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 >> 上市新药 >> XOLAIR(omalizumab Solution for Injection)奥马珠单抗

XOLAIR(omalizumab Solution for Injection)奥马珠单抗

2015-02-13 03:42:38  作者:新特药房  来源:互联网  浏览次数:294  文字大小:【】【】【
简介: 2014年3月21日,欧盟(EC)批准Xolair®(奥马珠单抗)用于H1抗组胺剂治疗应答不充分的成人和青少年(12岁及以上)慢性自发性荨麻疹(CSU)患者的辅助治疗。批准剂量为300mg,每四周皮下注射一次。批准新 ...

2014年3月21日,欧盟(EC)批准Xolair®(奥马珠单抗)用于H1抗组胺剂治疗应答不充分的成人和青少年(12岁及以上)慢性自发性荨麻疹(CSU)患者的辅助治疗。批准剂量为300mg,每四周皮下注射一次。
批准新适应证: 2014年3月21日:公司:Genentech
注射用XOLAIR(奥马珠单抗[omalizumab]),供皮下使用
适应证和用途
Xolair是一种抗-IgE抗体适用为:
⑴ 用皮试阳性或体外对常年吸入性过敏原反应性和症状用吸入性皮质激素控制不佳中度至严重持续性哮喘的患者。
⑵ 尽管H1抗组织胺治疗仍保留症状性的慢性特发性荨麻疹成年和青少年(12岁和以上)。
使用的重要限制:
⑴ 不适用为其他过敏性疾病或其他型式的荨麻疹。
⑵ 不适用为急性支气管痉挛或哮喘持续状态。
⑶ 不适用为小于12岁儿童患者。
剂量和给药方法
只为皮下(SC)给予。
超过150mg时分剂量多于一个注射部位以限制每个部位不超过150mg。
⑴ 过敏性哮喘:Xolair 150至375 mg SC每2或4周。通过治疗开始前测量血清总IgE水平(IU/mL) 和体重(kg)确定剂量(mg)和给药频数。见剂量测定图表。
⑵ 慢性特发性荨麻疹(Chronic idiopathic urticaria):Xolair 150或300mg SC每4周。在CIU中给药不依赖于血清IgE水平或体重。
剂型和规格
在单次使用5mL小瓶中150mg冻干无菌粉。
禁忌证
对Xolair或Xolair的任何成分严重超敏反应。
警告和注意事项
⑴ 过敏性反应—只在卫生保健情况给予准备处理可能是危及生命过敏性反应和给药后观察患者适当时间。
⑵ 恶性病—在临床研究中曾观察到恶性病。
⑶ 急性哮喘症状—急性支气管痉挛或哮喘持续状态不要使用治疗。
⑷ 皮质激素类减量—Xolair治疗开始不要突然终止皮质激素。
⑸ 发热,关节痛,和皮疹—如患者发生相似于血清病体征和症状停止Xolair。
⑹ 嗜酸性情况—警戒嗜酸粒细胞增多,血管炎性皮疹,肺部症状恶化,心脏并发症,和/或神经病变,特别是口服皮质激素减少时。
不良反应
⑴ 过敏性哮喘:最常见不良反应(在Xolair-治疗患者中较频≥1%)在临床研究是关节痛,疼痛(一般性),腿痛,疲劳,眩晕,骨折,手臂疼痛,瘙痒,皮炎,和耳痛。
⑵ 慢性特发性荨麻疹:最常见不良事件(≥2% Xolair-治疗患者和比安慰剂更频)包括以下:恶心,鼻咽炎,窦炎,上呼吸道感染,病毒性上呼吸道感染,关节痛,头痛,和咳嗽。
药物相互作用
未进行正式药物相互作用研究。


Xolair 150mg Solution for Injection
1. Name of the medicinal product
Xolair® 150 mg solution for injection
Omalizumab
2. Qualitative and quantitative composition
Each pre-filled syringe of 1 ml solution contains 150 mg of omalizumab*.
*Omalizumab is a humanised monoclonal antibody manufactured by recombinant DNA technology in a Chinese hamster ovary (CHO) mammalian cell line.
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Solution for injection.
Clear to opalescent, slightly yellow to brown solution.
4. Clinical particulars
4.1 Therapeutic indications
Allergic asthma
Xolair is indicated in adults, adolescents and children (6 to <12 years of age).
Xolair treatment should only be considered for patients with convincing IgE (immunoglobulin E) mediated asthma (see section 4.2).
Adults and adolescents (12 years of age and older)
Xolair is indicated as add-on therapy to improve asthma control in patients with severe persistent allergic asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and who have reduced lung function (FEV1 <80%) as well as frequent daytime symptoms or night-time awakenings and who have had multiple documented severe asthma exacerbations despite daily high-dose inhaled corticosteroids, plus a long-acting inhaled beta2-agonist.
Children (6 to <12 years of age)
Xolair is indicated as add-on therapy to improve asthma control in patients with severe persistent allergic asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and frequent daytime symptoms or night-time awakenings and who have had multiple documented severe asthma exacerbations despite daily high-dose inhaled corticosteroids, plus a long-acting inhaled beta2-agonist.
Chronic spontaneous urticaria (CSU)
Xolair is indicated as add-on therapy for the treatment of chronic spontaneous urticaria in adult and adolescent (12 years and above) patients with inadequate response to H1 antihistamine treatment.
4.2 Posology and method of administration
Xolair treatment should be initiated by physicians experienced in the diagnosis and treatment of severe persistent asthma or chronic spontaneous urticaria.
Allergic asthma
Posology
The appropriate dose and frequency of Xolair is determined by baseline IgE (IU/ml), measured before the start of treatment, and body weight (kg). Prior to administration of the initial dose, patients should have their IgE level determined by any commercial serum total IgE assay for their dose assignment. Based on these measurements, 75 to 600 mg of Xolair in 1 to 4 injections may be needed for each administration.
Patients with IgE lower than 76 IU/ml were less likely to experience benefit (see section 5.1). Prescribing physicians should ensure that adult and adolescent patients with IgE below 76 IU/ml and children (6 to < 12 years of age) with IgE below 200 IU/ml have unequivocal in vitro reactivity (RAST) to a perennial allergen before starting therapy.
See Table 1 for a conversion chart and Tables 2 and 3 for the dose determination charts in adults, adolescents and children (6 to <12 years of age).
Patients whose baseline IgE levels or body weight in kilograms are outside the limits of the dose table should not be given Xolair.
The maximum recommended dose is 600 mg omalizumab every two weeks.
Table 1: Conversion from dose to number of syringes, number of injections and total injection volume for each administration

Dose (mg)

Number of syringes

Number of injections

Total injection volume (ml)

75 mg

150 mg

75

1

0

1

0.5

150

0

1

1

1.0

225

1

1

2

1.5

300

0

2

2

2.0

375

1

2

3

2.5

450

0

3

3

3.0

525

1

3

4

3.5

600

0

4

4

4.0

Table 2: ADMINISTRATION EVERY 4 WEEKS. Xolair doses (milligrams per dose) administered by subcutaneous injection every 4 weeks

Body weight (kg)

Baseline IgE (IU/ml)

≥20-25

>25-30

>30-40

>40-50

>50-60

>60-70

>70-80

>80-90

>90-125

>125-150

≥30-100

75

75

75

150

150

150

150

150

300

300

>100-200

150

150

150

300

300

300

300

300

450

600

>200-300

150

150

225

300

300

450

450

450

600

 

>300-400

225

225

300

450

450

450

600

600

 

 

>400-500

225

300

450

450

600

600

 

 

 

 

>500-600

300

300

450

600

600

 

 

 

 

 

>600-700

300

 

450

600

 

 

 

 

 

 

>700-800

 

 

 

 

 

 

 

 

 

 

>800-900

 

 

 

 

ADMINISTRATION EVERY 2 WEEKS

SEE TABLE 3

Table 3: ADMINSTRATION EVERY 2 WEEKS. Xolair doses (milligrams per dose) administered by subcutaneous injection every 2 weeks

Body weight (kg)

Baseline IgE (IU/ml)

≥20-25

>25-30

>30-40

>40-50

>50-60

>60-70

>70-80

>80-90

>90-125

>125-150

≥30-100

ADMINISTRATION EVERY 4 WEEKS

SEE TABLE 2

 

 

 

 

 

>100-200

 

 

 

 

 

>200-300

 

 

 

 

 

 

 

 

 

375

>300-400

 

 

 

 

 

 

 

 

450

525

>400-500

 

 

 

 

 

 

375

375

525

600

>500-600

 

 

 

 

 

375

450

450

600

 

>600-700

 

225

 

 

375

450

450

525

 

 

>700-800

225

225

300

375

450

450

525

600

 

 

>800-900

225

225

300

375

450

525

600

 

 

 

>900-1000

225

300

375

450

525

600

 

 

 

 

>1000-1100

225

300

375

450

600

 

 

 

 

 

>1100-1200

300

300

450

525

600

DO NOT ADMINISTER– data is unavailable for dose recommendation

>1200-1300

300

375

450

525

 

 

 

 

 

 

>1300-1500

300

375

525

600

 

Treatment duration, monitoring and dose adjustments
Xolair is intended for long-term treatment. Clinical trials have demonstrated that it takes at least 12-16 weeks for Xolair treatment to show effectiveness. At 16 weeks after commencing Xolair therapy patients should be assessed by their physician for treatment effectiveness before further injections are administered. The decision to continue Xolair following the 16-week timepoint, or on subsequent occasions, should be based on whether a marked improvement in overall asthma control is seen (see section 5.1, Physician's overall assessment of treatment effectiveness).
Discontinuation of Xolair treatment generally results in a return to elevated free IgE levels and associated symptoms. Total IgE levels are elevated during treatment and remain elevated for up to one year after the discontinuation of treatment. Therefore, re-testing of IgE levels during Xolair treatment cannot be used as a guide for dose determination. Dose determination after treatment interruptions lasting less than one year should be based on serum IgE levels obtained at the initial dose determination. Total serum IgE levels may be re-tested for dose determination if treatment with Xolair has been interrupted for one year or more.
Doses should be adjusted for significant changes in body weight (see Tables 2 and 3).
Chronic spontaneous urticaria (CSU)
Posology
The recommended dose is 300 mg by subcutaneous injection every four weeks.
Prescribers are advised to periodically reassess the need for continued therapy.
Clinical trial experience of long-term treatment beyond 6 months in this indication is limited.
Special populations
Elderly (65 years of age and older)
There are limited data available on the use of Xolair in patients older than 65 years but there is no evidence that elderly patients require a different dose from younger adult patients.
Renal or hepatic impairment
There have been no studies on the effect of impaired renal or hepatic function on the pharmacokinetics of omalizumab. Because omalizumab clearance at clinical doses is dominated by the reticular endothelial system (RES) it is unlikely to be altered by renal or hepatic impairment. While no particular dose adjustment is recommended for these patients, Xolair should be administered with caution (see section 4.4).
Paediatric population
In allergic asthma, the safety and efficacy of Xolair in paediatric patients below the age of 6 years have not been established. No data are available.
In CSU, the safety and efficacy of Xolair in paediatric patients below the age of 12 years have not been established.
Method of administration
For subcutaneous administration only. Do not administer by the intravenous or intramuscular route.
The injections are administered subcutaneously in the deltoid region of the arm. Alternatively, the injections can be administered in the thigh if there is any reason precluding administration in the deltoid region.
There is limited experience with self-administration of Xolair. Therefore treatment is intended to be administered by a healthcare provider only (see section 6.6 and also information for the healthcare professional section of the package leaflet).
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
General
Xolair is not indicated for the treatment of acute asthma exacerbations, acute bronchospasm or status asthmaticus.
Xolair has not been studied in patients with hyperimmunoglobulin E syndrome or allergic bronchopulmonary aspergillosis or for the prevention of anaphylactic reactions, including those provoked by food allergy, atopic dermatitis, or allergic rhinitis. Xolair is not indicated for the treatment of these conditions.
Xolair therapy has not been studied in patients with autoimmune diseases, immune complex-mediated conditions, or pre-existing renal or hepatic impairment (see section 4.2). Caution should be exercised when administering Xolair in these patient populations.
Abrupt discontinuation of systemic or inhaled corticosteroids after initiation of Xolair therapy is not recommended. Decreases in corticosteroids should be performed under the direct supervision of a physician and may need to be performed gradually.
Immune system disorders
• Allergic reactions type I
Type I local or systemic allergic reactions, including anaphylaxis and anaphylactic shock, may occur when taking omalizumab, also with onset after a long duration of treatment. Most of these reactions occurred within 2 hours after the first and subsequent injections of Xolair but some started beyond 2 hours and even beyond 24 hours after the injection. Therefore medicinal products for the treatment of anaphylactic reactions should always be available for immediate use following administration of Xolair. Patients should be informed that such reactions are possible and prompt medical attention should be sought if allergic reactions occur.
Anaphylactic reactions were rare in clinical trials (see section 4.8).
Antibodies to omalizumab have been detected in a low number of patients in clinical trials (see section 4.8). The clinical relevance of anti-Xolair antibodies is not well understood.
• Serum sickness
Serum sickness and serum sickness-like reactions, which are delayed allergic type III reactions, have been seen in patients treated with humanised monoclonal antibodies including omalizumab. The suggested pathophysiologic mechanism includes immune-complex formation and deposition due to development of antibodies against omalizumab. The onset has typically been 1-5 days after administration of the first or subsequent injections, also after long duration of treatment. Symptoms suggestive of serum sickness include arthritis/arthralgias, rash (urticaria or other forms), fever and lymphadenopathy. Antihistamines and corticosteroids may be useful for preventing or treating this disorder, and patients should be advised to report any suspected symptoms.
• Churg-Strauss syndrome and hypereosinophilic syndrome
Patients with severe asthma may rarely present systemic hypereosinophilic syndrome or allergic eosinophilic granulomatous vasculitis (Churg-Strauss syndrome), both of which are usually treated with systemic corticosteroids.
In rare cases, patients on therapy with anti-asthma medicinal products, including omalizumab, may present or develop systemic eosinophilia and vasculitis. These events are commonly associated with the reduction of oral corticosteroid therapy.
In these patients, physicians should be alert to the development of marked eosinophilia, vasculitic rash, worsening pulmonary symptoms, paranasal sinus abnormalities, cardiac complications, and/or neuropathy.
Discontinuation of omalizumab should be considered in all severe cases with the above mentioned immune system disorders.
Parasitic (helminth) infections
IgE may be involved in the immunological response to some helminth infections. In patients at chronic high risk of helminth infection, a placebo-controlled trial in allergic patients showed a slight increase in infection rate with omalizumab, although the course, severity, and response to treatment of infection were unaltered. The helminth infection rate in the overall clinical programme, which was not designed to detect such infections, was less than 1 in 1,000 patients. However, caution may be warranted in patients at high risk of helminth infection, in particular when travelling to areas where helminthic infections are endemic. If patients do not respond to recommended anti-helminth treatment, discontinuation of Xolair should be considered.
Latex-sensitive individuals
The removable needle cap of this pre-filled syringe contains a derivative of natural rubber latex. No natural rubber latex has to date been detected in the removable needle cap. Nevertheless, the use of Xolair solution for injection in pre-filled syringe in latex-sensitive individuals has not been studied and thus there is a potential risk for hypersensitivity reactions which cannot be completely ruled out.
4.5 Interaction with other medicinal products and other forms of interaction
Cytochrome P450 enzymes, efflux pumps and protein-binding mechanisms are not involved in the clearance of omalizumab; thus, there is little potential for drug-drug interactions. Medicinal product or vaccine interaction studies have not been performed with Xolair. There is no pharmacological reason to expect that commonly prescribed medicinal products used in the treatment of asthma or CSU will interact with omalizumab.
Allergic asthma
In clinical studies Xolair was commonly used in conjunction with inhaled and oral corticosteroids, inhaled short-acting and long-acting beta agonists, leukotriene modifiers, theophyllines and oral antihistamines. There was no indication that the safety of Xolair was altered with these other commonly used anti-asthma medicinal products. Limited data are available on the use of Xolair in combination with specific immunotherapy (hypo-sensitisation therapy). In a clinical trial where Xolair was co-administered with immunotherapy, the safety and efficacy of Xolair in combination with specific immunotherapy were found to be no different to that of Xolair alone.
Xolair may indirectly reduce the efficacy of medicinal products for the treatment of helminthic or other parasitic infections (see section 4.4).
Chronic spontaneous urticaria (CSU)
In clinical studies in CSU, Xolair was used in conjunction with antihistamines (anti-H1, anti-H2) and leukotriene receptor antagonists (LTRAs). There was no evidence that the safety of omalizumab was altered when used with these medicinal products relative to its known safety profile in allergic asthma. In addition, a population pharmacokinetic analysis showed no relevant effect of H2 antihistamines and LTRAs on omalizumab pharmacokinetics (see section 5.2).
Paediatric population
Clinical studies in CSU included some patients aged 12 to 17 years taking Xolair in conjunction with antihistamines (anti-H1, anti-H2) and LTRAs. No studies have been performed in children under 12 years.
4.6 Fertility, pregnancy and lactation
Pregnancy
There are limited data from the use of omalizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). Omalizumab crosses the placental barrier and the potential for harm to the foetus is unknown. Omalizumab has been associated with age-dependent decreases in blood platelets in non-human primates, with a greater relative sensitivity in juvenile animals (see section 5.3). Xolair should not be used during pregnancy unless clearly necessary.
Breast-feeding
It is unknown whether omalizumab is excreted in human milk. Available pharmacodynamics/toxicological data in non-human primates have shown excretion of omalizumab into milk. A risk to the newborns/infants cannot be excluded. Omalizumab should not be given during breast-feeding.
Fertility
There are no human fertility data for omalizumab. In specifically-designed non-clinical fertility studies, including mating studies, no impairment of male or female fertility was observed following repeated dosing with omalizumab at dose levels up to 75 mg/kg. Furthermore, no genotoxic effects were observed in separate non-clinical genotoxicity studies (see section 5.3).
4.7 Effects on ability to drive and use machines
Xolair has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
Allergic asthma
Over 4,400 allergic asthma patients were randomised in controlled efficacy trials with Xolair.
During clinical trials in adult and adolescent patients 12 years of age and older, the most commonly reported adverse reactions were injection site reactions, including injection site pain, swelling, erythema, pruritus and headaches. In clinical trials in children 6 to <12 years of age, the most commonly reported adverse reactions suspected of being related to the medicinal product were headache, pyrexia and upper abdominal pain. Most of the reactions were mild or moderate in severity.
Table 4 lists the adverse reactions recorded in clinical studies in the total safety population treated with Xolair by MedDRA system organ class and frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequency categories are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000). Reactions reported in the post-marketing setting are listed with frequency not known (cannot be estimated from the available data).
Table 4: Adverse reactions in allergic asthma

Infections and infestations

Uncommon

Pharyngitis

Rare

Parasitic infection

Blood and lymphatic system disorders

Not known

Idiopathic thrombocytopenia, including severe cases

Immune system disorders

Rare

Anaphylactic reaction, other serious allergic conditions, anti-omalizumab antibody development

Not known

Serum sickness, may include fever and lymphadenopathy

Nervous system disorders

Common

Headache*

Uncommon

Syncope, paraesthesia, somnolence, dizziness

Vascular disorders

Uncommon

Postural hypotension, flushing

Respiratory, thoracic and mediastinal disorders

Uncommon

Allergic bronchospasm, coughing

Rare

Laryngoedema

Not known

Allergic granulomatous vasculitis (i.e. Churg-Strauss syndrome)

Gastrointestinal disorders

Common

Abdominal pain upper**

Uncommon

Dyspeptic signs and symptoms, diarrhoea, nausea

Skin and subcutaneous tissue disorders

Uncommon

Photosensitivity, urticaria, rash, pruritus

Rare

Angioedema

Not known

Alopecia

Musculoskeletal and connective tissue disorders

Not known

Arthralgia, myalgia, joint swelling

General disorders and administration site conditions

Very common

Pyrexia**

Common

Injection site reactions such as swelling, erythema, pain, pruritus

Uncommon

Influenza-like illness, swelling arms, weight increase, fatigue

*: Very common in children 6 to <12 years of age
**: In children 6 to <12 years of age
Chronic spontaneous urticaria (CSU)
The safety and tolerability of omalizumab were investigated with doses of 75 mg, 150 mg and 300 mg every four weeks in 975 CSU patients, 242 of whom received placebo. Overall, 733 patients were treated with omalizumab for up to 12 weeks and 490 patients for up to 24 weeks. Of those, 412 patients were treated for up to 12 weeks and 333 patients were treated for up to 24 weeks at the 300 mg dose.
A separate table (Table 5) shows the adverse reactions for the CSU indication resulting from differences in dosages and treatment populations (with significantly different risk factors, comorbidities, co-medications and ages [e.g. asthma trials included children from 6-12 years of age]).
Table 5 lists the adverse reactions (events occurring in ≥1% of patients in any treatment group and ≥2% more frequently in any omalizumab treatment group than with placebo (after medical review)) reported with 300 mg in the three pooled phase III studies. The adverse reactions presented are divided into two groups: those identified in the 12-week and the 24-week treatment periods.
The adverse reactions are listed by MedDRA system organ class. Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions listed first. The corresponding frequency category for each adverse reaction is based on the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000) and not known (cannot be estimated from the available data).
Table 5: Adverse reactions from the pooled CSU safety database (day 1 to week 24) at 300 mg omalizumab

12-Week

Omalizumab studies 1, 2 and 3 Pooled

Frequency category

Placebo N=242

300 mg N=412

 

Infections and infestations

Sinusitis

5 (2.1%)

20 (4.9%)

Common

Nervous system disorders

Headache

7 (2.9%)

25 (6.1%)

Common

Musculoskeletal and connective tissue disorders

Arthralgia

1 (0.4%)

12 (2.9%)

Common

General disorder and administration site conditions

Injection site reaction*

2 (0.8%)

11 (2.7%)

Common

24-Week

Omalizumab studies 1 and 3 Pooled

Frequency category

Placebo N=163

300 mg N=333

 

Infections and infestations

Upper respiratory tract infection

5 (3.1%)

19 (5.7%)

Common

* Despite not showing a 2% difference to placebo, injection site reactions were included as all cases were assessed causally related to study treatment.
Description of safety aspects of special interest pertinent to allergic asthma and CSU indications
No relevant data was obtained in clinical studies in CSU that would require a modification of the sections below.
Immune system disorders
For further information, see section 4.4.
Arterial thromboembolic events (ATE)
In controlled clinical trials and during interim analyses of an observational study, a numerical imbalance of ATE was observed. ATE included stroke, transient ischaemic attack, myocardial infarction, unstable angina, and cardiovascular death (including death from unknown cause). In the final analysis of the observational study, the rate of ATE per 1,000 patient years was 7.52 (115/15,286 patient years) for Xolair-treated patients and 5.12 (51/9,963 patient years) for control patients. In a multivariate analysis controlling for available baseline cardiovascular risk factors, the hazard ratio was 1.32 (95% confidence interval 0.91-1.91). In a new analysis of pooled clinical trials, which included all randomised double-blind, placebo-controlled clinical trials lasting 8 or more weeks, the rate of ATE per 1,000 patient years was 2.69 (5/1,856 patient years) for Xolair-treated patients and 2.38 (4/1,680 patient years) for placebo patients (rate ratio 1.13, 95% confidence interval 0.24-5.71).
Platelets
In clinical trials few patients had platelet counts below the lower limit of the normal laboratory range. None of these changes were associated with bleeding episodes or a decrease in haemoglobin. No pattern of persistent decrease in platelet counts, as observed in non-human primates (see section 5.3), has been reported in humans (patients above 6 years of age), even though isolated cases of idiopathic thrombocytopenia, including severe cases, have been reported in the post-marketing setting.
Parasitic infections
In allergic patients at chronic high risk of helminth infection, a placebo-controlled trial showed a slight numerical increase in infection rate with omalizumab that was not statistically significant. The course, severity, and response to treatment of infections were unaltered (see section 4.4).
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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
Maximum tolerated dose of Xolair has not been determined. Single intravenous doses up to 4,000 mg have been administered to patients without evidence of dose-limiting toxicities. The highest cumulative dose administered to patients was 44,000 mg over a 20-week period and this dose did not result in any untoward acute effects.
If an overdose is suspected, the patient should be monitored for any abnormal signs or symptoms. Medical treatment should be sought and instituted appropriately.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Drugs for obstructive airway diseases, other systemic drugs for obstructive airway diseases, ATC code: R03DX05
Omalizumab is a recombinant DNA-derived humanised monoclonal antibody that selectively binds to human immunoglobulin E (IgE). The antibody is an IgG1 kappa that contains human framework regions with the complementary-determining regions of a murine parent antibody that binds to IgE.
Allergic asthma
Omalizumab binds to IgE and prevents binding of IgE to FCεRI (high-affinity IgE receptor) on basophils and mast cells, thereby reducing the amount of free IgE that is available to trigger the allergic cascade. Treatment of atopic subjects with omalizumab resulted in a marked down-regulation of FCεRI receptors on basophils.
Furthermore, the in vitro histamine release from basophils isolated from Xolair-treated subjects was reduced by approximately 90% following stimulation with an allergen compared to pre-treatment values.
In clinical studies in allergic asthma patients, serum free IgE levels were reduced in a dose-dependent manner within one hour following the first dose and maintained between doses. One year after discontinuation of Xolair dosing, the IgE levels had returned to pre-treatment levels with no observed rebound in IgE levels after washout of the medicinal product.
Chronic spontaneous urticaria (CSU)
Omalizumab binds to IgE and lowers free IgE levels. Subsequently, IgE receptors (FcεRI) on cells down-regulate. It is not entirely understood how this results in an improvement of CSU symptoms.
In clinical studies in CSU patients, maximum suppression of free IgE was observed 3 days after the first subcutaneous dose. After repeated dosing once every 4 weeks, pre-dose serum free IgE levels remained stable between 12 and 24 weeks of treatment. After discontinuation of Xolair, free IgE levels increased towards pre-treatment levels over a 16-week treatment-free follow-up period.
Clinical experience in allergic asthma
Adults and adolescents ≥12 years of age
The efficacy and safety of Xolair were demonstrated in a 28-week double-blind placebo-controlled study (study 1) involving 419 severe allergic asthmatics, ages 12-79 years, who had reduced lung function (FEV1 40-80% predicted) and poor asthma symptom control despite receiving high dose inhaled corticosteroids and a long-acting beta2-agonist. Eligible patients had experienced multiple asthma exacerbations requiring systemic corticosteroid treatment or had been hospitalised or attended an emergency room due to a severe asthma exacerbation in the past year despite continuous treatment with high-dose inhaled corticosteroids and a long-acting beta2-agonist. Subcutaneous Xolair or placebo were administered as add-on therapy to >1,000 micrograms beclomethasone dipropionate (or equivalent) plus a long-acting beta2-agonist. Oral corticosteroid, theophylline and leukotriene-modifier maintenance therapies were allowed (22%, 27%, and 35% of patients, respectively).
The rate of asthma exacerbations requiring treatment with bursts of systemic corticosteroids was the primary endpoint. Omalizumab reduced the rate of asthma exacerbations by 19% (p = 0.153). Further evaluations which did show statistical significance (p<0.05) in favour of Xolair included reductions in severe exacerbations (where patient's lung function was reduced to below 60% of personal best and requiring systemic corticosteroids) and asthma-related emergency visits (comprised of hospitalisations, emergency room, and unscheduled doctor visits), and improvements in Physician's overall assessment of treatment effectiveness, Asthma-related Quality of Life (AQL), asthma symptoms and lung function.
In a subgroup analysis, patients with pre-treatment total IgE ≥76 IU/ml were more likely to experience clinically meaningful benefit to Xolair. In these patients in study 1 Xolair reduced the rate of asthma exacerbations by 40% (p = 0.002). In addition more patients had clinically meaningful responses in the total IgE ≥76 IU/ml population across the Xolair severe asthma programme. Table 6 includes results in the study 1 population.
Table 6: Results of study 1

Whole study 1 population

Xolair

N=209

Placebo

N=210

Asthma exacerbations

Rate per 28-week period

0.74

0.92

% reduction, p-value for rate ratio

19.4%, p = 0.153

Severe asthma exacerbations

Rate per 28-week period

0.24

0.48

% reduction, p-value for rate ratio

50.1%, p = 0.002

Emergency visits

Rate per 28-week period

0.24

0.43

% reduction, p-value for rate ratio

43.9%, p = 0.038

Physician's overall assessment

% responders*

60.5%

42.8%

p-value**

<0.001

AQL improvement

% of patients ≥0.5 improvement

60.8%

47.8%

p-value

0.008

* marked improvement or complete control
** p-value for overall distribution of assessment
Study 2 assessed the efficacy and safety of Xolair in a population of 312 severe allergic asthmatics which matched the population in study 1. Treatment with Xolair in this open label study led to a 61% reduction in clinically significant asthma exacerbation rate compared to current asthma therapy alone.
Four additional large placebo-controlled supportive studies of 28 to 52 weeks duration in 1,722 adults and adolescents (studies 3, 4, 5, 6) assessed the efficacy and safety of Xolair in patients with severe persistent asthma. Most patients were inadequately controlled but were receiving less concomitant asthma therapy than patients in studies 1 or 2. Studies 3-5 used exacerbation as primary endpoint, whereas study 6 primarily evaluated inhaled corticosteroid sparing.
In studies 3, 4 and 5 patients treated with Xolair had respective reductions in asthma exacerbation rates of 37.5% (p = 0.027), 40.3% (p<0.001) and 57.6% (p<0.001) compared to placebo.
In study 6, significantly more severe allergic asthma patients on Xolair were able to reduce their fluticasone dose to ≤500 micrograms/day without deterioration of asthma control (60.3%) compared to the placebo group (45.8%, p<0.05).
Quality of life scores were measured using the Juniper Asthma-related Quality of Life Questionnaire. For all six studies there was a statistically significant improvement from baseline in quality of life scores for Xolair patients versus the placebo or control group.
Physician's overall assessment of treatment effectiveness:
Physician's overall assessment was performed in five of the above studies as a broad measure of asthma control performed by the treating physician. The physician was able to take into account PEF (peak expiratory flow), day and night time symptoms, rescue medication use, spirometry and exacerbations. In all five studies a significantly greater proportion of Xolair treated patients were judged to have achieved either a marked improvement or complete control of their asthma compared to placebo patients.
Children 6 to <12 years of age
The primary support for safety and efficacy of Xolair in the group aged 6 to <12 years comes from one randomised, double-blind, placebo-controlled, multi-centre trial (study 7).
Study 7 was a placebo-controlled trial which included a specific subgroup (n=235) of patients as defined in the present indication, who were treated with high-dose inhaled corticosteroids (≥500 µg/day fluticasone equivalent) plus long-acting beta agonist.
A clinically significant exacerbation was defined as a worsening of asthma symptoms as judged clinically by the investigator, requiring doubling of the baseline inhaled corticosteroid dose for at least 3 days and/or treatment with rescue systemic (oral or intravenous) corticosteroids for at least 3 days.
In the specific subgroup of patients on high dose inhaled corticosteroids, the omalizumab group had a statistically significantly lower rate of clinically significant asthma exacerbations than the placebo group. At 24 weeks, the difference in rates between treatment groups represented a 34% (rate ratio 0.662, p = 0.047) decrease relative to placebo for omalizumab patients. In the second double-blind 28-week treatment period the difference in rates between treatment groups represented a 63% (rate ratio 0.37, p<0.001) decrease relative to placebo for omalizumab patients.
During the 52-week double-blind treatment period (including the 24-week fixed-dose steroid phase and the 28-week steroid adjustment phase) the difference in rates between treatment groups represented a 50% (rate ratio 0.504, p<0.001) relative decrease in exacerbations for omalizumab patients.
The omalizumab group showed greater decreases in beta-agonist rescue medication use than the placebo group at the end of the 52-week treatment period, although the difference between treatment groups was not statistically significant. For the global evaluation of treatment effectiveness at the end of the 52-week double-blind treatment period in the subgroup of severe patients on high-dose inhaled corticosteroids plus long-acting beta agonists, the proportion of patients rated as having 'excellent' treatment effectiveness was higher, and the proportions having 'moderate' or 'poor' treatment effectiveness lower in the omalizumab group compared to the placebo group; the difference between groups was statistically significant (p<0.001), while there were no differences between the omalizumab and placebo groups for patients' subjective Quality of Life ratings.
Clinical experience in chronic spontaneous urticaria (CSU)
The efficacy and safety of Xolair were demonstrated in two randomised, placebo-controlled phase III studies (study 1 and 2) in patients with CSU who remained symptomatic despite H1 antihistamine therapy at the approved dose. A third study (study 3) primarily evaluated the safety of Xolair in patients with CSU who remained symptomatic despite treatment with H1 antihistamines at up to four times the approved dose and H2 antihistamine and/or LTRA treatment. The three studies enrolled 975 patients aged between 12 and 75 years (mean age 42.3 years; 39 patients 12-17 years, 54 patients ≥65 years; 259 males and 716 females). All patients were required to have inadequate symptom control, as assessed by a weekly urticaria activity score (UAS7, range 0-42) of ≥16, and a weekly itch severity score (which is a component of the UAS7; range 0-21) of ≥8 for the 7 days prior to randomisation, despite having used an antihistamine for at least 2 weeks beforehand.
In studies 1 and 2, patients had a mean weekly itch severity score of between 13.7 and 14.5 at baseline and a mean UAS7 score of 29.5 and 31.7 respectively. Patients in safety study 3 had a mean weekly itch severity score of 13.8 and a mean UAS7 score of 31.2 at baseline. Across all three studies, patients reported receiving on average 4 to 6 medications (including H1 antihistamines) for CSU symptoms prior to study enrollment. Patients received Xolair at 75 mg, 150 mg or 300 mg or placebo by subcutaneous injection every 4 weeks for 24 and 12 weeks in studies 1 and 2, respectively, and 300 mg or placebo by subcutaneous injection every 4 weeks for 24 weeks in study 3. All studies had a 16-week treatment-free follow-up period.
The primary endpoint was the change from baseline to week 12 in weekly itch severity score. Omalizumab at 300 mg reduced the weekly itch severity score by 8.55 to 9.77 (p <0.0001) compared to a reduction of 3.63 to 5.14 for placebo (see Table 7). Statistically significant results were further observed in the responder rates for UAS7≤6 (at week 12) which were higher for the 300 mg treatment groups, ranging from 52-66% (p<0.0001) compared to 11-19% for the placebo groups, and complete response (UAS7=0) was achieved by 34-44% (p<0.0001) of patients treated with 300 mg compared to 5-9% of patients in the placebo groups. Patients in the 300 mg treatment groups achieved the highest mean proportion of angioedema-free days from week 4 to week 12, (91.0-96.1%; p<0.001) compared to the placebo groups (88.1-89.2%). Mean change from baseline to week 12 in the overall DLQI for the 300 mg treatment groups was greater (p<0.001) than for placebo showing an improvement ranging from 9.7-10.3 points compared to 5.1-6.1 points for the corresponding placebo groups.
Table 7: Change from baseline to week 12 in weekly itch severity score, studies 1, 2 and 3 (mITT population*)

Placebo

Omalizumab

300 mg

Study 1

 

N

80

81

Mean (SD)

−3.63 (5.22)

−9.40 (5.73)

Difference in LS means vs. placebo1

-

−5.80

95% CI for difference

-

−7.49,−4.10

P-value vs. placebo2

-

<0.0001

Study 2

 

N

79

79

Mean (SD)

−5.14 (5.58)

−9.77 (5.95)

Difference in LS means vs. placebo1

-

−4.81

95% CI for difference

-

−6.49,−3.13

P-value vs. placebo2

-

<0.0001

Study 3

 

N

83

252

Mean (SD)

−4.01 (5.87)

−8.55 (6.01)

Difference in LS means vs. placebo1

-

-4.52

95% CI for difference

-

−5.97, −3.08

P-value vs. placebo2

-

<0.0001

*Modified intent-to-treat (mITT) population: included all patients who were randomised and received at least one dose of study medication.
BOCF (Baseline Observation Carried Forward) was used to impute missing data.
1 The LS mean was estimated using an ANCOVA model. The strata were baseline weekly itch severity score (<13 vs. ≥13) and baseline weight (<80 kg vs. ≥80 kg).
2 p-value is derived from ANCOVA t-test.
Figure 1 shows the mean weekly itch severity score over time in study 1. The mean weekly itch severity scores significantly decreased with a maximum effect around week 12 that was sustained over the 24-week treatment period. The results were similar in study 3.
In all three studies the mean weekly itch severity score increased gradually during the 16-week treatment-free follow-up period, consistent with symptom re-occurrence. Mean values at the end of the follow-up period were similar to the placebo group, but lower than respective mean baseline values.
Figure 1: Mean weekly itch severity score over time, study 1 (mITT population)
BOCF=baseline observation carried forward; mITT=modified intention-to-treat population
Efficacy after 24 weeks of treatment
The magnitude of the efficacy outcomes observed at week 24 of treatment was comparable to that observed at week 12:
For 300 mg, in studies 1 and 3, the mean decrease from baseline in weekly itch severity score was 9.8 and 8.6, the proportion of patients with UAS7≤6 was 61.7% and 55.6%, and the proportion of patients with complete response (UAS7=0) was 48.1% and 42.5%, respectively, (all p<0.0001, when compared to placebo).
There is limited clinical experience in re-treatment of patients with omalizumab.
Clinical trial data on adolescents (12 to 17 years) included a total of 39 patients, of whom 11 received the 300 mg dose. Results for the 300 mg are available for 9 patients at week 12 and 6 patients at week 24, and show a similar magnitude of response to omalizumab treatment compared to the adult population. Mean change from baseline in weekly itch severity score showed a reduction of 8.25 at week 12 and of 8.95 at week 24. The responder rates were: 33% at week 12 and 67% at week 24 for UAS7=0, and 56% at week 12 and 67% at week 24 for UAS7≤6.
5.2 Pharmacokinetic properties
The pharmacokinetics of omalizumab have been studied in adult and adolescent patients with allergic asthma as well as in adult and adolescent patients with CSU. The general pharmacokinetic characteristics of omalizumab are similar in these populations.
Absorption
After subcutaneous administration, omalizumab is absorbed with an average absolute bioavailability of 62%. Following a single subcutaneous dose in adult and adolescent patients with asthma or CSU, omalizumab was absorbed slowly, reaching peak serum concentrations after an average of 6-8 days. In patients with asthma, following multiple doses of omalizumab, areas under the serum concentration-time curve from Day 0 to Day 14 at steady state were up to 6-fold of those after the first dose.
The pharmacokinetics of omalizumab are linear at doses greater than 0.5 mg/kg. Following doses of 75 mg, 150 mg or 300 mg every 4 weeks in patients with CSU, trough serum concentrations of omalizumab increased proportionally with the dose level.
Administration of Xolair manufactured as a lyophilised or liquid formulation resulted in similar serum concentration-time profiles of omalizumab.
Distribution
In vitro, omalizumab forms complexes of limited size with IgE. Precipitating complexes and complexes larger than one million Daltons in molecular weight are not observed in vitro or in vivo. Based on population pharmacokinetics, distribution of omalizumab was similar in patients with allergic asthma and patients with CSU. The apparent volume of distribution in patients with asthma following subcutaneous administration was 78 ± 32 ml/kg.
Elimination
Clearance of omalizumab involves IgG clearance processes as well as clearance via specific binding and complex formation with its target ligand, IgE. Liver elimination of IgG includes degradation in the reticuloendothelial system and endothelial cells. Intact IgG is also excreted in bile. In asthma patients the omalizumab serum elimination half-life averaged 26 days, with apparent clearance averaging 2.4 ± 1.1 ml/kg/day. Doubling of body weight approximately doubled apparent clearance. In CSU patients, based on population pharmacokinetic simulations, omalizumab serum elimination half-life at steady state averaged 24 days and apparent clearance at steady state for a patient of 80 kg weight was 3.0 ml/kg/day.
Characteristics in patient populations
Patients with asthma: The population pharmacokinetics of omalizumab were analysed to evaluate the effects of demographic characteristics. Analyses of these limited data suggest that no dose adjustments are necessary in patients with asthma for age (6-76 years), race/ethnicity, gender or body mass index (see section 4.2).
Patients with CSU: The effects of demographic characteristics and other factors on omalizumab exposure were evaluated based on population pharmacokinetics. In addition, covariate effects were evaluated by analysing the relationship between omalizumab concentrations and clinical responses. These analyses suggest that no dose adjustments are necessary in patients with CSU for age (12-75 years), race/ethnicity, gender, body weight, body mass index, baseline IgE, anti-FcεRI autoantibodies or concomitant use of H2 antihistamines or LTRAs.
Renal and hepatic impairment
There are no pharmacokinetic or pharmacodynamic data in allergic asthma or CSU patients with renal or hepatic impairment (see sections 4.2 and 4.4).
5.3 Preclinical safety data
The safety of omalizumab has been studied in the cynomolgus monkey, since omalizumab binds to cynomolgus and human IgE with similar affinity. Antibodies to omalizumab were detected in some monkeys following repeated subcutaneous or intravenous administration. However, no apparent toxicity, such as immune complex-mediated disease or complement-dependent cytotoxicity, was seen. There was no evidence of an anaphylactic response due to mast-cell degranulation in cynomolgus monkeys.
Chronic administration of omalizumab at dose levels of up to 250 mg/kg (more than 14-fold the maximum allowable clinical dose of 17.5 mg/kg according to the recommended dosing table) was well tolerated in non-human primates (both adult and juvenile animals), with the exception of a dose-related and age-dependent decrease in blood platelets, with a greater sensitivity in juvenile animals. The serum concentration required to attain a 50% drop in platelets from baseline in adult cynomolgus monkeys was roughly 4- to 20-fold higher than anticipated maximum clinical serum concentrations. In addition, acute haemorrhage and inflammation were observed at injection sites in cynomolgus monkeys.
Formal carcinogenicity studies have not been conducted with omalizumab.
In reproduction studies in cynomolgus monkeys, subcutaneous doses up to 75 mg/kg (about 12-fold exposure ratio based on 28-day AUC values at 75 mg/kg versus the clinical maximum dose) did not elicit maternal toxicity, embryotoxicity or teratogenicity when administered throughout organogenesis and did not elicit adverse effects on foetal or neonatal growth when administered throughout late gestation, delivery and nursing.
Omalizumab is excreted in breast milk in cynomolgus monkeys. Milk levels of omalizumab were 1.5% of the maternal blood concentration.
6. Pharmaceutical particulars
6.1 List of excipients
L-arginine hydrochloride
L-histidine hydrochloride
L-histidine
Polysorbate 20
Water for injections
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products.
6.3 Shelf life
15 months.
The shelf life includes potential temperature excursions. The product may be kept for a total of 4 hours at 25°C. If necessary, the product may be returned to the refrigerator for later use, but this must not be done more than once.
6.4 Special precautions for storage
Store in a refrigerator (2°C - 8°C).
Do not freeze.
Store in the original package in order to protect from light.
6.5 Nature and contents of container
1 ml solution in a pre-filled syringe barrel (type I glass) with staked needle (stainless steel), (type I) plunger stopper (latex-free rubber), and needle shield. Pack sizes of 1, 4 or 10.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Prior to completion of the injection, avoid contact with the device activation clips to keep from prematurely covering the needle with the needle guard.
Using the syringe
1. Holding the syringe with the needle pointing upwards, carefully pull off the needle cap from the syringe and discard it. Do not touch the exposed needle. Then, gently tap the syringe with your finger until the air bubble rises to the top of the syringe. Slowly push the plunger up to force the air bubble out of the syringe without inadvertently expelling solution.
2. Gently pinch the skin at the injection site and insert the needle.
3. Holding onto the finger flange, slowly depress the plunger as far as it will go. If any solution leaks from the injection site, insert the needle further.
4. Keeping the plunger fully depressed, carefully lift the needle straight out from the injection site.
5. Slowly release the plunger and allow the needle guard to automatically cover the exposed needle.
Disposal instructions
Dispose of the used syringe immediately in a sharps container.
7. Marketing authorisation holder
Novartis Europharm Limited
Frimley Business Park
Camberley, GU16 7SR
United Kingdom
8. Marketing authorisation number(s)
EU/1/05/319/008
EU/1/05/319/009
EU/1/05/319/010
9. Date of first authorisation/renewal of the authorisation
Date of first authorisation: 25 October 2005
Date of latest renewal: 25 October 2010
10. Date of revision of the text
02 December 2014
Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu

Xolair 150mg Solution for Injectionhttp://www.medicines.org.uk/emc/medicine/24912


Xolair 75mg Solution for Injectionhttp://www.medicines.org.uk/emc/medicine/28721
诺华奥马珠单抗获美国FDA批准用于慢性特发性荨麻疹
•近50%的CIU患者在使用获批剂量的H1-抗组胺药治疗后疗效不佳,对于此类患者Xolair®是目前第一个且唯一一个获美国批准的治疗药物
•CIU在美国以外的地区被称为CSU,这是一种严重的皮肤病,特征表现为慢性瘙痒,荨麻疹和血管性水肿。
•Xolair®获得美国食品药品管理局批准用于治疗CIU的治疗严格依照欧盟批准Xolair®用于CSU的治疗准则
2014年4月4日,诺华今天宣布,美国食品药品管理局(FDA)已批准Xolair®(奥马珠单抗)用于治疗慢性特发性荨麻疹(CIU),CIU是一种严重的皮肤病,该病在美国以外的地区也被称为慢性自发性荨麻疹(CSU)。在美国,Xolair®适用于正在接受H1-抗组胺药治疗但仍有症状的成人和青少年(≥12岁)。迄今为止,H1-抗组胺药是美国批准用于CIU唯一的治疗选择。
CIU/CSU是一种以皮肤出现红肿、瘙痒和甚至疼痛的荨麻疹或风团为特征的严重皮肤病,这些症状可自发出现和反复出现达6周以上。40%的CIU/CSU 患者还出现血管性水肿,即皮肤深层肿胀。
“美国食品药品管理局批准Xolair®用于CIU(在其他国家也被称为CSU)的适应症对患有这种严重慢性皮肤病的患者而言是一个激动人心的好消息”,诺华制药全球负责人David Epstein 表示,“50%的CIU患者在使用获批剂量的H1-抗组胺药治疗后疗效不佳,而目前H1-抗组胺药治疗是美国批准用于CIU的唯一治疗选择。”
在任一特定时间,慢性荨麻疹(CU)的患病率高达世界人口的1%,这些患者中的2/3患有CIU/CSU。在美国,预计约150万患者正遭受CIU的困扰。女性患病率是男性的两倍,并且多数患者都是在20到40岁出现症状。
美国食品药品管理局的批准主要基于2项重要的III期研究(ASTERIA I and II)得出的积极一致的结果。该研究入组了使用获批剂量的H1-抗组胺药治疗后疗效不佳的CIU/CSU患者。Xolair 300mg和150mg都达到所有主要终点,这些研究也显示,Xolair显著改善瘙痒和荨麻疹,包括快速缓解瘙痒,并且在许多病例中使症状完全消除。Xolair 300mg治疗组患者的生活质量也显著改善。CIU/CSU对生活质量的不良影响可能包括睡眠剥夺和精神合并症,如抑郁和焦虑。
在关键性III期临床研究中,Xolair®组与安慰剂组的不良事件(AEs)发生率和严重程度相似。
最近,Xolair®获欧盟批准用于H1抗组胺剂疗效不佳的成人和青少年(>/=)CSU患者的辅助治疗。Xolair®还在8个国家获批用于难以治疗的CSU:埃及,土耳其,危地马拉,萨尔瓦多和孟加拉国,巴基斯坦,厄瓜多尔和菲律宾。目前有20多个国家正在进行监管审查,包括加拿大、澳大利亚和瑞士。
目前,Xolair(奥马珠单抗)尚未在中国获得批准。
关于Xolair®(奥马珠单抗)
Xolair®是与免疫球蛋白E(IgE)结合的靶向治疗药物,可抑制组胺诱导的皮肤反应。探讨 Xolair®在 CSU中的作用机制的研究目前正在进行中,此研究可有助于进一步了解该病如何发生。
Xolair®已被包括美国(自2003年起)和欧盟(自2005年起)在内的90多个国家批准用于治疗中至重度持续性过敏性哮喘。在欧盟,Xolair®被批准用于治疗儿童(>/=6岁)、青少年和成人的重度持续性过敏性哮喘。此外,Xolair®的预填充注射器液体制剂已在欧盟获得批准,并在大部分欧洲国家上市。在美国,诺华制药公司和基因泰克公司共同推广Xolair®皮下制剂用于适当的过敏性哮喘患者。

责任编辑:admin


相关文章
NATPARA(parathyroid hormone for injection)
PENTASA Enema(美沙拉嗪,5-氨基水杨酸灌肠剂)
Vessel Due-F cap(舒洛地特软胶囊)
S-1Meiji Combination Capsules T20/T25(替加氟/吉莫斯特/氧嗪酸钾配合胶囊)
二甲双胍片|Metformin(metformin filmcoated tablets)
伟素注射液|Vessel(Sulodexide Injection)
SUREPOST Tabs(Repaglinide)瑞格列奈片
Signifor LAR(帕瑞肽长效注射剂)
肢端肥大症长效药物Signifor LAR注射剂获欧盟批准
Plenaxis injectable(阿巴瑞克注射混悬液)
Endoxan(环磷酰胺原末[口服散装粉])
 

最新文章

更多

· Dexilant(Dexlansoprazo...
· TALTZ(ixekizumab injec...
· SYMLIN(pramlintide ace...
· Avycaz(ceftazidime/avi...
· NATPARA(parathyroid ho...
· TAGRISSO(OSIMERTINIB M...
· 恩格列净片|JARDIANCE(e...
· SPIRIVA RESPIMAT(tiotr...
· Odefsey(rilpivirine/em...
· 依鲁替尼硬胶囊|IMBRUVI...

推荐文章

更多

· Dexilant(Dexlansoprazo...
· TALTZ(ixekizumab injec...
· SYMLIN(pramlintide ace...
· Avycaz(ceftazidime/avi...
· NATPARA(parathyroid ho...
· TAGRISSO(OSIMERTINIB M...
· 恩格列净片|JARDIANCE(e...
· SPIRIVA RESPIMAT(tiotr...
· Odefsey(rilpivirine/em...
· 依鲁替尼硬胶囊|IMBRUVI...

热点文章

更多

· 恩格列净片|JARDIANCE(e...
· TAGRISSO(OSIMERTINIB M...
· SPIRIVA RESPIMAT(tiotr...
· Odefsey(rilpivirine/em...
· 依鲁替尼硬胶囊|IMBRUVI...
· Avycaz(ceftazidime/avi...
· NATPARA(parathyroid ho...
· SYMLIN(pramlintide ace...
· TALTZ(ixekizumab injec...
· Dexilant(Dexlansoprazo...