44.肝灵素
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236页(9945字)
【中文释文】:
〔品名〕
商品名:肝灵素片
非专利名:α-干扰素
英文名:Immulin
活性成分:Human Interferon Alpha-nl
〔性状〕
本品为灰白色至淡黄色圆形片,每片刻有“P”字样。
〔介绍〕
每药片含有人α-干扰素200U,由固化工序到淀粉基质中,使活性α-干扰素稳定化。“肝灵素”含有16种天然人干扰素亚类,分子量13000~24000道尔顿。
〔特性〕
肝灵素中所含的干扰素类似人白细胞干扰素,其中含有多种α亚类干扰素,它与由细菌重组而成的α-干扰素不同,后者只含有单一的干扰素亚类。干扰素的活性成分是通过用仙台病毒诱导人淋巴细胞(Namalwa系)而制成的。
〔临床药理学〕
干扰素和其他淋巴因子对免疫反应的调节作用已被广泛地研究。如目前已了解到了人免疫系统包括一些细胞网络,当抗原干扰了内环境以后,该网络通过大量已知的环路产生各样特异性效应细胞,这些细胞亚类通过直接的细胞接触作用和大量的生物学活性介质,即淋巴因子作用而产生免疫调节效应。
干扰素在免疫系统被激活时由功能正常的淋巴细胞产生,是淋巴因子化学信使“瀑布”动态的一部分。α-干扰素在免疫系统中的作用及与其他淋巴因子之间的相互关系目前仍不十分清楚。但是,根据目前已知的人免疫学知识,有大量的证据显示α-干扰素在免疫反应的调节中是起作用的。干扰素在细胞表面的主要作用是增强MHC抗原的生物表达性,后者是许多免疫反应的一种重要控制机理。另一种重要的细胞表面效应是增加人单核细胞和巨噬细胞上IgG和Fc受体的数目。还有一个重要作用,就是通过对NK细胞介导溶解作用敏感性可逆转的变化而产生免疫调节,这可能也是另一种细胞表面效应。
当干扰素结合细胞表面受体时,便会发生一系列作用,包括诱导,增强合成和/或抑制特异性细胞蛋白和酶活性,并使之达到顶点。该过程的最终结果是抑制病毒复制及进而清除病毒。
干扰素为自我调节剂,在这种调节程序上,更高的浓度和不同药代途径可能与免疫反应的抑制有关。肌肉注射后4~8h,血清的浓度达到峰值。血清半衰期在6~12h之间,如给予常规剂量3×106~5×106U,尿液和脑脊髓液中则测不出干扰素。
〔适应证〕
可用于治疗多种病毒性疾病。研究显示肝灵素可对乙型及丙型肝炎,疱疹性口炎艾滋病(AIDS)病人等,都有一定的临床功效。肝灵素早被证实对艾滋病相关综合征(ARC)有疗效。服药应在有经验的医生指导下进行。
此外,干扰素对毛细胞白血病,卡波西肉瘤及生殖器疱疹亦被证实有相当疗效。
〔剂量与服法〕
1.成人 推荐剂量是每天至少1片(200U),舌下含服,连续服用至少半年。病人应将药片含在口里使其逐渐溶解,切勿咀嚼或吞下药片,如整片吞下去,则干扰素会被胃中的蛋白酶水解而使药力全失。将溶解的药片含在口里4~5min,以便口腔粘膜吸收,然后将唾液吞下。在服用肝灵素前后30min内不要进食或饮水。
2.儿童 尚未获得关于治疗儿童的资料。应当由医生评估临床效果,然后决定是否给予肝灵素片。
〔禁忌证〕
对于曾有干扰素过敏症的病人,禁忌服用肝灵素片。
〔副作用与不良反应〕
小剂量干扰素(即肝灵素片治疗)的激活口腔免疫反应机制,与不良反应无关。不良反应通常与胃肠道外注射大剂量干扰素有关。
大剂量(3×106~5×106U)注射治疗过程中可能产生明显的副作用和毒性。最常见的副作用包括发热、寒战、头痛、不适、肌肉痛以及流行性感冒的全部症状。连续用药可导致嗜睡、虚弱、疲倦,同时伴有厌食和消瘦。
有报道,接受大于500U/d干扰素的病人发生恶心,呕吐和食欲不振,有些病人可能出现一时性鼻腔分泌过多。但是口服200U/d的小剂量,刺激食欲是常见的相关副作用,而且未见有中枢神经系统不良反应的报道。
〔注意事项〕
1.妊娠 无妊娠期使用干扰素的资料,医生必须评估肝灵素的潜在益处与对胎儿的害处而加以取舍。
2.其他 已知有严重心脏病,肾脏或肝脏疾病的人;有癫痫发作或中枢神经功能障碍和同时患此两种疾病的人,应慎用肝灵素。此外,骨髓抑制病病人在使用时也须小心。
〔贮存〕
宜存放于4~8℃冰箱。如储存于室温环境,温度宜不超过25℃,而且需放置于阴凉干燥处。不使用的药片应迅速丢弃。
有效使用期为1.5年,于冰箱温度下储存期更长。
〔包装数量〕
肝灵素的包装为每包30片,片剂用隔绝空气及防潮的铝箔包装,每片刻有“P”字样。
〔生产厂家〕
新西兰太平洋制药有限公司
该产品为新西兰太平洋制药有限公司独家生产,在美国使用的商标为LOFERONORAL
【外文释文】:
Name and type of medication
Brand Name:IMMULIN*Tablet
Active ingredient:Human alpha-nl(α-Interferon)
Description
An off-white to pale yellow coloured biplanar circular tablet with flat bevelled edges.Tablets are engraved with“P”on one surface.
Presentation
Each package of Immulin contains 30 tablets protected in airtight,moisture resistant,blister strip with aluminum foil backing.Each tablet contains 200 U of Human Interferon(IFN)alpha stabilized on complex starch carrier.
Immulin contains 16 interferon alpha subtypes ranging in molecular weight from 13 000-24000 Daltons.
Properties
The interferon contained in Immulin resembles human leukocyte in that it is a mixture of natural alpha subtypes,and differs from recombinant alpha interferon preparations derived from bacteria which contain only a single subtype.The active ingredient in Immulin is produced by induction of human lymphoblastoid(Namalwa line)cells with Sendai virus.
Clincal pharmacology
The role of interferons and other lymphokines in immune response modulation has been studied extensively.The human immune system,as it is understood today,consists of a network of cells that interact in a number of defined circuits to produce a variety of specific effector cells when an antigen perturbs the homeostasis.Regulation of immune responses between subsets of these cells occurs by direct cellular interaction and the action of a number of biologically active mediators which are collectively called lymphokines.
Interferons are produced by normally functioning lymphocyte cells during the activation of an immune response and are part of a“cascade”of lymphokine chemical messengers.The role of IFN-alpha’s in the immune system,and their relationship to the other lymphokines are still not clearly defined.However,within the limits of current knowledge of human immunology,there is a lot of evidence for the role of IFN-alpha’s in the regulation of the immune response.
Lymphokines are the intracellular connecting molecues with over 50 regulatory activities which are currently ascribed to them.One major effect of IFN’s on the cell surface is the enhancement of expression of Major Histocompatability Complex(MHC)antigens subserving many immune responses.Another important cell surface effect is an enhancement of the number of receptors for the Fc portion of lgG on human monocytes and macrophages.IFN’s may also be important in the regulation of immune responses through a reversible alteraion in suseeptibility to NK cell-mediated lysis.
When interferon binds a cell surface receptor,a series of events is set in motion,culmination in the induction,enhanced synthesis and/or inhibition of specific cellular proteins and enzymatic activities.The net result of this process is the inhibition of viral replication and shedding.
Interferon appears to be self regulatory in that higher concentration or varying kinetics of exposure may be associated with suppression of immune responses.Following intramuscular injection,peak plasma levels are generally achieved within 4-8 hours.The plasma halflife is between 6-12 hours.Interferon is not detectable in the urine or cerebrospinal fluid when administrated at the conventional injectable dosage of 3-5 million IU.
Indications
Immulin is specially indicated for the treatment of a variety of viral diseases.Strdies on Immulin have been shown to be beneficial to patients suffering from human immunodeficiency virus(HIV),hepatitis B and C,aphthous stomatitis(oral ulcers)and Acquired Immunodeficiency Syndrome(AIDS),AIDS Related Cases(ARC).The tablets should be administered under physician’s guidance.
Interferon has also been shown to be efficacious for treating against hairy cell leukaemia,Kaposi’s sarcoma and genital warts.
Dosage and administration
Adults:The recommended dosage is a minimum of one tablet to be taken for a minimum of six months,once daily,by the sublingual route of administration.Patients should gently massage the tablet in their mouths until dissolved.Do not swallow the tablet.Interferon is inactivated by proteolytic enzymes in the stomach when swallowed.Hold the dissolved tablet in the moutfor 4-5 minutes before swallowing the saliva to allow oral mucosal adsorption.No food or liquid should be consumed for 30 min.before or after Immulin administration.
Children:No information is available on the treatment in children.The physician should determine whether the potential clinical benefits to the patient j ustify the decision to administer Immulin therapy.
Ccontraindications
Immulin is contraindicated in patients who have a history of hypersensitivity to interferOns.
Side effects and adverse reactions
Immulin therapy(low dosage interferon treatment for buccal activation of immune response mechanisms)has not been associated with adverse reactions commonly associated with parenteral use of interferons in high dosage.
For background information only,the most frequently reported side effects from high doses(3-5 million U)injectable interferons include fever,chills(occasionally rigors),headache,malaise and myalgia-all symptoms reminiscent of an influenza infection.Continuing therapy can result in lethargy,weakness and fatigue accompanied by anorexia and weight loss.
Nausea and anorexia have been reported in patients receiving dosages exceeding 500 U/day.Some patients experience a transient increase in flow of nasal secretions.
Appetite stimulation is a commonly associated side effect of Immulin therapy.Adverse central nervous system reactions have not been reported with Immulin.
Precautions
Pregnancy:No information is available on the use of interferon during human pregnancy.The physician must evaluate the potential benefits of Immulin therapy against the risk to the foetus.
Others:Immulin should be used with caution in patients with a known history of severe cardiac,renal or hepatic diseases,seizure and/or central nervous system dysfunction.Cautions should also be exercised when administering to myelosuppressed patients.
Storage
Immulin should ideally be stored under refrigeration at 4-8℃.Otherwise,it should be kept in a cool dry place at ambient room temperature not exceeding 25 ℃.Any unused tablets should be discarded.
The expiry of Immulin is 1.5 years from date of manufacturing and longer at fridge temperature.
How supplied
Immulin is available as tablets with engraved mark“P”on the surface supplied in blister packs with 30 tablets per pack.One display box contains 30 packs.
Manufacturer
Pharma Pacific Management ltd.
2 Sterling Avenue,Manurewa,Auckland,New Zealand.
*This product is solely manufactured by Pharma Pacific Management Ltd.(New Zealand).Trademark LOFERON ORALis used in the U.S.A.