繁体中文
设为首页
加入收藏
当前位置:药品说明书与价格首页 >> 免疫系统 >> 类风湿 >> 来氟米特片|Arava(leflunomide Tablets)

来氟米特片|Arava(leflunomide Tablets)

2012-05-09 23:19:02  作者:新特药房  来源:中国新特药网天津分站  浏览次数:582  文字大小:【】【】【
简介: 英文药名: Arava(leflunomide Tablets) 中文药名: 来氟米特片 品牌药生产厂家: Aventis 药品名称和成分 通用名称:来氟米特片 商品名称:爱若华 Arava 英文名称:Leflunomide Tablets 成份: 主要成 ...

英文药名: Arava(leflunomide Tablets)

中文药名: 来氟米特片

品牌药生产厂家: Aventis

药品名称和成分

通用名称:来氟米特片
商品名称:爱若华 Arava
英文名称:Leflunomide Tablets
成份: 主要成份为来氟米特。其化学名称为α,α,α-三氟-5-甲基-异?唑-N-酰基-对甲苯胺。
性状: 除去薄膜衣呈白色。
适应症

⑴适用于成人类风湿关节炎,有改善病情作用。
⑵狼疮性肾炎。
规格

(1)10mg (2)20mg (3)100mg
用法用量

⑴成人类风湿性关节炎:口服。由于来氟米特半衰期较长,建议间隔24小时给药。为了快速达到稳态血药浓度,参照国外临床试验资料并结合Ⅰ期临床试验结果,建议开始治疗的最初三天给予负荷剂量一日50mg,之后根据病情给予维持剂量一日10mg或20mg。在使用本药治疗期间可继续使用非甾体抗炎药或低剂量皮质类固醇激素。
⑵狼疮性肾炎:口服。根据病情选择适当剂量,推荐剂量一日一次,一次20-40mg,病情缓解后适当减量。可与糖皮质激素联用,或遵医嘱。
不良反应

用于类风湿关节炎的治疗:主要有腹泻、瘙痒、可逆性肝脏酶(ALT和AST)升高、脱发、皮疹等。在国外临床试验中,来氟米特治疗1339例类风湿关节炎病人中,发生率≥3%的不良事件包括:乏力、腹痛、背痛、高血压、厌食、腹泻、消化不良、胃肠炎、肝脏酶升高、恶心、口腔溃疡、呕吐、体重减轻、关节功能障碍、腱鞘炎、头晕、头痛、支气管炎、咳嗽、呼吸道感染、咽炎、脱发、瘙痒、皮疹、泌尿系统感染等。以上不良事件均在安慰剂对照或阳性对照柳氮磺胺吡啶治疗组及MTX治疗组中发现,其中来氟米特治疗组以腹泻、肝脏酶升高、脱发、皮疹较为明显,在应用过程中应加以注意。
用于狼疮性肾炎的治疗:国内临床试验资料显示,来氟米特治疗108例活动增殖型狼疮肾炎病人中,前6个月(20-40mg/日),共有43人发生与试验药物可能有关/有关的不良反应,发生率为39.81%;治疗期间,发生率≥3%的不良事件包括:脱发、血压升高、带状疱疹、转氨酶升高、腹泻/稀便、白细胞下降、皮疹、月经不调、心悸、腹痛;发生率<3%的不良事件包括:恶心/呕吐、上呼吸道感染、血小板下降、乏力、胃烧灼感、厌食、发热、牙周疼痛、视觉异常、尿路感染、咽痛、巨细胞病毒感染、体重下降、多毛、肺部感染等。治疗7-72个月(10-30mg/日),随访52例患者,共有12人发生与试验药物可能有关/有关的不良反应,发生率为23.08%,发生率≥3%的不良事件包括:白细胞下降、转氨酶升高、血小板减少;发生率<3%的不良事件包括:上呼吸道感染、脱发、带状疱疹、月经不调、尿路感染。
禁忌

对本品及其代谢产物过敏者及严重肝脏损害患者禁用。
注意事项

1.临床试验发现来氟米特可引起一过性的ALT升高和白细胞下降,服药初始阶段应定期检查ALT和白细胞。检查间隔视病人情况而定。
2.有肝脏损害和明确的乙肝或丙肝血清学指标阳性的患者慎用。用药前及用药后每月检查ALT,检测时间间隔视病人具体情况而定。如果用药期间出现ALT升高,调整剂量或中断治疗的原则:
①如果ALT升高在正常值的2倍(<80U/L)以内,继续观察。
②如果ALT升高在正常值的2~3倍之间(80~120U/L),减半量服用,继续观察,若ALT继续升高或仍然维持80~120U/L之间,应中断治疗。
③如果ALT升高超过正常值的3倍(>120U/L),应停药观察。停药后若ALT恢复正常可继续用药,同时加强护肝治疗及随访,多数病人ALT不会再次升高。
3.免疫缺陷、未控制的感染、活动性胃肠道疾病、肾功能不全、骨髓发育不良(bone marrowdysplasia)的患者慎用。
4.如果服药期间出现白细胞下降,调整剂量或中断治疗的原则如下。
(1)若白细胞不低于3.0×109/L,继续服药观察。
(2)若白细胞在2.0×109/L~3.0×109/L之间,减半量服药观察。继续用药期间,多数病人可以恢复正常。若复查白细胞仍低于3.0×109/L,中断服药。
(3)若白细胞低于2.0×109/L,中断服药。建议粒细胞计数不低于1.5×109/L。
5.准备生育的男性应考虑中断服药,同时服用考来烯胺(消胆胺)。
6.在本品治疗期间接种免疫活疫苗的效果和安全性没有临床资料,因此服药期间不应使用免疫活疫苗。
7.据国外报道,该药在国外上市后罕见间质性肺炎的发生,有肺部疾患者,请慎用或遵医嘱。
孕妇及哺乳期妇女用药

孕妇及尚未采取可靠避孕措施的育龄妇女及哺乳期妇女禁用。
儿童用药

对儿童应用本品的疗效和安全性还没有研究,故年龄小于18岁的患者,建议不要使用本品。
老年用药

未进行该项实验且无可靠参考文献。
药物相互作用

据文献资料报道:
(1)考来烯胺和活性炭 13例患者和96例志愿者给予考来烯胺或活性炭,血浆中Ml浓度很快减少。
(2)肝毒性药物 来氟米特和其它肝毒性药物合用可能增加不良反应,同时也应考虑到虽然中断来氟米特治疗,但没有采取药物消除措施就接着服用这些药物,同样有可能增加不良反应。在小样本(30例)来氟米特和MTX联合用药的研究中,有5例肝脏酶出现2~3倍升高。其中2例继续服用,3例中断来氟米特治疗,酶的升高都得到恢复。另外5例升高大于3倍,其中2例继续服用,3例中断来氟米特治疗,酶的升高也都得到恢复。
(3)非甾体抗炎药物 在体外一系列临床研究中,Ml可使血浆游离双氯芬酸和布洛芬的浓度升高13%~50%,此临床意义还不清楚。但在临床试验中曾观察了许多和非甾体药物同时应用的病例,没有发现有特殊影响。
(4)甲苯磺丁脲 在一系列临床研究中发现,Ml可使血浆游离甲苯磺丁脲浓度升高13%~50%,此临床意义还不清楚。
(5)利福平 单剂量来氟米特和多剂量利福平联合使用,M1峰浓度较单独使用来氟米特升高(约40%),由于随着利福平的使用,Ml浓度可能继续升高,因此当两药合用时,应慎重。
药物过量

据文献报道,如果剂量过大或出现毒性时,可给予考来烯胺或活性炭加以消除。方法:(1)口服考来烯胺(8g,3次/24小时),24小时内M1血浆浓度降低约40%,48小时内降低大约49%~65%。连续服用11天,M1血浆浓度可降至0.02μg /m1以下。(2)通过胃管或口服给予活性炭(混悬液),每6小时50克,24小时内M1血浆浓度降低37%,48小时降低48%。如果临床上需要,这些措施可以重复使用。
临床试验

国内来氟米特治疗狼疮性肾炎Ⅲ期临床试验,采用多中心、随机、平行对照临床研究。共入组患者184例,其中试验组(来氟米特)108例,对照组(环磷酰胺)76例。
患者入组标准:年龄18-65岁;狼疮性肾炎肾活检病理类型为Ⅲ、Ⅳ或伴Ⅴ型;病情有活动性,SLEDAI狼疮活动积分≥8分;持续性蛋白尿(≥1g/24h)、镜下血尿;3个月内未用过CTX等细胞毒药物。
治疗方案:试验组:口服来氟米特片,试验开始3天0.8-1.0mg/kg/日,以后20-40mg/日维持。对照组:静脉注射环磷酰胺,剂量为0.8-1.0g/月,每月1次。联合激素:口服强的松,剂量0.8 mg/kg/日(一般在40-60mg/日),1个月后改为0.5 mg/kg/日,然后逐渐减量(每2周减2.5-5 mg)至维持量5-10mg/日。疗程6个月。
疗效判定标准:完全缓解:24小时尿蛋白定量小于0.3g,且尿沉渣(RBC<5/HP,WBC<5/HP)血清白蛋白、血清SCr及CCr检测均正常。部分缓解:24小时尿蛋白定量介于0.3-3g之间,且下降≥50%,且血清白蛋白≥30g/L,且肾功能稳定。
治疗失败:24小时尿蛋白定量下降<50%;或24小时尿蛋白定量介于0.3-3g之间,但血清白蛋白<30g/L,或血清SCr上升及CCr下降幅度超过基础值的15%。
疗效:
综合疗效评价:治疗6个月后,试验组完全缓解22.22%,部分缓解59.60%,对照组分别为18.84%,62.32%;治疗6个月,同基线水平相比,试验组和对照组均能显著降低SLEDAI评分、降低24小时尿蛋白、提高血清白蛋白、降低SCr、提高C3、降低ds-DNA阳性率。
试验入组病例活检的病理类型为狼疮肾炎的Ⅲ、Ⅳ或伴Ⅴ型。其中试验组15例病例在治疗6个月后进行了重复肾活检。结果显示,经来氟米特治疗后,13例患者狼疮肾炎的活动性降低,急性活动指数下降。其中,7例患者治疗前为Ⅲ、Ⅳ型,经来氟米特治疗后全部转变为病理类型较轻的Ⅱ型。
不良反应:与药物可能有关/有关的不良反应发生率,试验组为39.81%,对照组为55.26%。试验组发生率≥3%的不良事件包括:脱发、血压升高、带状疱疹、转氨酶升高、腹泻/稀便、白细胞下降、皮疹、月经不调、心悸、腹痛;发生率<3%的不良事件包括:恶心/呕吐、上呼吸道感染、血小板下降、乏力、胃烧灼感、厌食、发热、牙周疼痛、视觉异常、尿路感染、咽痛、巨细胞病毒感染、体重下降、多毛、肺部感染等。
Ⅲ期临床试验结束后,试验组52例患者自愿继续服用试验药物,服药剂量为10-30 mg/日。平均随访时间32.7±18.2月,最长观察时间为72个月,治疗6个月时,52例患者完全缓解率为36.5%,部分缓解率为44.2%;经过7-72个月的继续治疗,完全缓解率为59.6%,部分缓解率为30.6%。临床观察期间,共有12人发生与试验药物可能有关/有关的不良反应,发生率为23.08%,发生率≥3%的不良事件包括:白细胞下降、转氨酶升高、血小板减少;发生率<3%的不良事件包括:上呼吸道感染、脱发、带状疱疹、月经不调、尿路感染。
药理毒理

本品为一个具有抗增殖活性的异?唑类免疫抑制剂,其作用机理主要是抑制二氢乳清酸脱氢酶的活性,从而影响活化淋巴细胞的嘧啶合成。体内外试验表明本品具有抗炎作用。来氟米特的体内活性主要通过其活性代谢产物A771726(M1)而产生。
药代动力学

本品口服吸收迅速,在胃肠粘膜与肝中迅速转变为活性代谢产物A771726(M1),口服后6~12小时内A771726的血药浓度达峰值,口服生物利用度(F)约80%,吸收不受高脂肪饮食影响。单次口服50mg或100mg后24小时,血浆A771726浓度分别为4μg /ml或8.5μg /ml。A771726主要分布于肝、肾和皮肤组织,而脑组织分布较少;A771726血浆浓度较低,血浆蛋白结合率大于99%,稳态分布容积为0.13L/kg。A771726在体内进一步代谢,并从肾脏与胆汁排泄,其半衰期约10天。

Arava Information:

 

ARAVA (Leflunomide) is indicated for the treatment of adult patients with: active rheumatoid arthritis as a "disease-modifying antirheumatic drug" (DMARD). Active psoriatic arthritis

Recent or concurrent treatment with hepatotoxic or haematotoxic DMARDs (e.g.methotrexate) may result in an increased risk of serious adverse reactions; therefore, the initiation of leflunomide treatment has to be carefully considered regarding these benefit/risk aspects.

Moreover, switching from leflunomide to another DMARD without following the washout procedure may also increase the risk of serious adverse reactions even for a long time after the switching.

Arava must not be used in patients with hypersensitivity to leflunomide (especially previous Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) or to any of the excipients in the tablets.

Leflunomide is contraindicated in:
- patients with impairment of liver function,
- patients with severe immunodeficiency states, e.g. AIDS,
- patients with significantly impaired bone marrow function or significant anaemia, leukopenia, neutropenia or thrombocytopenia due to causes other than rheumatoid or psoriatic arthritis,
- patients with serious infections,
- patients with moderate to severe renal insufficiency, because insufficient clinical experience is available in this patient group,
- patients with severe hypoproteinaemia, e.g. in nephrotic syndrome,
- pregnant women, or women of childbearing potential who are not using reliable contraception during treatment with leflunomide and thereafter as long as the plasma levels of the active metabolite are above 0.02 mg/l (see also section 4.6). Pregnancy must be excluded before start of treatment with leflunomide.
Women must not breast-feed while they are receiving leflunomide. Male patients should be aware of the possible male-mediated foetal toxicity. Reliable contraception during treatment with leflunomide should also be guaranteed.

Arava is not recommended for use in patients under 18 years as its safety and efficacy have not been studied in this age group.

Arava Side Effects:
Cardiac disorders Common: mild increase in blood pressure Rare: severe increase in blood pressure Gastrointestinal disorders Common: diarrhoea, nausea, vomiting, anorexia, oral mucosal disorders (e.g., aphthous stomatitis, mouth ulceration), abdominal pain Hepato-biliary disorders Common: elevation of liver parameters (transaminases [especially ALT], less often gamma-GT, alkaline phosphatase, bilirubin) Rare: hepatitis, jaundice/cholestasis and very rarely, severe liver injury such as hepatic failure and acute hepatic necrosis that may be fatal Very rare: pancreatitis Infections and infestations Very rare: severe infections, including sepsis which may be fatal Like other agents with immunosuppressive potential, leflunomide may increase susceptibility to infections, including opportunistic infections (see also section 4.4). Thus, the overall incidence of infections can increase (in particular of rhinitis, bronchitis and pneumonia) Metabolism and nutrition disorders Common: weight loss (usually insignificant) Uncommon: hypokalaemia Nervous system disorders Common: headache, dizziness, asthenia, paraesthesia Uncommon: taste disturbances, anxiety Very rare: peripheral neuropathy Musculoskeletal and connective tissue disorders Common: tenosynovitis Uncommon: tendon rupture Skin and subcutaneous tissue disorders Common: increased hair loss, eczema, dry skin Uncommon: urticaria Very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme Immune system disorders Common: mild allergic reactions, rash (including maculopapular rash), pruritus Very rare: severe anaphylactic/anaphylactoid reactions Respiratory, thoracic and mediastinal disorders Rare: interstitial lung disease (including interstitial pneumonitis), which may be fatal. Blood and lymphatic system disorders Common: leukopenia (leukocytes>2 G/l) Uncommon: anaemia, mild thrombocytopenia (platelets <100 G/l) Rare: eosinophilia, leukopenia (leukocytes <2 G/l), pancytopenia (probably by antiproliferative mechanism) Very rare: agranulocytosis, vasculitis Recent, concomitant or consecutive use of potentially myelotoxic agents may be associated with a higher risk of haematological effects. The risk of malignancy, particularly lymphoproliferative disorders, is increased with use of some immunosuppressive agents. Mild hyperlipidaemia may occur. Uric acid levels usually decrease. Laboratory findings for which a clinical relevance could not be established include small increases in LDH and CK. Mild hypophosphataemia is uncommon. Marginal (reversible) decreases in sperm concentration, total sperm count and rapid progressive motility cannot be excluded. The active metabolite of leflunomide, A771726, has a long half-life, usually 1 to 4 weeks. If a severe undesirable effect of leflunomide occurs, or if for any other reason A771726 needs to be cleared rapidly from the body, the washout procedure described in section 4.4 has to be followed. The procedure may be repeated as clinically necessary. For suspected severe immunological/allergic reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis, a complete washout is essential.

ALT (SGPT) and a complete blood cell count, including differential white blood cell count and a platelet count, must be checked simultaneously and with the same frequency: • Before initiation of leflunomide • every two weeks during the first six months of treatment and • every 8 weeks thereafter (see also section 4.4). Leflunomide therapy is started with a loading dose of 100 mg once daily for 3 days. The recommended maintenance dose for rheumatoid arthritis is leflunomide 10 mg to 20 mg once daily and is 20mg once daily for psoriatic arthritis (see section 5.1). The therapeutic effect usually starts after 4 to 6 weeks and may further improve up to 4 to 6 months. There is no dose adjustment recommended in patients with mild renal insufficiency. No dosage adjustment is required in patients above 65 years of age. The product should be prescribed by specialists experienced in the treatment of rheumatoid arthritis and psoriatic arthritis.

The generic alternative is not manufactured by the company that makes the brand product.

包装规格:
100mg *3 片
10mg *30 片 
20mg *30 片
10mg *100 片
20mg *100 片

责任编辑:admin


相关文章
Selincro(nalmefen film-coated tablets)
VALSARTAN TABLETS(缬沙坦片)
VICCILLIN-S COMBINATION TABLETS(氨苄西林/氯唑西林钠复合片)
ABILIFY OD tablets(阿立哌唑口腔崩解片)
非诺贝特片|LIPIDIL(Fenofibrate Tablets)
TAKELDA Combination Tablets(阿司匹林/兰索拉唑配合錠)
Valsartan Tablets(缬沙坦片)
RILUZOLE TABLETS(Riluzole)利鲁唑片
METHOTREXATE Tablets(氨甲喋呤片)
Azunol ST Tablets(呱仑酸钠片)
富马酸沃诺拉赞|Takecab Tablets((Vonoprazan,TAK-438)
 

最新文章

更多

· Enbrel (Etanercept Inj...
· 托美丁钠胶囊/片(TOLME...
· 酮基布洛芬控释胶囊Oru...
· 酮洛芬栓剂|Orudis(Keto...
· 倍他米松注射液|Betamet...
· IL-6受体单克隆抗体注射...
· 噻洛芬酸缓释胶囊|Surga...
· 噻洛芬酸片|Surgam(tiap...
· 瑞得(金诺芬胶囊)Rida...
· 泼尼松择时释药片|Lodot...

推荐文章

更多

· Enbrel (Etanercept Inj...
· 托美丁钠胶囊/片(TOLME...
· 酮基布洛芬控释胶囊Oru...
· 酮洛芬栓剂|Orudis(Keto...
· 倍他米松注射液|Betamet...
· IL-6受体单克隆抗体注射...
· 噻洛芬酸缓释胶囊|Surga...
· 噻洛芬酸片|Surgam(tiap...
· 瑞得(金诺芬胶囊)Rida...
· 泼尼松择时释药片|Lodot...

热点文章

更多