Product
Anti-cancer Products (Cytocristin)
Cytocristin
Vincristine Sulphate 1mg/ml
WARNING
Caution–This preparation should be administered by individuals experienced in the administration of Vincristine Sulfate Injection. It is extremely important that the intravenous needle or catheter be properly positioned before any vincristine is injected. Leakage into surrounding tissue during intravenous administration of Vincristine Sulfate Injection may cause considerable irritation. If extravasation occurs, the injection should be discontinued immediately, and any remaining portion of the dose should then be introduced into another vein. Local injection of hyaluronidase and the application of moderate heat to the area of leakage help disperse the drug and are thought to minimize discomfort and the possibility of cellulitis.
FATAL IF GIVEN INTRATHECALLY. FOR INTRAVENOUS USE ONLY.
COMPOSITION
CYTOCRISTIN
Each vial contains
Vincristine Sulphate ……………….... 1mg
DOSAGE FORM
I.V. Injection
PHARMACOLOGY
The mechanisms of action of vincristine sulfate remain under investigation. The mechanism of action of vincristine sulfate has been related to the inhibition of microtubule formation in mitotic spindle, resulting in an arrest of dividing cells at the metaphase stage.
Central nervous system leukemia has been reported in patients undergoing otherwise successful therapy with vincristine sulfate. This suggests that vincristine does not penetrate well into the cerebrospinal fluid.
Pharmacokinetic studies in patients with cancer have shown a triphasic serum decay pattern following rapid intravenous injection. The initial, middle and terminal half–lives are 5 minutes, 2.3 hours, and 85 hours respectively; however, the range of the terminal half–life in humans is from 19 to 155 hours. The liver is the major excretory organ in humans and animals. The metabolism of vinca alkaloids has been shown to be mediated by hepatic cytochrome P450 isoenzymes in the CYP 3A subfamily. This metabolic pathway may be impaired in patients with hepatic dysfunction or who are taking concomitant potent inhibitors of these isoenzymes. About 80% of an injected dose of vincristine sulfate appears in the feces and 10% to 20% can be found in the urine. Within 15 to 30 minutes after injection, over 90% of the drug is distributed from the blood into tissue, where it remains tightly, but not irreversibly, bound.
Current principles of cancer chemotherapy involve the simultaneous use of several agents. Generally, each agent used has a unique toxicity and mechanism of action so that therapeutic enhancement occurs without additive toxicity. It is rarely possible to achieve equally good results with single–agent methods of treatment. Thus, vincristine sulfate is often chosen as part of polychemotherapy because of lack of significant bone–marrow suppression (at recommended doses) and of unique clinical toxicity (neuropathy).
INDICATIONS
Vincristine sulfate injection is indicated in acute leukemia.Vincristine sulfate injection has also been shown to be useful in combination with other oncolytic agents in Hodgkin's disease, non–Hodgkin's malignant lymphomas (lymphocytic, mixed cell, histiocytic, undifferentiated, nodular and diffuse types), rhabdomyosarcoma, neuroblastoma, and Wilms' tumor.
DOSAGE AND ADMINISTRATION
This preparation is for intravenous use only. Neurotoxicity appears to be dose related. Extreme care must be used in calculating and administering the dose of Vincristine Sulfate Injection, since overdosage may have a very serious or fatal outcome.
Special Dispensing Information: WHEN DISPENSING VINCRISTINE SULFATE INJECTION, IN OTHER THAN THE ORIGINAL CONTAINER, IT IS IMPERATIVE THAT IT BE PACKAGED IN THE PROVIDED OVERWRAP WHICH BEARS THE FOLLOWING STATEMENT: “DO NOT REMOVE COVERING UNTIL MOMENT OF INJECTION. FATAL IF GIVEN INTRATHECALLY. FOR INTRAVENOUS USE ONLY. A syringe containing a specific dose must be labeled, using the auxiliary sticker provided, to state: “FATAL IF GIVEN INTRATHECALLY. FOR INTRAVENOUS USE ONLY.”
The concentration of Vincristine Sulfate Injection is 1 mg/mL. Do not add extra fluid to the vial prior to removal of the dose. Withdraw the solution of Vincristine Sulfate Injection into an accurate dry syringe, measuring the dose carefully. Do not add extra fluid to the vial in an attempt to empty it completely.
Caution: It is extremely important that the intravenous needle or catheter be properly positioned before any vincristine is injected. Leakage into surrounding tissue during intravenous administration of Vincristine Sulfate Injection may cause considerable irritation. If extravasation occurs, the injection should be discontinued immediately and any remaining portion of the dose should then be introduced into another vein. Local injection of hyaluronidase and the application of moderate heat to the area of leakage will help disperse the drug and may minimize discomfort and the possibility of cellulitis.
Vincristine Sulfate Injection, must be administered via an intact, free–flowing intravenous needle or catheter. Care should be taken that there is no leakage or swelling occurring during administration.
The solution may be injected either directly into a vein or into the tubing of a running intravenous infusion. Injection of Vincristine Sulfate Injection, should be accomplished within 1 minute.
The drug is administered intravenously at weekly intervals .
The usual dose of Vincristine Sulfate Injection for pediatric patients is 1.5–2 mg/m 2 . For pediatric patients weighing 10 kg or less, the starting dose should be 0.05 mg/kg, administered once a week. The usual dose of Vincristine Sulfate Injection, for adults is 1.4 mg/m 2 . A 50% reduction in the dose of Vincristine Sulfate Injection is recommended for patients having a direct serum bilirubin value above 3 mg/100 mL.
Vincristine Sulfate Injection, should not be given to patients while they are receiving radiation therapy through ports that include the liver . When Vincristine Sulfate Injection, is used in combination with L–asparaginase, Vincristine Sulfate Injection, should be given 12 to 24 hours before administration of the enzyme in order to minimize toxicity; administering L–asparaginase before Vincristine Sulfate Injection, may reduce hepatic clearance of vincristine.
Drug Interactions
Vincristine sulfate injection should not be diluted in solutions that raise or lower the pH outside the range of 3.5 to 5.5. It should not be mixed with anything other than normal saline or glucose in water.
Whenever solution and container permit, parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
CONTRAINDICATIONS
Patients with the demyelinating form of Charcot–Marie–Tooth syndrome should not be given vincristine sulfate injection.
WARNINGS AND PRECAUTIONS
Drug Interactions
The simultaneous oral or intravenous administration of phenytoin and antineoplastic chemotherapy combinations that included vincristine sulfate has been reported to reduce blood levels of the anticonvulsant and to increase seizure activity. Dosage adjustment should be based on serial blood level monitoring. The contribution of vincristine sulfate to this interaction is not certain. The interaction may result from reduced absorption of phenytoin and an increase in the rate of its metabolism and elimination.
Caution should be exercised in patients concurrently taking drugs known to inhibit drug metabolism by hepatic cytochrome P450 isoenzymes in the CYP 3A subfamily, or in patients with hepatic dysfunction. Concurrent administration of vincristine sulfate with itraconazole (a known inhibitor of the metabolic pathway) has been reported to cause an earlier onset and/or an increased severity of neuromuscular side effects. This interaction is presumed to be related to inhibition of the metabolism of vincristine.
General
Acute uric acid nephropathy, which may occur after the administration of oncolytic agents, has also been reported with vincristine sulfate. In the presence of leukopenia or a complicating infection, administration of the next dose of vincristine sulfate injection warrants careful consideration.
If central nervous system leukemia is diagnosed, additional agents may be required, because vincristine does not appear to cross the blood–brain barrier in adequate amounts.
Particular attention should be given to dosage and neurologic side effects if vincristine sulfate injection is administered to patients with preexisting neuromuscular disease and when other drugs with neurotoxic potential are also being used.
Acute shortness of breath and severe broncospasm have been reported following the administration of vinca alkaloids. These reactions have been encountered most frequently when the vinca alkaloid was used in combination with mitomycin–C and may require aggressive treatment, particularly when there is preexisting pulmonary dysfunction. The onset of these reactions may occur minutes to several hours after the vinca alkaloid is injected and may occur up to 2 weeks following the dose of mitomycin. Progressive dyspnea requiring chronic therapy may occur. Vincristine sulfate should not be readministered.
Care must be taken to avoid contamination of the eye with concentration of vincristine sulfate injection used clinically. If accidental contamination occurs severe irritation (or, if the drug was delivered under pressure, even corneal ulceration) may result. The eye should be washed immediately and thoroughly.
This preparation is for intravenous use only. It should be administered by individuals experienced in the administration of vincristine sulfate injection. The intrathecal administration of vincristine sulfate injection usually results in death. Syringes containing this product should be labeled, using the auxiliary sticker provided, to state “FATAL IF GIVEN INTRATHECALLY. FOR INTRAVENOUS USE ONLY.”
Extemporaneously prepared syringes containing this product must be packaged in an overwrap which is labeled “DO NOT REMOVE COVERING UNTIL MOMENT OF INJECTION. FATAL IF GIVEN INTRATHECALLY. FOR INTRAVENOUS USE ONLY.”
Treatment of patients following intrathecal administration of vincristine sulfate injection has included immediate removal of spinal fluid and flushing with Lactated Ringer's, as well as other solutions and has not prevented ascending paralysis and death. In one case, progressive paralysis in an adult was arrested by the following treatment initiated immediately after the intrathecal injection:
1. As much spinal fluid was removed as could be safely done through lumbar access.
2. The subarachnoid space was flushed with Lactated Ringer's solution infused continuously through a catheter in a cerebral lateral ventricle at the rate of 150 mL/h. The fluid was removed through a lumbar access.
3. As soon as fresh frozen plasma became available, the fresh frozen plasma, 25 mL, diluted in 1 L of Lactated Ringer's solution was infused through the cerebral
ventricular catheter at the rate of 75mL/h with removal through the lumbar access. The rate of infusion was adjusted to maintain a protein level in the spinal fluid of 150 mg/dL.
4. Glutamic acid, 10 g, was given intravenously over 24 hours followed by 500mg 3 times daily by mouth for 1 month or until neurological dysfunction stabilized.
The role of glutamic acid in this treatment is not certain and may not be essential.
Laboratory Tests
Because dose–limiting clinical toxicity is manifested as neurotoxicity clinical evaluation (e.g., history, physical examination) is necessary to detect the need for dosage modification. Following administration of vincristine sulfate injection, some individuals may have a fall in the white blood cell count or platelet count, particularly when previous therapy or the disease itself has reduced bone–marrow function. Therefore, a complete blood count should be done before administration of each dose. Acute elevation of serum uric acid may also occur during induction of remission in acute leukemia; thus, such levels should be determined frequently during the first 3 to 4 weeks of treatment or appropriate measures taken to prevent uric acid nephropathy. The laboratory performing these tests should be consulted for its range of normal values.
Pregnancy
Category D
Vincristine sulfate can cause fetal harm when administered to a pregnant woman. When pregnant mice and hamsters were given doses of vincristine sulfate that caused resorption of 23% to 85% of fetuses, fetal malformations were produced in those that survived. Five monkeys were given single doses of vincristine sulfate between days 27 and 34 of their pregnancies; 3 of the fetuses were normal at term, and 2 viable fetuses had grossly evident malformations at term. In several animal species, vincristine sulfate can induce teratogenesis as well as embryo death at doses that are nontoxic to the pregnant animal. There are no adequate and well–controlled studies in pregnant women. If this drug is used during pregnancy or if the patient becomes pregnant while receiving this drug, she should be apprised of the potential hazard to the fetus. Women of child–bearing potential should be advised to avoid becoming pregnant.
Lactation
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions due to vincristine sulfate in nursing infants, a decision should be made either to discontinue nursing or the drug, taking into account the importance of the drug to the mother.
Pediatric Use
See DOSAGE AND METHOD OF ADMINISTRATION section .
UNDESIRABLE EFFECTS
Prior to the use of this drug, patients and/or their parents/guardian should be advised of the possibility of untoward symptoms.
In general, adverse reactions are reversible and are related to dosage. The most common adverse reaction is hair loss; the most troublesome adverse reactions are neuromuscular in origin.
When single, weekly doses of the drug are employed, the adverse reactions of leukopenia, neuritic pain, and constipation occur but are usually of short duration (ie., less than 7 days). When the dosage is reduced, these reactions may lessen or disappear. The severity of such reactions seems to increase when the calculated amount of drug is given in divided doses. Other adverse reactions, such as hair loss, sensory loss, paresthesia, difficulty in walking, slapping gait, loss of deep–tendon reflexes, and muscle wasting, may persist for at least as long as therapy is continued. Generalized sensorimotor dysfunction may become progressively more severe with continued treatment. Although most such symptoms usually disappear by about the sixth week after discontinuance of treatment, some neuromuscular difficulties may persist for prolonged periods in some patients. Regrowth of hair may occur while maintenance therapy continues.
The following adverse reactions have been reported:
Hypersensitivity
Rare cases of allergic–type reactions, such as anaphylaxis, rash and edema, that are temporally related to vincristine therapy have been reported in patients receiving vincristine as a part of multidrug chemotherapy regimens.
Gastrointestinal
Constipation, abdominal cramps, weight loss, nausea, vomiting, oral ulceration, diarrhea, paralytic ileus, intestinal necrosis and/or perforation, and anorexia have occurred. Constipation may take the form of upper–colon impaction, and, on physical examination, the rectum may be empty. Colicky abdominal pain coupled with an empty rectum may mislead the physician. A flat film of the abdomen is useful in demonstrating this condition. All cases have responded to high enemas and laxatives. A routine prophylactic regimen against constipation is recommended for all patients receiving vincristine sulfate injection.
Paralytic ileus (which mimics the “surgical abdomen”) may occur, particularly in young pediatric patients. The ileus will reverse itself with temporary discontinuance of vincristine sulfate injection and with symptomatic care.
Genitourinary
Polyuria, dysuria, and urinary retention due to bladder atony have occurred. Other drugs known to cause urinary retention (particularly in the elderly) should, if possible, be discontinued for the first few days following administration of vincristine sulfate injection.
Cardiovascular
Hypertension and hypotension have occurred. Chemotherapy combinations that have included vincristine sulfate, when given to patients previously treated with mediastinal radiation, have been associated with coronary artery disease and myocardial infarction. Causality has not been established.
Neurologic
Frequently, there is a sequence to the development of neuromuscular side effects. Initially, only sensory impairment and paresthesia may be encountered. With continued treatment, neuritic pain and, later, motor difficulties may occur. There have been no reports of any agent that can reverse the neuromuscular manifestations that may accompany therapy with vincristine sulfate.
Loss of deep–tendon reflexes, foot drop, ataxia, and paralysis have been reported with continued administration. Cranial nerve manifestations, such as isolated paresis and/or paralysis of muscles controlled by cranial motor nerves including potentially life–threatening bilateral vocal cord paralysis, may occur in the absence of motor impairment elsewhere; extraocular and laryngeal muscles are those most commonly involved. Jaw pain, pharyngeal pain, parotid gland pain, bone pain, back pain, limb pain, and myalgias have been reported; pain in these areas may be severe. Convulsions, frequently with hypertension, have been reported in a few patients receiving vincristine sulfate. Several instances of convulsions followed by coma have been reported in pediatric patients. Transient cortical blindness and optic atrophy with blindness have been reported. Treatment with vinca alkaloids has resulted in both vestibular and auditory damage to the eighth cranial nerve. Manifestations include partial or total deafness which may be temporary or permanent, and difficulties with balance including dizziness, nystagmus, and vertigo. Particular caution is warranted when vincristine is used in combination with other agents known to be ototoxic such as the platinum–containing oncolytics.
Pulmonary
See WARNINGS AND PRECAUTIONS
Endocrine
Rare occurrences of a syndrome attributable to inappropriate antidiuretic hormone secretion have been observed in patients treated with vincristine sulfate. This syndrome is characterized by high urinary sodium excretion in the presence of hyponatremia; renal or adrenal disease, hypotension, dehydration, azotemia, and clinical edema are absent. With fluid deprivation, improvement occurs in the hyponatremia and in the renal loss of sodium.
Hematologic
Vincristine sulfate injection does not appear to have any constant or significant effect on platelets or red blood cells. Serious bone–marrow depression is usually not a major dose–limiting event. However, anemia, leukopenia, and thrombocytopenia have been reported. Thrombocytopenia, if present when therapy with vincristine sulfate injection is begun, may actually improve before the appearance of bone marrow remission.
Skin
Alopecia and rash have been reported.
Other
Fever and headache have occurred.
OVERDOSAGE
Side effects following the use of vincristine sulfate injection are dose related. In pediatric patients under 13 years of age, death has occurred following doses of vincristine sulfate that were 10 times those recommended for therapy. Severe symptoms may occur in this patient group following dosages of 3 to 4 mg/m 2 . Adults can be expected to experience severe symptoms after single doses of 3 mg/m 2 or more. Therefore, following administration of doses higher than those recommended, patients can be expected to experience exaggerated side effects. Supportive care should include the following: (1) prevention of side effects resulting from the syndrome of inappropriate antidiuretic hormone secretion (preventive treatment would include restriction of fluid intake and perhaps the administration of a diuretic affecting the function of Henle's loop and the distal tubule); (2) administration of anticonvulsants; (3) use of enemas or cathartics to prevent ileus (in some instances, decompression of the gastrointestinal tract may be necessary); (4) monitoring the cardiovascular system; (5) determining daily blood counts for guidance in transfusion requirements.
Folinic acid has been observed to have a protective effect in normal mice that were administered lethal doses of vincristine sulfate. Isolated case reports suggest that folinic acid may be helpful in treating humans who have received an overdose of vincristine sulfate. It is suggested that 100 mg of folinic acid be administered intravenously every 3 hours for 24 hours and then every 6 hours for at least 48 hours. Theoretically (based on pharmacokinetic data), tissue levels of vincristine sulfate can be expected to remain significantly elevated for at least 72 hours. Treatment with folinic acid does not eliminate the need for the above mentioned supportive measures.
Most of an intravenous dose of vincristine is excreted into the bile after rapid tissue binding. Because only very small amounts of the drug appear in dialysate, hemodialysis is not likely to be helpful in cases of overdosage. An increase in the severity of side effects may be experienced by patients with liver disease that is severe enough to decrease biliary excretion.
Enhanced fecal excretion of parenterally administered vincristine has been demonstrated in dogs pretreated with cholestyramine. There are no published clinical data on the use of cholestyramine as an antidote in humans.
There are no published clinical data on the consequences of oral ingestion of vincristine. Should oral ingestion occur, the stomach should be evacuated. Evacuation should be followed by oral administration of activated charcoal and a cathartic.
SHELF-LIFE
18 months
STORAGE AND HANDLING INSTRUCTIONS
Store between 2 ° C and 8 ° C in a refrigerator. Do not freeze. Protect from light.
PACKAGING INFORMATION
Vial of 1 ml.
cytocristin
长春新碱硫酸1mg/ml的
警告
注意，这准备，应该由硫酸长春新碱注射液管理经验的个人。正确定位静脉针或导管之前被注射长春新碱，这是非常重要的。硫酸长春新碱注射液静脉给药过程中泄漏到周围的组织可能会造成相当大的刺激。如果发生外渗，应立即停止注射，任何剂量的其余部分应被介绍到另一个静脉。泄漏区进行局部注射透明质酸和中度热的应用程序的帮助分散的药物，被认为不适和蜂窝组织炎的可能性降到最低。
致命的，如果交给鞘内。静脉使用。
组成
CYTOCRISTIN
每管含有
长春新碱硫酸...................... 1毫克
剂型
静脉注射注射
药
硫酸长春新碱的作用机制仍在调查之中。抑制纺锤体微管的形成，导致细胞分裂逮捕在中期阶段，已涉及到硫酸长春新碱的行动机制。
据报道，在经历与硫酸长春新碱否则成功治疗患者中枢神经系统白血病。这表明，长春新碱不渗透进入脑脊液。
在癌症患者中的药代动力学研究显示血清1三相快速静脉注射后的衰变模式。初期，中期和终端的半衰期是5分钟，2.3小时和85小时分别;然而，在人类的终端半衰期范围是从19至155小时。肝脏是人类和动物的主要排泄器官。长春花生物碱的代谢已经被证明是介导的细胞色素P450同工酶的CYP 3A亚科肝。在肝功能不全或正在伴随这些同工酶抑制剂的患者，可能会削弱这种代谢途径。硫酸长春新碱注射剂量的约80％出现在粪便中，可在尿液中发现，10％至20％。注射后15至30分钟内，超过90％的药物从血液分布到组织，它仍然紧紧的，但并非不可逆转，约束。
当前癌症化疗的原则，涉及的几家代理商同时使用。一般来说，每个剂具有独特的毒性和作用机制，使疗效增强无添加剂的毒性发生。这是很少有可能与单药治疗的方法同样实现了良好的效果。因此，硫酸长春新碱经常被选为多重化学部分由于缺乏明显的骨髓抑制（推荐剂量）和独特的临床毒性（神经病）。
适应症
硫酸长春新碱注射急性leukemia.Vincristine注射用硫酸也被证明是有用的组合与其他溶瘤剂在霍奇金病，非霍奇金恶性淋巴瘤（淋巴细胞，混合细胞，组织细胞，分化，结节型和弥漫型），横纹肌肉瘤，神经母细胞瘤，肾母细胞瘤。
剂量和用法
这种准备是仅用于静脉注射使用。神经毒性似乎是剂量相关。硫酸长春新碱注射的剂量计算和管理，必须格外谨慎使用，因为过量可能有一个非常严重的或致命的结果。
特别配药信息：当取水硫酸长春新碱注射液，中比原来的容器中，必要将其包装所提供的外包装负有以下声明：“不要删除直到注入开始覆盖。致命的，如果交给鞘内。静脉使用。必须贴上一个含有特定剂量的注射器，使用提供辅助贴纸，状态：“致命的，如果鞘内。静脉使用而已。“
硫酸长春新碱注射液的浓度为1毫克/毫升。不添加多余的液体之前去除剂量的小瓶。撤回到一个准确的干燥注射器硫酸长春新碱注射液的解决方案，测量剂量仔细。不添加多余的液体的小瓶，企图完全清空。
注意：正确定位静脉针或导管之前被注射长春新碱，这是非常重要的。硫酸长春新碱注射液静脉给药过程中泄漏到周围的组织可能会造成相当大的刺激。如果发生外渗，应立即停止注射，任何剂量的其余部分应被介绍到另一个静脉。局部注射透明质酸和温和的热泄漏面积应用，将有助于驱散毒品，并可能减少不适和蜂窝组织炎的可能性。
硫酸长春新碱注射液，必须通过一个完整的，自由流动的静脉针或导管管理。应小心有没有泄漏或肿胀发生的过程管理。
该解决方案可能被注入静脉或直接进入到正在运行的静脉输液管。注射硫酸长春新碱注射液，应在1分钟内完成。
该药物是静脉给药，每周一班。
硫酸长春新碱注射小儿患者的常用剂量为1.5-2毫克/立方米2。对于重达10公斤或以下的儿童患者，起始剂量应为0.05毫克/公斤，每星期一次的管理。硫酸长春新碱注射液常用剂量，成人为1.4毫克/立方米2。建议中的硫酸长春新碱注射剂量减少50％患者血清直接胆红素值超过3毫克毫升。
硫酸长春新碱注射液，不应给病人，而他们正在接受放射治疗，通过港口，包括肝脏。硫酸长春新碱注射液时，在L-门冬酰胺，硫酸长春新碱注射组合使用，应给予前12至24小时的酶，以减少毒性;管理大号-天门冬酰胺硫酸长春新碱注射前，可能会降低肝脏清除长春新碱。
药物相互作用
不应该被硫酸长春新碱注射稀释的解决方案，提高或降低3.5范围以外的pH值至5.5。它不应该与任何其他比生理盐水或葡萄糖水混合。
每当溶液及容器许可，注射药物产品应目视检查给药前的颗粒物质和变色。
禁忌
脱髓鞘形式的腓骨肌萎缩症的患者，不应给予硫酸长春新碱注射液。
注意事项：
药物相互作用
已报告的同时口服或静脉注射苯妥英和管理，包括硫酸长春新碱的抗肿瘤化疗组合，减少血液中的抗惊厥水平和增加癫痫发作。应根据串行血药浓度监测调整剂量。硫酸长春新碱这种相互作用的贡献是不能肯定。的相互作用，可能导致减少吸收苯妥英和在其代谢和消除率增加。
患者同时服用已知的抑制肝药物代谢的药物，细胞色素P450同工酶的CYP 3A亚科，或肝功能不全患者，应谨慎行事。并发管理与伊曲康唑（已知的代谢途径抑制剂）硫酸长春新碱已引起早期发病和/或增加肌肉副作用的严重性。这种相互作用被推定为抑制长春新碱代谢有关。
一般
急性尿酸肾病，后可能出现的溶瘤药物的管理，也有报道用硫酸长春新碱。中存在的白细胞减少症或一个复杂的感染，硫酸长春新碱注射值得认真考虑的下一个剂量的管理。
如果被诊断中枢神经系统白血病，额外的代理可能需要，因为长春新碱不会出现交叉在足够数量的血脑屏障。
硫酸长春新碱注射剂量和神经系统的副作用，如果管理与已经存在的神经肌肉疾病时具有潜在神经毒性的其他药物也被用于患者应给予特别注意。
急性呼吸急促和严重broncospasm已报告后，长春花生物碱的管理。遇到这些反应时，最常使用长春花生物碱结合丝裂霉素C和可能需要积极治疗，尤其是当已经存在的肺功能不全。这些反应的发生，可能会出现分钟到几个小时后长春花生物碱注射，可能会出现长达2周后剂量丝裂霉素。可能会出现渐进性呼吸困难，需要长期治疗。硫酸长春新碱，不应readministered。
必须小心，以避免污染浓度硫酸长春新碱注射液用于临床的眼睛。如果发生意外污染严重的刺激（或，如果该药物在压力下交付，甚至角膜溃疡），可能会导致。眼睛应立即彻底清洗。
这种准备是仅用于静脉注射使用。它应该由硫酸长春新碱注射液管理经验的个人。鞘内注射硫酸长春新碱注射液，通常会导致死亡。应标明含有这种产品的注射器，使用辅助提供贴纸，注明“致命的，如果鞘内。静脉使用而已。“
即兴准备的注射器含有这种产品必须打包在一个外包装标有“请勿移动直到注入开始覆盖。致命的，如果交给鞘内。静脉使用而已。“
硫酸长春新碱注射液鞘内注射后患者的治疗，包括立即解除对脊髓液与乳酸林格氏液冲洗，以及其他的解决方案，并没有阻止升麻痹而死亡。在一个案例中，逐步瘫痪在成人被逮捕鞘内注射后立即启动以下待遇：
1。尽可能多的脊髓液被删除，可以安全地通过腰椎访问。
2。 150个的速度在不断通过在大脑侧脑室导管注入的乳酸林格氏液冲洗蛛网膜下腔mL / h的。流体被删除通过腰访问。
3。新鲜冰冻血浆，新鲜冰冻血浆，25毫升，1 L乳酸林格氏液稀释尽快通过脑注射心室导管在通过腰椎访问的清除率75毫升/小时。调整输液速度保持在脊髓的蛋白质水平150毫克/升的液体。
4。谷氨酸，10克，静脉滴注24小时，超过1个月，或直至稳定神经功能障碍，经口每天500毫克的3倍。
谷氨酸在这种治疗中的作用是不能确定，可能是必不可少的。
实验室测试
由于剂量限制的临床毒性表现为神经毒性的临床评价（例如，病史，体格检查）是必要的检测剂量修改的必要性。硫酸长春新碱注射液的管理之后，可能会有一些个体的白细胞计数，血小板计数下降，尤其是在以前的治疗或疾病本身已减少的骨髓功能。因此，一个完整的血球计数，每次给药前应做。急性血尿酸升高也可能发生在急性白血病的诱导缓解，因此，各级应确定在第3至4周的治疗或采取适当措施，以防止尿酸性肾病频繁。执行这些测试的实验室，应征询其正常值范围。
怀孕
D类
硫酸长春新碱可引起孕妇胎儿造成伤害。当孕鼠和仓鼠分别给予23％至85％的胎儿造成吸收剂量的硫酸长春新碱，胎儿畸形的产生在那些幸存下来。五只猴子分别给予单剂量硫酸长春新碱怀孕27和34天之间;胎儿正常足月，在长期存活的胎儿2非常明显的畸形。在一些动物物种，硫酸长春新碱在怀孕的动物是无毒的剂量可诱发致畸作用以及胚胎死亡。孕妇有没有足够和良好对照的研究。如果在怀孕期间或如果怀孕，同时接受这种药物的病人使用这种药物，她应该了解胎儿的潜在危险。应尽量避免怀孕妇女生育潜力。
哺乳
它不知道这种药物是否在人类乳汁中排出。因为许多药物在人乳和排出体外，因为由于硫酸长春新碱在哺乳婴儿的严重不良反应的潜力，应作出决定或者终止哺乳或药物，考虑到母亲的药物的重要性。
儿童使用
见剂量和方法，行政组。
不良影响
使用这种药物之前，应告知患者和/或他们的父母/监护人的不良症状的可能性。
在一般情况下，不良反应是可逆的，相关的剂量。最常见的不良反应是脱发最头疼的不良反应是起源于神经肌肉。
受聘当单，每周剂量的药物，白细胞减少症，神经炎疼痛，便秘等不良反应的发生，但通常持续时间短（即不少于7天）。当剂量减少，这些反应可能会减轻或消失。这种反应的严重程度似乎增加计算量的药物时，分次给药。如毛发脱落，感觉丧失，感觉异常，行走困难，步态打耳光，深腱反射减退，肌肉萎缩等不良反应，可能会持续至少只要继续治疗。广义感觉功能障碍可能一年比一年严重，继续治疗。虽然大多数这样的症状通常消失，通过关于终止治疗后的第六周，一些神经肌肉的困难可能在某些患者长期坚持。头发生长，可能会出现继续维持治疗。
下列不良反应已有报道：
过敏症
据报道，在接受长春新碱多药化疗方案的一部分的患者过敏性反应，如过敏性休克，皮疹，水肿，长春新碱治疗时间有关的罕见的情况下。
胃肠道
便秘，腹部绞痛，体重减轻，恶心，呕吐，口腔溃疡，腹泻，麻痹性肠梗阻，肠坏死和/或穿孔，食欲不振时有发生。便秘可能要花上冒号嵌塞的形式，体检，直肠可能是空的。疝气腹痛加上一个空直肠可能误导医生。一个腹部平膜是在展示这个条件非常有用。所有案件已作出回应，以高灌肠和泻药。例行对便秘的预防方案，建议对所有患者接受硫酸长春新碱注射液。
麻痹性肠梗阻（模仿“外科急腹症”）可能发生，尤其是在年轻的儿科患者。肠梗阻会扭转暂时中止与硫酸长春新碱注射液和对症护理。
泌尿生殖系统
尿，排尿困难，尿潴留，膀胱乏力时有发生。其他药物已知可引起尿潴留（尤其是老年人），如有可能，应停止硫酸长春新碱注射管理后的头几天。
心血管
高血压和低血压时有发生。化疗，包括硫酸长春新碱给予以前纵隔辐射治疗的患者，当组合，已与冠心病和心肌梗死。因果关系尚未建立。
神经
经常有肌肉副作用的发展是一个序列。最初，只有感官障碍和感觉异常，可能会遇到。随着继续治疗，神经炎疼痛，后来，机动困难，可能会出现。已经没有任何代理人，可以扭转可能伴随着硫酸长春新碱治疗神经肌肉表现的报告。
深腱反射消失，足下垂，共济失调，瘫痪的损失已持续管理。颅神经的表现，如孤立的麻痹和/或控制电动机通过颅神经，包括潜在的威胁生命双侧声带麻痹，肌肉瘫痪，运动障碍的情况下可能会发生在其他地方;眼和喉部肌肉是最常受累。下巴疼痛，咽喉疼痛，腮腺疼痛，骨骼疼痛，背部疼痛，下肢疼痛，肌痛已经报道，在这些领域的疼痛可能是严重的。经常与高血压，抽搐，已报道少数患者接受硫酸长春新碱。据报道，在儿科患者昏迷抽搐的几个实例。瞬态皮质盲视神经萎缩和失明的报道。长春花生物碱治疗，导致在第八对脑神经前庭和听觉受损。表现包括部分或全聋这可能是暂时或永久的和平衡的困难，包括头晕，眼球震颤，眩晕。长春新碱必要时结合使用与其他药物如含铂oncolytics耳毒性特别谨慎。
肺
见警告和注意事项
内分泌
硫酸长春新碱治疗的患者中已发现罕见的出现归因于抗利尿激素分泌的一种综合征。这种综合征高尿钠排泄的特点，在低钠血症的存在;肾或肾上腺疾病，低血压，脱水，氮质血症，水肿临床缺席。与流体剥夺，改善发生低钠血症和肾钠的损失。
血液学
硫酸长春新碱注射不会出现血小板或红细胞上有任何持续或显着的效果。骨髓严重的抑郁症通常是没有剂量限制的一个重要事件。然而，贫血，白细胞减少，血小板减少的报道。血小板减少，硫酸长春新碱注射液治疗开始时，如果存在可能实际上改善前骨髓缓解的外观。
皮肤
脱发，皮疹已有报道。
其他
发烧和头痛时有发生。
过量
利用硫酸长春新碱注射后的副作用是剂量相关。在未满13岁的儿科患者，死亡发生硫酸长春新碱治疗建议的10倍以下的剂量。症状严重者，可能会出现在这组病人剂量的3至4毫克/立方米2。可以预计将遇到严重的症状后，单剂量3毫克/立方米2个或更多的成年人。因此，剂量高于建议的管理后，病人可以体验夸张的副作用。支持治疗应包括以下内容：（1）方导致抗利尿激素分泌综合征影响的预防（预防性治疗，包括限制液体的摄入量和可能1影响亨勒的循环和远端肾小管功能利尿管理） （2）抗惊厥药的管理;（3）使用灌肠剂或泻药，以防止肠梗阻（在某些情况下，胃肠道减压可能是必要的）（4）监测心血管系统;（5）确定每天的血球计数指导输血需求。
叶酸已被观察到有一定的保护作用，在管理正常小鼠致死剂量的硫酸长春新碱。孤立的事件的报告表明，叶酸可能有助于治疗人类已经收到了过量的硫酸长春新碱。据建议，静脉给药100毫克叶酸，至少48小时，24小时，每3个小时，然后每6小时。理论上（根据药代动力学数据），硫酸长春新碱的组织水平，可以预计将保持至少72小时显着升高。叶酸治疗并不能消除上述配套措施的必要性。
长春新碱静脉注射剂量的大部分被排出到胆汁后，迅速组织结合。因为只有极少量的药物出现在透析，血液透析是不会过量的情况下可能有帮助。在副作用的严重程度的增加，可能会经历肝病患者是严重到足以降低胆道排泄。
肠外管理长春新碱加强粪便排泄已被证明狗胆预处理。有没有胆作为人类的解毒剂的使用已发表的临床数据。
有没有对长春新碱口服后果公布的临床数据。口服发生时，应疏散胃。撤离之后，应口服活性碳和泻药。
保质期
18个月
储存和装卸注意事项
2℃和8℃之间存放在冰箱。不冻结。防止光线照射。
封装信息
1毫升的小瓶。