57．诺维本
出处：按学科分类—医药、卫生 军事医学科学出版社《临床常用进口药物手册》第321页（8827字）
【中文释文】：
(长春瑞滨)
5-去甲-脱水长春碱供静脉注射用
诺维本：10mg／1ml瓶
诺维本：50mg／5ml瓶
〔成分〕
诺维本10mg／1ml瓶
重酒石盐长春瑞滨 13．85mg
相当长春瑞滨含量 10．00mg
注射用水 1ml
诺维本 50mg／5ml瓶
重酒石盐长春瑞滨 69．25mg
相当长春瑞滨含量 50．00mg
注射用水 5ml
〔药理学特性〕
诺维本属长春花生物碱类抗肿瘤药物，直接作用于管蛋白／微管的动态平衡。
诺维本可抑制管蛋白的聚集，并主要作用于分裂期微管，仅在高浓度下影响轴突微管，对管蛋白螺旋化的作用低于长春新碱。
诺维本可阻断G2与M期细胞的有丝分裂，从而导致进入间期或下一分裂周期细胞的死亡。
〔药代动力学〕
静脉给药后，血浆动力学符合三室模型，末端相平均半衰期为40h，血浆清除率较高，约为0．8／l(kg·h)体重。
组织摄取诺维本广泛而持久。
因诺维本胆道排出率高，故主要从粪便排泄。诺维本与蛋白结合率达50%～80%。
〔适应证〕
非小细胞肺癌，转移性乳腺癌。
〔禁忌证〕
妊娠期，哺乳期，严重肝功能不全。
〔给药途径〕
诺维本必须严格地经静脉给药。
〔注意事项〕
治疗必须在严密的血液学监测下进行，每次用药前须测定血红蛋白、白细胞、粒细胞计数。
当粒细胞减少时(＜2000／mm3)，用药应延迟至病人血像恢复正常。
肝功能不全时应减少用药剂量。
如无法检测肾功能不全，须慎重使用本药治疗。
治疗操作时谨防药物污染眼球以引起严重刺激，药物在一定压力下喷射入眼时可导致角膜溃疡。
在进行包括肝脏的放疗时忌用本品。
〔副作用〕
1．血液学毒性 粒细胞减少属局限性毒性反应(参见注意事项)。贫血常见但多属中度。
2．神经毒性
(1)外周神经毒性：一般限于深腱反射消失，感觉异常少见。长期用药可出现下肢无力。
(2)植物神经毒性：主要表现为小肠麻痹引起的便秘。麻痹性肠梗阻罕见。
3．胃肠道毒性 便秘，恶心呕吐不常见。
4．呼吸道毒性 与其它长春花生物碱相似，诺维本可引起呼吸困难和支气管痉挛。这些反应可于注药后数分钟或数小时内发生。
可见有中度进行性脱发和下颌痛。
静脉注药外渗可引起局部皮肤毒性甚至坏死(参见剂量和用法)。
〔剂量和用法〕
本品只能静脉给药。
单药治疗：常用量为每周25～30mg／m2。
联合治疗：依照所用方案选用剂量和给药时间，药物必须溶于生理盐水(125ml)，并于短时间内(15～20min)静脉输入。
然后输大量生理盐水冲洗静脉。
肝功能不全时应减量。肾功能不全时参见注意事项。操作意外喷入眼睛立即用大量清水冲洗。
必须在确定注射针头插入静脉腔内方开可始输入本药。若药物渗入周围组织可引起严重局部刺激，一旦药物外渗应立即停止注药。余药从另一静脉输入。
〔过量〕
可引起严重的粒细胞减少，出现重复感染威胁生命。
〔包装〕
5ml玻璃瓶，每盒10支。
1ml玻璃瓶，每盒10支。
〔有效期〕
2年
〔贮藏〕
置于冰箱内(4℃)，避光保存。
开启后或配制后的稀释液〔盐溶液及(或)葡萄糖溶液〕，在密封的玻瓶或输液袋内于室温下可保存24h。
〔生产厂家〕
法国皮尔-法伯大药厂癌症部
(附本品别名：异长春花碱，去甲长春花碱，诺威本)
【外文释文】：
(Vinorelbine)
Solution for injection in vial
Navelbine 10 mg／1ml
Navelbine 50 mg／5ml
Unit composition
Navelbine 10 mg／ml
Injectable solution in vial
Vinorelbine ditartrate 13．85 mg
Quantity corresponding
to vinorelbine 10．00 mg
Water for injection q．s．f． 1 ml
q．f．one vial
Navelbine 50 mg／5 ml
injectable solution in vial
Vinorelbine ditartrate 69．25 mg
Quantity corresponding
to vinorelbine(base) 50．00 mg
Water for iniection q．s．f． 5 ml
q．f．one vial
Pharmacological properties
Navelbine is a cytostatic antineoplastic of the vinca alkaloid group．
The molecular target of its activity is tubulin／microtubule dynamic equilibrium．
Navelbine inhibits the polymerization of tubulin．It acts preferentially on mitotic microtubules and affects axonal microtubules only at high concentration．The effects on tubulin spiralization are lower than with vincristine．
Navelbine blocks mitosis in phase G2+M and induces cell death at interphase or at the following mitosis．
Pharmacokinetic features
Following intravenous injection，the plasma pharmacokinetic profile of Navelbine is triphasic．The mean half-life of the terminal phase is 40 h．Plasma clearance is very high(approximately 0．8 Ⅰ／(kg·d)．
Tissue uptake of Navelbine is intense and sustained．
Fecal excretion is preponderant related to a massive biliary elimination．
Plasma protein binding level is relatively high(50-80%)．
Indications
·Non-small cell lung cancer．
·Metastatic breast cancer．
Contra-indication
·Pregnancy．
·Nursing mothers．
·Severe hepatic insufficiency．
Warnings
Navelbine should be administered by strict intravenous route．
Precautions
·Treatment must be under strict haematological supervision(determination of haemoglobin)level，leucocyte and granulocyte count before any new injection)．
·In the event of granulocytopenia(＜2000／mm3)injection should be delayed until normalization and keep the patient under close surveillance．
·In case of hepatic insufficiency the dosage should be reduced．
·Due to the lack of studies concerning renal insufficiency，caution is highly recommanded when initiating treatment．
·Avoid any accidental contamination of the eyes：risk of severe irritation or even cornel ulceration if the drug is projected under pressure(see Dosage and Administration)．
·Navelbine should not be administered concomitantly with radiotherapy where the field includes the liver．
Side effects
Haematological toxicity
·Limiting toxicity is granulocytopenia(see Precautions)．
·Anaemia：frequent but moderate．
Neurotoxicity
·Peripheral：
Generally limited to abolition of the deep tendinous reflexes．
Parasthesiae are uncommon．Weakness in lower limbs may be observed after prolonged treatment．
·Digestive autonomic nervous system：
The main manifestation is paresis leading to constipation．
Rare cases of paralytic ileus have been described
Gastrointestinal toxicity
·Constipation(see Neurotoxicity)．
·Nausea，vomiting：the incidence is relatively low．
Bronchopulmonary toxicity
·Navelbine may bring on dyspnoea and bronchospasm like others vinca-alkaloids．
These reactions occur usually a few minutes following injecion or several hours later．
Also reported
·Alopecia(progressive and moderate)，jaw pain．
·All extravasation of the drug during intravenous injection may produce severe local reactions which may lead to necrosis(see Dosage and Administration)．
Dosage and administration
Strict intravenous route．
·As a single agent，the usual dose is 25-30 mg／m2 administered weekly．
·In polychemotherapy，the dose and frequency of administration are dependant upon protocol regimen．
The injected dose should be diluted in a saline solution(e．g．125 ml)and infused over a short period(15-20 minutes)．
Administration must be followed by a vein washout using isotonic solution．
·In the event of hepatic insufficiency，the dosage must be reduced．
·Renal insufficiency(see Precautions)．
It is extremely important to ensure that the needle is properly inserted into the vein before starting the injection of Navelbine．If Navelbine extravasates into surrounding tissues during intravenous administration，it may cause marked irritation．In such circumstances，the injection should be stopped and the remainder of the dose given via another vein．
If any accidental contact with the eye occurs，rinse immediately with water or isotonic solution．
Overdose
The major of overdose is the onset of a severe granulocytopenia with a risk of infection which may threaten the vital prognosis．
How supplied
5 ml in glass vial-pack of ten．
1 ml in glass vial-pack of ten．
Shelf-life
2 years．
Special storage precautions
To be stored in a refrigerator(4℃)and away from light．
After opening，the solution itself or in dilution in saline or glucose solution in a hermetically sealed glass bottle for infusion may be kept for 24 hours at room temperature．
Manufacturer
Pierre Fabre Ltd．，France