【药品名称】
通用名：伊班膦酸注射液
商品名：邦罗力
英文名：Bondronat


【性状】
邦罗力为无色的澄明液体。

【成份】
活性成分：伊班膦酸
每安瓿1或2毫升含注射用伊班膦酸浓缩物。
1毫升安瓿内含伊班膦酸单钠盐一水合物1.125毫克，相当于含伊班膦酸1毫克；2毫升安瓿内含伊班膦酸单钠盐一水合物2.25毫克，相当于伊班膦酸2毫克。
赋形剂：氯化钠，乙酸，乙酸钠，注射用水

【邦罗力药理毒理】
伊班膦酸属双膦酸盐化合物，能特异地作用于骨组织，对骨骼的特异性选择作用是由于双膦酸盐对骨骼中的无机物具有高度亲和性。双膦酸盐通过抑制破骨细胞的活性起作用，但其确切的作用机理尚不清楚。
体内试验中，伊班膦酸能预防因性腺功能丧失、维甲酸类化合物、肿瘤或肿瘤提取物引起的骨质破坏。通过对Ca45的代谢动力学研究和试验中观察到与骨结合的带放射性标记四环素从骨骼中的释放，证实了伊班膦酸能抑制骨的内源性重吸收。
当伊班膦酸的剂量远高于药理学有效剂量时，对成骨过程无任何影响。
研究表明，伊班膦酸抑制肿瘤引起的溶骨现象、尤其对肿瘤性高钙血症的临床治疗特点是能使血钙水平和尿钙排泄下降。

【药代动力学】
在正常健康志愿者体内进行了伊班膦酸0.5、1.0、2.0毫克单次静脉注射后的药代动力学研究，在20例绝经后妇女体内进行了2.0、4.0、6.0毫克单次静脉注射后的药代动力学研究。结果显示下列药代动力学参数与给药剂量无关：终末半衰期，10～16小时；总清除率130ml/min；肾脏清除率88ml/min；肾脏重吸收率（0～32小时）60％；表观分布容积150L。伊班膦酸的体内清除过程分两相进行。静脉给药后部分以原形经尿排出，其余部分与骨组织结合。
伊班膦酸单次2、4和6毫克静脉滴注2小时给药，其药代动力学参数与剂量相关。单次6毫克静脉滴注2小时后的血清峰浓度为328ng/ml，而单次2毫克静脉滴注2小时后的峰浓度为246ng/ml。
目前，尚无高钙血症、肝或肾功能不全时的药代动力学资料。
伊班膦酸与血浆蛋白的结合率与其血清浓度无关。当伊班膦酸浓度达2000ng/ml时，其蛋白结合率为99％，但治疗剂量下不会达到如此高的血药浓度。虽然推测伊班膦酸可能与骨组织长期结合，但缺乏相关的临床资料。

【适应症】
肿瘤引起的病理性（异常）血钙升高（高钙血症）。

【用法用量】
邦罗力静脉给药通常应在医院中进行。医生应根据下列因素决定给药剂量。
接受邦罗力治疗前必须给患者用生理盐水充分水化。应同时考虑高钙血症的严重程度和肿瘤类型。对大多数严重高钙血症（白蛋白纠正的血清钙浓度≥3mmol/L或≥12mg/dL）患者，单次4mg的剂量是足够的。对中度高钙血症（白蛋白纠正的血清钙浓度≤3mmol/L或≤12mg/dL），单次2mg有效。临床试验中的单次剂量为6mg，但并未提高疗效。
注意：
白蛋白纠正的血清钙浓度（mmol/L）＝血清钙浓度（mmol/L）－0.02×白蛋白浓度（g/L）＋0.8或白蛋白纠正的血清钙浓度（mmol/dL）＝血钙浓度（mmol/L）＋0.8×「4－白蛋白浓度（g/dL）」
大多数高钙血症病人的血钙水平在邦罗力治疗后7天内降至正常范围。
邦罗力单次2mg和4mg给药后中位病情复发时间（白蛋白纠正的血清钙浓度>3mmol/L）为18～19天，单次6mg，中位病情复发时间26天。
目前只有少数病人（50例）因高钙血症接受过第二次邦罗力静脉治疗。
复发性高钙血症和首次治疗疗效不佳时可考虑重复用药。
浓缩的注射用邦罗力应通过静脉滴注给药。用药时将药物加入等渗氯化钠溶液500ml或5％的葡萄糖液500ml中静脉滴注2小时。

【注意事项】
为避免配伍禁忌，浓缩的注射用邦罗力只允许与等渗氯化钠或5％葡萄糖液混合，不能与含钙溶液混合静脉输注。
特别说明不推荐邦罗力经动脉给药治疗高钙血症，如不小心经动脉或静脉外途径给药可以引起组织损伤，因此，必须确保邦罗力经静脉给药。
安瓿使用注意事项
蓝点向上握住并摇动或用手指弹打安瓿以保证瓶颈部的液体聚积到瓶身。在瓶颈处掰开安瓿。
一般情况下，邦罗力只给药一次。但如需要，可重复给药。

【不良反应】
静脉输注邦罗力后常出现发热。个别报告出现流感样综合征包括发热、寒战、骨和/或肌肉疼痛。大多数情况下这些症状于数小时或数天内消失，不需特殊治疗。
肾脏钙排泄降低通常伴随血清磷水平的下降，一般不需治疗。血钙浓度可降至正常水平以下。个别病例出现不可耐受的消化道反应（包括胃和小肠的副作用）。
对乙酰水杨酸敏感的哮喘病人接受其它的双磷酸盐治疗，可能诱发支气管痉挛（喘息、呼吸困难）。
如出现治疗作用以外的其它反应，尤其是药物说明书未列出的副作用，病人应及时通知医生或药理学家。

【禁忌】
对邦罗力药物成分过敏和有严重肾脏疾病（如肾功能不全，血肌酐>5mg/dL,或>442umol/L）者禁用。
对其它双膦酸盐化合物过敏者，使用邦罗力应谨慎。
妊娠和哺乳期妇女不应接受邦罗力治疗，因为目前尚缺乏有关生殖毒性试验的资料和人类怀孕时的临床用药经验。
邦罗力不能用于儿童，因为缺乏这方面的临床经验。

【注意事项】
邦罗力治疗期间应密切监测肾功能、血钙、磷和镁离子浓度。
由于缺乏临床资料，有严重肝脏疾病（肝功能不全）时不应按上述推荐剂量给药。
有心衰危险性的病人应避免过度水化。
尚未研究邦罗力用药后对病人的反应能力、警觉性和认知意识可能产生的影响。

【孕妇及哺乳期妇女用药】
妊娠和哺乳期妇女不应接受邦罗力治疗，因为目前尚缺乏有关生殖毒性试验的资料和人类怀孕时的临床用药经验。

【儿童用药】
邦罗力不能用于儿童，因为缺乏这方面的临床经验。

【老年患者用药】
见“用法用量”

【药物相互作用】
尚未研究伊班膦酸与其它药物之间的相互作用，目前未观察到邦罗力与其它药物产生相互作用。
邦罗力与氨基糖甙类药物同时应用应谨慎，因为两者均可导致延迟性血钙降低。低镁血症时使用邦罗力应小心。

【药物过量】
至今尚无邦罗力急性中毒的经验。
由于临床前试验中高剂量邦罗力对肝和肾脏均有毒性，因此疗中应监测肝肾功能。
如出现治疗相关的低钙血症（血钙水平很低），可予静脉葡萄糖酸钙纠正。

【规格】
6ml：6mg

【贮藏】
室温保存（15～25℃）。
稀释后的静脉注射液2～8℃可稳定24小时，未用的溶液应丢弃。

【生产企业】
Roche  Diagnostics GmbH 

Bondronat

Active Substance: ibandronic acid 
Common Name: ibandronic acid 
ATC Code: M05BA06
Marketing Authorisation Holder: Roche Registration Ltd.
Active Substance: ibandronic acid 
Status: Authorised
Authorisation Date: 1996-06-25
Therapeutic Area: Neoplasm Metastasis Hypercalcemia Breast Neoplasms Fractures, Bone
Pharmacotherapeutic Group: Drugs for treatment of bone diseases

Therapeutic Indication

Bondronat is indicated for:

· prevention of skeletal events (pathological fractures, bone complications requiring radiotherapy or surgery) in patients with breast cancer and bone metastases;

· treatment of tumour-induced hypercalcaemia with or without metastases.

What is Bondronat?

Bondronat is a medicine that contains the active substance ibandronic acid. It is available as a concentrate that is made up into a solution for infusion (drip) into a vein, and as tablets (50 mg).

What is Bondronat used for?

Bondronat is used in adults in the following ways:

· as an infusion or as a tablet to prevent ‘skeletal events’ (fractures [broken bones] or bone complications requiring treatment) in patients with breast cancer and bone metastases (when the cancer has spread to the bone);

· as an infusion to treat hypercalcaemia (high levels of calcium in the blood) caused by tumours.

The medicine can only be obtained with a prescription.

How is Bondronat used?

Bondronat treatment should only be started by a doctor who has experience in the treatment of cancer.

In the prevention of skeletal events, Bondronat is either given as a 6mg infusion lasting at least 15 minutes every three to four weeks, or as one tablet once a day. The tablet should be taken after the patient has not eaten anything for at least six hours overnight and at least 30 minutes before the first food or drink of the day. It should be taken with a full glass of plain water (in areas with hard water, where tap water contains a lot of dissolved calcium, bottled water with a low mineral content may be used). The patient should not lie down for one hour after taking the tablet. Patients with moderate or severe kidney problems should receive Bondronat infusions at a lower dose over an hour, or the tablet every two days or every week.

In the treatment of hypercalcaemia caused by tumours, Bondronat is given over 2 hours as an infusion of either 2 or 4 mg, depending on how severe the hypercalcaemia is. The infusion will normally bring the blood calcium level down to normal levels within a week.

How does Bondronat work?

The active substance in Bondronat, ibandronic acid, is a bisphosphonate. It stops the action of the osteoclasts, the cells in the body that are involved in breaking down the bone tissue. This leads to less bone loss. The reduction of bone loss helps to make bones less likely to break, which is useful in preventing fractures in cancer patients with bone metastases.

Patients with tumours can have high levels of calcium in their blood, released from the bones. By preventing the breakdown of bones, Bondronat also helps to reduce the amount of calcium released into the blood.

How has Bondronat been studied?

In the prevention of skeletal events in patients with breast cancer and bone metastases, Bondronat has been compared with placebo (a dummy treatment) in three main studies lasting two years: one with the infusions in 466 patients and two with the tablets in a total of 846 patients. The main measure of effectiveness was based on the number of new bone complications. These included spine fractures, fractures outside the spine and any bone complications that needed treatment with radiotherapy or surgery.

Bondronat has also been studied in the treatment of hypercalcaemia caused by tumours in three four-week studies involving a total of 343 patients. Bondronat was not compared with any other treatments in these studies. The main measure of effectiveness was the change in blood calcium levels.

What benefit has Bondronat shown during the studies?

Bondronat was more effective than placebo in preventing bone complications. It took longer for patients on Bondronat infusions or tablets to develop a new bone complication (50 to 76 weeks) than for patients on placebo (33 to 48 weeks). Bondronat reduced the risk of having a skeletal event by about 40% compared with placebo.

Bondronat was also effective in treating hypercalcaemia caused by tumours. About a half to two-thirds of the patients responded to a 2-mg dose of Bondronat, with blood calcium levels returning to within the normal range. About three-quarters responded to a 4-mg dose.

What is the risk associated with Bondronat?

The most common side effects with Bondronat infusions are a rise in body temperature, hypocalcaemia (low blood calcium levels), asthenia (weakness) and headache. The most common side effects with the tablets are hypocalcaemia and dyspepsia (heartburn). The most serious side effects with Bondronat are anaphylactic reaction (severe allergic reaction), atypical fractures of the femur (an unusual type of fracture of the bone of the upper leg), osteonecrosis of the jaw (damage to the bones of the jaw, which could lead to pain, sores in the mouth or loosening of teeth), and eye inflammation.

Bondronat must not be used in people with hypocalcaemia. The tablets must not be used in patients who have abnormalities of the oesophagus or who cannot stand or sit up for at least an hour. For the full list of all side effects and restrictions reported with Bondronat, see the package leaflet.

Why has Bondronat been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Bondronat’s benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Bondronat?

A risk management plan has been developed to ensure that Bondronat 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 Bondronat, including the appropriate precautions to be followed by healthcare professionals and patients.

In addition, the company that markets Bondronat will provide a card to inform patients receiving Bondronat infusion about the risk of osteonecrosis of the jaw and to instruct them to contact their doctor if they experience symptoms.

Other information about Bondronat

The European Commission granted a marketing authorisation valid throughout the European Union for Bondronat on 25 June 1996.

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