Botulinum toxin type A for injection

ATC classification M03AX01 Therapeutic botulinum toxin type A blocks the release of acetylcholine from the presynaptic membrane of peripheral cholinergic nerve terminals by cleaving SNAP-25. SNAP-25 is an essential protein that affects the smooth binding of vesicles in nerve terminals to the presynaptic membrane and promotes the release of acetylcholine. After injection, botulinum toxin rapidly and highly binds to specific receptors on the cell surface, and then passes through the plasma membrane through receptor-mediated phagocytosis, and finally the toxin is released into the cytoplasm. The latter process is accompanied by progressive inhibition of acetylcholine release function, clinical manifestations appear 2-3 days after injection, and the effect reaches a peak 5-6 weeks after injection. Later, nerve terminals can sprout and reconnect with the end plate, and synaptic function can generally be restored within 12 weeks. Reproduction study: The no-observed adverse effect level (NOEL) of this product was 4, 1 and 0.125U/kg, respectively, when it was injected intramuscularly into pregnant mice, rats and rabbits during organogenesis. High doses may be accompanied by weight loss and/or delayed ossification in fetal mice, as well as abortion in rabbits. Other studies: In addition to reproductive toxicity studies, the following preclinical safety studies were conducted: acute toxicity tests, repeated injection toxicity tests, local tolerance tests, mutagenicity tests, antigenicity tests, and human blood compatibility tests. These studies show that there is no special danger in the dose range used in clinical applications. The median lethal dose (LD50) of intramuscular injection in young monkeys has been published to be 39U/kg.

Each vial contains: Clostridium botulinum toxin type A (900kD), 100U/vial.

Blepharospasm, hemifacial spasm and related focal dystonias.

The recommended dose of this product is not interchangeable with the dose of other botulinum toxin preparations. This product must be used by a qualified and experienced physician with appropriate equipment. The optimal effective dose and the optimal number of injection sites per muscle have not been established, so individual treatment plans should be prepared by the physician and the optimal dose should be determined by titration. Allergan will assist in providing training in injection techniques for this product. The recommended dose range for each injection site is 0.05-0.1 mL (blepharospasm, hemifacial spasm). See the dilution table below. The dilution of this product is injected with a sterile, 27-30 gauge/0.40-0.30 mm needle, and electromyographic monitoring is not necessarily required. The recommended initial injection dose is 1.25-2.5 U in the medial and lateral parts of the orbicularis oculi muscle of the upper eyelid and the lateral part of the orbicularis oculi muscle of the lower eyelid. If spasm in the superior arch, lateral orbicularis oculi, and upper facial area affects vision, additional injection sites should be added in the corresponding areas. Avoiding injections close to the temporal side of the upper eyelid can reduce complications of ptosis. Avoid injections on the inside of the lower eyelid to reduce diffusion to the inferior oblique muscle and reduce complications of diplopia. The figure below shows the reference injection site: Generally, the effect takes effect within three days after injection and reaches a peak in 1-2 weeks. The efficacy of each treatment lasts for about 3 months, and the treatment can be repeated as needed. When repeating treatment, if the initial treatment dose is considered insufficient, the injection dose can be increased or even doubled. However, if the dose at one injection site exceeds 5.0U, there will be no better effect. The initial treatment dose for each eye should not exceed 25U. Generally, a treatment frequency greater than once every 3 months is not beneficial to the patient. When treating blepharospasm, the total dose every 12 weeks should not exceed 100U. Patients with hemifacial spasm and abnormal function of the VIIth cranial nerve are treated the same as patients with unilateral blepharospasm, and other affected facial muscles can be injected as needed. If the first treatment fails, that is, there is no significant clinical improvement 1 month after injection compared with before treatment, the following measures should be taken: clinical verification, including electromyographic examination of the blocking effect of the injected muscle by a specialist; analysis of the reasons for failure, such as improper selection of injected muscles, insufficient injection dose, poor injection technique, fixed muscle contracture, weak antagonist muscle strength, formation of neutralizing toxin antibodies, etc.; re-evaluation of whether to use type A botulinum toxin treatment; if the first treatment is not effective, the following measures can be taken for the second treatment: 1) Analyze the reasons for the failure of the first treatment and adjust the dose; 2) Inject under electromyographic monitoring; 3) Maintain a 3-month interval between two treatments. If the second injection treatment fails or is ineffective, alternative treatment methods should be considered. Use, operation and disposal of this product: It is recommended to perform dilution operations and syringe preparation on a paper towel with a plastic liner to prevent liquid splashing. Dilute this product with sterile, preservative-free saline (0.9% sodium chloride for injection). Draw an appropriate amount of dilution with a syringe (see the dilution table below). Because this product may be denatured by vibrations caused by bubbles or similar forces, the diluent should be gently pushed into the bottle. If there is no vacuum negative pressure in the bottle to draw out the diluent, the bottle of medicine should be discarded. After preparation, this product should be a clear liquid that is colorless to slightly yellow and free of impurities. Before using the prepared solution, the clarity and presence of impurities should be checked visually, and the prepared solution should be stored in a refrigerator (2C-8C) for no more than 4 hours. This product can only be used once, and the remaining solution should be discarded. For safety reasons, unused medicine bottles should be filled with a small amount of water and then autoclaved; all used medicine bottles, syringes, and utensils stained with splashed liquid should be autoclaved, or the residues of this product should be inactivated with 0.5% hypochlorite solution for 5 minutes.

General: Clinical controlled trial data show that after treatment with this product, about 35% of patients with blepharospasm may experience adverse reactions. Adverse reactions generally occur within a few days after treatment and last for a short time. Local muscle weakness reflects the result of the pharmacological action of Clostridium botulinum toxin. As with any intramuscular injection treatment, local pain, tenderness and/or bruising may occur during the injection process. The frequency of adverse reactions is as follows: Very common symptoms: ptosis. Common symptoms: epidermal punctate keratitis, lagophthalmos, dry eyes, eye irritation symptoms, photophobia, tearing. Uncommon symptoms: keratitis, ectropion, diplopia, dizziness, diffuse rash/dermatitis, entropion, facial muscle weakness, facial muscle ptosis, fatigue, visual impairment, blurred vision. Rare symptoms: eyelid swelling. Rare symptoms: angle-closure glaucoma, corneal ulcer. Additional instructions Mild to severe dysphagia, which may be accompanied by the potential risk of aspiration, occasionally requires intervention. See the [Precautions] section. There are rare reports of spontaneous death after treatment with this product, which may sometimes be related to dysphagia, pneumonia and/or other obvious symptoms of fatigue. Since the launch of this product, the following adverse reactions have been rarely reported: rash (including erythema multiforme, urticaria and psoriasiform rash), itching and allergic reactions. There are also rare reports of adverse reactions involving the cardiovascular system, including arrhythmia and myocardial infarction, which may have fatal consequences in some patients, some of whom have risk factors such as cardiovascular disease. There is a report of an allergic reaction after injection of this product. There is a report of an elderly male who developed peripheral neuropathy after receiving 4 treatments of this product totaling 1800U in 11 weeks (neck and back spasms and severe pain). There are rare reports of angle-closure glaucoma after this product is used to treat blepharospasm.

This product is contraindicated for use in: 1) patients with known allergy to Clostridium botulinum toxin type A or any of the ingredients in the formula; 2) patients with myasthenia gravis or myasthenic syndrome.

Theoretically, aminoglycoside antibiotics or spectinomycin, or other drugs that affect neuromuscular conduction (such as tubocurarine-type muscle relaxants) can enhance the effect of botulinum toxin. No specific tests have been conducted to determine the possibility of clinical interaction between botulinum toxin and other drugs, and no clinically significant interactions have been reported. There are no studies on incompatibility, and this product should not be mixed with other drugs.

Refrigerate at 2~8℃ or freeze below -5℃. 36 months.

50 units/piece