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商品名称：安曲希
通用名称：甲酰四氢叶酸钙注射液
英文名称：ANTREX
成份:叶酸
适应症
1）由缺乏叶酸所引起的巨幼细胞性贫血。
2）治疗叶酸拮抗剂(只是注射剂)所引起的不良反应及毒性。
3）保护正常细胞，防止大剂量甲氨喋呤所产生的毒性作用。
4）与5-氟尿嘧啶（5FU）并用治疗晚期结直肠癌。
规格:15毫克片剂
用法用量
1）因叶酸缺乏引起的巨幼细胞性贫血：推荐最初剂量为每日肌注9-12mg或口服7.5mg，连续使用10-15天。如疗效满意，可将剂量降低至能保证足够临床治疗效果的水平，直至血象正常，症状消失为止。
2）当用于治疗叶酸拮抗剂之毒性及不良反应时观察到任何毒副反应，应尽早进行治疗，并据骨髓抑制情况，调校其剂量。常用剂量为每日肌注一至二次，每次3至6mg。直至血象恢复正常为止。
3）作大剂量甲氨喋呤解毒剂，不同病人亚叶酸钙剂量差异很大。需紧密监测甲氨喋呤从血浆排除率来决定最佳剂量。继续服用亚叶酸钙直至甲氨喋呤浓度低于2×10-8mol/l。
以下为用于解救大剂量甲氨喋呤时不同的亚叶酸钙剂量指导：
一般情况，在甲氨喋呤静滴后24小时开始亚叶酸钙治疗，以15毫克静注，口服或肌注11次，每隔6小时1次。
不良反应:
口服应用本品偶有过敏反应报导。联合应用亚叶酸钙与5Fu主要剂量限制不良反应为口腔炎及腹泻。另外，造血系统抑制例如白细胞减少、血小板减少可发生。这些不良反应和剂量有关，降低细胞毒性药物剂量可减少不良反应发生。须密切监测造血系统数值例如血白细胞及血小板水平, 若有腹泻, 必需监测血浆电解质（例如：钠、钾、钙）及肌酐水平等来控制这些副反应。
禁忌:禁用于恶性贫血症或其他因维生素B12缺乏的巨幼细胞性贫血
联合甲酰四氢叶酸钙及氟尿嘧啶化疗，请看4.6项怀孕及哺乳。
注意事项:
应由对化疗药物有经验的医生方可使用与甲氨喋呤及5Fu联合治疗。
由于在甲酰四氢叶酸钙的钙含量，每分钟不能静注超过160毫克。
药物相互作用:
包装分量：
每卡纸盒1瓶
500 mg静滴粉剂：
浅黄色粉末或粉饼
基本包装
清晰，无色玻璃瓶（36ml）；
附有丁基冷冻干燥塞子及
可翻转盖（绿色）
包装分量：
每卡纸盒1瓶
药物过量:
过量亚叶酸钙剂量可令叶酸拮抗剂化疗作用无效。无特别针对亚叶酸钙的解毒剂。若过量，给与病人适当的支持治疗。若与5-FU联用时出现过量，依照5-FU过量指示来拯救。
药理作用:
亚叶酸钙乃四氢叶酸的5-甲酰衍生物对映异构体的混合体。S-（L）-异构体为生理有效物质，并不需要二氢叶酸还原酶还原就能参与DNA及RNA合成。
药代动力学:
口服或肌注亚叶酸钙迅速被胃肠道吸收及代谢成10-甲基四氢叶酸盐，5，10-亚甲基四氢叶酸盐，四氢叶酸盐，及5-甲基四氢叶酸盐(THF)等的主要代谢物。虽分布全身组织，叶酸盐集中在大脑脊髓中。
贮藏:
室温保存，远离儿童。3mg/ml注射液在2-15℃保存。
有效期:
50毫克片剂.粉剂注射：3年
3mg/ml 注射液：2年
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原产地英文商品名:
ANTREX 15mg/tab 100tabs/box
原产地英文药品名:
CALCIUM FOLINATE
中文参考商品译名:
安曲希 15毫克/片 100片/盒
中文参考药品译名:
亚叶酸钙
Calcium Folinate 15mg Tablets (Hospira UK Ltd)
1. Name Of The Medicinal Product
Calcium Folinate 15mg Tablets.
2. Qualitative And Quantitative Composition
Each tablet contains Calcium Folinate (Calcium Leucovorin) equivalent to folinic acid (leucovorin) 15mg.
For excipients, see 6.1
3. Pharmaceutical Form
Tablet
Light yellow, round, convex, uncoated tablets. The tablets are scored and marked “CF” on one side.
4. Clinical Particulars
4.1 Therapeutic Indications
Leucovorin (folinic acid) is the formyl derivative of tetrahydrofolic acid which is a metabolite and active form of folic acid.
4.2 Posology And Method Of Administration
Adults and Children
Calcium Folinate Rescue
Calcium Folinate may be used in conjunction with folic acid antagonists, e.g. methotrexate, to reduce their systemic toxicity. It is given 12 to 24 hours after the antineoplastic drug. Doses of up to 120mg may be given over 12 to 24 hours by intramuscular injection or intravenous injection or infusion, followed by 12 to 15mg intramuscularly, or 15mg orally, every 6 hours for the next 48 hours. With lower doses of methotrexate, folinate 15mg orally every 6 hours for 48 to 72 hours may be sufficient.
Treatment should be accompanied by alkalinisation of urine with maintenance of urinary output at 2000 ml/m²/24 hours and should be continued until plasma methotrexate is less than 10-7 molar. (see section 4.4)
Treatment of Megaloblastic Anaemia
The dose should not exceed 1mg daily given intramuscularly. When given orally, the recommended dosage is one Calcium Folinate Tablet (15mg) daily. Children up to 12 years; 0.25 mg/kg/day. Normal adult oral dosage; 10 – 20 mg daily.
Treatment of Overdosage of Folic Acid Antagonists
In cases of overdosage of folic acid antagonists, Calcium Folinate may be administered by intravenous infusion in doses of up to 75mg within 12 hours, followed by 12mg intramuscularly every 6 hours for 4 doses.
In general, where overdosage is suspected, the dose of Calcium Folinate should be equal to or greater than the offending dose of the folic acid antagonist administered, and should be given as soon as possible; preferably within the first hour and certainly within 4 hours after which it may not be effective.
Although Calcium Folinate may also be available as a solution for injection, Calcium Folinate should not be administered intrathecally.
4.3 Contraindications
Calcium Folinate is contraindicated in patients who have previously shown hypersensitivity to folinate or any of the excipients.
Calcium Folinate Injection is contraindicated in the treatment of pernicious anaemia or other megaloblastic anaemias where vitamin B12 is deficient. Its use can lead to an apparent response of the haematopoietic system, but neurological damage may occur or progress if already present.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take calcium folinate tablets.
4.4 Special Warnings And Precautions For Use
Calcium Folinate should only be used with methotrexate or 5-FU under the direct supervision of a clinician experienced in the use of cancer chemotherapeutic agents.
In the treatment of inadvertent overdosage of a folic acid antagonist, folinate should be administered as soon as possible; if a period exceeding 4 hours intervenes, the treatment may not be effective.
In general, Calcium Folinate should not be given simultaneously with folic acid antagonists, e.g. methotrexate, to abort clinical toxicity as the therapeutic effect of the antagonist may be nullified. However, Calcium Folinate given concurrently with folate antagonists, such as pyrimethamine and trimethoprim does not inhibit their antibacterial activity.
Parenteral administration of folinate is preferable to oral dosing following chemotherapy with folic acid antagonists if there is a possibility that the patient may vomit and not absorb the folinate.
Measures to ensure the prompt excretion of methotrexate are important as part of Calcium Folinate Rescue Therapy. These measures include:
1) Alkalinisation of urine so that the urinary pH is greater than 7.0 before methotrexate infusion (to increase solubility of methotrexate and its metabolites)
2) Maintenance of urine output of 1800-2000 cc/m2/24 hr by increased oral or intravenous fluids on days 2, 3 and 4 following methotrexate therapy.
3) Plasma methotrexate concentration, BUN and creatinine should be measured on days 2, 3 and 4.
These measures must be continued until the plasma methotrexate level is less than 10-7 molar (0.1μM).
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Folinates given in large amounts may counteract the antiepileptic effect of phenobarbitone, phenytoin and primidone and increase the frequency of seizures in susceptible patients.
Caution is required during concurrent administration of Calcium Folinate with fluoropyrimidine as this has been associated with seizures and syncope (see Section 4.8).
4.6 Pregnancy And Lactation
Reproduction studies have been performed in rats and rabbits at doses of at least 50 times the human dose. These studies have revealed no evidence of harm to the foetus due to Calcium Folinate. There are, however, no adequate and well-controlled studies in pregnant women. Because animal studies are not always predictive of human response, Calcium Folinate should only be used in pregnant women if the potential benefit justifies the potential risk to the foetus.
Since it is not known if Folinate is distributed into milk, the drug should be used with caution in nursing women.
4.7 Effects On Ability To Drive And Use Machines
Not applicable.
4.8 Undesirable Effects
Adverse reactions are rare but occasional allergic reactions including anaphylactoid reactions and urticaria have been reported; pyrexia has occurred after parenteral administration.
Seizures and/or syncope have been reported rarely in cancer patients receiving folinate, usually in association with fluoropyrimidine administration and most commonly in those with CNS metastases or other predisposing factors; however, a causal relationship has not been established.
4.9 Overdose
There is no specific antidote to calcium folinate overdose. In cases of overdosage patients should be given appropriate supportive care.
Should overdosage of the combination of 5-FU with Calcium Folinate occur, the overdosage instruction for 5-FU should be followed.
Calcium Folinate is indicated in:
a) Neutralising the immediate toxic effects of folic acid antagonists, e.g. Methotrexate.
b) Calcium Folinate Rescue - a treatment technique using Calcium Folinate in conjunction with folic acid antagonists, e.g. methotrexate, to minimise systemic toxicity.
c) The treatment of megaloblastic anaemias due to sprue, nutritional deficiency, pregnancy, infancy, liver disease and malabsorption syndrome.
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