12．哪些化疗药物有心脏毒性、如何监测心脏毒性？_百度知道
12．哪些化疗药物有心脏毒性、如何监测心脏毒性？
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目前我们采用的标准和国际上相同，我国没有进行过此药物的毒性研究、超声心动图、心律失常等；超声心动图检查左室射血分数不应该低于60%-------绝对标准、紫素等）对心脏的传导系统有影响，但是目前暂且定位总量400mg：国际上一般认为其终身剂量为900-1000mg&#47。 13．如何监测心脏毒性 答，但是接近终身剂量时每疗程需要检查一次，我国也没有相关毒性的研究。表阿霉素，使用蒽环类化疗药至少每3个月重复1次超声心动图。 紫杉类药物（泰素、心肌酶谱;m2：国际上一般认为其终身剂量为400mg&#47，和上次化疗相比左室射血分数下降不超过20%-------相对标准，主要表现房室传导阻滞、特素;m2：阿霉素终身剂量：用蒽环类及紫杉醇者要检查心电图
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化疗药物的相关知识
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赫赛汀联合紫杉类化疗药治疗转移性乳腺癌
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官方公共微信ZINECARD（DEXRAZOXANE）右雷佐生静脉注射-药品说明书与价格-中国新特药网天津站
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ZINECARD（DEXRAZOXANE）右雷佐生静脉注射
ZINECARD（DEXRAZOXANE）右雷佐生静脉注射
18:40:21&&作者：&&来源：&&浏览次数：45&&文字大小：【】【】【】
——右雷佐生（DEXRAZOXANE）-辛卡德（ZINECARD）-500毫克/瓶
【中文名】右雷佐生【英文名】Dexrazoxane 【其它名称】奥诺先、得拉唑沙、右丙亚胺、Cardioxane、Dextrazoxane、Eucardion、Zinecard
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——右雷佐生（DEXRAZOXANE）-辛卡德（ZINECARD）-500毫克/瓶
【中文名】右雷佐生【英文名】Dexrazoxane 【其它名称】奥诺先、得拉唑沙、右丙亚胺、Cardioxane、Dextrazoxane、Eucardion、Zinecard 【分类】肿瘤用药\抗肿瘤辅助药 【临床应用】减轻或减少蒽环类抗生素（如多柔比星）化疗引起的心肌毒性（国外资料） 【用法用量】国外参考信息 本药用量为多柔比星剂量的10倍。从开始给药计算，至少给予本药30min后使用多柔比星，应缓慢注射或较快的滴注。有亚硝基脲用药史者，本药最大耐受量为750mg/㎡；无亚硝基脲用药史者，本药最大耐受量为1250mg/㎡。& Zinecard& (dexrazoxane for injection) Pharmacia and Upjohn Company
DESCRIPTIONZINECARD& (dexrazoxane for injection) is a sterile, pyrogen-free lyophilizate intended for intravenous administration. It is a cardioprotective agent for use in conjunction with doxorubicin.Chemically, dexrazoxane is (S)-4,4'-(1-methyl-1,2-ethanediyl)bis-2,6piperazinedione.The structural formula is as follows:
Dexrazoxane, a potent intracellular chelating agent is a derivative of EDTA. Dexrazoxane is a whitish crystalline powder which melts at 191° to 197°C. It is sparingly soluble in water and 0.1 N HCl, slightly soluble in ethanol and methanol and practically insoluble in nonpolar organic solvents. The pKa is 2.1. Dexrazoxane has an octanol/water partition coefficient of 0.025 and degrades rapidly above a pH of 7.0.
ZINECARD is available in 250 mg and 500 mg single use only vials.
Each 250 mg vial contains dexrazoxane hydrochloride equivalent to 250 mg dexrazoxane. Hydrochloric Acid, NF is added for pH adjustment. When reconstituted as directed with the 25 mL vial of 0.167 Molar (M/6) Sodium Lactate Injection, USP diluent provided, each mL contains: 10 mg dexrazoxane. The pH of the resultant solution is 3.5 to 5.5.
Each 500 mg vial contains dexrazoxane hydrochloride equivalent to 500 mg dexrazoxane. Hydrochloric Acid, NF is added for pH adjustment. When reconstituted as directed with the 50 mL vial of 0.167 Molar (M/6) Sodium Lactate Injection, USP diluent provided, each mL contains: 10 mg dexrazoxane. The pH of the resultant solution is 3.5 to 5.5.
CLINICAL PHARMACOLOGY
Mechanism of Action
The mechanism by which ZINECARD exerts its cardioprotective activity is not fully understood. Dexrazoxane is a cyclic derivative of EDTA that readily penetrates cell membranes. Results of laboratory studies suggest that dexrazoxane is converted intracellularly to a ring-opened chelating agent that interferes with iron-mediated free radical generation thought to be responsible, in part, for anthracycline induced cardiomyopathy.
Pharmacokinetics
The pharmacokinetics of dexrazoxane have been studied in advanced cancer patients with normal renal and hepatic function. Generally, the pharmacokinetics of dexrazoxane can be adequately described by a two-compartment open model with first-order elimination. Dexrazoxane has been administered as a 15 minute infusion over a dose-range of 60 to 900 mg/m2 with 60 mg/m2 of doxorubicin, and at a fixed dose of 500 mg/m2 with 50 mg/m2 doxorubicin. The disposition kinetics of dexrazoxane are dose-independent, as shown by linear relationship between the area under plasma concentration-time curves and administered doses ranging from 60 to 900 mg/m2. The mean peak plasma concentration of dexrazoxane was 36.5 &g/mL at the end of the 15 minute infusion of a 500 mg/m2 dose of ZINECARD administered 15 to 30 minutes prior to the 50 mg/m2 doxorubicin dose. The important pharmacokinetic parameters of dexrazoxane are summarized in the following table.
SUMMARY OF MEAN (%CV*) DEXRAZOXANE PHARMACOKINETIC PARAMETERS AT A DOSAGE RATIO OF 10:1 OF ZINECARD: DOXORUBICIN
Dose Doxorubicin (mg/m2)
Dose Zinecard (mg/m2)
Number of Subjects
Elimination Half-Life (h)
Plasma Clearance (L/h/m2)
Renal Clearance (L/h/m2)
†Volume of Distribution (L/m2)
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Following a rapid distributive phase (~0.2 to 0.3 hours), dexrazoxane reaches post-distributive equilibrium within two to four hours. The estimated steady-state volume of distribution of dexrazoxane suggests its distribution primarily in the total body water (25 L/m2). The mean systemic clearance and steady-state volume of distribution of dexrazoxane in two Asian female patients at 500 mg/m2 dexrazoxane along with 50 mg/m2 doxorubicin were 15.15 L/h/m2 and 36.27 L/m2, respectively, but their elimination half-life and renal clearance of dexrazoxane were similar to those of the ten Caucasian patients from the same study. Qualitative metabolism studies with ZINECARD have confirmed the presence of unchanged drug, a diacid-diamide cleavage product, and two monoacid-monoamide ring products in the urine of animals and man. The metabolite levels were not measured in the pharmacokinetic studies.
Urinary excretion plays an important role in the elimination of dexrazoxane. Forty-two percent of the 500 mg/m2 dose of ZINECARD was excreted in the urine.
Protein Binding
In vitro studies have shown that ZINECARD is not bound to plasma proteins.
Special Populations
The pharmacokinetics of ZINECARD have not been evaluated in pediatric patients.
Analysis of pooled data from two pharmacokinetic studies indicate that male patients have a lower mean clearance value than female patients (110 mL/min/m2 versus 133 mL/min/m2). This gender effect is not clinically relevant.
Renal insufficiency
The pharmacokinetics of ZINECARD were assessed following a single 15 minute IV infusion of 150 mg/m2 of dexrazoxane in male and female subjects with varying degrees of renal dysfunction as determined by creatinine clearance (CLCR) based on a 24-hour urinary creatinine collection. Dexrazoxane clearance was reduced in subjects with renal dysfunction. Compared with controls, the mean AUC0–inf value was twofold greater in subjects with moderate (CLCR 30–50 mL/min) to severe (CLCR &30 mL/min) renal dysfunction. Modeling demonstrated that equivalent exposure (AUC0–inf) could be achieved if dosing were reduced by 50% in subjects with creatinine clearance values & 40 mL/min compared with control subjects (CLCR &80 mL/min) (see PRECAUTIONS, DOSAGE AND ADMINISTRATION).
Hepatic insufficiency
The pharmacokinetics of ZINECARD have not been evaluated in patients with hepatic impairment. The ZINECARD dose is dependent upon the dose of doxorubicin (see DOSAGE AND ADMINISTRATION). Since a doxorubicin dose reduction is recommended in the presence of hyperbilirubinemia, the ZINECARD dosage is proportionately reduced in patients with hepatic impairment.
Drug Interactions
There was no significant change in the pharmacokinetics of doxorubicin (50 mg/m2) and its predominant metabolite, doxorubicinol, in the presence of dexrazoxane (500 mg/m2) in a crossover study in cancer patients.
Clinical Studies
The ability of ZINECARD to prevent/reduce the incidence and severity of doxorubicin-induced cardiomyopathy was demonstrated in three prospectively randomized placebo-controlled studies. In these studies, patients were treated with a doxorubicin-containing regimen and either ZINECARD or placebo starting with the first course of chemotherapy. There was no restriction on the cumulative dose of doxorubicin. Cardiac function was assessed by measurement of the left ventricular ejection fraction (LVEF), utilizing resting multigated nuclear medicine (MUGA) scans, and by clinical evaluations. Patients receiving ZINECARD had significantly smaller mean decreases from baseline in LVEF and lower incidences of congestive heart failure than the control group. The difference in decline from baseline in LVEF was evident beginning with a cumulative doxorubicin dose of 150 mg/m2 and reached statistical significance in patients who received ≥400 mg/m2 of doxorubicin. In addition to evaluating the effect of ZINECARD on cardiac function, the studies also assessed the effect of the addition of ZINECARD on the antitumor efficacy of the chemotherapy regimens. In one study (the largest of three breast cancer studies) patients with advanced breast cancer receiving fluorouracil, doxorubicin and cyclophosphamide (FAC) with ZINECARD had a lower response rate (48% vs 63%; p=0.007) and a shorter time to progression than patients who received FAC + placebo, although the survival of patients who did or did not receive ZINECARD with FAC was similar.
Two of the randomized breast cancer studies evaluating the efficacy and safety of FAC with either ZINECARD or placebo were amended to allow patients on the placebo arm who had attained a cumulative dose of doxorubicin of 300 mg/m2 (six courses of FAC) to receive FAC with open-label ZINECARD for each subsequent course. This change in design allowed examination of whether there was a cardioprotective effect of ZINECARD even when it was started after substantial exposure to doxorubicin.
Retrospective historical analyses were then performed to compare the likelihood of heart failure in patients to whom ZINECARD was added to the FAC regimen after they had received six (6) courses of FAC (and who then continued treatment with FAC therapy) with the heart failure rate in patients who had received six (6) courses of FAC and continued to receive this regimen without added ZINECARD. These analyses showed that the risk of experiencing a cardiac event (see Table 1 for definition) at a given cumulative dose of doxorubicin above 300 mg/m2 was substantially greater in the 99 patients who did not receive ZINECARD beginning with their seventh course of FAC than in the 102 patients who did receive ZINECARD (See Figure 1).
Table 1 The development of cardiac events is shown by:
Figure 1 displays the risk of developing congestive heart failure by cumulative dose of doxorubicin in patients who received ZINECARD starting with their seventh course of FAC compared to patients who did not. Patients unprotected by ZINECARD had a 13 times greater risk of developing congestive heart failure. Overall, 3% of patients treated with ZINECARD developed CHF compared with 22% of patients not receiving ZINECARD.
Because of its cardioprotective effect, ZINECARD permitted a greater percentage of patients to be treated with extended doxorubicin therapy. Figure 2 shows the number of patients still on treatment at increasing cumulative doses.
In addition to evaluating the cardioprotective efficacy of ZINECARD in this setting, the time to tumor progression and survival of these two groups of patients were also compared. There was a similar time to progression in the two groups and survival was at least as long for the group of patients that received ZINECARD starting with their seventh course, i.e., starting after a cumulative dose of doxorubicin of 300 mg/m2. These time to progression and survival data should be interpreted with caution, however, because they are based on comparisons of groups entered sequentially in the studies and are not comparisons of prospectively randomized patients.
INDICATIONS AND USAGE
ZINECARD is indicated for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose of 300 mg/m2 and who will continue to receive doxorubicin therapy to maintain tumor control. It is not recommended for use with the initiation of doxorubicin therapy (see WARNINGS).
CONTRAINDICATIONS
ZINECARD should not be used with chemotherapy regimens that do not contain an anthracycline.
ZINECARD may add to the myelosuppression caused by chemotherapeutic agents.
There is some evidence that the use of dexrazoxane concurrently with the initiation of fluorouracil, doxorubicin and cyclophosphamide (FAC) therapy interferes with the antitumor efficacy of the regimen, and this use is not recommended. In the largest of three breast cancer trials, patients who received dexrazoxane starting with their first cycle of FAC therapy had a lower response rate (48% vs 63%; p=0.007) and shorter time to progression than patients who did not receive dexrazoxane (see Clinical Studies section of CLINICAL PHARMACOLOGY). Therefore, ZINECARD should only be used in those patients who have received a cumulative doxorubicin dose of 300 mg/m2 and are continuing with doxorubicin therapy.
Although clinical studies have shown that patients receiving FAC with ZINECARD may receive a higher cumulative dose of doxorubicin before experiencing cardiac toxicity than patients receiving FAC without ZINECARD, the use of ZINECARD in patients who have already received a cumulative dose of doxorubicin of 300 mg/m2 without ZINECARD, does not eliminate the potential for anthracycline induced cardiac toxicity. Therefore, cardiac function should be carefully monitored. Secondary malignancies (primarily acute myeloid leukemia) have been reported in patients treated chronically with oral razoxane. Razoxane is the racemic mixture, of which dexrazoxane is the S(+)-enantiomer. In these patients, the total cumulative dose of razoxane ranged from 26 to 480 grams and the duration of treatment was from 42 to 319 weeks. One case of T-cell lymphoma, a case of B-cell lymphoma and six to eight cases of cutaneous basal cell or squamous cell carcinoma have also been reported in patients treated with razoxane.
PRECAUTIONS
Doxorubicin should not be given prior to the intravenous injection of ZINECARD. ZINECARD should be given by slow I.V. push or rapid drip intravenous infusion from a bag. Doxorubicin should be given within 30 minutes after beginning the infusion with ZINECARD. (See DOSAGE AND ADMINISTRATION).
As ZINECARD will always be used with cytotoxic drugs, patients should be monitored closely. While the myelosuppressive effects of ZINECARD at the recommended dose are mild, additive effects upon the myelosuppressive activity of chemotherapeutic agents may occur.
Patients with Moderate or Severe Renal Insufficiency
Greater exposure to dexrazoxane may occur in patients with compromised renal function. The ZINECARD dose should be reduced by 50% in patients with creatinine clearance values &40 mL/min (see DOSAGE AND ADMINISTRATION).
Laboratory Tests
As ZINECARD may add to the myelosuppressive effects of cytotoxic drugs, frequent complete blood counts are recommended. (See ADVERSE REACTIONS).
Drug Interactions
ZINECARD does not influence the pharmacokinetics of doxorubicin.
Carcinogenesis & Mutagenesis & Impairment of Fertility
(see WARNINGS section for information on human carcinogenicity) - No long-term carcinogenicity studies have been carried out with dexrazoxane in animals. Dexrazoxane was not mutagenic in the Ames test but was found to be clastogenic to human lymphocytes in vitro and to mouse bone marrow erythrocytes in vivo (micronucleus test).
The possible adverse effects of ZINECARD on the fertility of humans and experimental animals, male or female, have not been adequately studied. Testicular atrophy was seen with dexrazoxane administration at doses as low as 30 mg/kg weekly for 6 weeks in rats (1/3 the human dose on a mg/m2 basis) and as low as 20 mg/kg weekly for 13 weeks in dogs (approximately equal to the human dose on a mg/m2 basis).
Pregnancy Category C
Dexrazoxane was maternotoxic at doses of 2 mg/kg (1/40 the human dose on a mg/m2 basis) and embryotoxic and teratogenic at 8 mg/kg (approximately 1/10 the human dose on a mg/m2 basis) when given daily to pregnant rats during the period of organogenesis. Teratogenic effects in the rat included imperforate anus, microphthalmia, and anophthalmia. In offspring allowed to develop to maturity, fertility was impaired in the male and female rats treated in utero during organogenesis at 8 mg/kg. In rabbits, doses of 5 mg/kg (approximately 1/10 the human dose on a mg/m2 basis) daily during the period of organogenesis were maternotoxic and dosages of 20 mg/kg (1/2 the human dose on a mg/m2 basis) were embryotoxic and teratogenic. Teratogenic effects in the rabbit included several skeletal malformations such as short tail, rib and thoracic malformations, and soft tissue variations including subcutaneous, eye and cardiac hemorrhagic areas, as well as agenesis of the gallbladder and of the intermediate lobe of the lung. There are no adequate and well-controlled studies in pregnant women. ZINECARD should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether dexrazoxane is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants exposed to dexrazoxane, mothers should be advised to discontinue nursing during dexrazoxane therapy.
Pediatric Use
Safety and effectiveness of dexrazoxane in pediatric patients have not been established.
Geriatric Use
Clinical studies of ZINECARD did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, elderly patients should be treated with caution due to the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.
ADVERSE REACTIONS
ZINECARD at a dose of 500 mg/m2 has been administered in combination with FAC in randomized, placebo-controlled, double-blind studies to patients with metastatic breast cancer. The dose of doxorubicin was 50 mg/m2 in each of the trials. Courses were repeated every three weeks, provided recovery from toxicity had occurred. Table 2 below lists the incidence of adverse experiences for patients receiving FAC with either ZINECARD or placebo in the breast cancer studies. Adverse experiences occurring during courses 1 through 6 are displayed for patients receiving ZINECARD or placebo with FAC beginning with their first course of therapy (column 1 & 3, respectively). Adverse experiences occurring at course 7 and beyond for patients who received placebo with FAC during the first six courses and who then received either ZINECARD or placebo with FAC are also displayed (column 2 & 4, respectively).
ADVERSE EXPERIENCE
PERCENTAGE (%) OF BREAST CANCER PATIENTS WITH ADVERSE EXPERIENCE
FAC + ZINECARD
FAC + PLACEBO
Courses 1– 6N = 413
Courses ≥ 7 N = 102
Courses 1– 6 N = 458
Courses ≥ 7 N = 99
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Pain on Injection
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Neurotoxicity
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Esophagitis
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The adverse experiences listed above are likely attributable to the FAC regimen with the exception of pain on injection that was observed mainly on the ZINECARD arm.
Myelosuppression
Patients receiving FAC with ZINECARD experienced more severe leucopenia, granulocytopenia and thrombocytopenia at nadir than patients receiving FAC without ZINECARD, but recovery counts were similar for the two groups of patients.
Hepatic and Renal
Some patients receiving FAC + ZINECARD or FAC + placebo experienced marked abnormalities in hepatic or renal function tests, but the frequency and severity of abnormalities in bilirubin, alkaline phosphatase, BUN, and creatinine were similar for patients receiving FAC with or without ZINECARD.
OVERDOSAGE
There have been no instances of drug overdose in the clinical studies sponsored by either Pharmacia & Upjohn Company or the National Cancer Institute. The maximum dose administered during the cardioprotective trials was 1000 mg/m2 every three weeks.
Disposition studies with ZINECARD have not been conducted in cancer patients undergoing dialysis, but retention of a significant dose fraction (&0.4) of the unchanged drug in the plasma pool, minimal tissue partitioning or binding, and availability of greater than 90% of the systemic drug levels in the unbound form suggest that it could be removed using conventional peritoneal or hemodialysis.
There is no known antidote for dexrazoxane. Instances of suspected overdose should be managed with good supportive care until resolution of myelosuppression and related conditions is complete. Management of overdose should include treatment of infections, fluid regulation, and maintenance of nutritional requirements.
DOSAGE AND ADMINISTRATION
The recommended dosage ratio of ZINECARD:doxorubicin is 10:1 (eg, 500 mg/m2 ZINECARD:50 mg/m2 doxorubicin). In patients with moderate to severe renal dysfunction (creatinine clearance values & 40 mL/min), the recommended dosage ratio of ZINECARD:doxorubicin is 5:1 (eg. 250 mg/m2 ZINECARD:50 mg/m2 doxorubicin). Creatinine clearance can be determined from a 24-hour urinary creatinine collection or estimated using the Crockroft-Gault equation (assuming stable renal function):
CLCR=[140–age (years)] × weight (kg) {× 0.85 for female patients} 72 × serum creatinine (mg/dL)
Since a doxorubicin dose reduction is recommended in the presence of hyperbilirubinemia, the ZINECARD dosage should be proportionately reduced (maintaining the 10:1 ratio) in patients with hepatic impairment. ZINECARD must be reconstituted with 0.167 Molar (M/6) Sodium Lactate Injection, USP, to give a concentration of 10 mg ZINECARD for each mL of sodium lactate. The reconstituted solution should be given by slow I.V. push or rapid drip intravenous infusion from a bag. After completing the infusion of ZINECARD, and prior to a total elapsed time of 30 minutes (from the beginning of the ZINECARD infusion), the intravenous injection of doxorubicin should be given.
Reconstituted ZINECARD, when transferred to an empty infusion bag, is stable for 6 hours from the time of reconstitution when stored at controlled room temperature, 15° to 30°C (59° to 86°F) or under refrigeration, 2° to 8°C (36° to 46°F). DISCARD UNUSED SOLUTIONS.
The reconstituted ZINECARD solution may be diluted with either 0.9% Sodium Chloride Injection, USP or 5.0% Dextrose Injection, USP to a concentration range of 1.3 to 5.0 mg/mL in intravenous infusion bags. The resultant solutions are stable for 6 hours when stored at controlled room temperature, 15° to 30°C (59° to 86°F) or under refrigeration, 2° to 8°C (36° to 46°F). DISCARD UNUSED SOLUTIONS.
Incompatibility
ZINECARD should not be mixed with other drugs.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Handling and Disposal
Caution in the handling and preparation of the reconstituted solution must be exercised and the use of gloves is recommended. If ZINECARD powder or solutions contact the skin or mucosae, immediately wash thoroughly with soap and water.
Procedures normally used for proper handling and disposal of anticancer drugs should be considered for use with ZINECARD. Several guidelines on this subject have been published.1–8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
HOW SUPPLIED
ZINECARD& (dexrazoxane for injection) is available in the following strengths as sterile, pyrogen-free lyophilizates.
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<FONT color=# mg single dose vial with a blue flip-top seal, packaged in single vial packs. (This package also contains a 50 mL vial of 0.167 Molar (M/6) Sodium Lactate Injection, USP.)
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Reconstituted solutions of ZINECARD are stable for 6 hours at controlled room temperature or under refrigeration, 2° to 8°C (36° to 46°F). DISCARD UNUSED SOLUTIONS.
Dexrazoxane（Cardioxane，Zinecard，右雷佐生）【简介】Dexrazoxane（Cardioxane，Zinecard，右雷佐生）是依地酸（edetic acid）的衍生物，是位点特异的心脏保护药物，可以有效地对抗蒽环类抗癌药所引起的心脏损伤。Dexrazoxane在美国和一些欧洲国家已获得批准，用于接受阿霉素治疗的进展期或转移性乳腺癌病人的心脏保护。在有些国家Dexrazoxane被批准的适应症范围更为广泛，可用于接受蒽环类抗癌药治疗的多种肿瘤病人的心脏保护。【药效和药理学】临床试验显示，静脉注射Dexrazoxane可以显著降低接受蒽环类抗癌药治疗的进展期乳腺癌、软组织肉瘤和小细胞肺癌患者的充血性心力衰竭以及其他心脏不良反应的发生率。无论Dexrazoxane在抗癌药使用之前或之后给药，甚至当阿霉素累积剂量超过300mg/m2，Dexrazoxane都可表现出心脏保护作用。此外，当患者本身有心血管风险因子时，Dexrazoxane也具有心脏保护作用。而且Dexrazoxane并不影响蒽环类抗癌药的疗效。该产品的耐受性良好，其不良反应和安慰剂类似，主要的不良反应是Dexrazoxane可以引起比较高的白细胞减少症（分别为78%和68%，p&0.01）。&&& Dexrazoxane进入细胞后的水解产物具有金属螯合活性，可以螯合游离铁以及与蒽环类抗癌药结合的铁，防止具有心脏毒性的氧自由基的形成。实验动物给药阿霉素或表阿霉素，经Dexrazoxane处理后的实验动物心脏损伤的发生率显著降低，而生存率显著提高。实验动物研究显示，Dexrazoxane在阿霉素给药前立即给药或同时给药的效果要好于之后给药。此外，在第一次给药阿霉素之前给药，其心脏保护效果要优于延迟给药。【药代动力学】静脉注射Dexrazoxane的药代动力学遵循2室模型的一级清除动力学。在60-900mg/m2剂量范围内,Dexrazoxane的吸收动力学为线性。该药物的组织分布迅速，在2-4小时内达到平衡，肝脏和肾脏是母体药物和水解产物浓度最高的器官。血浆蛋白结合少量。该药物在肝脏、肾脏、心脏、红细胞和白细胞内被酶水解为活性更强的开环形式。清除主要通过肾脏以原型形式排出体外。在阿霉素或表阿霉素之前15-30分钟使用dexrazoxane，对两种药物的药代动力学都没有显著影响。【临床疗效】Dexrazoxane对接受蒽环类化疗药治疗的进展期乳腺癌病人有显著的心脏保护作用。总结所有Ⅲ期临床试验的数据，Dexrazoxane使用情况下心脏事件的发生率为0-15%，而不使用时的发生率为16-50%，前者显著少于后者。充血性心力衰竭的发生率在Dexrazoxane使用时为0-3%，而不使用时的发生率为8-27%。接受阿霉素治疗的小细胞肺癌病人以及接受高剂量表阿霉素治疗的软组织肉瘤病人联合使用Dexrazoxane时，心血管事件（软组织肉瘤病人还包括充血性心力衰竭）的发生率都显著降低。对接受以蒽环类抗生素为基础的化疗方案的儿童或青少年恶性肿瘤（包括急性淋巴细胞白血病和各种肉瘤）患者（年龄小于24岁），Dexrazoxane可以提供有效的短期和中期心脏保护效果，但长期数据目前还没有。&&&&&&&&&& 根据两项荟萃分析的研究结果，Dexrazoxane可以使蒽环类抗癌药诱导的心脏毒性的相对风险（与不使用dexrazoxane的情况相比）减少72-76%，而化疗失败的相对风险并没有增高，病人的生存率也没有降低。【耐受性】Dexrazoxane的耐受性良好，耐受性情况和安慰剂类似，不同的是Dexrazoxane相关的严重白细胞减少的病例显著增高。虽然儿童应用的数据还有限，但已有的结果显示儿童对Dexrazoxane的耐受性也比较好。Dexrazoxane与阿霉素无论是以10∶1或20∶1的剂量比例给药，耐受性类似。
-----------------------------------------------------------产地国家：美国 所属类别：抗癌药物 -&化疗药物原产地英文药品名：DEXRAZOXANE 中文参考药品译名：未知 原产地英文商品名：ZINECARD-500mg/Vial 中文参考商品译名：辛卡德-500毫克/瓶 生产厂家英文名：Pharmacia & Upjohn Company 生产厂家中文参考译名：未知
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