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部分中文LUMIZYME处方资料（仅供参考）
美国食品药品管理局（FDA）近日批准Genzyme公司的Lumizyme(α-葡萄糖苷酶)用于治疗8岁及以上儿童的迟发性庞贝氏症（Pompe，糖原贮积病Ⅱ型）。
庞贝氏症是一种罕见的遗传性疾病，每4万至30万名新生儿中即有1例患者，因患者体内缺乏或缺失酸性α-葡萄糖苷酶（GAA），致使心肌与骨骼肌中糖原沉积，最终导致患者肌无力引发呼吸衰竭而死亡。
Lumizyme通过替代GAA而发挥作用，从而减少糖原在心脏和骨骼肌细胞中的累积。一项包含90名年龄为10~70岁的迟发性庞贝氏症患者的临床试验证明了Lumizyme的安全性和有效性。Lumizyme常见的不良反应有严重过敏反应、荨麻疹、腹泻、呕吐、呼吸急促、皮肤瘙痒、皮疹、颈痛、局部脱发、面色潮红、四肢疼痛和胸闷等，其说明书中也将增加黑框警告以提示患者使用该药可能存在过敏或严重过敏反应以及免疫调节反应等风险。
FDA药品审评与研究中心审评三室主任Julie Beitz说，“庞贝氏症是一种破坏性疾病，且尚无合适的治疗方法，Lumizyme的获批为患者提供了一个十分重要的治疗方法。”
Lumizyme在婴儿发病期或8岁及8岁以下迟发性庞贝氏症患者中的安全性和有效性尚未得到验证。
适应证和用途：
LUMIZYME(阿葡糖苷酶α)[见一般描述(11)]是一种溶酶体糖原-特异性酶，适用于8岁和以上与后期(非婴幼儿)发病庞贝氏症(Pompe disease，GAA缺乏症)没有心脏肥厚证据患者。尚未在婴幼儿发病患者，或在小于8岁后(非婴幼儿)发病患者的对照临床试验评价LUMIZYME的安全性和有效性。
剂量和给药方法：
LUMIZYME的推荐剂量是20 mg/kg体重每2周给药1次，用作静脉输注。
剂型和规格：
剂型：为静脉输注溶液的冻干粉。
规格：5 mg/mL。
禁忌证：
无
警告和注意事项：
1) 某些患者在输注LUMIZYME期间有危及生命的过敏反应。当给予LUMIZYME时。确保有适当医疗支持措施，包括容易得到心肺复苏仪器设备。
2) 如发生严重变态或过敏反应，考虑立即停止LUMIZYME给药和开始适当医学治疗。
3) 用阿葡糖苷酶α可能发生严重皮肤和全身免疫介导反应。所以，当接受LUMIZYME时，监查患者是否发生全身免疫复合物反应涉及皮肤和其它器官。
不良反应：
在临床研究中最常报道不良反应(≥5%)是输注反应和包括：过敏、荨麻疹、腹泻、呕吐、呼吸困难、瘙痒、皮疹/红斑、咽喉痛、颈痛、听觉迟钝、脸红/热感, 四肢痛, 下落(fall)和胸部不适。
特殊人群中的使用
1) 妊娠：医生鼓励妊娠患者参加庞贝氏病注册。
2) 哺乳母亲：医生鼓励哺乳患者参加庞贝氏病注册。
3) 儿童：LUMIZYME不用于婴幼儿-发病庞贝氏病或小于8岁庞贝氏病后(非婴幼儿)发病患儿。对照临床试验中尚未在这些患者评价的LUMIZYME的安全性和有效性。
Lumizyme
Generic Name: alglucosidase alfa
Dosage Form: injection, powder, for solution
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INDICATION
LUMIZYME® (alglucosidase alfa) is a lysosomal glycogen-specific enzyme indicated for patients 8 years and older with late (non-infantile) onset Pompe disease (GAA deficiency) who do not have evidence of cardiac hypertrophy. The safety and efficacy of LUMIZYME have not been evaluated in controlled clinical trials in infantile-onset patients, or in late (non-infantile) onset patients less than 8 years of age.
IMPORTANT SAFETY INFORMATION
WARNING
Life-threatening anaphylactic reactions, severe allergic reactions and immune mediated reactions have been observed in some patients during LUMIZYME infusions. Therefore, appropriate medical support should be readily available when LUMIZYME is administered.
Because of the potential risk of rapid disease progression in Pompe disease patients less than 8 years of age, LUMIZYME is available only through a restricted distribution program called the LUMIZYME ACE Program. Only prescribers and healthcare facilities enrolled in the program may prescribe, dispense, or administer LUMIZYME. LUMIZYME may be administered only to patients who are enrolled in and meet all the conditions of the LUMIZYME ACE Program. To enroll in the LUMIZYME ACE Program call 1-800-745-4447.
Anaphylaxis and Allergic Reactions: Anaphylaxis and severe allergic reactions have been observed in patients during and up to 3 hours after LUMIZYME infusion. Some of the reactions were life-threatening and included anaphylactic shock, respiratory arrest, apnea, dyspnea, bradycardia, tachycardia, and hypotension. Other accompanying reactions included chest discomfort/pain, throat tightness, bronchospasm, wheezing, tachypnea, cyanosis, decreased oxygen saturation/hypoxia, convulsions, angioedema (including tongue or lip swelling, periorbital edema, and face edema), pruritus, rash, urticaria, hyperhidrosis, nausea, dizziness, hypertension, flushing/erythema, fever, pallor, peripheral coldness, feeling hot, restlessness, nervousness, headache, back pain, and paraesthesia. Some of these reactions were IgE-mediated.
If anaphylaxis or other severe allergic reactions occur, immediate discontinuation of the administration of LUMIZYME should be considered, and appropriate medical treatment should be initiated. Severe reactions are generally managed with infusion interruption, administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen, when clinically indicated. In some cases of anaphylaxis, epinephrine has been administered. Because of the potential for severe allergic reactions, appropriate medical support, including cardiopulmonary resuscitation equipment, should be readily available when LUMIZYME is administered. The risk and benefits of re-administering LUMIZYME following an anaphylactic or severe allergic reaction should be considered. Extreme care should be exercised, with appropriate resuscitation measures available, if the decision is made to re-administer the product.
Immune Mediated Reactions: Severe cutaneous reactions have been reported with alglucosidase alfa including necrotizing skin lesions. Systemic immune mediated reactions, including possible type III immune complex-mediated reactions have been observed with alglucosidase alfa. These reactions occurred several weeks to 3 years after initiation of alglucosidase alfa infusions. Skin biopsy in one patient demonstrated deposition of anti-rhGAA antibodies in the lesion. Another patient developed severe inflammatory arthropathy in association with fever and elevated erythrocyte sedimentation rate. Patients should be monitored for the development of systemic immune complex-mediated reactions involving skin and other organs while receiving LUMIZYME. If immune mediated reactions occur, discontinuation of the administration of LUMIZYME should be considered, and appropriate medical treatment initiated. The risks and benefits of re-administering alglucosidase alfa following an immune mediated reaction should be considered. Some patients have successfully been rechallenged and have continued to receive alglucosidase alfa under close clinical supervision.
LUMIZYME ACE Program®: LUMIZYME is available only under a restricted distribution program called the LUMIZYME ACE (Alglucosidase Alfa Control and Education) Program. The purpose of the program is to ensure that the known risks of anaphylaxis and severe allergic reactions and the potential risks of severe cutaneous and systemic immune complex-mediated reactions associated with the use of LUMIZYME are communicated to patients and prescribers. In addition, the program is designed to mitigate the potential risk of rapid disease progression in infantile-onset Pompe disease patients and late (non-infantile) onset Pompe disease patients less than 8 years of age for whom the safety and effectiveness of LUMIZYME have not been evaluated.
For information about the ACE Program call 1-800-745-4447.
Risk of Acute Cardiorespiratory Failure: Patients with acute underlying respiratory illness or compromised cardiac and/or respiratory function may be at risk of serious exacerbation of their cardiac or respiratory compromise during infusions. Appropriate medical support and monitoring measures should be readily available during infusions and some patients may require prolonged observation times.
Precautions for General/Regional Anesthesia: Administration of general anesthesia can be complicated by the presence of severe cardiac and skeletal (including respiratory) muscle weakness, therefore, caution should be used when administering general anesthesia in Pompe disease patients.
Monitoring: Laboratory Tests: Patients should be monitored for IgG antibody formation every 3 months for 2 years and then annually thereafter.
Testing for IgG titers may also be considered if patients develop allergic or other immune mediated reactions. Patients who experience anaphylactic or allergic reactions may also be tested for IgE antibodies to alglucosidase alfa and other mediators of anaphylaxis.
Adverse Reactions:
Serious adverse reactions reported with LUMIZYME in the randomized, double-blind, placebo-controlled study included anaphylaxis. Anaphylactic reactions included: angioedema, throat tightness and chest pain/discomfort. One patient with a history of Wolff-Parkinson-White syndrome experienced a serious adverse reaction of supraventricular tachycardia. Other serious adverse events that occurred in a higher incidence in LUMIZYME treated patients compared to placebo included coronary artery disease, intervertebral disc protrusion, pneumonia, gastroenteritis, and dehydration.
The most common adverse reactions observed in clinical studies were infusion reactions. Infusion reactions that occurred in LUMIZYME treated patients at an incidence of ≥ 5% compared to placebo included anaphylaxis, urticaria, diarrhea, vomiting, dyspnea, pruritus, rash/erythema, pharyngolaryngeal pain, neck pain, hypoacusis, flushing/feeling hot, pain in extremity, fall and chest discomfort. Additional infusion reactions observed in other clinical trials and expanded access programs with LUMIZYME included respiratory distress, cough, livedo reticularis, agitation, irritability, retching, rigors, tremor and increased lacrimation. Infusion reactions may occur during or within 2 hours after completion of the infusion. Delayed onset infusion reactions defined as adverse reactions that occurred within 48 hours after completion of LUMIZYME infusion, occurred in LUMIZYME treated patients at an incidence of ≥3% compared to placebo treated patients in a controlled clinical trial. Patients should be counseled about the possibility of delayed onset infusion reactions and given proper follow up instructions.
If an infusion reaction occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administration of antihistamines and/or antipyretics may ameliorate the symptoms. If severe infusion or allergic reactions occur, immediate discontinuation of the administration of LUMIZYME should be considered, and appropriate medical treatment should be initiated. Patients who have experienced infusion reactions should be treated with caution when they are re-administered LUMIZYME.
In postmarketing experience with LUMIZYME, deaths, and serious adverse reactions have been reported, including anaphylaxis. Adverse events resulting in death reported in the postmarketing setting with LUMIZYME treatment included cardiorespiratory arrest, respiratory failure, hemothorax, pneumothorax, cardiac failure, sepsis, aortic dissection, cerebrovascular accident, and skin necrosis. The most frequently reported serious adverse reactions were infusion reactions. The following serious adverse events have been reported in at least 2 patients: dyspnea, respiratory failure, bronchospasm, stridor, decreased oxygen saturation/hypoxia, pharyngeal edema, chest discomfort, chest pain, hypotension, hypertension, erythema, flushing, lung infection, tachycardia, cyanosis, and hypersensitivity. One case of hyperparathyroidism has been reported.
Immunogenicity: In the randomized, double-blind, placebo-controlled study, all patients with available samples treated with LUMIZYME (N=59, 100%) developed IgG antibodies to alglucosidase alfa. All patients who developed IgG antibodies did so within the first 3 months of exposure (median time to seroconversion was 4 weeks). A small number of LUMIZYME treated patients in clinical trials and postmarketing setting who were evaluated tested positive for presence of alglucosidase alfa-specific IgE antibodies. Some of these patients experienced anaphylaxis. Some patients who tested positive for alglucosidase alfa-specific IgE antibodies were successfully rechallenged with LUMIZYME using a slower infusion rate at lower initial doses and have continued to receive treatment under close clinical supervision. Patients who develop IgE antibodies to alglucosidase alfa appear to be at a higher risk for the occurrence of anaphylaxis and severe allergic reactions.
Therefore, these patients should be monitored more closely during administration of LUMIZYME.
To report suspected adverse reactions, contact Genzyme Medical Information at 800-745-4447, option 2.
Please see the full prescribing information for complete details, including boxed warning.
庞倍氏症
心肌糖原沉积病[庞培氏(Pompe)病]
心肌糖厚沉积病由Pompe(1932)提出，为糖原合成和分解代谢中所需一系列酶的缺陷所致病变，是一种先天性代谢病，本病罕见，是引起婴儿心脏迅速增大的疾病之一，亦即所谓特发性心脏肥大。
[病因]
为糖原分解酶(如a-1，4-葡萄糖苷酶)的缺陷，不能分解为葡萄糖而造成糖原质和量的代谢障碍，使组织中的糖原累积，因此近年把这类疾患总称为糖原沉积病，由于受累的组织或器官不同，可区别为+或+ -型，绝大多数与常染色体隐性遗传有关。实际上可分为肝，心，肌肉三大类，如1型称为肝糖原沉积病（GSDI 亦称VonGierke病），2型为心肌糖原沉积病（GSDI，pampe病等）。3型即肌性糖原沉积病。
[病理]
由于组织中糖原积累，造成器官的肿大与功能不全，如心脏明显增大，主要是心室壁增厚，左室可厚达30毫米（正常为7~10毫米）糖原代谢了肌纤维，并有空泡形成，退行性坏死，但无炎症改变，同时可累及肝，肾和有纹肌等。
[临床情况]
1.病人出生后数周或数月发病，男女相等，病情发展快，常早年死于心力衰竭或呼吸道感染，但也有见于成人者。
2.心脏明显增大但一般无杂音，肌肉软弱无力，巨舌，面容与呆小症或伸舌痴愚相似，肝脾肿大常不明显。
3.胃纳差，呕吐，呼吸困难，紫绀，水肿以及营养不良，发育迟缓等表现。
4.心电图左心肥厚，T波倒置，S~T段下降，血液检查末梢白细胞的酸性麦芽糖酶（葡萄糖苷酶）的活性显著降低。
[X线表现]
1，心脏呈对称性的原形或球形明显扩大，主要是心室，不侵犯心房，搏动减弱，并可压迫左上支气管，引起左上叶肺不张，晚期有时合并肺郁血或肺炎的表现。
2，心血管造影，显示左心室壁增厚，血液循环正常，有时左肺动脉压升高。
[鉴别诊断]
应与心内膜弹力纤维增生症鉴别，二者X线表现大致相同，又可并存。其它如支气管肺炎伴心力衰竭，先天性心血管畸形，心肌炎等相区别。 |
