48．康泉
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266页（8082字）
【中文释文】：
格雷西隆
〔成分〕
每安瓿含3mg格雷西隆盐酸盐，于3ml等张生理盐水中，为一澄清、无色或微黄色液体。
〔作用〕
康泉用于预防或治疗因细胞毒治疗引起的呕吐及恶心，康泉是一具止呕作用的有效及高选择性的5-羟色胺(5-HT3)受体拮抗剂。
〔剂量及用法〕
康泉针剂只能作输注使用。
成人：康泉3mg应以20～50ml输液稀释，输注时间需超过5min。
预防：临床实验证明，大部分病人只需单一剂量康泉3mg便可防止呕吐及恶心超过24h以上。于24h内，可给药二次，康泉3mg。临床经验显示，于一疗程中，康泉可连续使用5d。康泉预防给药须于细胞毒治疗开始前完成。
每日最高剂量：24h内最多可给药3次，康泉3mg。而24h内最大剂量不应超过9mg。
老年人：不需调整剂量。
儿童：现时无足够资料以评估康泉于儿童的效果与安全性。
对患有肝肾功能不全病人无需调整剂量。
配制康泉3mg输液时，将3ml康泉稀释于20～50ml下列输液中：0．9%(w／v)氯化钠注射溶液(英国药典)；0．18%(w／v)氯化钠+4%(w／v)葡萄糖注射溶液(英国药典)；5%(w／v)葡萄糖注射溶液(英国药典)；Hartman注射溶液(英国药典)；乳酸钠注射溶液(英国药典)或10%甘露醇注射液(英国药典)；其他溶液则不应使用。
〔禁忌证及警告〕
禁忌证：对格雷西隆或有关化合物过敏。
注意事项：康泉会减低大肠蠕动，病人若有亚急性肠阻塞时，使用康泉需严密监察。
人体观察表明对警觉性无影响。
两年致癌性研究资料显示，给予两性小鼠及大鼠极大量康泉时(50mg／kg，大鼠剂量于59周时降至每天25mg／kg，发现有肝细胞瘤及／或腺瘤增加现象，于接受5mg／kg康泉的雄性大鼠亦发现有肝细胞瘤生成。而于低剂量时(1mg／kg)时未见此种药物诱发肝细胞瘤生成。
而在多个体外及体内测定证实康泉对哺乳类细胞无遗传毒性。
药物配伍：健康受试者试验显示康泉与西咪替丁或氯羟去甲安定无相互作用。临床实验亦未显示有药物相互作用。
孕妇及哺乳妇：动物观察证实无致畸胎性，但于人体则无此经验。因此，除临床必须外，康泉不应应用于孕妇。由于无康泉在母乳中的资料，在接受康泉治疗时应终止哺乳。
〔副作用〕
人体实验中显示，对康泉耐受性很高。此外，严重锥体外系反应证实与康泉无关。如同类其药物一样。头痛、便秘是最常见副作用，但大多为轻微的。临床实验显示有一过性肝转氨酶增加，只是超过平均水平，但仍在正常范围内。
过量：现仍无专门解毒剂。若过量时，应以对症治疗。1病人曾服用10倍于建议剂量的康泉，此病人只有轻微头痛而无其他后遗症。
〔其他注意事项〕
康泉安瓿应避免阳光直射。应置30℃以下贮存，不可冷冻。康泉静脉输注剂最理想为用药时配制。稀释后(见剂量与用法)若置室温下，避光，其稳定期可维持24h。若制剂放置超过24h应丢弃。如康泉于配制后需贮存，则需以无菌操作。康泉不应与其他药一起混合输注。
〔包装〕
每盒5安瓿。
〔其他资料〕
康泉于体内分布广泛，血浆蛋白结合率约为65%。康泉很快且大部分被代谢，其途径主要通过N-去烷基化及芳香环氧化后再被聚合。排泄途径通过尿液及粪便。无效成分为氯化钠及注射用水。
〔生产厂家〕
英国史克必成药厂
(附本品别名：格兰西龙Granisetron)
【外文释文】：
For intravenous infusion
Presentation
Clear glass ampoules，each containing 3 mg granisetron present as the hydrochloride in 3 ml isotonic saline as a clear，colourless or slightly straw-coloured liquid．
Uses
Kytril is indicatedfor the prevention or treatment of nausea and vomiting induced by cytostatic therapy．
Granisetron is a potent and highly selective 5-hydroxytryptamine(5-HT3)receptor antagonist with anti-emetic activity．
Dosage and administration
Kytril ampoules are for intravenous infusion only．
Adults：3 mg kytril，which should be diluted in 20-50 ml infusion fluid and administered over five minutes．
Prevention：In clinical trials，the majority of patients have required only a single dose of kytril to control nausea and vomiting over 24 hours．Up to two additional five-minute infusions of the 3 mg kytril may be administered within a 24-hour period．There is clinical experience in patients receiving daily administration for up to five consecutive days in one course of therapy．Prophylactic administration of kytril should be completed prior to the start of cytostatic therapy．
Treatment：The same dose of kytril should be used as for prevention．Additional infusions should be administered at least 10 minutes apart．
Maximum daily dosage：Up to three five-minute infusions of 3 mg kytril may be administered within a 24-hour period．The maximum dose of kytril administered over 24 hours should not exceed 9mg．
Elderly：No special requirements apply to elderly patients．
Children：There are currently insufficient data on the safety and efficacy of kytril in children．
No special requirements apply to those patients with renal or hepatic impairment．
To prepare the dose of 3mg，3ml is withdrawn from the ampoule and diluted with infusion fluid to a total volume of 20-50ml in any of the following solutions：0．9%w／v Sodium Chloride Injection BP；0．18%w／v Sodium Chloride and 4%w／v Glucose Injection BP；5% w／v Glucose Injection BP；Hartmann’s Solution for Injection BP；Sodium Lactate Injection BP，or 10%Mannitol Injection BP．No other diluents should be used．
Contra indications，warnings，etc．
Contra indication：Hypersensitivity to granisetron or related substances．
Precautions：As kytril may reduce lower bowel motility，patients with signs of subacute intestinal obstruction should be monitored following adminstration of kytril．
There has been no evidence from human studies that kytril has any adverse effect on alertness．
Data from two-year carcinogenicity studies have shown an increase in hepatocellular carcinoma and／or adenoma in rats and mice of both sexes given 50mg／kg(rat dosage reduced to 25 mg／kg／day at week 59)．Increases in hepatocellular neoplasia were also detected at 5mg／kg in male rats．In both species，drug-induced effects(hepatocellular neoplasia)were not observed in the low-dose group(1mg／kg)．In several in vitro and in vivo assays，kytril was shown to be non-genotoxic in mammalian cells．
Drug interactions：In studies in healthy subjects，no evidence of any interaction has been indicated between kytril and cimetidine or lorazepam．No evidence of drug interactions has been observed in clinical studies．
Use in pregnancy and lactation：While animal studies have shown no teratogenic effects，there is no experience of kytril in human pregnancy．Therefore kytril should not be administered to women who are pregnant unless there are compelling clinical reasons．There are nodata on the excretion of kytril in breast milk．Breast feeding should therefore be discontinued during therapy．
Adverse reactions：kytril has been generally well tolerated in human studies．No extrapyramidal effects of other serious adverse reactions definitely related to the administration of kytril have been observed．As reported with other drugs of this class，headache and constipation have been the most frequently noted adverse events，but the majority have been mild or moderate in nature．In clinical trials，transient increases in mean levels of hepatic transaminases，remaining within the normal range，have been seen．
Overdosage：There is no specific antidote for kytril．In the case of overdosage，symptomatic treatment should be given．One patient has received 10 times the recommended dose of kytril．The patient reported a slight headache but no other sequelae were observed．
Pharmaceutical precautions
Store below 30℃．Ampoules removed from the pack should be protected from direct sunlight．Do not freeze．
Ideally，intravenous infusions of kytril should be prepared at the time of administration．After dilution(see Dosage and administration)the shelf life is 24 hours when stored at ambient temperature in normal indoor illumination protected from direct sunlight．It must not be used after 24 hours．If to be stored after preparation，kytril infusions must be prepared under appropriate aseptic conditions．
As a general precaution，kytril should not be mixed in solution with other drugs．
Package quantities
Ampoules in boxes of 5
Further information
Kytril is widely distributed with plasma protein binding of approximataly 65%．It is rapidly and extensively metabolised mainly by N-demethlation and aromatic ring oxidation followed by conjugation；excretion is both urinary and faecal．
Inactive ingredients are sodium chloride and water for injections．
Manufacturer
Kytril Granisetron is a product of research from smithkline Beecham pharmaceuticals，Brentford，England．