繁体中文
设为首页
加入收藏
当前位置:药品说明书与价格首页 >> 综合药讯 >> Fabrazyme powder(agalsidase beta solution infusion)

Fabrazyme powder(agalsidase beta solution infusion)

——Anderson Fabry病:酶替代疗法改善冠脉微血管功能疗效待评价

2006-04-06 03:53:57  作者:新特药房  来源:中国新特药网天津分站  浏览次数:114  文字大小:【】【】【

Fabrazyme(β-agalsidase,β-半乳糖苷酶A)冻干静脉
制造商:
Genzyme(健赞公司)
Fabrazyme是法布里(Fabry)病的酶替代治疗药物。法布里病是一种因半乳糖苷酶A缺乏导致的罕见的遗传性疾病,在临床上表现为脂肪在患者血管内多年累积,导致多器官功能障碍,使病人产生显著的疼痛并失能,最终引发器官衰竭和卒中。全球大约共有2200例患者。
最初美国批准:2003年
适应症
fabrazyme表示在与法布里病的患者使用。 fabrazyme globotriaosylceramide(GL-3)沉积在肾脏的毛细血管内皮细胞和某些其他类型的细胞降低。
剂量和用法
1毫克/公斤体重静脉滴注,每两个星期。患者应接受输液之前的退烧药。
剂型和优势
冻干粉,注射用无菌水配制USP产生5毫克/毫升
可为35毫克或5毫克单次用小瓶。
禁忌
没有。
注意事项
危及生命的过敏性和严重的过敏反应已被观察到一些病人在Fabrazyme输液。如果发生严重的过敏反应或过敏性反应,立即停止的Fabrazyme管理和提供必要的紧急治疗。 Fabrazyme是因为潜在的严重的输液反应管理时,适当的医疗保障措施,应该是一应俱全。
输液反应发生在约50%至55%的患者在临床试验期间Fabrazyme管理。一些反应严重。在遇到输液反应的患者,解热和抗组织胺预处理建议。如果发生输液反应,降低输注速率,暂时停止输液,和/或管理的其他退烧药,抗组胺药,和/或类固醇可改善症状。
如果发生严重的输液反应,立即停止的Fabrazyme管理,应考虑,应该开始适当的治疗。严重的反应,一般管理与管理抗组胺药,皮质激素,静脉输液和/或氧气作为临床指征。
与先进的Fabry病的患者可能会损害心脏功能,这可能会使他们从输液反应的严重并发症的风险较高,这些病人应密切监测,Fabrazyme管理。
Fabrazyme重新管理,谁曾经历Fabrazyme严重或严重的过敏反应的患者应继续治疗的风险和利益的慎重考虑后,只有合格人员直接监督下,适当的医疗支持措施容易。
不良反应
最常见的不良反应是输液反应。严重和/或相关的不良反应频繁发生(发生率≥5%),其中包括输液反应,由一个或多个下列:畏寒,发热的感觉过热或过冷,呼吸困难,恶心,潮红,头痛,呕吐,感觉异常,周边高血压,胸痛,咽痛,腹痛,头晕,心动过速,鼻塞,腹泻,水肿,肌痛,乏力,皮肤瘙痒,下肢疼痛,背部疼痛,脸色苍白,心动过缓,荨麻疹,低血压,面部水肿,皮疹,嗜睡。
药物相互作用
无药物相互作用的研究。
在没有进行体外代谢研究。
在特殊人群中使用


Fabrazyme 35 mg, powder for concentrate for solution for infusion
1. Name of the medicinal product
Fabrazyme 35 mg powder for concentrate for solution for infusion
2. Qualitative and quantitative composition
Each vial of Fabrazyme contains a nominal value of 35 mg of agalsidase beta. After reconstitution with 7.2 ml water for injections, each vial of Fabrazyme contains 5 mg/ml (35 mg/7 ml) of agalsidase beta. The reconstituted solution must be diluted further (see section 6.6).
Agalsidase beta is a recombinant form of human α-galactosidase A and is produced by recombinant DNA technology using a mammalian Chinese Hamster Ovary (CHO) cell culture. The amino acid sequence of the recombinant form, as well as the nucleotide sequence which encoded it, are identical to the natural form of α-galactosidase.
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Powder for concentrate for solution for infusion.
White to off-white lyophilised cake or powder.
4. Clinical particulars
4.1 Therapeutic indications
Fabrazyme is indicated for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry disease (α-galactosidase A deficiency).
Fabrazyme is indicated in adults, children and adolescents aged 8 years and older.
4.2 Posology and method of administration
Fabrazyme treatment should be supervised by a physician experienced in the management of patients with Fabry disease or other inherited metabolic diseases.
Posology
The recommended dose of Fabrazyme is 1 mg/kg body weight administered once every 2 weeks as an intravenous infusion.
Alternative dosing regimens have been used in clinical studies. In one of these studies, after an initial dose of 1.0 mg/kg every 2 weeks for 6 months, 0.3 mg/kg every 2 weeks may maintain clearance of GL-3 in certain cell types in some patients; however, the long term clinical relevance of these findings has not been established (see section 5.1).
The initial infusion rate should be no more than 0.25 mg/min (15 mg/hour) to minimise the potential occurrence of infusion-associated reactions. After patient tolerance is established, the infusion rate may be increased gradually with subsequent infusions.
Infusion of Fabrazyme at home may be considered for patients who are tolerating their infusions well. The decision to have a patient move to home infusion should be made after evaluation and recommendation by the treating physician. Patients experiencing adverse events during the home infusion need to immediately stop the infusion process and seek the attention of a healthcare professional. Subsequent infusions may need to occur in a clinical setting. Dose and infusion rate should remain constant while at home, and not be changed without supervision of a healthcare professional.
Special populations
Patients with renal impairment
No dose adjustment is necessary for patients with renal insufficiency.
Patients with hepatic impairment
Studies in patients with hepatic insufficiency have not been performed.
Elderly patients
The safety and efficacy of Fabrazyme in patients older than 65 years have not been established and no dosage regimen can presently be recommended in these patients.
Paediatric population
Studies in children 0-7 years have not been performed and no dosage regimen can presently be recommended in patients in this paediatric age group as safety and efficacy have not yet been established. No dose adjustment is necessary for children 8-16 years.
Method of administration
For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.
4.3 Contraindications
Life threatening hypersensitivity (anaphylactic reaction) to the active substance or any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
Immunogenicity
Since agalsidase beta (r-hαGAL) is a recombinant protein, the development of IgG antibodies is expected in patients with little or no residual enzyme activity. The majority of patients developed IgG antibodies to r-hαGAL, typically within 3 months of the first infusion with Fabrazyme. Over time, the majority of seropositive patients in clinical trials demonstrated either a downward trend in titers (based on a ≥ 4-fold reduction in titer from the peak measurement to the last measurement) (40% of the patients), tolerised (no detectable antibodies confirmed by 2 consecutive radioimmuno-precipitation (RIP) assays) (14% of the patients) or demonstrated a plateau (35% of the patients).
Infusion associated reactions
Patients with antibodies to r-hαGAL have a greater potential to experience infusion-associated reactions (IARs), which are defined as any related adverse event occurring on the infusion day. These patients should be treated with caution when re-administering agalsidase beta (see section 4.8). Antibody status should be regularly monitored.
In clinical trials, sixty seven percent (67 %) of the patients experienced at least one infusion-associated reaction (see section 4.8). The frequency of IARs decreased over time. Patients experiencing mild or moderate infusion-associated reactions when treated with agalsidase beta during clinical trials have continued therapy after a reduction in the infusion rate (~0.15 mg/min; 10 mg/hr) and/or pre-treatment with antihistamines, paracetamol, ibuprofen and/or corticosteroids.
Hypersensitivity
As with any intravenous protein medicinal product, allergic-type hypersensitivity reactions are possible.
A small number of patients have experienced reactions suggestive of immediate (Type I) hypersensitivity. If severe allergic or anaphylactic-type reactions occur, immediate discontinuation of the administration of Fabrazyme should be considered and appropriate treatment initiated. The current medical standards for emergency treatment are to be observed. With careful rechallenge Fabrazyme has been re-administered to all 6 patients who tested positive for IgE antibodies or had a positive skin test to Fabrazyme in a clinical trial. In this trial, the initial rechallenge administration was at a low dose and a lower infusion rate ( the therapeutic dose at  the initial standard recommended rate). Once a patient tolerates the infusion, the dose may be increased to reach the therapeutic dose of 1 mg/kg and the infusion rate may be increased by slowly titrating upwards, as tolerated.
Patients with advanced renal disease
The effect of Fabrazyme treatment on the kidneys may be limited in patients with advanced renal disease.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies and no in vitro metabolism studies have been performed. Based on its metabolism, agalsidase beta is an unlikely candidate for cytochrome P450 mediated drug-drug interactions.
Fabrazyme should not be administered with chloroquine, amiodarone, benoquin or gentamycin due to a theoretical risk of inhibition of intra-cellular α-galactosidase activity.
4.6 Fertility, pregnancy and lactation
Pregnancy
There are no adequate data from the use of agalsidase beta in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to embryonal/foetal development (see section 5.3).
Fabrazyme should not be used during pregnancy unless clearly necessary.
Breast-feeding
Agalsidase beta may be excreted in milk. Because there are no data available on effects in neonates exposed to agalsidase beta via breast milk, it is recommended to stop breast-feeding when Fabrazyme is used.
Fertility
Studies have not been conducted to assess the potential effects of Fabrazyme on impairment of fertility.
4.7 Effects on ability to drive and use machines
Fabrazyme may have a minor influence on the ability to drive or use machines on the day of Fabrazyme administration because dizziness, somnolence, vertigo and syncope may occur (see section 4.8).
4.8 Undesirable effects
Summary of the safety profile
Since agalsidase beta (r-hαGAL) is a recombinant protein, the development of IgG antibodies is expected in patients with little or no residual enzyme activity. Patients with antibodies to r-hαGAL have a greater potential to experience infusion-associated reactions (IARs). Reactions suggestive of immediate (Type I) hypersensitivity have been reported in a small number of patients (see section 4.4).
Very common adverse reactions included chills, pyrexia, feeling cold, nausea, vomiting, headache and paraesthesia. Sixty seven percent (67%) of the patients experienced at least one infusion-associated reaction. Anaphylactoid reactions have been reported in the postmarketing setting.
Tabulated list of adverse reactions
Adverse reactions reported from clinical trials with a total of 168 patients (154 males and 14 females) treated with Fabrazyme administered at a dose of 1 mg/kg every 2 weeks for a minimum of one infusion up to a maximum of 5 years are listed by System Organ Class and frequency (very common ≥ 1/10; common ≥ 1/100 to < 1/10 and uncommon ≥ 1/1000 to < 1/100) in the table below. The occurrence of an adverse reaction in a single patient is defined as uncommon in light of the relatively small number of patients treated. Adverse reactions only reported during the Post Marketing period are also included in the table below at a frequency category of “not known” (cannot be estimated from the available data). Adverse reactions were mostly mild to moderate in severity:
Incidence of adverse reactions with Fabrazyme treatment

System organ class

Very common

Common

Uncommon

Not known

Infections and infestations

---

nasopharyngitis

rhinitis

 

Immune system disorders

---

---

---

anaphylactoid reaction

Nervous system disorders

headache, paraesthesia

dizziness, somnolence, hypoaesthesia, burning sensation, lethargy, syncope

hyperaesthesia, tremor

---

Eye disorders

---

lacrimation increased

eye pruritus, ocular hyperaemia

---

Ear and labyrinth disorders

---

tinnitus, vertigo

auricular swelling, ear pain

---

Cardiac Disorders

---

tachycardia, palpitations, bradycardia

sinus bradycardia

---

Vascular disorders

---

flushing, hypertension, pallor, hypotension, hot flush

peripheral coldness

---

Respiratory, thoracic and mediastinal disorders

---

dyspnoea, nasal congestion, throat tightness, wheezing, cough, dyspnoea exacerbated

bronchospasm, pharyngolaryngeal pain, rhinnorhoea, tachypnoea, upper respiratory tract congestion

hypoxia

Gastrointestinal Disorders

nausea, vomiting

abdominal pain, abdominal pain upper, abdominal discomfort, stomach discomfort, hypoaesthesia oral, diarrhoea

dyspepsia, dysphagia

---

Skin and subcutaneous tissue disorders

---

pruritus, urticaria, rash, erythema, pruritus generalized, angioneurotic oedema, swelling face, rash maculo-papular

livedo reticularis, rash erythematous, rash pruritic, skin discolouration, skin discomfort

leukocytoclastic vasculitis

Musculoskeletal and connective tissue disorders

---

pain in extremity, myalgia, back pain, muscle spasms, arthralgia, muscle tightness, musculoskeletal stiffness

musculoskeletal pain

---

General disorders and administration site conditions

chills, pyrexia, feeling cold

fatigue, chest discomfort, feeling hot, oedema peripheral, pain, asthenia, chest pain, face oedema, hyperthermia

feeling hot and cold, influenza-like illness, infusion site pain, infusion site reaction, injection site thrombosis, malaise, oedema

---

Investigations

 

 

 

oxygen saturation decreased

For the purpose of this table, ≥1% is defined as reactions occurring in 2 or more patients.

Adverse reaction terminology is based upon the Medical Dictionary for Regulatory Activities (MedDRA)

Description of selected adverse reactions
Infusion associated reactions
Infusion associated reactions consisted most often of fever and chills. Additional symptoms included mild or moderate dyspnoea, hypoxia (oxygen saturation decreased), throat tightness, chest discomfort, flushing, pruritus, urticaria, face oedema, angioneurotic oedema, rhinitis, bronchospasm, tachypnoea, wheezing, hypertension, hypotension, tachycardia, palpitations, abdominal pain, nausea, vomiting, infusion-related pain including pain at the extremities, myalgia, and headache.
The infusion-associated reactions were managed by a reduction in the infusion rate together with the administration of non-steroidal anti-inflammatory medicinal products, antihistamines and/or corticosteroids. Sixty seven percent (67%) of the patients experienced at least one infusion-associated reaction. The frequency of these reactions decreased over time. The majority of these reactions can be attributed to the formation of IgG antibodies and/or complement activation. In a limited number of patients IgE antibodies were demonstrated (see section 4.4).
Paediatric population
Limited information suggests that the safety profile of Fabrazyme treatment in paediatric patients (above the age of 7) is not different with that seen in adults.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed below:
United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard
Ireland
HPRA Pharmacovigilance
Earlsfort Terrace
IRL - Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.hpra.ie
e-mail: medsafety@hpra.ie
4.9 Overdose
In clinical trials doses up to 3 mg/kg body weight were used.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other alimentary tract and metabolism products, enzymes. ATC code: A16AB04.
Fabry disease
Fabry disease is an inherited heterogeneous and multisystemic progressive disease, that affects both males and females. It is characterised by the deficiency of α-galactosidase. Reduced or absent α-galactosidase activity results in the accumulation of GL-3 in the lysosomes of many cell types including the endothelial and parenchymal cells, ultimately leading to life-threatening clinical deteriorations as a result of renal, cardiac and cerebrovascular complications.
Mechanism of action
The rationale for enzyme replacement therapy is to restore a level of enzymatic activity sufficient to clear the accumulating substrate in the organ tissues; thereby, preventing, stabilizing or reversing the progressive decline in function of these organs before irreversible damage has occurred.
After intravenous infusion, agalsidase beta is rapidly removed from the circulation and taken up by vascular endothelial and parenchymal cells into lysosomes, likely through the mannose-6 phosphate, mannose and asialoglycoprotein receptors.
Clinical efficacy and safety
Efficacy and safety of Fabrazyme was evaluated in one study with children, one dose-finding study, two double-blind placebo-controlled studies, and one open-label extension study in both male and female patients.
In the dose finding study, the effects of 0.3, 1.0 and 3.0 mg/kg once every 2 weeks and 1.0 and 3.0 mg/kg once every 2 days were evaluated. A reduction in GL-3 was observed in kidney, heart, skin and plasma at all doses. Plasma GL-3 was cleared in a dose dependent manner, but was less consistent at the dose of 0.3 mg/kg. In addition, infusion-associated reactions were dose dependent.
In the first placebo-controlled clinical trial, Fabrazyme was effective in clearing GL-3 from the vascular endothelium of the kidney after 20 weeks of treatment. This clearance was achieved in 69% (20/29) of the Fabrazyme treated patients, but in none of the placebo patients (p<0.001). This finding was further supported by a statistically significant decrease in GL-3 inclusions in kidney, heart and skin combined and in the individual organs in patients treated with agalsidase beta compared to placebo patients (p<0.001). Sustained clearance of GL-3 from kidney vascular endothelium upon agalsidase beta treatment was demonstrated further in the open label extension of this trial. This was achieved in 47 of the 49 patients (96%) with available information at month 6, and in 8 of the 8 patients (100%) with available information at the end of the study (up to a total of 5 years of treatment). Clearance of GL-3 was also achieved in several other cell types from the kidney. Plasma GL-3 levels rapidly normalised with treatment and remained normal through 5 years.
Renal function, as measured by glomerular filtration rate and serum creatinine, as well as proteinuria, remained stable in the majority of the patients. However, the effect of Fabrazyme treatment on the kidney function was limited in some patients with advanced renal disease.
Although no specific study has been conducted to assess the effect on the neurological signs and symptoms, the results also indicate that patients may achieve reduced pain and enhanced quality of life upon enzyme replacement therapy.
Another double-blind, placebo-controlled study of 82 patients was performed to determine whether Fabrazyme would reduce the rate of occurrence of renal, cardiac, or cerebrovascular disease or death. The rate of clinical events was substantially lower among Fabrazyme-treated patients compared to placebo-treated patients (risk reduction = 53% intent-to-treat population (p=0.0577); risk reduction = 61 % per-protocol population (p=0.0341)). This result was consistent across renal, cardiac and cerebrovascular events.
The results of these studies indicate that Fabrazyme treatment at 1 mg/kg every other week provides clinical benefit on key clinical outcomes in patients with early and advanced Fabry disease. Because this condition is slowly progressive, early detection and treatment is critical to achieve the best outcomes.
In an additional study, 21 male patients were enrolled to follow GL3 clearance in kidney and skin tissues at an alternative dosing regimen. Following treatment with 1 mg/kg every other week for 24 weeks, a dose regimen of 0.3 mg/kg every 2 weeks for 18 months was able to maintain the clearance of cellular GL-3 in the capillary endothelium of the kidney, other kidney cell types and skin (superficial skin capillary endothelium) in the majority of patients. However, at the lower dose, IgG antibodies may play a role with respect to GL-3 clearance in some patients. Due to the limitations of the study design (small number of patients), no definitive conclusion regarding the dose maintenance regimen can be drawn, but these findings suggest that, after an initial debulking dose of 1.0 mg/kg every 2 weeks, 0.3 mg/kg every 2 weeks may be sufficient in some patients to maintain clearance of GL-3.
In the postmarketing setting, experience was gained in patients who initiated treatment at a dose of 1 mg/kg every 2 weeks and subsequently received a reduced dose for an extended period. In some of these patients, an increase of some of the following symptoms was spontaneously reported: pain, paraesthesia and diarrhoea, as well as cardiac, central nervous system and renal manifestations. These reported symptoms resemble the natural course of Fabry disease.
Paediatric population
In the open-label paediatric study, sixteen patients with Fabry disease (8-16 years old; 14 males, 2 females) had been treated for one year. Clearance of GL-3 in the superficial skin vascular endothelium was achieved in all patients who had accumulated GL-3 at baseline. The 2 female patients had little or no GL-3 accumulation in the superficial skin vascular endothelium at baseline, making this conclusion applicable in male patients only.
5.2 Pharmacokinetic properties
Following an intravenous administration of agalsidase beta to adults at doses of 0.3 mg, 1 mg and 3 mg/kg body weight, the AUC values increased more than dose proportional, due to a decrease in clearance, indicating a saturated clearance. The elimination half-life was dose dependent and ranged from 45 to 100 minutes.
After intravenous administration of agalsidase beta to adults with an infusion time of approximately 300 minutes and at a dose of 1 mg/kg body weight, biweekly, mean Cmax plasma concentrations ranged from 2000-3500 ng/ml, while the AUCinf ranged from 370-780 μg min/ml. Vss ranged from 8.3-40.8 l, plasma clearance from 119-345 ml/min and the mean elimination half-life from 80-120 minutes.
Agalsidase beta is a protein and is expected to be metabolically degraded through peptide hydrolysis. Consequently, impaired liver function is not expected to affect the pharmacokinetics of agalsidase beta in a clinically significant way. Renal elimination of agalsidase beta is considered to be a minor pathway for clearance.
Paediatric population
Fabrazyme pharmacokinetics was also evaluated in 15 paediatric patients (8.5 to 16 years old weighing 27.1 to 64.9 kg). Agalsidase clearance was not influenced by weight in this population. Baseline clearance was 77 ml/min with a volume of distribution at steady-state (Vss) of 2.6 l; half-life was 55 min. After IgG seroconversion, clearance decreased to 35 ml/min, Vss increased to 5.4 l, and half-life increased to 240 min. The net effect of these changes after seroconversion was an increase in exposure of 2- to 3-fold based on AUC and Cmax. No unexpected safety issues were encountered in patients with an increase in exposure after seroconversion.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, single dose toxicity, repeated dose toxicity and embryonal/foetal toxicity. Studies with regard to other stages of the development have not been carried out. Genotoxic and carcinogenic potential are not expected.
6. Pharmaceutical particulars
6.1 List of excipients
Mannitol
Sodium phosphate monobasic, monohydrate
Sodium phosphate dibasic, heptahydrate
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products in the same infusion.
6.3 Shelf life
3 years.
Reconstituted and diluted solutions
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage and conditions prior to use are the responsibility of the user. The reconstituted solution cannot be stored and should be promptly diluted; only the diluted solution can be held for up to 24 hours at 2°C-8°C.
6.4 Special precautions for storage
Store in a refrigerator (2°C – 8°C).
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.
6.5 Nature and contents of container
Fabrazyme 35 mg is supplied in clear Type I glass 20 ml vials. The closure consists of a siliconised butyl stopper and an aluminium seal with a plastic flip-off cap.
Package sizes: 1, 5 and 10 vials per carton.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
The powder for concentrate for solution for infusion has to be reconstituted with water for injections, diluted with 0.9% sodium chloride intravenous solution and then administered by intravenous infusion. Use Aseptic Technique
1. Determine the number of vials to be reconstituted based on the individual patient's weight and remove the required vials from the refrigerator in order to allow them to reach room temperature (in approximately 30 minutes). Each vial of Fabrazyme is intended for single use only.
Reconstitution
2. Reconstitute each vial of Fabrazyme 35 mg with 7.2 ml water for injections. Avoid forceful impact of the water for injections on the powder and avoid foaming. This is done by slow drop-wise addition of the water for injection down the inside of the vial and not directly onto the lyophilized cake. Roll and tilt each vial gently. Do not invert, swirl or shake the vial.
3. The reconstituted solution contains 5 mg agalsidase beta per ml, and appears as a clear colourless solution. The pH of the reconstituted solution is approximately 7.0. Before further dilution, visually inspect the reconstituted solution in each vial for particulate matter and discoloration. Do not use the solution if foreign particles are observed or if the solution is discoloured.
4. After reconstitution it is recommended to promptly dilute the vials, to minimise protein particle formation over time.
5. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Dilution
6. Prior to adding the reconstituted volume of Fabrazyme required for the patient dose, it is recommended to remove an equal volume of 0.9% sodium chloride intravenous solution, from the infusion bag.
7. Remove the airspace within the infusion bag to minimize the air/liquid interface.
8. Slowly, withdraw 7.0 ml (equal to 35 mg) of the reconstituted solution from each vial up to the total volume required for the patient dose. Do not use filter needles and avoid foaming.
9. Then slowly inject the reconstituted solution directly into the 0.9% sodium chloride intravenous solution (not in any remaining airspace) to a final concentration between 0.05 mg/ml and 0.7 mg/ml. Determine the total volume of sodium chloride 0.9% solution for infusion (between 50 and 500 ml) based on the individual dose. For doses lower than 35 mg use a minimum of 50 ml, for doses 35 to 70 mg use a minimum of 100 ml, for doses 70 to 100 mg use a minimum of 250 ml and for doses greater than 100 mg use only 500 ml. Gently invert or lightly massage the infusion bag to mix the diluted solution. Do not shake or excessively agitate the infusion bag.
Administration
10. It is recommended to administer the diluted solution through an in-line low protein-binding 0.2 µm filter to remove any protein particles which will not lead to any loss of agalsidase beta activity. The initial infusion rate should be no more than 0.25 mg/min (15 mg/hour) to minimise the potential occurrence of infusion-associated reactions. After patient tolerance is established, the infusion rate may be increased gradually with subsequent infusions.
7. Marketing authorisation holder
Genzyme Europe B.V., Gooimeer 10, NL-1411DD Naarden, The Netherlands
8. Marketing authorisation number(s)
EU/1/01/188/001-003
9. Date of first authorisation/renewal of the authorisation
Date of first authorisation: 03 August 2001
Date of last renewal: 03 August 2006
10. Date of revision of the text
06/2014
Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.

附:Fabrazyme 5 mg, powder for concentrate for solution for infusion(http://www.medicines.org.uk/EMC/medicine/18405/SPC/Fabrazyme+5+mg%2c+powder+for+concentrate+for+solution+for+infusion/
Anderson Fabry病:酶替代疗法改善冠脉微血管功能疗效待评价
英国伦敦大学Elliott等报告,酶替代疗法并不能有效改善男性Anderson Fabry病(α-半乳糖苷酶A缺乏症,X染色体连锁隐性遗传病)患者的冠脉微血管功能。
该研究比较了10例不吸烟的男性Anderson Fabry病患者(平均年龄53.8岁,平均胆固醇浓度5.5 mmol/L)和24名不吸烟的男性(平均年龄52.0岁,平均胆固醇浓度4.5 mmol/L,对照组)的冠脉微血管功能。
结果显示,在α-半乳糖苷酶A治疗前,无论是静息还是充血状态(输注腺苷140 μg/kg/min),Anderson Fabry病患者的心肌血流和冠脉血流储备都显著低于对照者,充血状态下的血管最小阻力也显著高于对照者;5例患者在应用α-半乳糖苷酶A治疗10.1个月后,虽然沉积在心肌细胞中的神经酰胺三己糖苷减少,但静息及充血状态下的心肌血流和冠脉血流储备均未出现显著改变,充血状态下的血管最小阻力亦没有改变。
研究提示:
冠脉微血管功能障碍是Anderson Fabry病患者的一个重要的病理生理学表现。鉴于该研究的病例数少,研究对象的年龄偏大,心脏表现也偏重,因此酶替代疗法(无其是早期酶替代疗法)是否对改善微血管功能有益还需要更研究多来评估。

责任编辑:


相关文章
ALDURAZYME(laronidase solution for infusion)
FABRAZYME(AGALSIDASE BETA) 重组人β-半乳糖苷酶A注射剂
Betaferon(interferon beta-1b injection)
PLEGRIDY(peginterferon beta-1a injection)
REPLAGAL(α-半乳糖苷酶注射剂[基因重组])
AVONEX Pen(interferon beta-1a)injection
PLEGRIDY(Peginterferon Beta-1a)注射剂
PLEGRIDY(长效聚乙二醇干扰素β-1a预充填笔/注射器)
PLEGRIDY(聚乙二醇干扰素β-1a)临床用于复发型多发性硬化症的治疗
Puregon(重组促卵泡素β注射液)
Betaseron(Interferon Beta-1B)预充式注射剂
 

最新文章

更多

· 美国FDA批准FilmArray M...
· 无水酒精注射液(DEHYDR...
· DEHYDRATED ALCOHOL(无...
· 除铁能注射剂DESFERAL(D...
· ALBUMINAR IV SOLUTION(...
· Dantrium Intravenous I...
· Bunavail(盐酸丁丙诺啡...
· Dyloject(diclofenac so...
· THAM SOLUTION(trometha...
· THAM Injection SET(Tr...

推荐文章

更多

· 美国FDA批准FilmArray M...
· 无水酒精注射液(DEHYDR...
· DEHYDRATED ALCOHOL(无...
· 除铁能注射剂DESFERAL(D...
· ALBUMINAR IV SOLUTION(...
· Dantrium Intravenous I...
· Bunavail(盐酸丁丙诺啡...
· Dyloject(diclofenac so...
· THAM SOLUTION(trometha...
· THAM Injection SET(Tr...

热点文章

更多

· 美国FDA批准FilmArray M...