Rasuvo（甲氨蝶呤 methotrexate）是一种由Medac制药生产的甲氨蝶呤单剂量自动注射器，于2014年7月14日经美国FDA上市的新药，每周一次给药，用于治疗活动性类风湿关节炎（RA）和多关节幼年特发性关节炎（pJIA）
RASUVO（甲氨蝶呤 methotrexate）注射剂，皮下使用
最初美国批准：1953年
警告：
严重毒性反应，包括EMBRYO-胚胎毒性和完整的黑框警告DEATHSee完整的处方信息。
严重的毒性反应和死亡已报告的使用甲氨蝶呤。患者应严密监测骨髓，肝，肺，皮肤和肾毒性。
甲氨蝶呤有报道引起胎儿死亡和/或先天性异常和妊娠禁忌。
出乎意料严重（有时是致命的）骨髓抑制，再生障碍性贫血，和胃肠道毒性，已报告有一些非甾体抗炎药（NSAIDs）一起同时给予甲氨蝶呤（通常在高剂量）。
长时间使用后，可能会发生肝毒性，纤维​​化和肝硬化。
甲氨喋呤可以治疗期间的任何时间引起间质性肺炎，并已在低剂量的报道。肺部症状（特别是干燥，干咳）可能需要治疗和精心的调查中断。
腹泻，溃疡性口炎，出血性肠炎和死亡肠穿孔可能发生。
严重的，据报道偶尔会致命，皮肤反应也。
潜在的可能发生致命的机会性感染。
作用机理
氨甲蝶呤抑制二氢叶酸还原酶。 Dihydrofolates必须通过此酶减至tetrahydrofolates才可以被用作在嘌呤核苷酸和胸苷酸合成一碳基团的载体。因此，甲氨蝶呤与DNA合成，修复和细胞复制干扰。活跃增殖的组织，如恶性细胞，骨髓，胎儿细胞，颊和肠粘膜和膀胱细胞在一般甲氨蝶呤的这种影响更为敏感。
在类风湿关节炎的作用机制是未知的;它可能会影响免疫功能。
适应症和用法
Rasuvo对于叶酸类似物代谢抑制剂表示：
重症患者，活动性类风湿关节炎（RA）和多关节幼年特发性关节炎（pJIA），谁是不能容忍或有一个不充分的反应一线治疗管理
严重的，顽固的，禁用牛皮癣症状控制成年人谁没有充分反映其他形式的治疗
使用限制
注：Rasuvo不应被用于治疗肿瘤性疾病
用法用量
Rasuvo仅用于每周一次皮下注射使用。
在腹部或大腿施用Rasuvo。
用氨甲喋呤的另一种制剂用于需要口服，肌内，静脉内，动脉内，或鞘内给药的病人，剂量每周少于7.5毫克，剂量高于每星期，高剂量方案30毫克，或剂量小于2.5毫克的调整增量
起始剂量甲氨蝶呤：
RA：7.5毫克，一次口服或皮下注射制剂
pJIA：10毫克/米2，每周一次
银屑病：10至25毫克，一次口服，肌内，皮下，或静脉内制剂的每周
调整药物剂量逐步实现最佳响应
剂型和规格
注射：单剂量手动触发自动注射器递送在下列剂量浓度甲氨蝶呤：7.5毫克，10毫克，12.5毫克，15毫克，17.5毫克，20毫克，22.5毫克，25毫克，27.5毫克和30毫克。
禁忌症
怀孕
乳母
酒精中毒或肝脏疾病
免疫缺陷综合征
预存血液恶液质
过敏甲氨蝶呤
警告和注意事项
器官系统毒性：潜在的严重毒性。仅适用于由医生使用经验的抗代谢药物治疗。
胚胎 - 胎儿毒性：治疗前排除妊娠。避免怀孕，如果任何一方接收Rasuvo。劝男性避免怀孕最少治疗三个月后，女性避免怀孕对治疗后的至少一个排卵周期。
对生殖的影响：可能引起生育，少精症和月经功能紊乱的损害
实验室检查：监测全血细胞计数，肾功能和肝功能检查。
从剂量不当的风险：误日常使用已经导致致命的毒性
患者肾功能受损，腹水或胸腔积液：消除降低。
头晕和疲劳：影响驾车和机械操作能力
不良反应
常见的不良反应有：恶心，腹痛，消化不良，口腔炎/口腔溃疡，皮疹，鼻咽炎，腹泻，肝功能试验异常，呕吐，头痛，支气管炎，血小板减少，脱发，白细胞减少，全血细胞减少，头晕，光敏性，而“燃烧皮肤损伤“。
要报告疑似不良反应，请在Medac或1-855-336-3322 FDA电话1-800-FDA-1088或www.fda.gov/medwatch。
药物相互作用
阿司匹林的NSAIDs和类固醇：同时使用可提高并延长甲氨蝶呤血清水平，导致增加毒性
质子泵抑制剂：同时使用可提高并延长甲氨蝶呤血清水平，导致增加毒性
特殊人群中使用
儿童用药：安全和甲氨蝶呤疗效，包括Rasuvo，尚未确定在儿童牛皮癣患者。安全和Rasuvo疗效尚未确定在儿科患者恶性肿瘤
老年用药：在剂量选择谨慎使用
存储在控制
室温，25°C（77°F）;游览允许15°到30°C（59°至86°F）。避光。
处理和处置
手柄和与细胞毒性drugs.1的处理和处置建议Rasuvo一致的处理

完整处方来源：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d0075461-0e7e-4967-9c9b-d6440e912c0e
Indications and Important Safety Information, Including Boxed Warning
Expand
CollapseINDICATIONS:
Rasuvo is indicated for the:
•Management of adults with severe, active rheumatoid arthritis (RA) (ACR criteria) or children with active polyarticular juvenile idiopathic arthritis (pJIA), who are intolerant of or had an inadequate response to first‑line therapy, including full dose non‑steroidal anti‑inflammatory agents (NSAIDs).
•Symptomatic control of severe, recalcitrant, disabling psoriasis in adults who are not adequately responsive to other forms of therapy, but only when the diagnosis has been established, as by biopsy and/or after dermatologic consultation. It is important to ensure that a psoriasis "flare" is not due to an undiagnosed concomitant disease affecting immune response.
Limitations of Use
Rasuvo is not indicated for treatment of neoplastic diseases.
This product includes the following Boxed Warning:
WARNING: SEVERE TOXIC REACTIONS, INCLUDING EMBRYO‑FETAL TOXICITY AND DEATH
Rasuvo should be used only by physicians whose knowledge and experience include the use of antimetabolite therapy. Because of the possibility of serious toxic reactions (which can be fatal), Rasuvo should be used only in patients with psoriasis or rheumatoid arthritis with severe, recalcitrant, disabling disease which is not adequately responsive to other forms of therapy. Deaths have been reported with the use of methotrexate in the treatment of malignancy, psoriasis, and rheumatoid arthritis. Patients should be closely monitored for bone marrow, liver, lung, skin, and kidney toxicities. Patients should be informed by their physician of the risks involved and be under a physician's care throughout therapy.
1.Methotrexate has been reported to cause fetal death and/or congenital anomalies. Therefore, Rasuvo is not recommended for females of childbearing potential unless there is clear medical evidence that the benefits can be expected to outweigh the considered risks. Rasuvo is contraindicated in pregnant women.
2.Methotrexate elimination is reduced in patients with impaired renal functions, ascites, or pleural effusions. Such patients require especially careful monitoring for toxicity, and require dose reduction or, in some cases, discontinuation of Rasuvo administration.
3.Unexpectedly severe (sometimes fatal) bone marrow suppression, aplastic anemia, and gastrointestinal toxicity have been reported with concomitant administration of methotrexate (usually in high dosage) along with some nonsteroidal anti‑inflammatory drugs (NSAIDs).
4.Methotrexate causes hepatotoxicity, fibrosis and cirrhosis, but generally only after prolonged use. Acutely, liver enzyme elevations are frequently seen. These are usually transient and asymptomatic, and also do not appear predictive of subsequent hepatic disease. Liver biopsy after sustained use often shows histologic changes, and fibrosis and cirrhosis have been reported; these latter lesions may not be preceded by symptoms or abnormal liver function tests in the psoriasis population. For this reason, periodic liver biopsies are usually recommended for psoriatic patients who are under long‑term treatment. Persistent abnormalities in liver function tests may precede appearance of fibrosis or cirrhosis in the rheumatoid arthritis population.
5.Methotrexate‑induced lung disease, including acute or chronic interstitial pneumonitis, is a potentially dangerous lesion, which may occur acutely at any time during therapy and has been reported at low doses. It is not always fully reversible and fatalities have been reported. Pulmonary symptoms (especially a dry, nonproductive cough) may require interruption of treatment and careful investigation.
6.Diarrhea and ulcerative stomatitis require interruption of therapy: otherwise, hemorrhagic enteritis and death from intestinal perforation may occur.
7.Malignant lymphomas, which may regress following withdrawal of methotrexate, may occur in patients receiving low‑dose methotrexate and, thus, may not require cytotoxic treatment. Discontinue Rasuvo first and, if the lymphoma does not regress, appropriate treatment should be instituted.
8.Like other cytotoxic drugs, methotrexate may induce "tumor lysis syndrome" in patients with rapidly growing tumors.
9.Severe, occasionally fatal, skin reactions have been reported following single or multiple doses of methotrexate. Reactions have occurred within days of oral, intramuscular, intravenous, or intrathecal methotrexate administration. Recovery has been reported with discontinuation of therapy.
10.Potentially fatal opportunistic infections, especially Pneumocystis jiroveci pneumonia, may occur with methotrexate therapy.
11.Methotrexate given concomitantly with radiotherapy may increase the risk of soft tissue necrosis and osteonecrosis.
CONTRAINDICATIONS:
Rasuvo is contraindicated in the following:
•Pregnancy: Rasuvo can cause fetal death or teratogenic effects when administered to a pregnant woman. Rasuvo is contraindicated in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
•Nursing Mothers: Because of the potential for serious adverse reactions from methotrexate in breast fed infants, Rasuvo is contraindicated in nursing mothers.
•Alcoholism or Liver Disease: Patients with alcoholism, alcoholic liver disease or other chronic liver disease.
•Immunodeficiency Syndromes: Patients who have overt or laboratory evidence of immunodeficiency syndromes.
•Preexisting Blood Dyscrasias: Patients who have preexisting blood dyscrasias, such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia.
•Hypersensitivity: Patients with a known hypersensitivity to methotrexate. Severe hypersensitivity reactions have been observed with methotrexate use.
WARNINGS AND PRECAUTIONS
•Organ System Toxicity: Rasuvo has the potential for serious toxicity. Rasuvo should be used only by physicians whose knowledge and experience include antimetabolite therapy. Because of the possibility of severe toxic reactions (which can be fatal), Rasuvo should be used only in patients with psoriasis or rheumatoid arthritis with severe, recalcitrant, disabling disease which is not adequately responsive to other forms of therapy.
•Embryo‑Fetal Toxicity: Methotrexate has been reported to cause fetal death and/or congenital anomalies. Rasuvo is not recommended for females of childbearing potential unless there is clear medical evidence that the benefits can be expected to outweigh the considered risks. Rasuvo is contraindicated in pregnant women with psoriasis or rheumatoid arthritis. Exclude pregnancy before treatment. Females should be counseled on the serious risks to the fetus should they become pregnant while undergoing treatment. Avoid pregnancy if either partner is receiving Rasuvo. Advise males to avoid pregnancy for a minimum of three months after therapy and females to avoid pregnancy for at least one ovulatory cycle after therapy.
•Effects on Reproduction: Methotrexate has been reported to cause impairment of fertility, oligospermia and menstrual dysfunction in humans, during and for a short period after cessation of therapy.
•Laboratory Tests: Patients undergoing Rasuvo therapy should be closely monitored so that toxic effects are detected promptly. Baseline assessment should include a complete blood count with differential and platelet counts, hepatic enzymes, renal function tests and a chest X‑ray.
•Risks from Improper Dosing: The physician and/or pharmacist should emphasize to the patient that Rasuvo is administered once weekly and mistaken daily use has led to fatal toxicity.
•Patients with Impaired Renal Function, Ascites, or Pleural Effusions: Elimination is reduced. Such patients require especially careful monitoring for toxicity and require dose reduction or, in some cases, discontinuation of Rasuvo administration.
•Dizziness and Fatigue: May impair ability to drive or operate machinery.
•Malignant Lymphomas: Non‑Hodgkin's lymphoma and other tumors have been reported in patients receiving low‑dose oral methotrexate. However, there have been instances of malignant lymphoma arising during treatment with low‑dose methotrexate, which have regressed completely following withdrawal of methotrexate, without requiring active anti‑lymphoma treatment. Discontinue Rasuvo first and, if the lymphoma does not regress, appropriate treatment should be instituted.
•Tumor Lysis Syndrome: Like other cytotoxic drugs, methotrexate may induce "tumor lysis syndrome" in patients with rapidly growing tumors.
•Concomitant Radiation Therapy: Methotrexate given concomitantly with radiotherapy may increase the risk of soft tissue necrosis and osteonecrosis.
ADVERSE REACTIONS
Common adverse reactions are: nausea, abdominal pain, dyspepsia, stomatitis/mouth sores, rash, nasopharyngitis, diarrhea, liver function test abnormalities, vomiting, headache, bronchitis, thrombocytopenia, alopecia, leukopenia, pancytopenia, dizziness, photosensitivity, and "burning of skin lesions". The most frequently reported adverse reactions include ulcerative stomatitis, leukopenia, nausea, and abdominal distress. Other frequently reported adverse reactions are malaise, undue fatigue, chills and fever, dizziness and decreased resistance to infection.
DRUG INTERACTIONS
•Aspirin, NSAIDs, and Steroids: Concomitant use may elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal toxicity.
•Proton Pump Inhibitors (PPIs): Concomitant use of some PPIs may elevate and prolong serum levels of methotrexate and cause increased toxicity.
•Oral Antibiotics: Certain oral antibiotics may decrease intestinal absorption of methotrexate or interfere with enterohepatic circulation by inhibiting bowel flora and suppressing metabolism of the drug by bacteria. Use of Rasuvo with penicillins should be carefully monitored.
•Hepatotoxins: Patients receiving concomitant therapy with Rasuvo and other potential hepatotoxins should be closely monitored for possible increased risk of hepatotoxicity.
•Theophylline: Methotrexate may decrease the clearance of theophylline, therefore theophylline levels should be monitored.
•Folic Acid and Antifolates: Vitamin preparations containing folic acid or its derivatives may decrease responses to systemically administered methotrexate. Folate deficiency states may increase methotrexate toxicity.
•Mercaptopurine: Methotrexate increases the plasma levels of mercaptopurine, therefore dose adjustment may be required.
•Other Drugs: Toxicity may be increased because of displacement of certain drugs. Use of Rasuvo with probenecid should be carefully monitored.
USE IN SPECIFIC POPULATIONS
•Pregnancy: Methotrexate has been reported to cause embryotoxicity, fetal death, congenital anomalies, and abortion in humans and is contraindicated in pregnant women.
•Nursing Mothers: Because of the potential for serious adverse reactions from methotrexate in breast fed infants, Rasuvo is contraindicated in nursing mothers.
•Females and Males of Reproductive Potential: Contraception should be used by both females and males while taking Rasuvo. Pregnancy should be avoided if either partner is receiving Rasuvo:
•for a minimum of 3 months after treatment with Rasuvo for males.
•during and for at least 1 menstrual cycle after treatment with Rasuvo for females.
•Pediatric Use: Safety and efficacy of Rasuvo have not been established in pediatric patients with psoriasis or neoplastic disease.
•Geriatric Use: Use caution in dose selection. Elderly patients should be closely monitored for early signs of hepatic, bone marrow and renal toxicity.
•Renal Impairment: Elimination is reduced. Patients require careful monitoring for toxicity and require dose reduction or discontinuation of Rasuvo.
•Hepatic Impairment: Contraindicated in patients with alcoholic liver disease or other chronic liver disease.
DOSAGE AND ADMINISTRATION
Rasuvo is for once weekly subcutaneous use only.
Administer Rasuvo in the abdomen or thigh.