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Botulinum Toxin Type A

FDA Drug Information • Also known as: Daxxify, Dysport

Brand Names
Daxxify, Dysport
Dosage Form
POWDER
Product Type
DRUG FOR FURTHER PROCESSING

⚠ Boxed Warning (Black Box)

WARNING: DISTANT SPREAD OF TOXIN EFFECT The effects of all botulinum toxin products, including DAXXIFY, may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. 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. The risk of symptoms is probably greatest in children treated for spasticity, an unapproved use for DAXXIFY, but symptoms can also occur in adults, particularly in those patients who have an underlying condition that would predispose them to these symptoms [see Warnings and Precautions (5.1) ]. WARNING: DISTANT SPREAD OF TOXIN EFFECT See full prescribing information for complete boxed warning. The effects of DAXXIFY and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. 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. The risk of symptoms is probably greatest in children treated for spasticity, an unapproved use for DAXXIFY, but symptoms can also occur in adults, particularly in those patients who have an underlying condition that would predispose them to these symptoms. ( 5.1 )

Description

11 DESCRIPTION DaxibotulinumtoxinA-lanm is an acetylcholine release inhibitor and neuromuscular blocking agent. DaxibotulinumtoxinA-lanm is a 150 kDa botulinum toxin without accessory proteins purified from the bacterium Clostridium botulinum type A. DAXXIFY (daxibotulinumtoxinA-lanm) for injection is supplied as a sterile, preservative-free, white to off- white lyophilized powder in a single-dose vial for intramuscular use after reconstitution. DAXXIFY is formulated with a 35 amino acid peptide excipient (RTP004) that prevents surface adsorption and promotes thermal stability of DAXXIFY. Each vial contains 50 Units or 100 Units of daxibotulinumtoxinA-lanm, L- histidine (0.14 mg), L-histidine HCl monohydrate (0.65 mg), polysorbate 20 (0.1 mg), RTP004 peptide (11.7 mcg), and trehalose dihydrate (36 mg).

What Is Botulinum Toxin Type A Used For?

1 INDICATIONS AND USAGE DAXXIFY is an acetylcholine release inhibitor and neuromuscular-blocking agent indicated 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.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Glabellar Lines : the recommended dose is 0.1 mL (8 Units) by intramuscular injection into each of five sites, for a total dose of 40 Units. ( 2.2 ) Cervical Dystonia : the recommended dose is 125 Units to 250 Units given intramuscularly as a divided dose among affected muscles. ( 2.3 ) 2.1 Important Administration Instructions The potency units of DAXXIFY for injection are specific to the preparation and test method utilized. They are not interchangeable with other preparations of botulinum toxin products, and, therefore, units of biological activity of DAXXIFY cannot be compared to, or converted into, units of any other botulinum toxin products assessed with any other specific test method [see Warnings and Precautions (5.2) and Description (11) ]. The safe and effective use of DAXXIFY depends upon proper storage of the product, selection of the correct dose, and proper reconstitution and administration techniques. DAXXIFY should be administered no more frequently than every three months for any indication. Consideration of the cumulative dose is necessary when treating adult patients with DAXXIFY. Physicians should be aware of whether patients are receiving treatment with other botulinum toxin products for other indications. Reconstituted DAXXIFY is intended for intramuscular injection only. After reconstitution, only use each DAXXIFY vial for only one injection session and for only one patient. Discard any remaining solution in vial immediately after administration. Reconstitution instructions are provided specifically for the 50 Unit and the 100 Unit vials (Table 1; Table 2). 2.2 Recommended Dosage and Administration for Glabellar Lines Recommended Dosage for Glabellar Lines The total recommended dose is 40 Units per treatment session divided into five equal intramuscular injections of 8 Units each (two injections in each corrugator muscle and one injection in the procerus muscle). Administration for Glabellar Lines Glabellar lines arise from the contraction of the corrugator and procerus muscles. These can be identified by palpation of the glabellar muscle mass while having the patient frown maximally. Contraction of the corrugator muscles compresses the skin, creating a vertical line or lines surrounded by ridges of tensed muscle. Because the exact location, size, and activity of the muscles can vary markedly among individuals, physicians administering DAXXIFY must understand the relevant anatomy of the area involved and any alterations to the anatomy due to prior surgical procedures and diseases [see Warnings and Precautions (5.3) ] . After assessment, the location of the corrugator muscle injection sites may need to be adjusted based on individual facial anatomy and the pattern of muscle contraction. The upper eyelid margin position should be carefully examined for separation or weakness of the levator palpebrae superioris muscle. Evaluate the range of upper eyelid excursion while manually immobilizing the...

Side Effects (Adverse Reactions)

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...

Drug Interactions

7 DRUG INTERACTIONS No formal drug interaction studies have been conducted with DAXXIFY. However, the potential for certain drugs to potentiate the effects of DAXXIFY warrants consideration given the potential risks involved and should be used with caution. Aminoglycosides or other agents interfering with neuromuscular transmission Anticholinergic drugs Botulinum neurotoxin products Muscle relaxants Aminoglycoside antibiotics, anticholinergic agents, or any other agents that interfere with neuromuscular transmission may potentiate the effect of DAXXIFY; co-administer only with caution and close observation. ( 7 )

Contraindications

4 CONTRAINDICATIONS DAXXIFY is contraindicated in: patients with known hypersensitivity to any botulinum toxin preparation, DAXXIFY, or any of the components in the DAXXIFY formulation [see Warnings and Precautions (5.4) ]. the presence of infection at the proposed injection sites. Known hypersensitivity to any botulinum toxin preparation, DAXXIFY, or any of the components in the DAXXIFY formulation. ( 4 ) Infection at the injection sites. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no available data on DAXXIFY use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, intramuscular administration of DAXXIFY during pregnancy resulted in adverse effects on fetal growth (decreased fetal body weight and skeletal ossification) at maternally toxic doses approximately equivalent to 40 times the maximum recommended human dose (MRHD) ( see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Embryofetal development studies were conducted in rats and rabbits with DAXXIFY. For comparison of animal to human doses based on a body weight comparison, the MRHD is set at 40 Units/subject (0.67 Units/kg for an average 60 kg subject). Intramuscular administration of DAXXIFY (3, 10, or 30 Units/kg) to pregnant rats four times during the period of organogenesis (on gestation days 7, 10, 13, and 16) caused decreased fetal body weight and decreased fetal skeletal ossification at the highest dose, which was associated with maternal toxicity. No embryofetal developmental toxicity was noted at doses up to 10 Units/kg, which is 15 times the MRHD. Intramuscular administration of DAXXIFY (0.02, 0.1, 0.48, or 2.4 Units/kg/day) to pregnant rabbits during the period of organogenesis (total of 13 doses) resulted in maternal lethality at 2.4 Units/kg/day and significant decreased maternal body weight at 0.48 Units/kg/day. No embryofetal developmental toxicity was noted at doses up to 0.48 Units/kg/day, which is approximately equivalent to the MRHD.

Overdosage

10 OVERDOSAGE Excessive doses of DAXXIFY may be expected to produce neuromuscular weakness with a variety of symptoms. Respiratory support may be required where excessive doses cause paralysis of the respiratory muscles. In the event of overdose, the patient should be medically monitored for symptoms or excessive muscle weakness or muscle paralysis [see Warnings and Precautions (5.1) , (5.7) ] . Symptomatic treatment may be necessary. Symptoms of overdose are not likely to be present immediately following injection. Should accidental injection or oral ingestion occur, the person should be medically supervised for several weeks for signs and symptoms of excessive muscle weakness or paralysis. In the event of overdose, antitoxin raised against botulinum toxin is available from the Centers for Disease Control and Prevention (CDC) in Atlanta, GA. However, the antitoxin will not reverse any botulinum toxin-induced effects already apparent by the time of antitoxin administration. In the event of suspected or actual cases of botulinum toxin poisoning, please contact your local or state Health Department to process a request for antitoxin through the CDC. If you do not receive a response within 30 minutes, please contact the CDC directly at 1-770-488-7100.

How Supplied

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.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.