部分中文Aralast原处方资料（仅供参考）

商品名

Aralast

开发商与上市厂商
本品由美国Alpha Therapeutic Corp公司研制开发，2003年5月在美国首次上市。

适应证

本品可用于先天性α1-蛋白酶抑制因子（PI）缺乏且具有临床肺气肿症状患者的治疗。

药理作用

本品可抑制肺部丝氨酸蛋白酶如中性粒细胞弹性蛋白酶(NE)。NE能降解肺泡壁的蛋白组分，并长期存在于肺部。通常认为肺部正常者，下呼吸道90%以上抗NE保护作用由 α1-PI提供。

α1-PI缺乏症是一种常染色体显性遗传性疾病，表现为血清和肺部α1- PI水平较低。较为严重的α1-PI缺乏症常与30～40岁之间发生的、缓慢渐进的中到重度全腺泡性肺气肿有关，可显著缩短患者的预期寿命。 NE由下呼吸道的中性粒细胞低水平缓慢释放，可导致肺部蛋白酶和蛋白酶抑制因子比例失衡。与α1-PI缺乏有关的肺气肿在下肺区尤其严重。由于在下呼吸道内没有足够的α1-PI 来对抗NE，病情会进一步发展。蛋白酶和蛋白酶抑制因子比例失衡，使得肺薄壁组织的结缔组织框架很容易遭到毁坏。

临床评价

α1-PI缺乏症有很多显型差异。 PiZZ显型患者的平均血清α1-PI低于正常水平的35%，Pi显型患者的血清(α1-PI低于检测下限。血清α1-PI水平较低即低于11μmol/L(80mg/dL) 者，有发生肺气肿的危险。两项研究显示，此类患者肺气肿发生率为 54.2%和57.0％。α1-PI严重缺乏且吸烟者，发生肺气肿的危险性高于曾经吸烟或不吸烟者。α1-PI缺乏症是最常见的可能致死的遗传性疾病之一。

一项临床研究对本品和已上市的 Prolastin(由拜耳公司生产的α1-PI产品）进行了比较。所有受试者都为确诊的患有先天性α1-PI缺乏症的肺气肿患者，并且之前6个月内未接受α1- PI补充治疗。28例受试者随机接受本品或对照药物，每周静注60mg/ kg，连续，0周。2例受试者过早从研究中退出：1例接受本品的受试者在6次输液后退出；1例接受 Prolastin的受试者在1次输液后，由于未预先安排支气管镜检查去除异物导致肺炎而退出。治疗前每例患者均检测血清α1-PI最低水平（抗原测定）和抗NE能力（功能测定）。在第一个为期10周的输液之后，接受对照药物的受试者转而使用本品，先前接受本品的则继续原先的治疗。在第7 周治疗前，对受试者进行支气管肺泡灌洗（BALs）。在12～24周治疗之前，对平均血清α1-PI最低水平的维持情况进行评估。

每周进行补充治疗后，可见血清α1-PI的最高和最低水平均稳步上升并维持数周。本品的代谢半衰期（t1/2为5.9天。所有受试者的血清抗 NE能力的最低水平在第2周均明显上升，到第3周，大多数受试者的血清抗NE能力的最低水平超过11μmol/ L。除少数患者以外，研究第3到24 周期间，受试者的血清α1-PI水平均保持在推荐的临界水平以上。

综上所述，每周1次静脉给予 60mg/kg补充治疗，本品和对照药物在保持目标血清α1-PI的最低水平和升高粘膜上皮液中α1-PI的抗原水平方面效果相似。

不良反应

临床最常见的不良反应为咽炎（1.6%）、头痛（0.7%）和咳嗽增加 (0.6%）。此外，支气管炎、鼻窦炎、皮疹、背痛、病毒性感染、周围性水肿、腹胀、眩晕、嗜睡、哮喘和鼻炎也较常见。所有症状均为轻到中度。

注意事项

本品应在配制完毕并达到室温后 3个小时之内使用。超过3小时后未使用的药品只能丢弃，不可留用。该溶液中不含防腐剂。

本品应单独使用，不可与其他制剂或稀释溶液混合使用。

本品对患者生育能力的影响以及对孕妇和哺乳期妇女的安全性尚未确定，临床使用需谨慎。

本品对儿童的安全性和有效性也尚未明确。
 
用法与用量

本品仅可静脉使用。推荐剂量为 60mg/kg，每周静注1次。推荐在配制完毕并达到室温后3个小时之内使用以避免在配制过程中可能造成的微生物污染。未用完的药品应丢弃。

本品的滴注速度不应超过每分钟 0.08mL/kg。如出现不良反应，应减慢滴速或停止滴注直至症状消失，然后以受试者可以耐受的速度重新继续滴注。

制剂

本品为无菌、无热原的冻干粉剂，每瓶为单次剂量，还包括注射所需的符合美国药典规定的适量无菌注射用水（每瓶25mL/0.5g；每瓶 50mL/1.0g)。本品单位以对猪胰弹性蛋白酶的抑制能力计。制剂包装还包括一只无菌双头转移针头和一个无菌的20μm过滤器。

Aralast NP
[Alpha1-Proteinase Inhibitor (Human)]
Solvent Detergent Treated
Nanofiltered
Aralast NP Description
Aralast NP is a sterile, stable, lyophilized preparation of purified human alpha1–proteinase inhibitor (α1–PI), also known as alpha1–antitrypsin.1 Aralast NP is a similar product to ARALAST, containing the same active components of plasma α1-PI with identical formulations.

Aralast NP is prepared from large pools of human plasma by using the cold ethanol fractionation process, followed by purification steps including polyethylene glycol and zinc chloride precipitations and ion exchange chromatography. All U.S. licensed α1-PI plasma derived products contain chemical modifications which arise during manufacturing and occur in varying levels from product to product.11 Aralast NP contains approximately 2% α1-PI with truncated C-terminal lysine (removal of Lys394), whereas ARALAST contains approximately 67% α1-PI with the C-terminal lysine truncation.12 No known data suggest influence of these structural modifications on the functional activity and immunogenicity of α1-PI.13

To reduce the risk of viral transmission, the manufacturing process includes treatment with a solvent detergent (S/D) mixture [tri–n–butyl phosphate and polysorbate 80] to inactivate enveloped viral agents such as human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV). In addition, a nanofiltration step is incorporated into the manufacturing process to reduce the risk of transmission of enveloped and non–enveloped viral agents. Based on in vitro studies, the process used to produce Aralast NP has been shown to inactivate and/or partition various viruses as shown in Table 1 below.2

Table 1: Virus Log Reduction in Aralast NP Manufacturing Process

Reduction factors ≤1.0 are not used for calculation of the overall reduction factor Not applicable; study did not test for virus indicated
Processing Step	Virus Log Reduction Factors
	HIV-1	BVDV	PRV	HAV	MMV
Cold ethanol fractionation	4.6	1.4	2.1	1.4	≤ 1.0*
Solvent Detergent-treatment	> 5.8	> 6.0	> 5.5	N/A†	N/A†
15 N nanofiltration	> 5.3	> 6.0	> 5.6	> 5.1	4.9
Overall reduction factor	> 15.7	> 13.4	> 13.2	> 6.5	4.9
HIV-1: Human immunodeficiency virus-1, BVDV (Bovine Viral Diarrhea Virus, model for Hepatitis C Virus and other lipid-enveloped RNA viruses), PRV (Pseudorabies Virus, model for lipid-enveloped DNA viruses, to which also Hepatitis B also belongs): HAV: Hepatitis A Virus, MMV (Mice Minute Virus, model for small non-lipid-

The unreconstituted, lyophilized cake should be white or off-white to slightly yellow-green or yellow in color. When reconstituted as directed, the concentration of functionally active α1–PI is ≥16 mg/mL and the specific activity is ≥0.55 mg active α1–PI/mg total protein. The composition of the reconstituted product is as follows:

Component	Quality/mL
Elastase Inhibitory Activity	≥400 mg Active α1–PI/0.5 g vial*
	≥800 mg Active α1–PI/1.0 g vial**
Albumin	≤5 mg/mL
Polyethylene Glycol	≤112 µg/mL
Polysorbate 80	≤50 µg/mL
Sodium	≤230 mEq/L
Tri-n-buyl Phosphate	≤1.0 µg/mL
Zinc	≤3 ppm
Reconstitution volume: 25mL/0.5 g vial  Reconstitution volume: 50mL/1.0 g vial

Each vial of Aralast NP is labeled with the amount of functionally active α1–PI expressed in mg/vial. The formulation contains no preservative. The pH of the solution ranges from 7.2 to 7.8. Product must only be administered intravenously.

Aralast NP - Clinical Pharmacology

Aralast NP functions in the lungs to inhibit serine proteases such as neutrophil elastase (NE), which is capable of degrading protein components of the alveolar walls and which is chronically present in the lung. In the normal lung, α1–PI is thought to provide more than 90% of the anti–NE protection in the lower respiratory tract.3,4

α1–PI deficiency is an autosomal, co-dominant, hereditary disorder characterized by low serum and lung levels of α1–PI.1,3,5,6 Severe forms of the deficiency are frequently associated with slowly progressive, moderate-to-severe panacinar emphysema that most often manifests in the third to fourth decades of life, resulting in a significantly lower life expectancy.1,3,4,6,7 However, an unknown percentage of individuals with severe α1–PI deficiency are not diagnosed with or may never develop clinically evident emphysema during their lifetimes. Individuals with α1–PI deficiency have little protection against NE released by a chronic, low–level of neutrophils in their lower respiratory tract, resulting in a protease:protease inhibitor imbalance in the lung.3,8 The emphysema associated with severe α1–PI deficiency is typically worse in the lower lung zones.5 It is believed to develop because there are insufficient amounts of α1–PI in the lower respiratory tract to inhibit NE. This imbalance allows relatively unopposed destruction of the connective tissue framework of the lung parenchyma.8

There are a large number of phenotypic variants of this disorder.1,3,4 Individuals with the PiZZ variant typically have serum α1–PI levels less than 35% of the average normal level.1,5 Individuals with the Pi(null)(null) variant have undetectable α1–PI protein in their serum.1,3 Individuals with these low serum α1-PI levels, i.e., less than 11 µM, have an increased risk of developing emphysema over their lifetimes. In addition, PiSZ individuals, whose serum α1-PI levels range from approximately 9 to 23 μΜ14, are considered to have moderately increased risk for developing emphysema, regardless of whether their serum α1-PI levels are above or below 11 μΜ. Two Registry studies have shown 54% and 72% of α1-PI deficient individuals had emphysema and pulmonary symptoms such as cough, phlegm, wheeze, breathlessness, and chest colds, respectively.9,10 The risk of accelerated development and progression of emphysema in individuals with severe α1–PI deficiency is higher in smokers than in ex-smokers or non-smokers.3

Not all individuals with severe genetic variants of α1-PI deficiency have emphysema. Augmentation therapy with Alpha1-Proteinase Inhibitor (Human) is indicated only in patients with congenital α1-PI deficiency who have clinically evident emphysema.

Augmenting the levels of functional α1-proteinase inhibitor by intravenous infusion is an approach to therapy for patients with α1-PI deficiency. However, the efficacy of augmentation therapy in affecting the progression of emphysema has not been demonstrated in randomized, controlled clinical trials. The intended theoretical goal is to provide protection to the lower respiratory tract by correcting the imbalance between neutrophil elastase and protease inhibitors. Whether augmentation therapy with Aralast NP actually protects the lower respiratory tract from progressive emphysematous changes has not been evaluated. Although the maintenance of blood serum levels of α1-PI (antigenically measured) above 11 µM has been historically postulated to provide therapeutically relevant anti-neutrophil elastase protection, this has not been proven. Individuals with severe α1-PI deficiency have been shown to have increased neutrophil and neutrophil elastase concentrations in lung epithelial lining fluid compared to normal PiMM individuals, and some PiSZ individuals with α1-PI above 11 µM have emphysema attributed to α1-PI deficiency. These observations underscore the uncertainty regarding the appropriate therapeutic target serum level of α1-PI during augmentation therapy. The clinical benefit of the increased blood levels of Alpha1-Proteinase Inhibitor at the recommended dose has not been established.

The clinical efficacy of Aralast NP in influencing the course of pulmonary emphysema or the frequency, duration, or severity of pulmonary exacerbations has not been demonstrated in randomized, controlled clinical trials.

Pharmacokinetics

The pharmacokinetics of Aralast NP were compared with ARALAST in a multicenter, single-dose, randomized, double-blind, crossover clinical study (Study 460501). Twenty-five subjects with congenital α1-PI deficiency received a single intravenous (IV) infusion of 60 mg/kg Aralast NP or ARALAST. The 25 subjects in this study were between 20 and 75 years old, with a median age of 59. Plasma α1-PI concentrations were measured using an enzyme linked immunosorbent assay (ELISA). Figure 1 shows that the mean ± standard deviation (SD) plasma α1-PI concentration-time profiles after a single IV infusion of Aralast NP and ARALAST at 60 mg/kg were comparable. Table 2 summarizes the pharmacokinetic parameters of Aralast NP and ARALAST. The 90% confidence intervals for Cmax and AUC 0-inf/dose were well within the pre-defined acceptance limits of 80 to 125%.

Table 2: Mean (± SD) Pharmacokinetic Parameters of ARALAST NP and ARALAST Following a Single IV infusion of 60 mg/kg (n=25)

Parameters	Units	Aralast NP	ARALAST
Cmax	mg/mL	1.6 ± 0.3	1.7 ± 0.3
AUC0-inf/dose	days*kg/mL	0.0868 ± 0.0253	0.0920 ± 0.0238
Half-life	days	4.7 ± 2.7	4.8 ± 2.0
Clearance	mL/day	940 ± 275	862 ± 206
Vss	mL	5632 ± 2006	5618 ± 1618
Cmax = Maximum increase in plasma α1-PI concentration following infusion; AUC0-inf/dose = Area under the curve from time 0 to infinity divided by dose; Half life = terminal phase half-life determined using non-compartmental method; Vss = Volume of distribution at steady state.

A clinical study (ATC 97-01) was conducted to compare ARALAST to a commercially available preparation of α1–PI (Prolastin®, manufactured by Bayer Corporation). All subjects were to have been diagnosed as having congenital α1–PI deficiency and emphysema but no α1–PI augmentation therapy within the preceding six months.

Twenty-eight subjects were randomized to receive either ARALAST or Prolastin®, 60 mg/kg intravenously per week, for 10 consecutive weeks. Two subjects withdrew from the study prematurely: 1 subject receiving ARALAST withdrew consent after 6 infusions; 1 subject receiving Prolastin® withdrew after 1 infusion due to pneumonia following unscheduled bronchoscopy to remove a foreign body. Trough levels of α1–PI (antigenic determination) and anti–NE capacity (functional determination) were measured prior to treatment at Weeks 8 through 11. Following their first 10 weekly infusions, the subjects who were receiving Prolastin® were switched to ARALAST while those who already were receiving ARALAST continued to receive it. Maintenance of mean serum α1–PI trough levels was assessed prior to treatments at Weeks 12 through 24. Bronchoalveolar lavages (BALs) were performed on subjects at baseline and prior to treatment at Week 7. The epithelial lining fluid (ELF) from each BAL meeting acceptance criteria was analyzed for the α1–PI level and anti–NE capacity.

With weekly augmentation therapy with ARALAST or Prolastin®, a gradual increase in peak and trough serum α1–PI levels was noted, with stabilization after several weeks. The metabolic half–life of ARALAST was 5.9 days. Serum anti–NE capacity trough levels rose substantially in all subjects by Week 2, and by Week 3, serum anti–NE capacity trough levels exceeded 11 µM in the majority of subjects. With few exceptions, levels remained above this recommended threshold level in individual subjects for the duration of the period Weeks 3 through 24 on study. Although only five of fourteen subjects (35.7%) receiving ARALAST had BALs meeting acceptance criteria for analysis at both baseline and Week 7, a statistically significant increase in the antigenic level of α1–PI in the ELF was observed. No statistically significant increase in the anti-NE capacity in the ELF was detected.

Viral serology of all subjects was determined periodically throughout the study, including testing for antibodies to hepatitis A (HAV) and C (HCV), presence of circulating HBsAg, and presence of antibodies to HIV–1, HIV–2, and Parvovirus B–19. Subjects who were seronegative to parvovirus B–19 at enrollment were retested by PCR at Week 2. There were no seroconversions in subjects treated with ARALAST through Week 24. None of the subjects became HBsAg positive during the study, although five of 13 (38%) evaluable subjects treated with ARALAST and eight of 13 (62%) treated with Prolastin® had not been vaccinated to hepatitis B. No patient developed antibodies against α1–PI.

It was concluded that at a dose of 60 mg/kg administered intravenously once weekly, ARALAST and Prolastin® had similar effects in maintaining target serum α1–PI trough levels and increasing antigenic levels of α1–PI in epithelial lining fluid (ELF) with maintenance augmentation therapy.

Indications and Usage for Aralast NP

Congenital Alpha1–Proteinase Inhibitor Deficiency

Aralast NP is indicated for chronic augmentation therapy in patients having congenital deficiency of α1–PI with clinically evident emphysema. Clinical and biochemical studies have demonstrated that with such therapy, ARALAST is effective in maintaining target serum α1–PI trough levels and increasing α1–PI levels in epithelial lining fluid (ELF). Aralast NP pharmacokinetics are comparable with the pharmacokinetics of ARALAST after single-dose administration in 25 subjects with congenital deficiency of α1–PI. Clinical data demonstrating the long–term effects of chronic augmentation or replacement therapy of individuals with Aralast NP or ARALAST are not available.

The effect of augmentation therapy with Aralast NP on pulmonary exacerbations and on the progression of emphysema in alpha1-antitrypsin deficiency has not been demonstrated in randomized, controlled clinical trials.

Aralast NP is not indicated as therapy for lung disease patients in whom congenital α1–PI deficiency has not been established.

Contraindications

Aralast NP is contraindicated in IgA deficient patients with antibodies against IgA, due to the risk of severe hypersensitivity.

Warnings

Because Aralast NP is derived from pooled human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses and theoretically, the Creutzfeldt–Jakob disease (CJD) agent. Stringent procedures designed to reduce the risk of adventitious agent transmission have been employed in the manufacture of this product, from the screening of plasma donors and the collection and testing of plasma through the application of viral elimination/reduction steps such as ethanol fractionation, PEG precipitation, solvent detergent treatment, and nanofiltration. Despite these measures, such products can still potentially transmit disease; therefore, the risk of infectious agents cannot be totally eliminated. ALL infections thought by a physician possibly to have been transmitted by this product should be reported to the manufacturer at 1-800-423-2090 (US). The physician should weigh the risks and benefits of the use of this product and should discuss these with the patient.

Aralast NP may contain trace amounts of IgA. Patients with known antibodies to IgA, which can be present in patients with selective or severe IgA deficiency, have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. Aralast NP is contraindicated in patients with antibodies against IgA due to risk of severe hypersensitivity.

The rate of administration specified in DOSAGE AND ADMINISTRATION should be closely followed, at least until the physician has had sufficient experience with a given patient. Vital signs should be monitored continuously and the patient should be carefully observed throughout the infusion. IF ANAPHYLACTIC OR SEVERE ANAPHYLACTOID REACTIONS OCCUR, THE INFUSION SHOULD BE DISCONTINUED IMMEDIATELY. Epinephrine and other appropriate supportive therapy should be available for the treatment of any acute anaphylactic or anaphylactoid reaction.

Precautions

General

Aralast NP should be administered at room temperature within three (3) hours after reconstitution. Partially used vials should be discarded and not saved for future use. The solution contains no preservative.

Aralast NP should be administered alone, without mixing with other agents or diluting solutions.

Pregnancy Category C

Animal reproduction studies have not been conducted with Aralast NP. It is also not known whether Aralast NP can cause fetal harm when administered to pregnant women or can affect reproductive capacity.

Nursing Mothers

It is not known whether alpha1-proteinase inhibitor is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Aralast NP is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of Aralast NP did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. As for all patients, dosing for geriatric patients should be appropriate to their overall situation. Safety and effectiveness in patients over age 65 years of age have not been established.

Information for Patients

Inform patients that administration of Aralast NP has been demonstrated to raise the plasma level of α1-PI, but that the effect of this augmentation on the frequency of pulmonary exacerbations and on the rate of progression of emphysema has not been established by clinical trials.

Adverse Reactions

The safety of Aralast NP was evaluated with ARALAST after a single-dose IV infusion in a multicenter, randomized, double-blind, crossover clinical PK comparability study (Study 460501). The number of subjects with one or more adverse events, regardless of causality, was 23 of 25 (92%) when receiving Aralast NP and 19 of 25 (76%) when receiving ARALAST. Treatment-related adverse events were reported in 8 of 25 subjects (32%) for Aralast NP and 7 of 25 subjects (28%) for ARALAST. Of a total of 61 adverse events reported for Aralast NP, 43 (70%) were mild, 16 (26%) moderate, and 2 (3%) severe. Seventeen of 61 (28%) adverse events were deemed possibly or probably related to Aralast NP of which 14 (82%) were mild and 3 (18%) were moderate. Of a total of 60 adverse events reported for ARALAST, 45 (75%) were mild, 12 (20%) moderate, and 3 (5%) severe. Eleven of 60 (18%) adverse events were deemed possibly or probably related to ARALAST of which 8 (73%) were mild and 3 (27%) were moderate. No serious adverse events or deaths were reported in the study. No clinically significant changes in the peri-infusion vital signs (blood pressure, heart rate, or respiratory rate) were reported. The most common adverse events deemed related to Aralast NP included: headache (4 of 61 [7%] events) and musculoskeletal discomfort (4 of 61 [7%] events). These adverse events, as well as most of the other adverse events, were also reported in subjects treated with ARALAST.

In Clinical Study ATC 97-01, ARALAST was evaluated for up to 96 weeks in 27 subjects with a congenital deficiency of α1–PI and clinically evident emphysema. The number of subjects with an adverse event, regardless of causality, was 22 of 27 (81.5%). The number of subjects with an adverse event deemed possibly, probably, or definitely related to study drug was 7 of 27 (25.9%).

The frequency of infusions associated with an adverse event, regardless of causality, was 108 of 1127 (9.6%) infusions administered per protocol. The most common symptoms were pharyngitis (1.6%), headache (0.7%), and increased cough (0.6%). Symptoms of bronchitis, sinusitis, pain, rash, back pain, viral infection, peripheral edema, bloating, dizziness, somnolence, asthma, and rhinitis were each associated with ≥0.2% but < 0.6% of infusions. All symptoms were mild to moderate in severity.

The overall frequency of adverse events deemed to be possibly, probably, or definitely related to study drug was 15 of 1127 (1.3%) infusions. The most common symptoms included headache (0.3%) and somnolence (0.3%). Symptoms of chills and fever, vasodilation, dizziness, pruritus, rash, abnormal vision, chest pain, increased cough, and dyspnea were each associated with one (0.1%) infusion. Five (5) of 27 (18.5%) subjects experienced eight (8) serious adverse reactions during the study. None of these serious adverse events were considered to be causally related to the administration of ARALAST.

Twenty-six (26) of 27 (96.3%) subjects experienced a total of 94 upper and lower respiratory-tract infections during the 96-week study (median: 3.0; range: 1 to 8; mean ± SD: 3.6 ± 2.3 infections). Twenty-eight (29.8%) of the respiratory infections occurred in 19 (70.4%) subjects during the first 24 weeks of the 96-week study suggesting that the risk of infection did not change with time on ARALAST. In a post-hoc analysis, subjects experienced a range of 0 to 8 exacerbations of COPD over the 96-week study with a median of less than one exacerbation per year (median: 0.61; mean ± SD: 0.83 ± 0.87 exacerbations per year).

Treatment-emergent elevations (> two times the upper limit of normal) in aminotransferases (ALT or AST), up to 3.7 times the upper limit of normal, were noted in 3 of 27 (11.1%) subjects. Elevations were transient lasting three months or less. No subject developed any evidence of viral hepatitis or hepatitis seroconversion while being treated with ARALAST, including 13 evaluable subjects who were not vaccinated against hepatitis B.

No clinically relevant alterations in blood pressure, heart rate, respiratory rate, or body temperature occurred during infusion of ARALAST. Mean hematology and laboratory parameters were little changed over the duration of the study, with individual variations not clinically meaningful.

During the initial 10 weeks of the study, subjects were randomized to receive either ARALAST or a commercially available preparation of α1-PI (Prolastin®). The overall frequency, severity and symptomatology of adverse reactions were similar in both the ARALAST and Prolastin® groups. There were two serious adverse events in the Prolastin® group, both of which were considered to be possibly related to Prolastin®. These included chest pain, dyspnea and bilateral pulmonary infiltrates in one individual that withdrew from the study prematurely following an unscheduled bronchoscopy to remove a foreign body and the other, a positive seroconversion to Parvovirus B-19. There were no serious adverse events or seroconversions reported for the ARALAST group during the 96 week study period. No subject developed an antibody to α1–PI.

Aralast NP Dosage and Administration

Dose ranging studies using efficacy endpoints have not been performed.

Chronic Augmentation Therapy

FOR INTRAVENOUS USE ONLY. The recommended dosage of Aralast NP is 60 mg/kg body weight administered once weekly by intravenous infusion. Each vial of Aralast NP has the functional activity, as determined by inhibition of porcine pancreatic elastase, stated on the label. Administration of Aralast NP within three hours after reconstitution is recommended to avoid the potential ill effect of any inadvertent microbial contamination occurring during reconstitution. Discard any unused contents.

Infusion Rate

Aralast NP should be administered at a rate not exceeding 0.08 mL/kg body weight/minute. If adverse events occur, the rate should be reduced or the infusion interrupted until the symptoms subside. The infusion may then be resumed at a rate tolerated by the subject.

RECONSTITUTION

Use Aseptic Technique

1. Aralast NP and diluent should be at room temperature before reconstitution.

2. Remove caps from the diluent and product vials.

3. Swab the exposed stopper surfaces with alcohol.

4.Open the package of the BAXJECT II Hi-Flow device by peeling away the lid without touching the inside contents. (Fig. A). Do not remove the transfer system from the package. Do not touch the clear spike.

5. Turn the package over and insert the clear plastic spike through the diluent vial by pressing straight down (Fig B).

6. Grip the BAXJECT II Hi-Flow package at the edges and pull the package off the device
(Fig. C). Do not remove the blue protective cap from the BAXJECT II Hi-Flow device. Do not touch the purple spike.

7. Turn the system over so that the diluent vial is on top. Press the purple spike of the BAXJECT II Hi-Flow device into the Aralast NP vial. The vacuum will draw the diluent into the Aralast NP vial. (Fig. D).

8. Let the vial stand until most of the contents is in solution, then GENTLY swirl until the powder is completely dissolved. Reconstitution requires no more than five minutes for a 0.5 gram vial and no more than 10 minutes for a 1.0 gram vial.

9. DO NOT SHAKE THE CONTENTS OF THE VIAL. DO NOT INVERT THE VIAL UNTIL READY TO WITHDRAW CONTENTS

10. Use within three hours of reconstitution.

1. After reconstituting the product as described under Reconstitution, inspect parenteral drug products visually for particulate matter and discoloration prior to administration. The reconstituted product should be a colorless or slightly yellowish to yellowish-green solution and be essentially free of visible particles.
2. Remove the blue protective cap from the BAXJECT II Hi-Flow device. Connect the syringe to the BAXJECT II Hi-Flow device (DO NOT DRAW AIR INTO THE SYRINGE) (Fig. E).
3. Invert the system (with the Aralast NP concentrate vial on top). Draw the dissolved product into the syringe by pulling the plunger back SLOWLY(Fig. F).
4. Disconnect the syringe. Reconstituted product from several vials may be pooled into an empty, sterile IV solution container by using aseptic technique.

How is Aralast NP Supplied

Aralast NP is supplied as a sterile, non-pyrogenic, lyophilized powder in single–dose vials. The following product packages are available:

Fill Size	NDC
0.5 g	0944-2812-01
1 g	0944-2822-02

Aralast NP is packaged with a suitable volume of Sterile Water for Injection, USP diluent (25 mL/0.5 g vial; 50 mL/1 g vial), one BAXJECT II Hi-Flow Needleless Transfer Device and one package insert..

STORAGE

Aralast NP should be stored at temperatures not to exceed 25°C (77°F). Do not freeze. Do not use after the expiration date printed on the label.

FDA批准Aralast治疗ALP1缺乏引起的肺气肿

Alphatherapeutic公司与百特公司1月9日联合宣布，FDA已批准Alpha公司开发的α—1蛋白酶抑制剂Aralast作为增补疗法（augmentarytherapy）治疗先天性α—1蛋白酶抑制剂缺乏,且临床上已显示出肺气肿症状的患者。百特公司被指定为Aralast的独家分销商。　　

α—1蛋白酶（ALP1）抑制剂缺乏（有时又称做抗胰蛋白酶缺乏）常导致先天性肺气肿，患有这种病症的病人肝内产生的α—1蛋白酶水平减少，α—1蛋白酶主要用于保护肺组织免受白细胞释放的酶的破坏。如果ALP1缺乏，病人的肺则易受到破坏，受到影响的个体常在30岁或40岁时出现肺病的各种症状。　
　
如果ALP1缺乏的患者得不到及时治疗，最终常会导致肺气肿和早年死亡，而且这种疾病常被误诊为哮喘或慢性阻塞性肺病。　
　
ALP1缺乏可通过增补疗法进行治疗，患者每周接受一次由血浆制成的α—1蛋白酶抑制剂。只是增补疗法既不能治愈也不能逆转已形成的肺损伤,但它可防止肺进一步受损，有助于疾病的早期诊断和治疗。另外这种疗法对于通常的肺气肿无效，只能用于那些先天性α—1蛋白酶缺乏的患者。
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原产地英文商品名:
ARALAST NP 1G/50ML/VIAL
原产地英文药品名:
ALPHA-1-PROTEINASE INHIBITOR
中文参考商品译名:
ARALAST NP 1克/50毫升/瓶
中文参考药品译名:
α1-蛋白酶抑制剂
生产厂家中文参考译名:
美国百特
生产厂家英文名:
Baxter Healthcare Corporation

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原产地英文商品名:
ARALAST NP 0.5G/25ML/VIAL
原产地英文药品名:
ALPHA-1-PROTEINASE INHIBITOR
中文参考商品译名:
ARALAST NP 0.5克/25毫升/瓶
中文参考药品译名:
α1-蛋白酶抑制剂
生产厂家中文参考译名:
美国百特
生产厂家英文名:
Baxter Healthcare Corporation