Botulinum Toxin Type A
Acetylcholine Release Inhibitor [EPC], Neuromuscular Blocker [EPC]
What it is used for
for: Temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/ or procerus muscle activity in adult patients. ( 1.1 ) The treatment of cervical dystonia in adult patients. ( 1.2 ) 1.1 Glabellar Lines DAXXIFY is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult patients. 1.2 Cervical Dystonia DAXXIFY is indicated for the treatment of cervical dystonia in adult patients.
Warnings
5 WARNINGS AND PRECAUTIONS The potency units of DAXXIFY are not interchangeable with other preparations of other botulinum toxin products. ( 5.2 , 11) Spread of toxin effects, swallowing and breathing difficulties can lead to death. Seek immediate medical attention if respiratory, speech, or swallowing difficulties occur. ( 5.1 ) Adverse event reports have been received involving the cardiovascular system with botulinum toxin products, some with fatal outcomes. Use caution when administering to patients with pre-existing cardiovascular disease. ( 5.5 ) Concomitant neuromuscular disorder may exacerbate clinical effects of treatment. ( 5.6 ) Use with caution in patients with compromised respiratory function or dysphagia. ( 5.7 ) Potential serious adverse reactions after administration of DAXXIFY for unapproved use. ( 5.3 ) 5.1 Spread of Toxin Effect Postmarketing safety data from other approved botulinum toxins suggest that botulinum toxin effects may be observed beyond the site of local injection. The symptoms are consistent with the mechanism of action of botulinum toxin and may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life-threatening, and there have been reports of death related to the spread of toxin effects. The risk of symptoms is greatest in children treated for spasticity, an unapproved use for DAXXIFY, but symptoms can occur in adults treated for spasticity and other conditions, and particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including upper limb spasticity in children, and approved indications, symptoms consistent with spread of toxin effect have been reported at doses comparable to, or lower than, the maximum recommended total dose. Patients or caregivers should be advised to seek immediate medical care if swallowing, speech, or respiratory difficulties occur. 5.2 Lack of Interchangeability between Botulinum Toxin Products The potency units of DAXXIFY are specific to the preparation and assay method utilized. They are not interchangeable with other preparations of botulinum toxin products; therefore, units of biological activity of DAXXIFY cannot be compared to or converted to units of any other botulinum toxin products assessed with any other specific assay method [see Description (11) ] . 5.3 Serious Adverse Reactions with Unapproved Use Serious adverse reactions, including excessive weakness, dysphagia, and aspiration pneumonia, with some adverse reactions associated with fatal outcomes, have been reported in patients who received botulinum toxin injections for unapproved uses. In these cases, the adverse reactions may have resulted from the administration of botulinum toxin products to the site of injection and/or adjacent structures. In some cases, patients had pre-existing dysphagia or other significant disabilities. There is insufficient information to identify factors associated with an increased risk for adverse reactions associated with the unapproved uses of botulinum toxin products. 5.4 Hypersensitivity Reactions Serious and/or immediate hypersensitivity reactions have been reported for botulinum toxin products. These reactions include anaphylaxis, serum sickness, urticaria, soft tissue edema, and dyspnea. If such a reaction occurs, discontinue further injection of DAXXIFY and immediately institute appropriate medical therapy. The use of DAXXIFY in patients with a known hypersensitivity to any botulinum toxin preparation, DAXXIFY, or any of its formulation components could lead to a life-threatening allergic reaction [see Contraindications (4) ]. 5.5 Cardiovascular System Adverse Reactions There have been reports following administration of botulinum toxins of adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes. Some of these patients had risk factors, including pre-existing cardiovascular disease. Use caution when administering to patients with pre-existing cardiovascular disease. 5.6 Increased Neuromuscular Compromise in Patients with Pre-Existing Neuromuscular Disorders Monitor patients with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscular junctional disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome) for increased neuromuscular compromise following botulinum toxin treatment. Patients with neuromuscular disorders may be at increased risk of clinically significant effects, including generalized muscle weakness, diplopia, ptosis, dysphonia, dysarthria, severe dysphagia, and respiratory compromise from typical doses of DAXXIFY. 5.7 Dysphagia and Breathing Difficulties Treatment with botulinum toxin products, including DAXXIFY, can result in swallowing or breathing difficulties. These reactions can occur within hours to weeks after injection with botulinum toxin. Patients with pre-existing swallowing or breathing difficulties may be more susceptible to these complications. In most cases, this is a consequence of weakening of muscles in the area of injection that are involved in breathing or swallowing. When distant effects occur, additional respiratory mechanisms may be involved [see Warnings and Precautions (5.3) ]. Deaths as a complication of severe dysphagia have been reported after treatment with botulinum toxin products. Dysphagia may persist for several months. Aspiration may result from severe dysphagia and is a particular risk when treating patients in whom swallowing or respiratory function is already compromised. Treatment with botulinum toxins, including DAXXIFY, may weaken neck muscles that serve as accessory muscles of ventilation. This may result in a critical loss of breathing capacity in patients with respiratory disorders who may have become dependent upon these accessory muscles. There have been postmarketing reports from other botulinum toxin products of serious breathing difficulties, including respiratory failure. Patients treated with botulinum toxin may require immediate medical attention should they develop problems with swallowing, speech, or respiratory disorders. 5.8 Facial Anatomy in the Treatment of Glabellar Lines Use caution when administering DAXXIFY to patients with surgical alterations to the facial anatomy, marked facial asymmetry, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin, inflammation at the injection site(s), pre-existing eyelid or eyebrow ptosis, when excessive weakness or atrophy is present in the target muscles, or the inability to substantially lessen glabellar lines even by physically spreading them apart. 5.9 Ophthalmic Adverse Reactions in Patients Treated for Glabellar Lines Dry eye has been reported with the use of botulinum toxin products in the treatment of glabellar lines. Reduced tear production, reduced blinking, and corneal disorders may occur with use of botulinum toxins, including DAXXIFY. If symptoms of dry eye (e.g., eye irritation, photophobia, or visual changes) persist, consider referring patient to an ophthalmologist.
Possible side effects
6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Spread of Toxin Effect [see Warnings and Precautions (5.1) ] Hypersensitivity Reactions [see Warnings and Precautions (5.4) ] Cardiovascular System Adverse Reactions [see Warnings and Precautions (5.5) ] Increased Neuromuscular Compromise in Patients with Pre-Existing Neuromuscular Disorders [see Warnings and Precautions (5.6) ] Dysphagia and Breathing Difficulties [see Warnings and Precautions (5.7) ] Ophthalmic Adverse Reactions in Patients Treated for Glabellar Lines [see Warnings and Precautions (5.9) ] The most commonly observed adverse reactions are: Glabellar Lines (≥1%): headache (6%), eyelid ptosis (2%), and facial paresis (1%). ( 6.1 ) Cervical Dystonia (≥5%): headache (9%), injection site pain (8%), injection site erythema (5%), muscular weakness (5%), and upper respiratory tract infection (5%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Revance Therapeutics, Inc. at 1-877-373-8669 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common side effects from treatment with DAXXIFY usually occur within one to two weeks after injection and, while generally transient, may have a duration of several weeks or months. Glabellar Lines In the two randomized, placebo-controlled, Phase 3 clinical trials that assess the use of DAXXIFY for the temporary improvement in the appearance of moderate to severe glabellar lines, GL-1 and GL-2, 406 subjects received a single-dose treatment of 40 Units DAXXIFY, and 203 subjects received placebo. The most frequent adverse reactions are presented in Table 3. TABLE 3: Most Common Adverse Reactions ≥1% and More Frequent than Placebo in Pooled Double- Blind, Placebo-Controlled Trials for Glabellar Lines Adverse Reaction DAXXIFY N=406 n (%) Placebo N=203 n (%) Headache 26 (6%) 4 (2%) Eyelid ptosis 9 (2%) 0 (0%) Facial paresis Facial paresis, including facial asymmetry. 5 (1%) 0 (0%) Injection site reactions were reported in 6% of subjects treated with DAXXIFY and in 6% of subjects treated with placebo (these reactions included injection site pain, injection site erythema, injection site oedema, injection site bruising, injection site hematoma, injection site papule, and injection site pruritus). In an 84-week, open-label, repeat-dose safety study in glabellar lines, 2691 subjects were treated with 40 Units of DAXXIFY. Of these, 2380 subjects received one treatment with DAXXIFY, 882 received two treatments with DAXXIFY, and 568 subjects received three treatments with DAXXIFY. Adverse reactions were reported in 535 of the 2691 subjects (20%). The adverse reaction profile was similar to that reported in single-dose trials. Injection site reactions were the most common adverse reactions, reported in 9% of subjects [including injection site pain (4%), injection site erythema (3%), injection site oedema (3%), injection site bruising (1%), injection site papule (<1%), and injection site pruritus (<1%)], followed by headache (5%), edema (2%), erythema (2%), and eyelid ptosis in 1% of subjects. The incidence of these adverse reactions did not increase with multiple re- treatments. Cervical Dystonia In the randomized, placebo-controlled, Phase 3 clinical trial to assess the use of DAXXIFY for the treatment of cervical dystonia, 255 patients received a dose of DAXXIFY (n=125 for 125 Units and n=130 for 250 Units), and 46 patients received placebo. Table 4 lists adverse reactions that occurred in ≥2% of patients treated with DAXXIFY and more frequently than placebo. TABLE 4: Most Common Adverse Reactions ≥2% and More Frequent than Placebo in the Phase 3 Double-Blind, Placebo-Controlled Clinical Trial for Cervical Dystonia Adverse Reaction DAXXIFY 125 Units N=125 n (%) DAXXIFY 250 Units N = 130 n (%) Placebo N=46 n (%) Headache 11 (9%) 9 (7%) 1 (2%) Injection site pain 10 (8%) 7 (5%) 2 (4%) Injection site erythema 6 (5%) 3 (2%) 1 (2%) Muscular weakness 6 (5%) 3 (2%) 0 (0%) Musculoskeletal pain 5 (4%) 5 (4%) 0 (0%) Nasopharyngitis 4 (3%) 3 (2%) 0 (0%) Arthralgia 3 (2%) 1 (1%) 0 (0%) Upper respiratory tract infection 2 (2%) 7 (5%) 2 (4%) Spinal pain 3 (2%) 4 (3%) 1 (2%) Atrioventricular block first degree 2 (2%) 0 (0%) 0 (0%) Urinary tract infection 3 (2%) 0 (0%) 0 (0%) Dysphagia 2 (2%) 5 (4%) 0 (0%) In a 52-week, open-label, repeat-dose safety study in cervical dystonia, 357 subjects (271 from the randomized trial, 86 newly enrolled) received up to 4 treatments with DAXXIFY. Of these, 28 subjects received one treatment with DAXXIFY, 95 subjects received two treatments, 169 received three treatments, and 65 received four treatments with DAXXIFY. Adverse reactions were reported in 138 patients (20%).
Storage
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied DAXXIFY (daxibotulinumtoxinA-lanm) for injection is a sterile lyophilized powder supplied in a single-dose vial in the following sizes: Carton containing one 50 Units/Vial NDC 72960-111-01 Carton containing one 100 Units/Vial NDC 72960-112-01 Storage and Handling Unopened DAXXIFY vials should be stored at room temperature 20°C to 25°C (68°F to 77°F) or refrigerated at 2°C to 8° C (36°F to 46°F) in the original carton to protect from light.
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