Zometa is indicated for patients with advanced malignancies involving bone which include multiple myeloma, prostate cancer, renal cancer, breast cancer, lung cancer, and other solid tumour types.

【商品名称】择泰 Zometa
【通用名称】唑来膦酸 Zoledronic acid
药物分类：影响骨代谢的药物
【性状】唑来膦酸的化学名为 ：1-羟基-2-(咪唑-1-yl)-亚乙基-1,1-二磷酸一水化物，分子式 ：C5H10N2O7P2·H2O，分子量 ：290.11。本品为白色冻干粉。
【药理作用】
含氮双膦酸盐对骨吸收具有强大的抑制作用。此类药物作用机制独特，可通过抑制蛋白质异戊二烯化影响破骨细胞功能，导致细胞凋亡。择泰 （唑来膦酸）是一种强效含氮双膦酸盐，其咪唑环上含有两个氮原子，是目前已知作用最强的双膦酸盐。
唑来膦酸是一种特异性地作用于骨的二磷酸化合物，它能抑制因破骨活性增加而导致的骨吸收。二磷酸化合物对骨组织的选择性作用依赖于其对矿化骨的高亲和性。作用的分子机理还不清楚。长期动物研究表明，唑来膦酸可抑制骨吸收，但对骨的形成、骨的矿化及力学特性没有不良影响。
临床研究 与帕米磷酸的临床研究表明，对于肿瘤引起的高钙血症，唑来膦酸能降低血清钙和尿液中的钙排泄量。唑来膦酸4 mg组给药10天后的完全缓解率是88.4%，唑来膦酸8mg组为86.7%，帕米磷酸组为69.7%。唑来膦酸两个剂量组的疗效没有显著差异，但是，唑来膦酸组和帕米磷酸钠组之间有显著性的统计学差异。唑来膦酸8 mg组中低血钙症的发生频率较高。单剂使用本品，有一半的病例在给药后4天内升高的血钙浓度降低至正常值范围之内。唑来膦酸组的高钙血症复发的中位时间是30-40天，而帕米磷酸组为20-22天。血钙重又升高的患者（>2.9 mmol/L）再次治疗的缓解率(完全缓解率)为52%，只对8 mg本品剂量组进行了该项指标的研究。由于没有数据可与4 mg剂量组进行比较，所以8 mg剂量的缓解率是否更好尚不清楚。
【药代动力学】
分布 ：在初始24小时内，给药量的44±18%排泄到尿中，其余的主要滞留在骨组织中。
唑来膦酸与血细胞没有亲和性，与血浆蛋白的结合性也较低（大约为22%），而且不依赖于唑来膦酸的浓度。
将注射时间从5分钟增加到15分钟，在注射结束时，唑来膦酸浓度降低了30%，但对AUC没有影响。
与其它二磷酸化合物相比，患者间唑来膦酸的药代动力学参数变化较大。
代谢 ：唑来膦酸在体外不抑制人P450酶，不发生代谢。通过肾脏排泄。缓慢地从骨组织中释放进入全身循环，通过肾清除，半衰期（t½γ）至少为167小时。全身的清除率是5.6±2.5升/小时，不依赖于剂量，也不受性别、年龄、人种和体重的影响。
消除 ：静脉给药的唑来膦酸通过两个阶段消除 ：以0.23小时（t½β）的半衰期从全身循环中快速二相消除 ；1.75小时（t½α），然后是一个长期消除阶段。
特殊临床状态下的药代动力学 ：高钙血症患者 - 没有关于唑来膦酸对高钙血症患者的药代动力学的研究数据。
肝功能不全患者 - 没有关于唑来膦酸对肝功能不全患者的药物动力学的数据。唑来膦酸在体外不抑制人P450酶且不被代谢。动物实验研究发现，粪便中含有小于给药量3%的残留物。这表明肝脏在唑来膦酸的药代动力学中不起作用。
肾功能不全患者 - 没有关于严重的肾功能不全患者的试验资料。
【适应症】用于恶性肿瘤引起的高钙血症（HCM）。
【用法用量】
成人和老年人 对于HCM患者（白蛋白修正的血清钙≥ (greater than or equal to) 3.0 mmol/L或12 mg/dl），推荐剂量为4 mg，用0.9%氯化钠或5%葡萄糖溶液100 mL稀释，进行不少于15分钟静脉输注。
白蛋白修正的血清钙（ mg/dL）=患者血钙（ mg/dL）+0.8×[中位血清白蛋白（g/L）-患者血清白蛋白（g/L）]。给药前必须测试患者的水化状态，治疗中尿排量应维持2 L/天，应根据患者的临床状态进行给药。由于该药对肾功能损害可能导致肾衰的危险性，一次给药剂量不得超过4 mg。
再次治疗 血钙浓度重又升高而需再次治疗的病例是有限的（只出现在8 mg剂量组中）。再次治疗必须与前一次至少相隔7-10天。同时，治疗前应检测患者的血清肌酐水平。
肾功能不全患者 到目前为止的研究表明，对于轻度、中度肾功能损伤的患者无需调整剂量和给药时间（血清肌酐<400 umol/L或4.5 mg/dl）。
肝功能不全者 由于临床上严重肝功能不全患者的病例数有限，因此，对于此类患者没有特别的建议。
【不良反应】
本品的不良反应与其它双磷酸盐报告的不良反应相似，约在1/3患者中出现。最常出现的不良反应是流感样症状（约9%），包括骨痛（9.1%）、发热（7.2%）、疲乏（4.1%）、寒战（2.8%）以及关节痛和肌痛（约3%）。目前尚没有这些不良反应可逆性的信息。
肾钙分泌减少常伴有不需要治疗的无症状的血浆磷酸盐水平降低（约20%的患者）。约3%的患者会出现无症状的低钙血症。
在临床研究中出现了下列不良反应，主要是在长期给予唑来膦酸后发生的。根据发生频率列出不良反应，最常见的在先，采用下列发生率评估 ：很常见 ：>10%，常见 ：>1%-<10%，少见 ：>0.1%-<1%，偶发 ：>0.01%-<0.1%，罕见 ：<0.001%(包括个例)。
血液和淋巴系统 ：常见贫血，少见血小板减少，白细胞减少症，罕见全血细胞减少。
神经系统 ：常见头痛，少见头晕、感觉错乱、味觉障碍、感觉迟钝、感觉过敏和震颤。
精神障碍 ：少见焦虑、睡眠失调，罕见精神混乱。
眼部 ：常见结膜炎，少见视觉模糊，罕见葡萄膜炎，巩膜外层炎。
胃肠道 ：常见恶心、呕吐、食欲减退，少见腹泻、便秘、腹痛、消化不良、胃炎、口干。
呼吸、胸部和纵隔 ：少见呼吸困难、咳嗽。
皮肤和皮下组织 ：少见瘙痒症、皮疹（包括红斑状和斑点皮疹）、出汗增加。
骨骼肌、结缔组织和骨 ：常见骨痛、肌痛、关节痛，肌肉痉挛。
心血管系统 ：罕见心动过缓。
肾和泌尿系统 ：常见肾功能损害，少见急性肾功能衰竭、血尿、蛋白尿。
免疫系统 ：少见过敏反应，罕见血管神经性水肿。
全身和给药部位 ：常见发烧、流感样症状（包括疲劳、寒战、不适感和面部潮红），少见衰弱、外周水肿、注射部位反应（包括疼痛、刺激、红肿、硬化），胸痛、体重增加。
实验室检查异常 ：很常见低磷血症，常见血肌酐和血尿素氮升高、低钙血症，少见低镁血症，罕见高钾血症、低钾血症、高钠血症。
上市后：有很少病例报告：应用双膦酸盐治疗的患者发生骨坏死（主要是颌骨坏死），这些病例主要发生在拔牙或其他口腔外科治疗后。颌骨坏死的发生有多种危险因素存在，包括癌症疾病本身、合并治疗（如化疗、放射治疗和皮质激素）与并发症（如贫血、凝血疾病、感染、已存在的口腔疾病）。尽管原因还不能肯定，治疗过程中应尽量避免口腔外科治疗。
【禁忌症】对唑来膦酸、其它二磷酸盐或本品任何成份过敏者禁用。
【注意事项】
应用本品治疗初期，应仔细监测血清肌酐、血清钙、磷酸盐和镁的含量。
甲状腺术后患者由于甲状腺机能减退特别容易产生低血钙。
二磷酸盐类药物与肾功能紊乱相关。由于血清肌酐水平能够上升，同时缺少严重肾损伤的资料（血清肌酐>400 umol/L或4.5 mg/dl），建议此类患者不使用本品，除非利大于弊。
需要再次使用本品的患者，治疗前应检查血清肌酐水平。应对肾功能明显恶化的患者进行正确的评估，判断一下益处是否大于风险。
由于严重肝功能不全的患者的临床数据有限，因此，没有对此类患者有特别的建议。
对于同时使用二磷酸盐和氨基苷药物的患者应严密监视血钙浓度，因为这两类药物对血钙的降低将产生叠加作用，可导致长期低血钙。
【孕妇及哺乳期妇女用药】
怀孕 ：在动物生殖研究的大鼠中，观察到致畸作用。兔子实验中没有致畸毒性或胚胎毒性，但观察到母体毒性。由于没有对人类怀孕和哺乳期应用本品的经验，所以，怀孕期不应使用本品，除非对母亲的益处大于对胎儿的风险。
哺乳 ：二磷酸盐类化合物不仅很难从消化道中吸收，而且它在牛奶中以二磷酸盐-钙复合物的形式存在，几乎不被人体吸收。由于没有相关经验，哺乳期妇女应慎用本品。
【儿童用药】尚不清楚。
【药物相互作用】
临床研究表明，本品与常用的抑制细胞生长药物（如利尿药、抗生素和止痛药等）同时用药时未发现明显的相互作用。
没有进行过正式的临床相互作用的研究。由于二磷酸盐类药物与氨基苷同时使用能够产生降低血钙的叠加作用，从而导致长期低血钙。因而建议使用时需格外小心。另外，在治疗过程中也应注意低血镁的发生。
本品不得与含钙溶液配伍使用，应与其它药品分开进行单次静脉输注。
【药物过量】
应用本品时没有发生过急性中毒事件。当剂量高于推荐剂量时，可出现明显低钙血症、低磷酸血症和低镁血症，应对患者仔细监测并采取对应措施。如临床上出现给严重的低血钙症状，输注葡萄糖酸钙可逆转。
【用药须知】
唑来膦酸4 mg粉剂和所需溶剂制备成的输注用溶液仅限于静脉给药。首先用安瓿瓶中的5 mL无菌注射用水将冻干粉溶解，抽取前溶解必须完全。形成的溶液应进一步用100 mL的无钙输注溶液（0.9%氯化钠溶液或5%葡萄糖溶液）稀释。如果先前保存于冰箱内，那么，使用前应使溶液恢复到室温。
配制好的溶液的有效期 ：室温下，配制好的溶液的物理和化学性质在24小时内稳定。冻干粉经无菌溶解和稀释后，应立即使用。从溶解、稀释、在2-8°C冰箱内存储至最后使用的全过程不应超过24小时。

【贮藏/有效期】
30°C以下保存。有效期3年。

【原产地英文商品名】ZOMETA-4mg/20ml/Vial
【原产地英文药品名】ZOLEDRONIC ACID
【中文参考商品译名】
注：以下产品不同规格和不同价格，购买时请以电话咨询为准！
·择泰 4毫克/30毫升/瓶
·择泰 4毫克/25毫升/瓶
·择泰 4毫克/20毫升/瓶
·择泰 4毫克/15毫升/瓶
·择泰 4毫克/10毫升/瓶
【中文参考药品译名】唑来磷酸
【生产厂家中文参考译名】诺华
【生产厂家英文名】,Novartis

Zometa

Generic Name: zoledronic acid (Intravenous route)

zoe-le-DRON-ik AS-id

Commonly used brand name(s):

In the U.S.

• Reclast
• Zometa

Available Dosage Forms:

• Solution
• Powder for Solution

Therapeutic Class: Calcium Regulator

Chemical Class: Bisphosphonate

Uses For Zometa

Zoledronic acid is used to treat hypercalcemia (high levels of calcium in the blood) that may occur in patients with some types of cancer. It is also used to treat a cancer called multiple myeloma (tumors formed by the cells of the bone marrow) or certain types of bone metastases (the spread of cancer to the bone).

Zoledronic acid is used to treat Paget's disease of the bone in men and women. It is also used in men with osteoporosis and in women with osteoporosis who have gone through menopause. This medicine is used to reduce the risk of having more fractures in patients who have had a recent hip fracture.

This medicine is to be administered only by or under the supervision of your doctor.

This medicine is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, zoledronic acid is used in certain patients with the following medical conditions:

• Bone loss, in men, from taking certain medicines for prostate cancer.
• Bone loss, in breast cancer patients, from hormone therapy (prevention).

Before Using Zometa

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of zoledronic acid in children. However, safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of zoledronic acid in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require caution in patients receiving zoledronic acid.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	D	Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia or
• Cancer, history of or
• Cancer treatment, history of or
• Dental disease, history of or
• Poor dental hygiene, history of or
• Radiation therapy, history of or
• Steroid therapy, history of—May increase the risk for a serious jaw problem.

• Asthma or
• Heart disease or
• Kidney disease—May make these conditions worse.

• Bowel resection or
• Parathyroid disease (e.g., hypoparathyroidism) or
• Parathyroid surgery or
• Stomach absorption problems or
• Thyroid surgery—These conditions may increase your risk of having hypocalcemia (low levels of calcium in the blood).

• Dehydration (not enough water or fluid in your body)—May increase the risk of severe kidney problems.

• Hypocalcemia (low calcium in the blood) or
• Kidney disease, severe—Should not be used in patients with these conditions.

Proper Use of zoledronic acid

This section provides information on the proper use of a number of products that contain zoledronic acid. It may not be specific to Zometa. Please read with care.

A nurse or other trained health professional will give you this medicine. This medicine is given through a needle placed into one of your veins. The medicine must be injected slowly, so your IV tube will need to stay in place for at least 15 minutes.

Your doctor may also give you vitamins containing Vitamin D and calcium. Tell your doctor if you are unable to take these supplements.

Drink extra fluids so you will pass more urine while you are using this medicine. This will keep your kidneys working well and help prevent kidney problems.

Precautions While Using Zometa

It is important that your doctor check your progress at regular visits after you have received zoledronic acid. If your condition has improved, your progress must still be checked. The results of laboratory tests or the occurrence of certain symptoms will tell your doctor if your condition is coming back and if a second treatment is needed. You will need a yearly dose of this medicine if you are being treated for postmenopausal osteoporosis, so check with your doctor regularly.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away. Do not breastfeed while you are using this medicine.

This medicine may cause low calcium in your blood. Check with your doctor immediately if you experience numbness or tingling around the mouth, or if you have muscle spasms.

Tell your doctor right away if you experience symptoms of agitation; blood in the urine; coma; confusion; decreased urine output; depression; dizziness; headache; irritability; lethargy; muscle twitching; nausea; rapid weight gain; seizures; stupor; swelling of the face, ankles, or hands; or unusual tiredness or weakness. These could be a sign of serious kidney problems.

It is important that you check with your doctor before having any dental procedures or surgeries done while you are receiving zoledronic acid. Tell your doctor right away if you experience jaw tightness, swelling, numbing, or pain or a loose tooth. It could be the sign of a serious jaw disease.

Tell your doctor if you have severe muscle, bone, or joint pain after receiving this medicine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription (e.g., other medicines that also contain zoledronic acid) or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Zometa Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

More common

• Agitation
• black, tarry stools
• blurred vision
• chest pain
• chills
• coma
• confusion
• convulsions
• cough
• depression
• dizziness
• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
• fever
• irregular heartbeat
• irritability
• lack or loss of strength
• lethargy
• lower back or side pain
• mood or mental changes
• muscle pain or cramps
• muscle trembling or twitching
• nausea or vomiting
• numbness and tingling around the mouth, fingertips, or feet
• painful or difficult urination
• pale skin
• rapid weight gain
• seizures
• shaking of the hands, arms, feet, legs, or face
• shortness of breath, difficult or labored breathing
• skin rash, cracks in the skin at the corners of the mouth, or soreness or redness around the fingernails and toenails
• sore throat
• sores, ulcers, or white spots on the lips or mouth
• stupor
• sudden sweating
• swollen glands
• tightness in the chest
• trouble breathing with exercise
• unusual bleeding or bruising
• unusual tiredness or weakness
• wheezing

Less common

• Feeling of constant movement of self or surroundings
• muscle cramps in the hands, arms, feet, legs, or face
• muscle spasms
• neck pain
• pounding in the ears
• rapid breathing
• sensation of spinning
• slow or fast heartbeat
• sunken eyes
• tingling of the hands or feet
• tremor

Incidence not known

• Decreased frequency or amount of urine
• heavy jaw feeling
• increased blood pressure
• increased thirst
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loosening of a tooth
• pain, swelling, or numbness in the mouth or jaw
• swelling of the face, hands, fingers, lower legs, or ankles
• troubled breathing
• weight gain

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Abdominal pain
• anxiety, nervousness, restlessness, or irritability
• back pain
• bad, unusual, or unpleasant (after) taste
• bladder pain, bloody or cloudy urine
• blistering, crusting, irritation, itching, or reddening of the skin
• bone pain
• burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
• change in taste
• constipation
• cracked lips
• cracked, dry, or scaly skin
• diarrhea
• difficulty swallowing
• discouragement
• dry mouth
• ear congestion
• fear or nervousness
• feeling sad or empty
• frequent urge to urinate
• hair loss or thinning hair
• headache
• hyperventilation
• irregular heartbeats
• joint pain or swollen joints
• loss of appetite
• loss of interest or pleasure
• loss of voice
• muscle stiffness or difficulty in moving
• nasal congestion or runny nose
• pain, swelling, or redness in the joints
• partial loss of feeling
• seeing, hearing, or feeling things that are not there
• sleepiness or unusual drowsiness
• sleeplessness, trouble sleeping, or unable to sleep
• swelling or inflammation of the mouth
• thirst
• trouble with concentrating
• unusually cold, shivering
• vomiting
• weight loss

Less common

• Acid or sour stomach
• belching
• eye pain
• heartburn
• indigestion
• stomach discomfort, upset, or pain
• unusual drowsiness, dullness, tiredness, weakness or feeling of sluggishness
• wrinkled skin

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

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