简介：

药品简介
氨磷汀(amifostine)是1996年FDA批准在美国上市的第二个细胞保护剂(抗辐射药)。商品名为Ethyol,Ethiofos.
通常用多剂量顺铂对晚期卵巢癌或非小细胞肺癌化疗和用环磷酰胺对晚期卵巢癌化疗时，易出现累积肾毒性。本品可预防和减少这种累积肾毒性。
药理作用
药效学
本品是硫代磷酸盐的前体药物。它的细胞保护作用是由于正常组织中pH较高、碱基磷酸酯酶活性较强，可将氨磷汀迅速完全地去磷酸化而成游离硫羟基(thiol-)的、有药理活性的代谢物(代号WR-1065)，因而保护非肿瘤组织免于化疗和放射疗法的毒性作用，降低环磷酰胺和顺铂对晚期卵巢癌化疗时引起的、与中性白血球减少症有关的感染发生率。正常组织的血液供应较好，提取的氨磷汀多于癌变组织，因而正常组织细胞内活性代谢物WR-1065的浓度较高，可起到区分保护的作用。
药动学
本品的胃肠吸收很差，故不宜口服。在10s内静脉推注本品150mg.m-2后癌症患者的血清药物峰浓度为100～900μmol.L-1，注射后1～4min活性代谢物WR-1065的峰浓度为7～22μmol.L-1。若给癌症患者以740mg.m-2剂量15min静脉输注本品，则5min内可达到血浆浓度100μmol.L-1，输注结束时可达到100～200μmol.L-1。输注后30min时血浆浓度可下降至10μmol.L-1，45min时为2μmol.L-1左右。
本品自血浆中清除迅速，静脉推注或输注后6min内血浆药物水平可下降90%。分布半衰期不到1min，消除半衰期约9min，仅少量原型药物及代谢物自尿中排出。稳态时的平均分布容积为6L。
有限的资料表明，以910mg.m-2静脉输注本品后2.5h时，病人骨髓中WR-1065的水平较低，提示为了对抗半衰期较长的细胞毒性药物(如环磷酰胺)，需多剂量给予氨磷汀才能起到细胞保护作用。
动物实验结果表明，本品在骨髓、胃肠粘膜、皮肤、肝脏及唾液中的浓度较高，而在肌肉中水平较低，脑组织中几乎没有。
适应症
本品可预防顺铂引起的肾毒性和外周神经病，预防环磷酰胺引起的粒细胞白血病和放射疗法引起的骨髓抑制。与顺铂合用可增加顺铂的抗肿瘤效果。用于晚期卵巢癌及转移黑素瘤的放射疗法。亦可用于头颈部癌症、食道癌、肺癌及头部以上的放射疗法。颈动脉病或高钙血症的患者静脉给予本品易发生低血压，建议用较低剂量。
用法用量
建议本品的初始剂量为910mg.m-2，化疗前30min开始静脉输注，输注时间为15min。若收缩压显著低于正常低限则应停止输注。若停药5min内血压恢复正常且患者无任何症状，可继续输注，以使患者获得全部剂量。若患者不能耐受足量氨磷汀，则下一疗程的剂量应减为740mg.m2。本品的最大耐受剂量是每周4d按340mg.m2给予，连续5周。
本品为单剂量包装，每支500mg，应冷藏。
不良反应
本品最重要的不良反应是一过性低血压，在临床研究中约占62%。有低血压的或正处在脱水状态的患者，不得使用本品。正在服用抗高血压药物且24h内不能中断治疗的患者也不能使用本品。给予氨磷汀输注前，应给患者适当水化，静脉补充一些液体。输液氨磷汀的过程中患者应卧床，每隔5min测一次血压。若收缩压明显下降，应立即停药。
恶心或呕吐常发生于氨磷汀输液后，接受顺铂-环磷酰胺化疗第1天并给予本品的患者中有19%出现严重的反应，而未接受本品的患者反应发生率为10%。建议在给予本品之前给予抗呕吐治疗，如地塞米松20mg静注、或5-羟色胺受体阻断剂昂丹司琼和格拉司琼。抗呕吐剂也可与本品合用。
本品可降低血清钙水平，但引致临床上明显的低钙血症发生率低于1%。对有低钙血症危险性的患者(如肾病综合征)应监测血钙水平，必要时补充钙剂。
其它不良反应还有面色潮红、寒战、眩晕、嗜睡、呃逆和打喷嚏。皮疹变态反应发生率低于1%。
禁忌
属孕期用药C级(美国FDA颁布的妊娠期间使用药物危险性等级的分类之一，即动物实验证明对胎儿有不良反应——致畸或致死，尚未在孕妇中进行对照研究)，因可能危及胎儿而在怀孕期间禁用。哺乳期妇女若使用氨磷汀应停止授乳。本品对儿童和老年人的疗效和安全性尚未知。对氨磷汀、氨硫羟化合物、甘露醇等高敏的不良反应禁用。
不良反应有如下情况时慎用：脑血管病或心血管病、低钙血症的不良反应；有脱水或低血压的不良反应；孕妇和哺乳期妇女；正在服用抗高血压药物且24h内不能停药者。
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Generic Name: Amifostine
Brand Name: Ethyol
Definition:
Amifostine is a cytoprotective adjuvant which is used in cancer chemotherapy including DNA-binding chemotherapeutic agents. Also usually known as WR-1065 in its active form.
Amifostine is used therapeutically to decrease the incidence of neutropenia-related fever and infection caused by DNA-binding chemotherapeutic agents containing alkylating agents (e.g. cyclophosphamide) and platinum-containing agents (e.g. cisplatin). It is also used to reduce the cumulative nephrotoxicity related with platinum-containing agents. Amifostine is also denoted to decrease the incidence of xerostomia in patients undergoing radiotherapy for head and neck cancer.
Amifostine was actually indicated to decrease the cumulative renal toxicity from cisplatin in non-small cell lung cancer. However, while nephroprotection was watched, the fact that amifostine could protect tumors couldn’t be eliminated.
Uses:
Amifostine is used to reduce the risk of kidney problems occurred by treatment with a several anti-cancer drug (cisplatin). It is also used to help stop a various side effect (dry mouth) occurred by radiation treatment for head and neck cancer. Amifostine is thought to work by stopping several chemicals from spoiling healthy cells. It can also help repair cells damaged by cisplatin or radiation treatment.
Dosage:
Amifostine is normally given as an injection at your doctor’s office, hospital, or clinic.
For Reduction of Cumulative Renal Toxicity with Chemotherapy:
The recommended beginning dose of ETHYOL (amifostine) is 910 mg/m2 given once daily as a 15-minute i.v. infusion, beginning 30 minutes prior to chemotherapy.
The 15-minute infusion is better endured than more extended infusions. Additional reductions in infusion times for chemotherapy regimens haven’t been systematically examined.
Patients must be adequately hydrated prior to ETHYOL (amifostine) infusion and kept in a supine position at the time of the infusion. Blood pressure must be observed every 5 minutes at the time of the infusion.
For Reduction of Moderate to Severe Xerostomia from Radiation of the Head and Neck:
The recommended dose of ETHYOL (amifostine) is 200 mg/m2 given once daily as a 3-minute i.v. infusion, beginning 15-30 minutes prior to standard fraction radiation therapy (1.8-2.0 Gy).
Patients must be adequately hydrated prior to ETHYOL (amifostine) infusion. Blood pressure must be observed at least before and immediately after the infusion.
It is recommended that antiemetic medication be given prior to and in conjunction with ETHYOL (amifostine) . Oral 5HT3 receptor antagonists, alone or in interaction with other antiemetics, have been used effectively in the radiotherapy setting.
■Patients who take blood pressure medicines may require to stop taking them within 24 hours before or after taking Amifostine. If you take medicine for high blood pressure, consult your doctor how to take it along with Amifostine.
■Keep this product, as well as syringes and needles, away from children and pets. Don’t reuse needles, syringes, or other materials.
■If you missed a dose of Amifostine, consult your doctor right away.
■Call for emergency medical help if you have taken overdose of this medication. Overdose symptoms can contain seizures; severe or persistent dizziness; shortness of breath.
Precautions:
Consult your doctor or pharmacist, if you are feeling allergic to it or if you experience any other allergies, before using this medicine. This product can include inactive components, that may cause allergic reactions or other problems. Before using this medication, inform your doctor or pharmacist your medical history, specially of: low/high blood pressure, heart disease (e.g., irregular heartbeat, congestive heart failure), kidney disease, previous stroke. This medication can cause you dizziness or drowsiness. Don’t drive, use machinery, or do any activity which needs alertness or clear vision until you are sure you may conduct such activities safely. Limit alcohol during this medication. At the time of pregnancy, this medication must be used only when clearly required. It isn’t unknown whether this drug excretes into breast milk, so consult your doctor before breast-feeding.
Side effects:
Amifostine can cause side effects. Consult your doctor if any of these symptoms are serious or don’t go away:
■nausea
■vomiting
■flushing (feeling of warmth)
■chills ( feeling of coldness)
■fever
■dizziness or lightheadedness
■drowsiness
■sneezing
■hiccups
Some side effects may be severe. The following symptoms are unusual, but if you have any of them, consult your doctor immediately:
■shortness of breath
■fainting
■seizures
■chest tightness
■skin rash
■hives
■swelling of the throat
Amifostine can cause other side effects. Consult your doctor if you have experienced any uncommon problems at the time of taking this drug.
Interaction:
Your doctor or pharmacist can already be aware of any feasible drug interactions and will be telling you for them. Don’t start or stop or change the dosage of any medicine before consulting with your doctor first. Before taking this medication, inform your doctor about all prescription and nonprescription/herbal products you can use, specially of: blood pressure medications. Consult your doctor if you also using drugs that cause drowsiness like: certain antihistamines (e.g., diphenhydramine), anti-seizure drugs (e.g., carbamazepine), medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., chlorpromazine, risperidone, trazodone). Verify the labels on all your medicines (e.g., cough-and-cold products) because they can include ingredients it can cause drowsiness. Consult your pharmacist about taking those products safely. Before taking this product, consult your doctor or pharmacist of all the products you use.
Contraindication:
Don’t use this medication in below conditions
■you have allergic reaction to any ingredient in Amifostine or to similar medicines
■you have experienced low blood pressure or you are dehydrated
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