if you experience any unusual symptoms.

Precautions:
•Before starting denileukin diftitox treatment, make sure you tell your doctor about any other medications you are taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.).   Do not take aspirin, products containing aspirin unless your doctor specifically permits this.
•Denileukin diftitox may be inadvisable if you have had a hypersensitivity (allergic) reaction to denileukin diftitox, diphtheria toxin or interleukin-2.
•Do not receive any kind of immunization or vaccination without your doctor's approval while taking denileukin diftitox.
•Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment.  Pregnancy category C (use in pregnancy only if benefit to mother outweighs risk to fetus).
•For both men and women: It is not recommended to conceive a child (get pregnant) while taking denileukin diftitox. Barrier methods of contraception, such as condoms, are recommended. Discuss with your doctor when you may safely become pregnant or conceive a child after therapy.
•Do not breast feed while taking this medication.

Self-care tips:
•Drink at least two to three quarts of fluid every 24 hours, unless you are instructed otherwise.
•Wash your hands often.
•Avoid contact sports or activities that could cause injury.
•To reduce nausea, take anti-nausea medications as prescribed by your doctor, and eat small, frequent meals.  
•Avoid sun exposure.  Wear SPF 15 (or higher) sunblock and protective clothing.
•In general, drinking alcoholic beverages should be kept to a minimum or avoided completely.  You should discuss this with your doctor
•Get plenty of rest
•Maintain good nutrition
•If you experience symptoms or side effects, be sure to discuss them with your health care team.  They can prescribe medications and/or offer other suggestions that are effective in managing such problems.

Monitoring and testing:
You will be checked regularly by your health care professional while you are taking denileukin diftitox, to monitor side effects and check your response to therapy.  Periodic blood work to monitor your complete blood count (CBC) as well as the function of other organs (such as your kidneys and liver) will also be ordered by your doctor.   

How this drug works:
Targeted therapy:
Targeted therapy is the result of about 100 years of research dedicated to understanding the differences between cancer cells and normal cells.  To date, cancer treatment has focused primarily on killing rapidly dividing cells because one feature of cancer cells is that divide rapidly.  Unfortunately, some of our normal cells divide rapidly too, causing multiple side effects. 

Targeted therapy is about identifying other features of cancer cells.  Scientists look for specific differences in the cancer cells and the normal cells.  This information is used to create a targeted therapy to attack the cancer cells without damaging the normal cells, thus leading to fewer side effects.  Each type of targeted therapy works a little bit differently but all interfere with the ability of the cancer cell to grow, divide, repair and/or communicate with other cells. 

There are different types of targeted therapies, defined in three broad categories.  Some targeted therapies focus on the internal components and function of the cancer cell.  The targeted therapies use small molecules that can get into the cell and disrupt the function of the cells, causing them to die.  There are several types of targeted therapy that focus on the inner parts of the cells.   Other targeted therapies target receptors that are on the outside of the cell.   Therapies that target receptors are also known as monoclonal antibodies.  Antiangiogenesis inhibitors target the blood vessels that supply oxygen to the cells, ultimately causing the cells to starve.

Researchers agree that targeted therapies are not a replacement for traditional therapies.  They may best be used in combination with traditional therapies.  More research is needed to identify which cancers may be best treated with targeted therapies and to identify additional targets for more types of cancer.

Targeted therapies:
•Signal Transduction inhibitors:  Imatinib Mesylate (protein-tyrosine kinase inhibitor).
•Biologic Response Modifier Agent:  Denileukin Diftitox. Denileukin diftitox is a fusion protein (a combination of diphtheria toxin and interleukin-2) which selectively delivers the cell-killing activity of the diphtheria toxin to targeted cells.  The lymphoma cells need to be a specific type -- they must express the high affinity IL-2 receptor on the surface of the cancer cell which then permits the IL-2 part of the fusion protein to attach/bind to the cell, halt protein synthesis and lead to cell death because of the diptheria toxin.

Note:  We strongly encourage you to talk with your health care professional about your specific medical condition and treatments. The information contained in this website is meant to be helpful and educational, but is not a substitute for medical advice.

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 详细处方信息以本药内容附件PDF文件（201182818434834.pdf）的“原文Priscribing Information”为准
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