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英文药名：XEOMIN（incobotulinumtoxinA powder for solution injection）
中文药名：肉毒毒素类型A粉末注射液
生产厂家：梅尔茨制药（英国）
药品介绍
新生物制品Xeomin(肉毒毒素类型A[incobotulinumtoxinA])治疗颈部肌张力障碍和眼睑痉挛
——新的适应症获得批准
Xeomin一种A型肉毒杆菌毒素。该药品适用于治疗成人颈部肌张力障碍，降低异常头位和颈部疼痛的严重程度(无论患者之前是否接受过肉毒杆菌毒素治疗)，还适用于治疗有Botox(onabotulinumtoxinA)治疗史的成人眼睑痉挛。
Xeomin是目前惟一一种在配液前无需冷藏的肉毒杆菌毒素。FDA在审查两项关键性美国临床试验的结果后做出批准Xeomin的决定，这两项试验的受试者是确诊为颈部肌张力障碍或眼睑痉挛的成人患者。
另外，在递交至FDA的审批材料中还包括在欧洲进行的有效性比较研究的数据，比较药物为Xeomin与Botox(onabotulinumtoxinA)。
接受Xeomin注射的颈部肌张力障碍患者最常见的不良反应为吞咽困难、颈部疼痛、肌无力、注射部位疼痛和肌肉骨骼疼痛。在眼睑痉挛的患者中最常见的不良反应包括眼睑下垂、眼干、口干、腹泻、头痛、视力损害、呼吸困难、鼻咽炎和呼吸道感染。
临床医生应知道，颈部肌张力障碍的患者、颈部肌肉量较少者以及需要胸锁乳突肌双侧注射者发生吞咽困难的风险增加。胸锁乳突肌内限量注射可减少吞咽困难的发生。
内科医生还应知道，眼睑痉挛的患者眼轮匝肌内注射Xeomin可导致眨眼动作减少和角膜暴露，且可能会发生溃疡或穿孔。若在先前注射肉毒杆菌毒素时出现复视，则不应反复行下眼睑注射。
生产厂家警告：Xeomin及所有的肉毒杆菌毒素制品的作用都可能会由注射区向远处扩散，产生肉毒杆菌毒素效应。目前有报告指出，这些症状可在注射后数小时至数周发生。因强直而接受治疗的儿童出现症状的风险可能最大，但成人亦可出现相关症状，尤其是存在易出现这些症状的基础疾病的患者。
Xeomin 100 Units
1. Name of the medicinal product
XEOMIN 100 LD50 units powder for solution for injection
2. Qualitative and quantitative composition
One vial contains 100 LD50 units* of Clostridium Botulinum neurotoxin type A (150 kD), free from complexing proteins**.
One unit corresponds to the median lethal dose (LD50) when the reconstituted product is injected intraperitoneally into mice under defined conditions
Botulinum neurotoxin type A, purified from cultures of Clostridium Botulinum (Hall strain)
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Powder for solution for injection
White powder
4. Clinical particulars
4.1 Therapeutic indications
XEOMIN is indicated for the symptomatic treatment of blepharospasm, cervical dystonia of a predominantly rotational form (spasmodic torticollis) and of post-stroke spasticity of the upper limb presenting with flexed wrist and clenched fist in adults.
4.2 Posology and method of administration
Due to unit differences in the LD50 assay, XEOMIN units are specific to XEOMIN.
Therefore unit doses recommended for XEOMIN are not interchangeable with those for other preparations of Botulinum toxin.
For detailed information regarding clinical studies with XEOMIN in comparison to conventional Botulinum toxin type A complex (900kD) see section 5.1.
XEOMIN may only be administered by physicians with suitable qualifications and proven experience in the application of Botulinum toxin and in the use of the necessary equipment, e.g. electromyography (EMG).
Reconstituted XEOMIN is intended for intramuscular injection.
The optimum dosage and number of injection sites in the treated muscle should be determined by the physician individually for each patient. A titration of the dose should be performed.
For instructions on reconstitution / dilution of the vials, see section 6.6. After reconstitution, XEOMIN should be used for only one injection session and for only one patient.
A decrease or increase in the XEOMIN dose is possible by administering a smaller or larger injection volume. The smaller the injection volume the less pressure sensation and the less spread of Botulinum neurotoxin type A in the injected muscle occurs. This is of benefit in reducing effects on nearby muscles when small muscle groups are being injected.
Blepharospasm
Posology
The initial recommended dose is 1.25 to 2.5 U (0.05-0.1 ml volume) per injection site. The initial dose should not exceed 25 U per eye. In the management of blepharospasm, total dosing should not exceed 100 U every 12 weeks.
The median time to first onset of effect is observed within four days after injection. The effect of each treatment generally lasts approximately 3-4 months, however, it may last significantly longer or shorter. The treatment can be repeated if required.
At repeat treatment sessions, the dose may be increased up to two-fold if the response to the initial treatment is considered insufficient – usually defined as an effect that does not last longer than two months. However, there appears to be no additional benefit obtainable from injecting more than 5.0 U per site. Normally, no additional benefit is conferred by treating more frequently than every three months.
Method of administration
After reconstitution, the XEOMIN solution is injected using a suitable sterile needle (e.g. 27-30 gauge / 0.30-0.40 mm). Electromyographic guidance is not necessary. An injection volume of approximately 0.05 to 0.1 ml is recommended.
XEOMIN is injected into the medial and lateral orbicularis oculi of the upper lid and the lateral orbicularis oculi of the lower lid. Additional sites in the brow area, the lateral orbicularis and in the upper facial area may also be injected if spasms here interfere with vision.
Injections near the levator palpebrae superioris should be avoided to reduce the occurrence of ptosis. Diplopia may develop as a result of Botulinum neurotoxin type A diffusion into the inferior oblique. Avoiding medial injections into the lower lid may reduce this adverse reaction.
Spasmodic torticollis
Posology
In the management of spasmodic torticollis, XEOMIN dosing must be tailored to the individual patient, based on the patient's head and neck position, location of possible pain, muscle hypertrophy, patient's body weight, and response to the injection.
Normally, in practice, the total dose administered does not exceed 200 U. Doses of up to 300 U may be given. No more than 50 U should be given at any one injection site.
The median first onset of effect is observed within seven days after injection. The effect of each treatment generally lasts approximately 3-4 months, however, it may last significantly longer or shorter. The period between each treatment session should be at least 10 weeks.
Method of administration
A suitable sterile needle (e.g. 25-30 gauge / 0.30-0.50 mm) is used for injections into superficial muscles, and an e.g. 22 gauge / 0.70 mm needle may be used for injections into deeper musculature. An injection volume of approximately 0.1 to 0.5 ml per injection site is recommended.
In the management of spasmodic torticollis, XEOMIN is usually injected into the sternocleidomastoid, levator scapulae, scalenus, splenius capitis, and/or the trapezius muscle(s). This list is not exhaustive as any of the muscles responsible for controlling head position may be involved and therefore require treatment. If difficulties arise isolating single muscles, injections should be performed using electromyographic guidance. The muscle mass and the degree of hypertrophy or atrophy are factors to be taken into consideration when selecting the appropriate dose.
Multiple injection sites permit XEOMIN more uniform coverage of the innervated areas of the dystonic muscle and are especially useful in larger muscles. The optimum number of injection sites is dependent upon the size of the muscle to be chemically denervated.
The sternocleidomastoid should not be injected bilaterally as there is an increased risk of adverse reactions (in particular dysphagia) when bilateral injections or doses in excess of 100 U are administered into this muscle.
Post-stroke spasticity of the upper limb
Posology
The exact dosage and number of injection sites should be tailored to the individual patient based on the size, number and location of muscles involved, the severity of spasticity, and the presence of local muscle weakness.
In the management of post-stroke spasticity of the upper limb the following initial doses (units) were administered in the pivotal clinical trial:
In the pivotal clinical trial, the minimum and maximum total doses were 170 U and 400 U per treatment session, respectively.
For repeated treatments dosing should be tailored to the individual patient's need. The recommended dose ranges per muscle are provided in the following table:
The maximum total recommended dose is up to 400 units per treatment session.
Patients reported the onset of action 4 days after treatment. The maximum effect as an improvement of muscle tone was perceived within 4 weeks. In general, the treatment effect lasted 12 weeks. Reinjections should not be performed within intervals of less than 12 weeks.
Method of administration
Reconstituted XEOMIN is injected using a suitable sterile needle (e.g. 26 gauge / 0.45 mm diameter / 37 mm length, for superficial muscles and a longer needle, e.g. 22 gauge / 0.7 mm diameter / 75 mm length, for deeper musculature).
Localisation of the involved muscles with electromyographic guidance or nerve stimulation techniques may be useful. Multiple injection sites may allow XEOMIN to have more uniform contact with the innervation areas of the muscle and are especially useful when larger muscles are injected.
All indications
If no treatment effect occurs within one month after the initial injection, the following measures should be taken:
- Clinical verification of the neurotoxin effect on the injected muscle: e.g. an electromyographic investigation in a specialised facility
- Analysis of the reason for non-response, e.g
 [1] [ 2] [ 3] [ 4] 
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