BOTOX Cosmetic

6 ADVERSE REACTIONS The following adverse reactions to BOTOX Cosmetic (onabotulinumtoxinA) for injection are discussed in greater detail in other sections of the labeling: Spread of Toxin Effects [see Warnings and Precautions ( 5.2 )] Hypersensitivity [see Contraindications ( 4.1 ) and Warnings and Precautions ( 5.4 )] Dysphagia and Breathing Difficulties [see Warnings and Precautions ( 5.7 )] The most common adverse reactions are ( 6.1 ): Glabellar Lines: eyelid ptosis (3%) Lateral Canthal Lines: eyelid edema (1%) Forehead Lines: headache (9%) and brow ptosis (2%) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the 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 clinical practice. BOTOX and BOTOX Cosmetic contain the same active ingredient in the same formulation, but have different labeled Indications and Usage. Therefore, adverse events observed with the use of BOTOX also have the potential to be observed with the use of BOTOX Cosmetic. In general, adverse reactions occur within the first week following injection of BOTOX Cosmetic and while in many cases are transient, may have a duration of several months or longer. Localized pain, infection, inflammation, tenderness, swelling, erythema, and/or bleeding/bruising may be associated with the injection. Needle-related pain and/or anxiety may result in vasovagal responses (including e.g., syncope, hypotension), which may require appropriate medical therapy. Local weakness of the injected muscle(s) represents the expected pharmacological action of botulinum toxin. However, weakness of nearby muscles may also occur due to spread of toxin [see Warnings and Precautions ( 5.2 )] . Glabellar Lines Table 5 lists selected adverse reactions reported by ≥1% of BOTOX Cosmetic treated subjects (N=405) aged 18 to 75 who were evaluated in the randomized, placebo-controlled clinical studies to assess the use of BOTOX Cosmetic in the improvement of the appearance of glabellar lines. Table 5: Adverse Reactions Reported by ≥1% of BOTOX Cosmetic treated Subjects and More Frequent than in Placebo-treated Subjects in Double-blind, Placebo-controlled Clinical Studies of Treatment of Glabellar Lines Adverse Reactions by System Organ Class BOTOX Cosmetic (N=405) Placebo (N=130) General Disorders and Administration Site Conditions Facial pain 6 (1%) 0 (0%) Nervous System Disorders Facial paresis 5 (1%) 0 (0%) Eye Disorders Eyelid ptosis 13 (3%) 0 (0%) Musculoskeletal and Connective Tissue Disorders Muscular Weakness 6 (1%) 0 (0%) Lateral Canthal Lines Table 6 lists selected adverse reactions reported within 90 days following injection by ≥1% of BOTOX Cosmetic treated subjects (N=526) aged 18 to 75 who were evaluated in two randomized, double-blind, placebo-controlled clinical studies to assess the use of BOTOX Cosmetic in the improvement of the appearance of lateral canthal lines alone. Table 6: Adverse Reaction Reported by ≥1% of BOTOX Cosmetic Treated Subjects and More Frequent than in Placebo-treated Subjects Within 90 Days, in Double-blind, Placebo-controlled Clinical Studies of Treatment of Lateral Canthal Lines Adverse Reactions by System Organ Class BOTOX Cosmetic 24 Units (N=526) Placebo (N=530) Eye disorders Eyelid edema 5 (1%) 0 (0%) Forehead Lines Table 7 lists selected adverse reactions reported by ≥1% of BOTOX Cosmetic treated subjects (N=665) aged 18 to 77 who were evaluated in two randomized, double-blind, placebo-controlled clinical studies to assess the use of BOTOX Cosmetic in the improvement of the appearance of forehead lines with glabellar lines. Table 7: Adverse Reactions Reported by ≥1% of BOTOX Cosmetic treated Subjects More Frequently than in Placebo-treated Subjects, in Double-blind, Placebo-controlled Clinical Studies of Treatment of Forehead Lines Adverse Reactions by System Organ Class BOTOX Cosmetic (20 Units forehead lines with 20 Units glabellar lines ) (N=665) Placebo (N=315) Nervous System Disorders Headache 58 (9%) 17 (5%) Eye Disorders Eyelid ptosis 12 (2%) 1 (0%) Skin and Subcutaneous Tissue Disorders Brow ptosis Skin tightness 13 (2%) 10 (2%) 0 (0%) 0 (0%) There were no additional adverse drug reactions reported with the simultaneous treatment of forehead lines, glabellar lines, and lateral canthal lines. Platysma Bands The safety of BOTOX Cosmetic (26 Units, 31 Units, or 36 Units) was evaluated in two double-blind, placebo-controlled, clinical trials with 407 BOTOX Cosmetic-treated subjects and 425 subjects receiving placebo. The safety profile of BOTOX Cosmetic treatment of platysma bands is consistent with the known safety profile of BOTOX Cosmetic for other indications. 6. 2 Postmarketing Experience Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. There have been spontaneous reports of death, sometimes associated with dysphagia, pneumonia, and/or other significant debility or anaphylaxis, after treatment with botulinum toxin [see Warnings and Precautions ( 5.4 , 5.7 )] . There have also been reports of adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes. Some of these patients had risk factors including cardiovascular disease. New onset or recurrent seizures have also been reported, typically in patients who are predisposed to experiencing these events. The following adverse reactions by System Organ Class have been identified during post-approval use of BOTOX/BOTOX Cosmetic: Ear and labyrinth disorders Hypoacusis; tinnitus; vertigo Eye disorders Diplopia; dry eye; eyelid edema; lagophthalmos; strabismus; visual disturbances; vision blurred Gastrointestinal disorders Abdominal pain; diarrhea; dry mouth; nausea; vomiting General disorders and administration site conditions Denervation; malaise; pyrexia Metabolism and nutrition disorders Anorexia Musculoskeletal and connective tissue disorders Localized muscle twitching/involuntary muscle contractions; Mephisto sign; muscle atrophy; myalgia Nervous system disorders Brachial plexopathy; dysarthria; facial palsy; hypoaesthesia; localized numbness; myasthenia gravis; paresthesia; peripheral neuropathy; radiculopathy; syncope Respiratory, thoracic and mediastinal disorders Aspiration pneumonia; dyspnea; respiratory depression and/or respiratory failure Skin and subcutaneous tissue disorders Alopecia, including madarosis; hyperhidrosis; pruritus; skin rash (including erythema multiforme, dermatitis psoriasiform, and psoriasiform eruption)

4 CONTRAINDICATIONS Hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation ( 4.1 , 5.4 ) Infection at the injection site ( 4.2 ) 4.1 Known Hypersensitivity to Botulinum Toxin BOTOX Cosmetic is contraindicated in individuals with known hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation [see Warnings and Precautions ( 5.4 )] . 4.2 Infection at the Injection Site(s) BOTOX Cosmetic is contraindicated in the presence of infection at the proposed injection site(s).

11 DESCRIPTION BOTOX Cosmetic (onabotulinumtoxinA) for injection, is a sterile, vacuum-dried purified botulinum toxin type A, produced from fermentation of Hall strain Clostridium botulinum type A intended for intramuscular use. It is purified from the culture solution by dialysis and a series of acid precipitations to a complex consisting of the neurotoxin, and several accessory proteins. The complex is dissolved in sterile sodium chloride solution containing Albumin Human and is sterile filtered (0.2 microns) prior to filling and vacuum-drying. The primary release procedure for BOTOX Cosmetic uses a cell-based potency assay to determine the potency relative to a reference standard. The assay is specific to AbbVie’s products BOTOX and BOTOX Cosmetic. One Unit of BOTOX Cosmetic corresponds to the calculated median intraperitoneal lethal dose (LD 50 ) in mice. Due to specific details of this assay such as the vehicle, dilution scheme and laboratory protocols, Units of biological activity of BOTOX Cosmetic cannot be compared to nor converted into Units of any other botulinum toxin or any toxin assessed with any other specific assay method. The specific activity of BOTOX Cosmetic is approximately 20 Units/nanogram of neurotoxin complex. Each vial of BOTOX Cosmetic contains either 50 Units of Clostridium botulinum type A neurotoxin complex, 0.25 mg of Albumin Human, and 0.45 mg of sodium chloride; or 100 Units of Clostridium botulinum type A neurotoxin complex, 0.5 mg of Albumin Human, and 0.9 mg of sodium chloride in a sterile, vacuum-dried form without a preservative.

2 DOSAGE AND ADMINISTRATION Glabellar Lines Administration: 0.1 mL (4 Units) into each of 5 sites, for a total dose of 20 Units ( 2.4 ) Lateral Canthal Lines Administration: 0.1 mL (4 Units) into each of 3 sites per side (6 total injection points), for a total of 24 Units ( 2.4 ) Forehead Lines Administration: 0.1 mL (4 Units) into each of 5 forehead line sites (20 Units) with 0.1 mL (4 Units) into each of 5 glabellar line sites (20 Units), for a recommended total of 40 Units ( 2.4 ) Platysma Bands Administration: 0.05 mL (2 Units) into each of 4 sites in the upper segment of the platysma muscles, below the jawline on each side and 0.025 mL (1 Unit) into 5 sites on each vertical neck band per side (1 to 2 bands per side) for a total of 26 Units, 31 Units, or 36 Units (18, 23, or 28 injection sites, respectively) ( 2.4 ) BOTOX Cosmetic is administered by intramuscular injection ( 2.2 ) Follow dosage and administration recommendations. Do not exceed the maximum recommended cumulative dose in a treatment session for any indication ( 2.1 , 2.2 ) See Preparation and Reconstitution Instructions for information on BOTOX Cosmetic reconstitution, storage, and preparation before injection ( 2.3 ) Figure 1: Figure 2 and 3 Figure 4: Figure 5: Injection Sites for Platysma Prominence (2 Bands) Figure 6: Injection Sites for Platysma Prominence (1 Band) 2.1 Instructions for Safe Use The potency Units of BOTOX Cosmetic (onabotulinumtoxinA) for injection are specific to the preparation and assay method utilized. BOTOX Cosmetic is not equivalent to other preparations of botulinum toxin products, and therefore, units of biological activity of BOTOX Cosmetic cannot be compared to nor converted into units of any other botulinum toxin products assessed with any other specific assay method [see Warnings and Precautions ( 5.1 ) and Description ( 11 )] . Follow indication specific dosage and administration recommendations. Do not exceed the maximum recommended cumulative dose in a treatment session for any indication. The safe and effective use of BOTOX Cosmetic depends upon proper storage of the product, selection of the correct dose, and proper reconstitution and administration techniques. Physicians administering BOTOX Cosmetic must understand the relevant neuromuscular and structural anatomy of the area involved and any alterations to the anatomy due to prior surgical procedures and disease. Do not use BOTOX Cosmetic and contact AbbVie (1-800-678-1605) if: The tamper evident features on the carton appear to be broken or compromised, or The U.S. License number 1889 is not present on the vial label and carton labeling [see How Supplied/Storage and Handling ( 16 )] 2.2 Recommended Dose The total recommended dose in adult patients by treatment area is shown in Table 1. BOTOX Cosmetic is administered by intramuscular injection. Table 1: Total Recommended Treatment Dose Treatment Area Total Recommended Treatment Dose Glabellar lines 20 Units in 0.5 mL Lateral canthal lines 24 Units in 0.6 mL Forehead lines and glabellar lines 40 Units in 1 mL Platysma bands One band on each side: 26 Units in 0.65 mL 1 band on one side, 2 bands on the other side: 31 Units in 0.78 mL Two bands on each side: 36 Units in 0.9 mL The safety and effectiveness of dosing with BOTOX Cosmetic more frequently than every 3 months have not been clinically evaluated. 2.3 Preparation and Reconstitution Instructions BOTOX Cosmetic is supplied in single-dose 50 Units and 100 Units per vial. Prior to intramuscular injection, reconstitute each vacuum-dried vial of BOTOX Cosmetic with sterile, preservative-free 0.9% Sodium Chloride Injection USP (see Table 2). Draw up the proper amount of diluent in the appropriate size needle and syringe to obtain a reconstituted solution at a concentration of 4 Units/0.1 mL. Table 2: Dilution Instructions for BOTOX Cosmetic Vials (50 Units and 100 Units) Vial Amount of Diluent* Added Resulting Dose Units per 0.1 mL 50 Units 1.25 mL 4 Units 100 Units 2.5 mL 4 Units *Preservative-free 0.9% Sodium Chloride Injection, USP Only Slowly inject the diluent into the vial. Discard the vial if a vacuum does not pull the diluent into the vial. Gently mix BOTOX Cosmetic with the saline by rotating the vial. Record the date and time of reconstitution on the space on the label. Administer BOTOX Cosmetic within 24 hours after reconstitution. During this time period, store reconstituted BOTOX Cosmetic in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze reconstituted BOTOX Cosmetic. BOTOX Cosmetic vials are for single-dose only. Discard any remaining solution. Reconstituted BOTOX Cosmetic is clear, colorless to slightly yellow solution, and free of particulate matter. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration and whenever the solution and the container permit. Do not use if the solution is cloudy or contains flakes or particles. 2. 4 Administration Draw properly reconstituted toxin into the sterile syringe, preferably a tuberculin syringe, and expel any air bubbles in the syringe barrel (see Table 3). Remove the needle used to reconstitute the product and attach a 30-33 gauge needle. Confirm the patency of the needle. Table 3: Amount of Reconstituted Toxin to Draw Per Treatment Area Treatment Area Amount of Reconstituted Toxin to Draw Glabellar lines At least 0.5 mL Lateral canthal lines At least 0.6 mL Forehead lines and glabellar lines At least 1 mL Platysma bands 1 band on each side: At least 0.65 mL 1 band on one side, 2 bands on the other side: At least 0.78 mL 2 bands on each side: At least 0.9 mL Glabellar Lines An effective dose for facial lines is determined by gross observation of the patient’s ability to activate the superficial muscles injected. In order to reduce the complication of ptosis, take the following steps: Avoid injection near the levator palpebrae superioris, particularly in patients with larger brow depressor complexes. Place lateral corrugator injections at least 1 cm above the bony supraorbital ridge. Ensure the injected volume/dose is accurate and where feasible kept to a minimum. Do not inject toxin closer than 1 cm above the central eyebrow. Inject 4 Units (0.1 mL) of reconstituted BOTOX Cosmetic intramuscularly into each of 5 sites, 2 in each corrugator muscle and 1 in the procerus muscle for a total dose of 20 Units (see Figure 1). Typically, the initial doses of reconstituted BOTOX Cosmetic induce chemical denervation of the injected muscles one to two days after injection, increasing in intensity during the first week. The duration of effect of BOTOX Cosmetic for glabellar lines is approximately 3-4 months. Figure 1: Lateral Canthal Lines Give injections with the needle bevel tip up and oriented away from the eye. Inject 4 Units (0.1 mL) of reconstituted BOTOX Cosmetic into 3 sites per side (6 total injection points) in the lateral orbicularis oculi muscle for a total of 24 Units (0.6 mL) (12 Units per side). Administer the first injection (A) approximately 1.5-2.0 cm temporal to the lateral canthus and just temporal to the orbital rim. If the lines in the lateral canthal region are above and below the lateral canthus, inject per Figure 2. Alternatively, if the lines in the lateral canthal region are primarily below the lateral canthus, inject per Figure 3. For simultaneous treatment with glabellar lines, the dose is 24 Units for lateral canthal lines and 20 Units for glabellar lines (see Glabellar Lines Administration and Figure 1), with a total dose of 44 Units. Forehead Lines in Conjunction with Glabellar Lines Treat forehead lines in conjunction with glabellar lines (see Glabellar Lines Administration and Figure 1) to minimize the potential for brow ptosis. The recommended total dose for treatment of forehead lines (20 Units [0.5 mL]) in conjunction with glabellar lines (20 Units [0.5 mL]) is 40 Units (1 mL). When identifying the location of the appropriate injection sites in the frontalis muscle, assess the overall relationship between the size of the subject’s forehead, and the distribution of frontalis muscle activity. Locate the following horizontal treatment rows by light palpation of the forehead at rest and maximum eyebrow elevation: Superior Margin of Frontalis Activity: approximately 1 cm above the most superior forehead crease Lower Treatment Row: midway between the superior margin of frontalis activity and the eyebrow, at least 2 cm above the eyebrow Upper Treatment Row: midway between the superior margin of frontalis activity and lower treatment row Inject 4 Units (0.1 mL) of reconstituted BOTOX Cosmetic into 5 sites in the frontalis muscle, for a total of 20 Units (0.5 mL). Place the 5 injections at the intersection of the horizontal treatment rows with the following vertical landmarks (see Figure 4): On the lower treatment row at the midline of the face, and 0.5 – 1.5 cm medial to the palpated temporal fusion line (temporal crest); repeat for the other side. On the upper treatment row, midway between the lateral and medial sites on the lower treatment row; repeat for the other side. Figure 4: For simultaneous treatment with lateral canthal lines, the total dose is 64 Units, comprised of 20 Units for forehead lines, 20 Units for glabellar lines, and 24 Units for lateral canthal lines (see Lateral Canthal Lines Administration and Figures 2 and 3). Platysma Bands Using an appropriately sized sterile syringe, needle, and aseptic technique, inject 2 Units (0.05 mL) of reconstituted BOTOX Cosmetic into 4 sites in the upper segment of platysma muscle, below the jawline on each side. For each side, administer the 4 jawline injections to the upper platysma muscle approximately 1 to 2 cm inferior and parallel to the lower mandibular border. Ensure the anterior injection site is in line with the oral commissure, and the posterior injection is slightly anterior to the angle of the mandible. Administer the remaining 2 injections equidistant (approximately 1 to 2 cm apart) between the anterior and posterior injection points (see Figures 5 and 6). In addition, inject 1 Unit (0.025 mL) of reconstituted BOTOX Cosmetic into 5 sites along each vertical neck band, 1 to 2 vertical neck bands per side. For each vertical neck band identified, 1 to 2 per side, distribute 5 injections vertically approximately 1 to 2 cm apart (see Figures 5 and 6). Ensure the most superior injection site is approximately 1 to 2 cm inferior to the jawline injections. Depending on platysma band severity, the total dose may be 26 Units (1 band/side), 31 Units (1 band one side, 2 bands other side), or 36 Units (2 bands/side) (see Table 4 and Figures 5 and 6 below). Figure 5 : Injection Sites for Platysma Band (2 Bands) Figure 6 : Injection Sites for Platysma Band (1 Band) Administer all platysma muscle injections superficially and intramuscularly with the needle perpendicular to the surface of the skin. For vertical neck band injections, identify each band while the patient is contracting their platysma. Gently pinch the band to isolate the muscle from nearby anatomical structures during administration (see Table 4). To reduce injection-related complications, administer injection at least 1 cm inferior to the lower mandibular border. Do not inject into structures deep to the platysma muscle, particularly in the anterior region of the neck. Table 4: Dosing for Platysma Bands Platysma Bands Presentation Jawline Injections Neck Band Injections Total Number of Injection Sites Total Dose 1 band on each side 2 Units (0.05 mL) into 4 sites per side (total of 8 sites and 16 Units) 1 Unit (0.025 mL) into 5 sites per band (total of 10 sites and 10 Units) 18 sites 26 Units (0.65 mL) 1 band on one side, 2 bands on the other side 2 Units (0.05 mL) into 4 sites per side (total of 8 sites and 16 Units) 1 Unit (0.025 mL) into 5 sites per band (total of 15 sites and 15 Units) 23 sites 31 Units (0.78 mL) 2 bands on each side 2 Units (0.05 mL) into 4 sites per side (total of 8 sites and 16 Units) 1 Unit (0.025 mL) into 5 sites per band (total of 20 sites and 20 Units) 28 sites 36 Units (0.9 mL)

10 OVERDOSAGE Excessive doses of BOTOX Cosmetic (onabotulinumtoxinA) for injection may be expected to produce neuromuscular weakness with a variety of symptoms. Symptoms of overdose are likely not to be present immediately following injection. Should accidental injection or oral ingestion occur or overdose be suspected, consider patients for further medical evaluation and immediately institute appropriate medical therapy, which may include hospitalization. The patient should be medically supervised for several weeks for signs and symptoms of systemic muscular weakness which could be local, or distant from the site of injection [see Boxed Warning and Warnings and Precautions ( 5.2 , 5.7 )] . If the musculature of the oropharynx and esophagus are affected, aspiration may occur which may lead to development of aspiration pneumonia. If the respiratory muscles become paralyzed or sufficiently weakened, intubation and assisted respiration may be necessary until recovery takes place. Supportive care could involve the need for a tracheostomy and/or prolonged mechanical ventilation, in addition to other general supportive care. 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. More information can be obtained at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5232a8.htm.

7 DRUG INTERACTIONS No formal drug interaction studies have been conducted with BOTOX Cosmetic (onabotulinumtoxinA) for injection. Patients receiving concomitant treatment of BOTOX Cosmetic and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like agents), or muscle relaxants, should be observed closely because the effect of BOTOX Cosmetic may be potentiated ( 7 ) 7.1 Aminoglycosides and Other Agents Interfering with Neuromuscular Transmission Co-administration of BOTOX Cosmetic and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like compounds) should only be performed with caution as the effect of the toxin may be potentiated. 7.2 Anticholinergic Drugs Use of anticholinergic drugs after administration of BOTOX Cosmetic may potentiate systemic anticholinergic effects. 7.3 Other Botulinum Neurotoxin Products The effect of administering different botulinum neurotoxin products at the same time or within several months of each other is unknown. Excessive neuromuscular weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin. 7.4 Muscle Relaxants Excessive weakness may also be exaggerated by administration of a muscle relaxant before or after administration of BOTOX Cosmetic.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action BOTOX Cosmetic blocks neuromuscular transmission by binding to acceptor sites on motor nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine. This inhibition occurs as the neurotoxin cleaves SNAP-25, a pre-synaptic protein integral to the successful docking and release of acetylcholine from vesicles situated within nerve endings. When injected intramuscularly at therapeutic doses, BOTOX Cosmetic produces partial chemical denervation of the muscle resulting in a localized reduction in muscle activity. In addition, the muscle may atrophy, axonal sprouting may occur, and extrajunctional acetylcholine receptors may develop. There is evidence that reinnervation of the muscle may occur, thus slowly reversing muscle denervation produced by BOTOX Cosmetic. 12.2 Pharmacodynamics No formal pharmacodynamic studies have been conducted with BOTOX Cosmetic (onabotulinumtoxinA) for injection. 12.3 Pharmacokinetics Using currently available analytical technology, it is not possible to detect BOTOX Cosmetic in the peripheral blood following intramuscular injection at the recommended doses. 12. 6 Immunogenicity Since BOTOX Cosmetic is a therapeutic protein, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to BOTOX Cosmetic in the studies described below with the incidence of antibodies in other studies or to other products may be misleading. In three Lateral Canthal Line trials, 916 subjects (517 subjects at 24 Units and 399 subjects at 44 Units) treated with BOTOX Cosmetic had specimens analyzed for antibody formation. Among the 916 BOTOX Cosmetic treated subjects, 14 subjects (1.5%) developed binding antibodies and no subjects (0%) developed the presence of neutralizing antibodies. The data reflect the subjects whose test results were considered positive or negative for neutralizing activity to BOTOX Cosmetic in a mouse protection assay. The critical factors for neutralizing antibody formation have not been well characterized. The results from some studies suggest that botulinum toxin injections at more frequent intervals or at higher doses may lead to greater incidence of antibody formation. The potential for antibody formation may be minimized by injecting with the lowest effective dose given at the longest feasible intervals between injections.

12.1 Mechanism of Action BOTOX Cosmetic blocks neuromuscular transmission by binding to acceptor sites on motor nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine. This inhibition occurs as the neurotoxin cleaves SNAP-25, a pre-synaptic protein integral to the successful docking and release of acetylcholine from vesicles situated within nerve endings. When injected intramuscularly at therapeutic doses, BOTOX Cosmetic produces partial chemical denervation of the muscle resulting in a localized reduction in muscle activity. In addition, the muscle may atrophy, axonal sprouting may occur, and extrajunctional acetylcholine receptors may develop. There is evidence that reinnervation of the muscle may occur, thus slowly reversing muscle denervation produced by BOTOX Cosmetic.

12.2 Pharmacodynamics No formal pharmacodynamic studies have been conducted with BOTOX Cosmetic (onabotulinumtoxinA) for injection.

12.3 Pharmacokinetics Using currently available analytical technology, it is not possible to detect BOTOX Cosmetic in the peripheral blood following intramuscular injection at the recommended doses.

20241018

52

3 DOSAGE FORMS AND STRENGTHS For injection: 50 Units, vacuum-dried powder in a single-dose vial for reconstitution For injection: 100 Units, vacuum-dried powder in a single-dose vial for reconstitution For Injection: 50 Units or 100 Units vacuum-dried powder in a single-dose vial for reconstitution ( 3 )

BOTOX Cosmetic onabotulinumtoxinA BOTULINUM TOXIN TYPE A BOTULINUM TOXIN TYPE A ALBUMIN HUMAN SODIUM CHLORIDE BOTOX Cosmetic onabotulinumtoxinA BOTULINUM TOXIN TYPE A BOTULINUM TOXIN TYPE A ALBUMIN HUMAN SODIUM CHLORIDE

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long term studies in animals have not been performed to evaluate carcinogenic potential of BOTOX Cosmetic. BOTOX Cosmetic was negative in a battery of in vitro (microbial reverse mutation assay, mammalian cell mutation assay, and chromosomal aberration assay) and in vivo (micronucleus assay) genetic toxicologic assays. In fertility studies of BOTOX Cosmetic (4, 8, or 16 Units/kg) in which either male or female rats were injected intramuscularly prior to mating and on the day of mating (3 doses, 2 weeks apart for males, 2 doses, 2 weeks apart for females) to untreated animals, reduced fertility was observed in males at the intermediate and high doses and in females at the high dose. The no-effect doses for reproductive toxicity (4 Units/kg in males, 8 Units/kg in females) are approximately 4-8 times the average high human dose for glabellar lines, lateral canthal lines, and forehead lines of 64 Units on a body weight basis (Units/kg).

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long term studies in animals have not been performed to evaluate carcinogenic potential of BOTOX Cosmetic. BOTOX Cosmetic was negative in a battery of in vitro (microbial reverse mutation assay, mammalian cell mutation assay, and chromosomal aberration assay) and in vivo (micronucleus assay) genetic toxicologic assays. In fertility studies of BOTOX Cosmetic (4, 8, or 16 Units/kg) in which either male or female rats were injected intramuscularly prior to mating and on the day of mating (3 doses, 2 weeks apart for males, 2 doses, 2 weeks apart for females) to untreated animals, reduced fertility was observed in males at the intermediate and high doses and in females at the high dose. The no-effect doses for reproductive toxicity (4 Units/kg in males, 8 Units/kg in females) are approximately 4-8 times the average high human dose for glabellar lines, lateral canthal lines, and forehead lines of 64 Units on a body weight basis (Units/kg).

BLA103000

BOTOX Cosmetic

onabotulinumtoxinA

0023-9232

HUMAN PRESCRIPTION DRUG

INTRAMUSCULAR

PRINCIPAL DISPLAY PANEL Botox Cosmetic onabotulinumtoxinA for Injection 50 Units/Vial NDC 0023-3919-50 Botox Cosmetic onabotulinumtoxinA for Injection 50 Units/Vial NDC 0023-3919-50

Indications and Usage ( 1 ) 10/2024 Dosage and Administration ( 2.2 , 2.3 , 2.4 ) 10/2024

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Provide a copy of the Medication Guide and review the contents with the patient. Swallowing, Speaking or Breathing Difficulties, or Other Unusual Symptoms Advise patients to inform their doctor or pharmacist if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing), or if any existing symptom worsens [see Boxed Warning and Warnings and Precautions ( 5.2 , 5.7 )] . Ability to Operate Machinery or Vehicles Advise patients that if loss of strength, muscle weakness, blurred vision, or drooping eyelids occur, avoid driving a car or engaging in other potentially hazardous activities. Ophthalmic Adverse Reactions Inform patients that BOTOX Cosmetic injection may cause eye dryness. Advise patients to report symptoms of eye dryness (e.g., eye pain, eye irritation, photosensitivity, or changes in vision) to their doctor. Manufactured by: AbbVie Inc. 1 N Waukegan Rd. North Chicago, IL 60064 U.S. License number 1889 © 2024 AbbVie. All rights reserved. BOTOX and its design are trademarks of Allergan, Inc., an AbbVie company. V4.1USPI3919 Logo Description automatically generated

MEDICATION GUIDE BOTOX ® BOTOX ® Cosmetic (Boe-tox) (onabotulinumtoxinA) for i njection , for intramuscular, intradetrusor, or intradermal use What is the most important information I should know about BOTOX and BOTOX Cosmetic? BOTOX and BOTOX Cosmetic may cause serious side effects that can be life threatening, including: Problems breathing or swallowing Spread of toxin effects These problems can happen hours, days, to weeks after an injection of BOTOX or BOTOX Cosmetic. Call your doctor or get medical help right away if you have any of these problems after treatment with BOTOX or BOTOX Cosmetic: Problems swallowing, speaking, or breathing. These problems can happen hours, days, to weeks after an injection of BOTOX or BOTOX Cosmetic usually because the muscles that you use to breathe and swallow can become weak after the injection. Death can happen as a complication if you have severe problems with swallowing or breathing after treatment with BOTOX or BOTOX Cosmetic . People with certain breathing problems may need to use muscles in their neck to help them breathe. These people may be at greater risk for serious breathing problems with BOTOX or BOTOX Cosmetic . Swallowing problems may last for several months. People who cannot swallow well may need a feeding tube to receive food and water. If swallowing problems are severe, food or liquids may go into your lungs. People who already have swallowing or breathing problems before receiving BOTOX or BOTOX Cosmetic have the highest risk of getting these problems. Spread of toxin effects. In some cases, the effect of botulinum toxin may affect areas of the body away from the injection site and cause symptoms of a serious condition called botulism. The symptoms of botulism include: loss of strength and muscle weakness all over the body double vision, blurred vision and drooping eyelids hoarseness or change or loss of voice (dysphonia) trouble saying words clearly (dysarthria) loss of bladder control trouble breathing trouble swallowing These symptoms can happen hours, days, to weeks after you receive an injection of BOTOX or BOTOX Cosmetic . These problems could make it unsafe for you to drive a car or do other dangerous activities. See "What should I avoid while receiving BOTOX or BOTOX Cosmetic ?" There has not been a confirmed serious case of spread of toxin effect away from the injection site when BOTOX has been used at the recommended dose to treat chronic migraine, severe underarm sweating, blepharospasm, or strabismus, or when BOTOX Cosmetic has been used at the recommended dose to treat frown lines, crow’s feet lines, forehead lines, or vertical bands connecting the jaw and neck. What are BOTOX and BOTOX Cosmetic? BOTOX is a prescription medicine that is injected into muscles and used: to treat overactive bladder symptoms such as a strong need to urinate with leaking or wetting accidents (urge urinary incontinence), a strong need to urinate right away (urgency) and urinating often (frequency) in adults when another type of medicine (anticholinergic) does not work well enough or cannot be taken. to treat leakage of urine (incontinence) in adults with overactive bladder due to neurologic disease when another type of medicine (anticholinergic) does not work well enough or cannot be taken. to treat overactive bladder due to a neurologic disease in children 5 years of age and older when another type of medicine (anticholinergic) does not work well enough or cannot be taken. to prevent headaches in adults with chronic migraine who have 15 or more days each month with headache lasting 4 or more hours each day. to treat increased muscle stiffness in people 2 years of age and older with spasticity. to treat the abnormal head position and neck pain that happens with cervical dystonia (CD) in adults. to treat certain types of eye muscle problems (strabismus) or abnormal spasm of the eyelids (blepharospasm) in people 12 years of age and older. BOTOX is also injected into the skin to treat the symptoms of severe underarm sweating (severe primary axillary hyperhidrosis) when medicines used on the skin (topical) do not work well enough. BOTOX Cosmetic is a prescription medicine for adults that is injected into muscles and used for a short period of time (temporary) to improve the look of: moderate to severe frown lines between the eyebrows (glabellar lines) moderate to severe crow’s feet lines moderate to severe forehead lines moderate to severe vertical bands connecting the jaw and neck (platysma bands) You may receive treatment for frown lines, crow’s feet lines, forehead lines, and vertical bands connecting the jaw and neck at the same time. It is not known whether BOTOX is safe and effective in people younger than: 18 years of age for treatment of overactive bladder with urinary incontinence 5 years of age for the treatment of overactive bladder due to a neurologic disease 18 years of age for treatment of chronic migraine 16 years of age for treatment of cervical dystonia 18 years of age for treatment of hyperhidrosis 12 years of age for treatment of strabismus or blepharospasm 2 years of age for treatment of spasticity BOTOX Cosmetic is not recommended for use in children younger than 18 years of age. It is not known whether BOTOX and BOTOX Cosmetic are safe and effective to prevent headaches in people with migraine who have 14 or fewer headache days each month (episodic migraine). It is not known whether BOTOX and BOTOX Cosmetic are safe and effective for severe sweating anywhere other than your armpits. It is not known if BOTOX Cosmetic is safe and effective for use more than 1 time every 3 months. Who should not receive BOTOX or BOTOX Cosmetic? Do not receive BOTOX or BOTOX Cosmetic if you: are allergic to any of the ingredients in BOTOX or BOTOX Cosmetic . See the end of this Medication Guide for a complete list of ingredients in BOTOX and BOTOX Cosmetic . had an allergic reaction to any other botulinum toxin product such as Myobloc ® (rimabotulinumtoxinB), Dysport ® (abobotulinumtoxinA), Xeomin ® (incobotulinumtoxinA), Jeuveau ® (prabotulinumtoxinA-xvfs), Daxxify ® (daxibotulinumtoxinA-lanm), or Letybo ® (letibotulinumtoxinA-wlbg). This may not be a complete list of all botulinum toxin products. have a skin infection at the planned injection site. are being treated for urinary incontinence and have a urinary tract infection (UTI). are being treated for urinary incontinence and find that you cannot empty your bladder on your own (only applies to people who are not routinely catheterizing). What should I tell my doctor before receiving BOTOX or BOTOX Cosmetic? Tell your doctor about all your medical conditions, including if you: have a disease that affects your muscles and nerves (such as amyotrophic lateral sclerosis [ALS or Lou Gehrig's disease], myasthenia gravis or Lambert-Eaton syndrome). See "What is the most important information I should know about BOTOX and BOTOX Cosmetic ?" have allergies to any botulinum toxin product. had any side effect from any botulinum toxin product in the past. have or have had a breathing problem, such as asthma or emphysema. have or have had swallowing problems. have or have had bleeding problems. have plans to have surgery. had surgery on your face. have weakness of your forehead muscles, such as trouble raising your eyebrows. have drooping eyelids. have any other change in the way your face normally looks. have symptoms of a urinary tract infection (UTI) and are being treated for urinary incontinence. Symptoms of a urinary tract infection may include pain or burning with urination, frequent urination, or fever. have problems emptying your bladder on your own and are being treated for urinary incontinence. are pregnant or plan to become pregnant. It is not known if BOTOX or BOTOX Cosmetic can harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if BOTOX or BOTOX Cosmetic passes into breast milk. Tell your doctor about all the medicines you take , including prescription and over-the-counter medicines, vitamins and herbal supplements. Using BOTOX or BOTOX Cosmetic with certain other medicines may cause serious side effects. Do not start any new medicines until you have told your doctor that you have received BOTOX or BOTOX Cosmetic in the past. Especially tell your doctor if you: have received any other botulinum toxin product in the last four months. have received injections of botulinum toxin, such as Myobloc ® (rimabotulinumtoxinB), Dysport ® (abobotulinumtoxinA), Xeomin ® (incobotulinumtoxinA), Jeuveau ® (prabotulinumtoxinA-xvfs), Daxxify ® (daxibotulinumtoxinA-lanm), or Letybo ® (letibotulinumtoxinA-wlbg) in the past. This may not be a complete list of all botulinum toxin products. Be sure your doctor knows exactly which product you received. have recently received an antibiotic by injection. take muscle relaxants. take an allergy or cold medicine. take a sleep medicine. take anti-platelets (aspirin-like products) or anti-coagulants (blood thinners). Ask your doctor if you are not sure if your medicine is one that is listed above. Know the medicines you take. Keep a list of your medicines with you to show your doctor and pharmacist each time you get a new medicine. How will I receive BOTOX or BOTOX Cosmetic? BOTOX or BOTOX Cosmetic is an injection that your doctor will give you. BOTOX is injected into your affected muscles, skin, or bladder. BOTOX Cosmetic is injected into your affected muscles. Your doctor may change your dose of BOTOX or BOTOX Cosmetic , until you and your doctor find the best dose for you. Your doctor will tell you how often you will receive your dose of BOTOX or BOTOX Cosmetic injections. What should I avoid while receiving BOTOX or BOTOX Cosmetic? BOTOX and BOTOX Cosmetic may cause loss of strength or general muscle weakness, vision problems, or dizziness within hours to weeks of taking BOTOX or BOTOX Cosmetic . If this happens, do not drive a car, operate machinery, or do other dangerous activities. See "What is the most important information I should know about BOTOX and BOTOX Cosmetic ?" What are the possible side effects of BOTOX and BOTOX Cosmetic? BOTOX and BOTOX Cosmetic can cause serious side effects. See "What is the most important information I should know about BOTOX and BOTOX Cosmetic ?" Other side effects of BOTOX and BOTOX Cosmetic include: dry mouth. discomfort or pain at the injection site. tiredness. headache. neck pain. eye problems: double vision, blurred vision, decreased eyesight, drooping eyelids, swelling of your eyelids, and dry eyes. drooping eyebrows. urinary tract infection in both children and adults being treated for urinary incontinence. painful urination in adults being treated for urinary incontinence. bacteria, white blood cells, and blood in the urine of children being treated for urinary incontinence. inability to empty your bladder on your own and are being treated for urinary incontinence. If you have difficulty fully emptying your bladder after getting BOTOX , you may need to use disposable self-catheters to empty your bladder up to a few times each day until your bladder is able to start emptying again. allergic reactions. Symptoms of an allergic reaction to BOTOX or BOTOX Cosmetic may include: itching, rash, red itchy welts, wheezing, asthma symptoms, or dizziness or feeling faint. Tell your doctor or get medical help right away if you are wheezing or have asthma symptoms, or if you become dizzy or faint. upper respiratory tract infection. Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of BOTOX and BOTOX Cosmetic . For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. General information about the safe and effective use of BOTOX and BOTOX Cosmetic: Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. This Medication Guide summarizes the most important information about BOTOX and BOTOX Cosmetic . If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about BOTOX and BOTOX Cosmetic that is written for health professionals. What are the ingredients in BOTOX and BOTOX Cosmetic? Active ingredient: onabotulinumtoxinA Inactive ingredients: human albumin and sodium chloride Manufactured by: AbbVie Inc. 1 N Waukegan Rd. North Chicago, IL 60064 U.S. License Number 1889 © 2024 AbbVie. All rights reserved. BOTOX and its design are trademarks of Allergan, Inc., an AbbVie company. All trademarks are the property of their respective owners. V8.0MG1145 This Medication Guide has been approved by the U.S. Food and Drug Administration Revised: 10/2024 A black and white logo Description automatically generated

14 CLINICAL STUDIES Figure 7 Figure 8: Percentage of Subjects with Treatment Success (Achieving None or Mild FHL from Baseline at Maximum Eyebrow Elevation) by Visit (Study 1) Figure 9: Percentage of Subjects with Treatment Success (Achieving None or Mild FHL from Baseline at Maximum Eyebrow Elevation) by Visit (Study 2) Figure 10 Figure 11 14.1 Glabellar Lines Two randomized, multi-center, double-blind, placebo-controlled studies of identical design were conducted to evaluate BOTOX Cosmetic for use in the temporary improvement of the appearance of moderate to severe glabellar facial lines. The studies enrolled healthy adults (ages 18 to 75) with glabellar lines of at least moderate severity at maximum frown. Subjects were excluded if they had ptosis, deep dermal scarring, or an inability to substantially lessen glabellar lines even by physically spreading them apart. Subjects received a single treatment with BOTOX Cosmetic (N=405, combined studies) or placebo (N=132, combined studies). Injection volume was 0.1 mL/injection site, for a dose/injection site in the active treatment groups of 4 Units. Subjects were injected intramuscularly in five sites, 1 in the procerus muscle and 2 in each corrugator supercilii muscle, for a total dose in the active treatment groups of 20 Units. The co-primary efficacy endpoints were the investigator’s rating of glabellar line severity at maximum frown and the subject’s global assessment of change in appearance of glabellar lines, both at Day 30 post-injection. For the investigator rating, using a 4-point grading scale (0=none, 3=severe) a responder was defined as having a severity grade of 0 or 1. For the subject’s global assessment of change, the ratings were from +4 (complete improvement) to -4 (very marked worsening). A responder was defined as having a grade of at least +2 (moderate improvement). After completion of the randomized studies, subjects were offered participation in an open label, repeat treatment study to assess the safety of repeated treatment sessions. The combined results of these two efficacy studies are presented here. The mean age was 46 years, with 32 subjects (6%) ≥65 years of age. Most of the subjects were women (82%), and White (84%). At baseline, 210 subjects (39%) had glabellar line severity scores at rest of moderate or severe. In these studies, the severity of glabellar lines was reduced for up to 120 days in the BOTOX Cosmetic group compared to the placebo group as measured both by investigator rating of glabellar line severity at maximum frown (Table 8), and by subject’s global assessment of change in appearance of glabellar lines (Table 9). Table 8: Investigator’s Assessment of Glabellar Line Severity at Maximum Frown – Responder Rates (% and Number of Subjects with Severity of None or Mild) Day BOTOX Cosmetic Placebo Difference a 7 74% 299/405 6% 8/132 68% (62, 74) 30 b 80% 325/405 3% 4/132 77% (72, 82) 60 70% 283/403 2% 2/130 69% (64, 74) 90 48% 192/403 2% 3/128 45% (40, 51) 120 25% 102/403 2% 2/128 24% (19, 29) a 95% confidence intervals are shown in parenthesis b Day 30: Co-Primary Efficacy Time point, p<0.001 Table 9: Subject’s Assessment of Change in Appearance of Glabellar Lines – Responder Rates (% and Number of Subjects with at Least Moderate Improvement) Day BOTOX Cosmetic Placebo Difference a 7 82% 334/405 9% 12/132 73% (68, 80) 30 b 89% 362/405 7% 9/132 83% (77, 88) 60 82% 330/403 4% 5/130 78% (73, 83) 90 63% 254/403 3% 4/128 60% (54, 66) 120 39% 157/403 1% 1/128 38% (33, 43) a 95% confidence intervals are shown in parenthesis b Day 30: Co-Primary Efficacy Time point, p<0.001 In the subset of subjects with resting severity scores of moderate or severe, the investigator assessment of a resting severity of mild or none at Day 30 was also achieved by more BOTOX Cosmetic treated subjects (74%, 119/161) than placebo treated subjects (20%, 10/49). Analysis of the limited number of subjects 65 years or older suggested a lower treatment-associated response compared to subjects less than 65 years of age (Table 10). Table 10: Investigator’s and Subject’s Assessment – Responder Rates for Subjects <65 and ≥65 Years of Age at Day 30 Assessment Age Group BOTOX Cosmetic (N=405) Placebo (N=132) Difference a Investigators (maximal frown) <65 83% 316/382 2% 2/123 81% (77, 86) Subjects <65 91% 346/382 7% 8/123 84% (79, 90) Investigators (maximal frown) ≥65 39% 9/23 22% 2/9 17% (-17, 51) Subjects ≥65 70% 16/23 11% 1/9 58% (31, 86) a 95% confidence intervals are shown in parenthesis Exploratory analyses by gender suggested that responder rates in the BOTOX Cosmetic treated group were higher for women than for men for both the investigator assessment (Day 30; 85% of 334 women, 59% of 71 men) and the Subject Assessment (Day 30; 93% of women, 72% of men). In the limited number of subjects that identified as other races (n=64 in the BOTOX Cosmetic treated group) the responder rates were similar to those observed in White subjects. 14.2 Lateral Canthal Lines Two multicenter, randomized, double-blind, placebo-controlled studies evaluated BOTOX Cosmetic (N=833, randomized to receive any BOTOX Cosmetic treatment or N=529 randomized to receive placebo) for the temporary improvement in the appearance of moderate to severe lateral canthal lines (LCL). Study 1 assessed BOTOX Cosmetic treatment of LCL alone; Study 2 also assessed simultaneous treatment of LCL and glabellar lines (GL). Both studies enrolled healthy adults with moderate to severe LCL at maximum smile at baseline; Study 2 also required subjects to have moderate to severe GL at maximum frown at baseline. In the 5-month Study 1, subjects were randomized to receive a single blinded treatment of 24 Units/0.6 mL (12 Units per side) consisting of 4 Units/0.1 mL into 3 sites of each orbicularis oculi muscle with either BOTOX Cosmetic (N=222) or placebo (N=223). In the 7-month Study 2, subjects were randomized to receive either BOTOX Cosmetic in the LCL region and placebo in the GL region (24 Units; N=306), or BOTOX Cosmetic in the LCL and GL regions (44 Units [24 Units for LCL and 20 Units for GL]; N=305), or placebo in the LCL and GL regions (0 Units; N=306). Subjects received the same 24 Units regimen for LCL as in Study 1, and the labeled 20 Units (5 injections, 4 Units per site) for GL. Subjects received the same treatment at days 1 and 120. The primary efficacy measure was the assessment of LCL severity at maximum smile using the 4-point Facial Wrinkle Scale with Photonumeric Guide (FWS; 0=none, 1= mild, 2=moderate, 3=severe). The FWS assessment was performed independently by both investigators and subjects. The primary timepoint was day 30 following the first treatment, as compared to baseline. The primary efficacy response definition was a composite ≥2-grade improvement from baseline in LCL severity at maximum smile, assessed by both investigator and subject on a per-subject basis. For Studies 1 and 2, the proportion of responders was statistically significant favoring BOTOX Cosmetic (24 Units [LCL alone] and 44 Units [LCL and GL]) compared to placebo at day 30 (Table 11). Table 11: Studies 1 and 2: Composite Investigator and Subject Assessment of LCL at Maximum Smile at Day 30 – Responder Rates (% and Number of Subjects Achieving ≥2-Grade Improvement from Baseline) Study BOTOX Cosmetic 24 Units BOTOX Cosmetic 24 Units LCL and 20 Units GL Placebo Study 1 26.1% 58/222 - 1.3% 3/223 Study 2 20.3% 62/306 21.3% 65/305 0.0% 0/306 The secondary endpoint of a responder defined as achieving a grade of none or mild for Study 1 as measured by the investigator is presented in Figure 7 below. Figure 7 : Percentage of Subjects with Treatment Success (% of Subjects achieving None or Mild from Baseline) by Visit (Study 1) 14.3 Forehead Lines Two multicenter, randomized, double-blind, placebo-controlled studies evaluated BOTOX Cosmetic (N=921, randomized to receive any BOTOX Cosmetic treatment or N=257, randomized to receive placebo) for the temporary improvement in the appearance of moderate to severe forehead lines (FHL). Study 1 assessed BOTOX Cosmetic treatment of FHL with glabellar lines (GL); Study 2 also assessed simultaneous treatment of FHL, GL, and lateral canthal lines [LCL]. Both studies enrolled healthy adults with moderate to severe FHL at maximum eyebrow elevation at baseline and moderate to severe GL at maximum frown at baseline; Study 2 also required subjects to have moderate to severe LCL at maximum smile at baseline. In the 12-month Study 1, subjects were randomized to receive BOTOX Cosmetic 20 Units to the frontalis muscle with 20 Units to the glabellar region (for a total of 40 Units) or placebo in both areas. In the 12-month Study 2, subjects were randomized to receive BOTOX Cosmetic 20 Units to the frontalis muscle, 20 Units to the glabellar region, and 0 Units to the LCL region (for a total of 40 units) or BOTOX Cosmetic 20 Units to the frontalis muscle, 20 Units to the glabellar region, and 24 Units to the LCL region (for a total of 64 Units) or placebo in all three areas. The primary efficacy measure was the assessment of FHL severity at maximum eyebrow elevation using the 4-point Facial Wrinkle Scale with Photonumeric Guide (FWS; 0=none, 1= mild, 2=moderate, 3=severe). The FWS assessment was performed independently by both investigators and subjects. The primary timepoint was Day 30 following the first treatment. The primary efficacy response definition was a composite ≥2-grade improvement from baseline in FHL severity at maximum eyebrow elevation, assessed by both investigator and subject on a per-subject basis. For Studies 1 and 2, the proportion of responders was greater in the BOTOX Cosmetic arms compared to placebo at Day 30 (p<0.0001 for Studies 1 and 2) (Table 12). Table 12: Studies 1 and 2: Composite Investigator and Subject Assessment of FHL Severity at Maximum Eyebrow Elevation at Day 30 – Responder Rates (% and Number of Subjects Achieving ≥2-Grade Improvement from Baseline) Study BOTOX Cosmetic (20 Units FHL with 20 Units GL) BOTOX Cosmetic (20 Units FHL, 20 Units GL, and 24 Units LCL) Placebo Study 1 N=290 61% - N=101 0% Study 2 N=318 46% N=313 53% N=156 1% A total of 165 and 197 subjects received 3 cycles over 1 year of BOTOX Cosmetic 40 Units (20 Units FHL with 20 Units GL) and 64 Units (20 Units FHL, 20 Units GL, and 24 Units LCL), respectively. The response rate for FHL was similar across all treatment cycles. The results for a key secondary endpoint of responders achieving a grade of none or mild on investigator ratings at maximum eyebrow elevation of FHL severity are presented below for Studies 1 and 2. Figure 8 : Percentage of Subjects with Treatment Success ( A chieving None or Mild FHL from Baseline at Maximum Eyebrow Elevation ) by Visit (Study 1) Figure 9 : Percentage of Subjects with Treatment Success ( A chieving None or Mild FHL from Baseline at Maximum Eyebrow Elevation ) by Visit (Study 2) The results of the Facial Line Satisfaction Questionnaire are presented in Table 13. Table 13: Facial Lines Satisfaction Questionnaire Response Frequency at Day 60 (Percentage of Subjects) Study 1 Study 2 BOTOX Cosmetic (20 Units FHL with 20 Units GL) N=289 Placebo N=99 BOTOX Cosmetic (20 Units FHL with 20 Units GL) N=317 Placebo N=155 “Very satisfied” 57% 1% 35% 0% “Mostly satisfied” 33% 0% 47% 3% “Neither dissatisfied nor satisfied” 4% 22% 9% 23% “Mostly dissatisfied” 4% 21% 7% 20% “Very dissatisfied” 2% 56% 2% 54% 14.4 Platysma Bands Two multicenter, randomized, double-blind, placebo-controlled trials (Study M21-309 [NCT04949399] and Study M21-310 [NCT04994535]) evaluated BOTOX Cosmetic (N=408 BOTOX Cosmetic and N=426 placebo) for the temporary improvement in the appearance of moderate to severe platysma bands. Based on baseline severity, subjects were randomized to receive a single treatment of BOTOX Cosmetic (26 Units, 31 Units, or 36 Units), or placebo. The primary efficacy measure was the assessment of platysma band severity at maximum contraction using the 5-grade clinician platysma band scale by the investigators, and the 5-grade participant platysma band scale by the subjects. For both scales, the 5 grades are 1=Minimal, 2=Mild, 3=Moderate, 4=Severe, 5=Extreme (Table 14). The investigator and subject assessments were performed independently. Table 14: Platysma Band Severity Grades and Descriptions Grade Severity Description 1 Minimal; no visible neck bands and no impact to jawline definition 2 Mild; visible neck bands and no impact to jawline definition 3 Moderate; 1 visible continuous neck band impacting jawline definition 4 Severe; 2 visible continuous neck bands impacting jawline definition 5 Extreme; 3 or more visible neck bands impacting jawline definition The primary timepoint was Day 14 after the first treatment. The studies enrolled healthy adults with moderate to severe platysma bands. In these studies, 94% were female, 91% were White, 5% were Asian, 3% were Black or African American; for ethnicity, 86% identified as not Hispanic or Latino. Subjects were 19 to 82 years old, with a mean age of 49 years. The primary efficacy endpoint was a multi-component endpoint defined as achievement of Grade 1 or 2 (Minimal or Mild) and at least a 2-grade improvement from baseline in platysma band severity at maximum contraction, assessed by both investigator and subject at Day 14 (Table 15). Table 15: Studies M21-309 and M21-310: Percentage of Subjects Achieving a Grade 1 or 2 (Minimal or Mild) with ≥ 2-Grade Improvement from Baseline Based on Both Investigator and Subject Assessments of Platysma Band Severity at Maximum Contraction at Day 14 Study M21-309 Study M21-310 BOTOX Cosmetic 26, 31, or 36 Units (N=199) Placebo (N=209) Difference d BOTOX Cosmetic 26, 31, or 36 Units (N=209) Placebo (N=217) Difference d Multi-component Assessment a 32% 2% 30% (24%, 37%) 31% 0% 31% (24%, 37%) Individual Components Investigator Assessment b 45% 4% - 42% 2% - Subject Assessment c 44% 4% - 40% 3% - Grade 1 or 2 (Minimal or Mild) and ≥ 2-grade improvement from baseline at maximum contraction on both the investigator and subject assessments at Day 14. Grade 1 or 2 (Minimal or Mild) and ≥ 2-grade improvement from baseline at maximum contraction on the investigator assessment at Day 14. Grade 1 or 2 (Minimal or Mild) and ≥ 2-grade improvement from baseline at maximum contraction on the subject assessment at Day 14. 95% confidence intervals are shown in parentheses. The percentages of subjects achieving these endpoints over time are shown in Figure 10 (Study M21-309) and Figure 11 (Study M21-310). Figure 10 : Percentages of Subjects Achieving a Grade 1 or 2 (Minimal or Mild) and at Least 2-Grade Improvement from Baseline Based on Both the Investigator and Subject Assessments of Platysma Band Severity at Maximum Contraction Over Time (Study M21-309) Figure 11 : Percentages of Subjects Achieving a Grade 1 or 2 (Minimal or Mild) and at Least 2-Grade Improvement from Baseline Based on Both the Investigator and Subject Assessments of Platysma Band Severity at Maximum Contraction Over Time (Study M21-310) The results for Appearance of Neck and Lower Face Questionnaire: Satisfaction (Follow-up) Item 5 at Day 14 secondary efficacy endpoints are presented for Studies M21-309 and M21-310 in Table 16. Table 16: Studies M21-309 and M21-310: Results for Appearance of Neck and Lower Face Questionnaire: Satisfaction (Follow-up) Item 5 (Satisfaction with Effect of Treatment on Platysma Bands) at Day 14 (Percentage of Subjects) Responses Study M21-309 Study M21-310 BOTOX Cosmetic 26, 31, or 36 Units (N = 199) Placebo (N = 209) BOTOX Cosmetic 26, 31, or 36 Units (N = 209) Placebo (N = 217) “Very satisfied” 31% 3% 22% 2% “Satisfied” 34% 9% 40% 10% “Neither satisfied nor dissatisfied” 25% 31% 25% 32% “Dissatisfied” 7% 34% 10% 29% “Very dissatisfied” 2% 24% 3% 27%

8.5 Geriatric Use Glabellar Lines In the two initial glabellar lines clinical studies of BOTOX Cosmetic, the responder rates appeared to be higher for subjects younger than age 65 than for subjects 65 years or older [see Clinical Studies ( 14 )] . Lateral Canthal Lines In the two lateral canthal lines clinical studies of BOTOX Cosmetic, the responder rates appeared to be higher for subjects younger than age 65 than for subjects 65 years or older. Forehead Lines In the two forehead lines clinical studies of BOTOX Cosmetic, the responder rates appeared to be higher for subjects younger than age 65 than for subjects 65 years or older. Platysma Bands In the two platysma bands clinical studies of BOTOX Cosmetic, 3.6% of subjects (13 subjects) treated with BOTOX Cosmetic were 65 years or older. Although the responder rates appeared to be higher for subjects younger than age 65 than for subjects 65 years or older, clinical studies of BOTOX Cosmetic did not include sufficient numbers of subjects 65 years or older to determine whether they respond differently from younger subjects.

8.4 Pediatric Use The safety and effectiveness of BOTOX Cosmetic have not been established in pediatric patients.

8.1 Pregnancy Risk Summary There are no studies or adequate data from postmarketing surveillance on the developmental risk associated with use of BOTOX Cosmetic in pregnant women. In animal studies, administrations of BOTOX Cosmetic during pregnancy resulted in adverse effects on fetal growth (decreased fetal body weight and skeletal ossification) at clinically relevant doses, which were associated with maternal toxicity [see Data]. The background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. 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 When BOTOX Cosmetic (4, 8, or 16 Units/kg) was administered intramuscularly to pregnant mice or rats two times during the period of organogenesis (on gestation days 5 and 13), reductions in fetal body weight and decreased fetal skeletal ossification were observed at the two highest doses. The no-effect dose for developmental toxicity in these studies (4 Units/kg) is approximately 4 times the average high human dose for glabellar lines, lateral canthal lines, and forehead lines of 64 Units on a body weight basis (Units/kg). When BOTOX Cosmetic was administered intramuscularly to pregnant rats (0.125, 0.25, 0.5, 1, 4, or 8 Units/kg) or rabbits (0.063, 0.125, 0.25, or 0.5 Units/kg) daily during the period of organogenesis (total of 12 doses in rats, 13 doses in rabbits), reduced fetal body weights and decreased fetal skeletal ossification were observed at the two highest doses in rats and at the highest dose in rabbits. These doses were also associated with significant maternal toxicity, including abortions, early deliveries, and maternal death. The developmental no-effect doses in these studies of 1 Unit/kg in rats is approximately equal the average high human dose of 64 Units based on Units/kg, and the developmental no-effect dose of 0.25 Units/kg in rabbits is less than the average high human dose based on Units/kg. When pregnant rats received single intramuscular injections (1, 4, or 16 Units/kg) at three different periods of development (prior to implantation, implantation, or organogenesis), no adverse effects on fetal development were observed. The developmental no-effect level for a single maternal dose in rats (16 Units/kg) is approximately 16 times the average high human dose of 64 Units based on Units/kg.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no studies or adequate data from postmarketing surveillance on the developmental risk associated with use of BOTOX Cosmetic in pregnant women. In animal studies, administrations of BOTOX Cosmetic during pregnancy resulted in adverse effects on fetal growth (decreased fetal body weight and skeletal ossification) at clinically relevant doses, which were associated with maternal toxicity [see Data]. The background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. 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 When BOTOX Cosmetic (4, 8, or 16 Units/kg) was administered intramuscularly to pregnant mice or rats two times during the period of organogenesis (on gestation days 5 and 13), reductions in fetal body weight and decreased fetal skeletal ossification were observed at the two highest doses. The no-effect dose for developmental toxicity in these studies (4 Units/kg) is approximately 4 times the average high human dose for glabellar lines, lateral canthal lines, and forehead lines of 64 Units on a body weight basis (Units/kg). When BOTOX Cosmetic was administered intramuscularly to pregnant rats (0.125, 0.25, 0.5, 1, 4, or 8 Units/kg) or rabbits (0.063, 0.125, 0.25, or 0.5 Units/kg) daily during the period of organogenesis (total of 12 doses in rats, 13 doses in rabbits), reduced fetal body weights and decreased fetal skeletal ossification were observed at the two highest doses in rats and at the highest dose in rabbits. These doses were also associated with significant maternal toxicity, including abortions, early deliveries, and maternal death. The developmental no-effect doses in these studies of 1 Unit/kg in rats is approximately equal the average high human dose of 64 Units based on Units/kg, and the developmental no-effect dose of 0.25 Units/kg in rabbits is less than the average high human dose based on Units/kg. When pregnant rats received single intramuscular injections (1, 4, or 16 Units/kg) at three different periods of development (prior to implantation, implantation, or organogenesis), no adverse effects on fetal development were observed. The developmental no-effect level for a single maternal dose in rats (16 Units/kg) is approximately 16 times the average high human dose of 64 Units based on Units/kg. 8. 2 Lactation Risk Summary There are no data on the presence of BOTOX Cosmetic in human or animal milk, the effects on the breastfed child, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BOTOX Cosmetic and any potential adverse effects on the breastfed infant from BOTOX Cosmetic or from the underlying maternal conditions. 8.4 Pediatric Use The safety and effectiveness of BOTOX Cosmetic have not been established in pediatric patients. 8.5 Geriatric Use Glabellar Lines In the two initial glabellar lines clinical studies of BOTOX Cosmetic, the responder rates appeared to be higher for subjects younger than age 65 than for subjects 65 years or older [see Clinical Studies ( 14 )] . Lateral Canthal Lines In the two lateral canthal lines clinical studies of BOTOX Cosmetic, the responder rates appeared to be higher for subjects younger than age 65 than for subjects 65 years or older. Forehead Lines In the two forehead lines clinical studies of BOTOX Cosmetic, the responder rates appeared to be higher for subjects younger than age 65 than for subjects 65 years or older. Platysma Bands In the two platysma bands clinical studies of BOTOX Cosmetic, 3.6% of subjects (13 subjects) treated with BOTOX Cosmetic were 65 years or older. Although the responder rates appeared to be higher for subjects younger than age 65 than for subjects 65 years or older, clinical studies of BOTOX Cosmetic did not include sufficient numbers of subjects 65 years or older to determine whether they respond differently from younger subjects.

16 HOW SUPPLIED/STORAGE AND HANDLING BOTOX Cosmetic (onabotulinumtoxinA) for injection is a vacuum-dried powder supplied in a single-dose vial in the following sizes: 50 Units: NDC 0023-3919-50 100 Units: NDC 0023-9232-01 BOTOX Cosmetic cartons have features to alert users if contents may have been compromised. Each BOTOX Cosmetic vial label and carton labeling also contain the U.S. License number 1889 [see Dosage and Administration ( 2.1 )] . Do not use the product and contact AbbVie for additional information at 1-800-678-1605 if the labeling is not as described above. Storage Store unopened vials of BOTOX Cosmetic in a refrigerator 2°C to 8°C (36ºF to 46ºF). Do not use after the expiration date on the vial. Store reconstituted BOTOX Cosmetic in a refrigerator 2°C to 8°C (36ºF to 46ºF) and administer within 24 hours [see Dosage and Administration ( 2.3 )] .

WARNING: DISTANT SPREAD OF TOXIN EFFECT Postmarketing reports indicate that the effects of BOTOX Cosmetic and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, 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. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults treated for spasticity and other conditions, particularly in those patients who have an underlying condition that would predispose them to these symptoms. In unapproved uses and in approved indications, cases of spread of effect have been reported at doses comparable to those used to treat cervical dystonia and spasticity and at lower doses. [see Warnings and Precautions ( 5.2 )] WARNING: DISTANT SPREAD OF TOXIN EFFECT See full prescribing information for complete boxed warning. The effects of BOTOX Cosmetic 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 but symptoms can also occur in adults, particularly in those patients who have an underlying condition that would predispose them to these symptoms. ( 5.2 )