Ceplene

活性物质：组胺二盐酸盐

俗名：组胺二盐酸盐

ATC代码：L03AX14

营销授权持有人：Noventia Pharma Srl

活性物质：组胺二盐酸盐

状态：已授权

授权日期：2008-10-07

治疗领域：白血病，骨髓，急性

药物治疗组：免疫刺激剂

治疗指征

Ceplene维持治疗适用于伴有白细胞介素-2（IL-2）同时治疗的急性髓性白血病的成人患者。 Ceplene的疗效尚未在60岁以上的患者中得到充分证实。

什么是Ceplene？

Ceplene是注射用溶液，含有活性物质组胺二盐酸盐（0.5mg / 0.5ml）。

什么是Ceplene用于？

Ceplene与白细胞介素-2（一种抗癌药物）联合使用，作为成人急性髓性白血病（AML）的维持治疗，AML是一种影响白细胞的癌症。它在患者首次“缓解”期间使用（在第一疗程后没有疾病症状的时期）。 Ceplene的有效性尚未在60岁以上的患者中得到充分证实。

由于患有AML的人数较少，这种疾病很少见，并且Ceplene于2005年4月11日被指定为“孤儿药”（一种用于罕见疾病的药物）。

该药只能通过处方获得。

Ceplene是如何使用的？

Ceplene应在具有治疗AML经验的医生的监督下给予。推荐剂量的Ceplene是皮下注射0.5mg，每日两次，白细胞介素-2注射后一至三分钟。给予Ceplene和白细胞介素-2 10个循环。

对于前三个周期，每个周期包括三周的治疗，然后是三周的休息期。对于以下七个周期，每个周期包括三周的治疗，然后是六周的休息期。

首次给予Ceplene时，必须监测患者的血压，心率和肺功能。根据患者对治疗的反应和副作用，可能必须暂停治疗或调整剂量。

每次Ceplene注射必须在5至15分钟内缓慢给予，在与白细胞介素-2注射不同的部位，并且优选在大腿或腹部（腹部）。患者可以在接受适当培训后自行注射。

Ceplene如何运作？

Ceplene中的活性物质，组胺二盐酸盐，是一种免疫调节剂。这意味着它会改变免疫系统的活动（身体的自然防御）。组胺是体内天然存在的物质，参与许多过程。在AML的治疗中，认为通过保护免疫系统细胞免受损害起作用。这提高了白细胞介素-2的有效性，白细胞介素-2是一种刺激免疫系统攻击癌细胞的药物。当Ceplene给予白细胞介素-2时，它有助于免疫系统杀死在缓解期间可能留在体内的白血病细胞。这可以增加患者保持缓解的时间长度。

Ceplene是如何被研究过的？

Ceplene的有效性已经在一项主要研究中进行了研究，该研究涉及320名患有AML的成人，他们在白血病治疗后处于缓解期。 Ceplene与白细胞介素-2联合给药并与未治疗相比较。有效性的主要衡量标准是疾病复发或患者死亡的时间长度。

Ceplene在研究期间表现出什么好处？

Ceplene和白细胞介素-2的组合比没有治疗更有效，直到AML复发或患者死亡的时间增加：在首次完全缓解的患者中，没有疾病的平均时间从没有治疗的291天增加到450用Ceplene和白细胞介素-2治疗后数天。在第二次或晚期缓解的患者中未见Ceplene和白细胞介素-2的作用。

Ceplene的风险是什么？

Ceplene最常见的副作用（10例中超过1名患者）是上呼吸道感染（感冒），嗜酸性粒细胞增多（嗜酸性粒细胞水平升高，白细胞类型增加），血小板减少症（低血小板计数），头痛，头晕，味觉障碍（口腔内有苦味或不寻常的味道），心动过速（心跳加快），潮红（发红），低血压（低血压），咳嗽，呼吸困难（呼吸短促），恶心（感觉不舒服），消化不良（消化不良），腹泻，皮疹，关节痛（关节疼痛），肌痛（肌肉疼痛），发热（发烧），畏寒，疲劳（疲倦），流感样症状，感觉发热和注射部位反应（发红，瘙痒） ，疼痛和炎症）。有关Ceplene报告的所有副作用的完整列表，请参阅包装说明书。

Ceplene不得用于有严重心脏病的患者或孕妇或哺乳期妇女。它也不能用于接受过捐献者骨髓移植的患者，或者服用类固醇（用于减少或预防炎症的药物）全身给药（全身给予治疗），可乐定（用于降低高血压）的患者血压）或组胺H2阻滞剂（用于治疗胃溃疡，消化不良或胃灼热）。有关限制的完整列表，请参阅包传单。

为什么Ceplene被批准了？

CHMP决定Ceplene的利益大于其风险，并建议获得上市许可。

Ceplene已根据“特殊情况”获得授权。这意味着由于这种疾病很罕见，因此无法获得有关Ceplene的完整信息。每年，欧洲药品管理局将审查可能出现的任何新信息，并在必要时更新本摘要。

Ceplene还在等待什么信息？

该公司将进行进一步的研究，以更详细地了解Ceplene和白细胞介素-2的组合的有效性以及该组合如何起作用。

正在采取哪些措施来确保安全有效地使用Ceplene？

已经制定了风险管理计划，以确保尽可能安全地使用Ceplene。根据该计划，安全信息已包含在产品特性摘要和Ceplene包装说明书中，包括医疗保健专业人员和患者应遵循的相应预防措施。

关于Ceplene的其他信息

欧盟委员会于2008年10月7日授予整个欧盟Ceplene的上市许可。

有关使用Ceplene治疗的更多信息，请阅读包装说明书（也是EPAR的一部分）或联系您的医生或药剂师。

Active Substance: histamine dihydrochloride
Common Name: histamine dihydrochloride
ATC Code: L03AX14
Marketing Authorisation Holder: Noventia Pharma Srl
Active Substance: histamine dihydrochloride
Status: Authorised
Authorisation Date: 2008-10-07
Therapeutic Area: Leukemia, Myeloid, Acute
Pharmacotherapeutic Group: Immunostimulants

Ceplene maintainance therapy is indicated for adult patients with acute myeloid leukaemia in first remission concomitantly treated with interleukin-2 (IL-2). The efficacy of Ceplene has not been fully demonstrated in patients older than age 60.

Ceplene is a solution for injection that contains the active substance histamine dihydrochloride (0.5 mg/0.5 ml).

Ceplene is used in combination with interleukin-2 (an anticancer medicine) as maintenance treatment in adults with acute myeloid leukaemia (AML), a type of cancer affecting the white blood cells. It is used during the patients’ first ‘remission’ (a period without symptoms of the disease after the first course of treatment). The effectiveness of Ceplene has not been fully demonstrated in patients older than 60 years of age.

Because the number of people with AML is low, the disease is rare, and Ceplene was designated as an ‘orphan medicine’ (a medicine used in rare disease) on 11 April 2005.

The medicine can only be obtained with a prescription.

Ceplene should be given under the supervision of a doctor who has experience in the treatment of AML. The recommended dose of Ceplene is a 0.5-mg injection under the skin, twice a day, one to three minutes after an interleukin-2 injection. Ceplene and interleukin-2 are given for 10 cycles.

For the first three cycles, each cycle consists of three weeks of treatment, followed by a three-week rest period. For the following seven cycles, each cycle consists of three weeks of treatment, followed by a six-week rest period.

When Ceplene is first given, the patient’s blood pressure, heart rate and lung function must be monitored. Depending on the patient’s response to treatment and side effects, the treatment may have to be suspended or the dose adjusted.

Each Ceplene injection must be given slowly over five to 15 minutes, in a different site from the interleukin-2 injection, and preferably in the thigh or abdomen (tummy). Patients can inject themselves once they have been trained appropriately.

The active substance in Ceplene, histamine dihydrochloride, is an immune modulator. This means that it alters the activity of the immune system (the body’s natural defences). Histamine is a naturally occurring substance in the body that is involved in many processes. In the treatment of AML, it is thought to work by protecting immune system cells from damage. This improves the effectiveness of interleukin-2, a medicine that stimulates the immune system to attack cancerous cells. When Ceplene is given with interleukin-2, it helps the immune system to kill the leukaemia cells that may remain in the body during remission. This can increase the length of time the patient stays in remission.

The effectiveness of Ceplene has been studied in one main study involving 320 adults with AML who were in remission following leukaemia treatment. Ceplene was given in combination with interleukin-2 and compared with no treatment. The main measure of effectiveness was the length of time until the disease came back or the patient died.

The combination of Ceplene and interleukin-2 was more effective than no treatment in increasing the time until AML came back or the patient died: in the patients in their first complete remission, the average time without disease increased from 291 days with no treatment to 450 days after treatment with Ceplene and interleukin-2. No effect of Ceplene and interleukin-2 was seen in patients in second or later remission.

The most common side effects with Ceplene (seen in more than 1 patient in 10) are upper respiratory tract infection (colds), eosinophilia (an increase in eosinophil levels, a type of white blood cell), thrombocytopenia (low blood platelet counts), headache, dizziness, dysgeusia (a bitter or unusual taste in the mouth), tachycardia (rapid heart beat), flushing (reddening), hypotension (low blood pressure), cough, dyspnoea (shortness of breath), nausea (feeling sick), dyspepsia (indigestion), diarrhoea, rash, arthralgia (pain in the joints), myalgia (muscle pain), pyrexia (fever), chills, fatigue (tiredness), flu-like symptoms, feeling hot and injection site reactions (redness, itching, pain and inflammation). For the full list of all side effects reported with Ceplene, see the package leaflet.

Ceplene must not be used in patients who have severe heart problems or in women who are pregnant or breast-feeding. It must also not be used in patients who have received a bone marrow transplant from a donor, or who are taking steroids (medicines used to reduce or prevent inflammation) given systemically (given as treatment throughout the body), clonidine (used to reduce high blood pressure) or histamine H2 blockers (used to treat stomach ulcers, indigestion or heartburn). For the full list of restrictions, see the package leaflet.

The CHMP decided that Ceplene’s benefits are greater than its risks and recommended that it be given marketing authorisation.

Ceplene has been authorised under ‘exceptional circumstances’. This means that because the disease is rare, it has not been possible to obtain complete information about Ceplene. Every year, the European Medicines Agency will review any new information that may become available and this summary will be updated as necessary.

The company will carry out further studies to look in more detail at the effectiveness of the combination of Ceplene and interleukin-2 and at how the combination works.

A risk management plan has been developed to ensure that Ceplene is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Ceplene, including the appropriate precautions to be followed by healthcare professionals and patients.

The European Commission granted a marketing authorisation valid throughout the European Union for Ceplene on 7 October 2008.

For more information about treatment with Ceplene, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.