Xeomin

WARNING: DISTANT SPREAD OF TOXIN EFFECT Postmarketing reports indicate that the effects of XEOMIN 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, 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. 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 underlying conditions that would predispose them to these symptoms. In unapproved uses, including lower limb spasticity in children, and in approved indications, cases of spread of effect have been reported at doses comparable to those used to treat cervical dystonia and at lower doses [see Warnings and Precautions (5.1) ] . WARNING: DISTANT SPREAD OF TOXIN EFFECT See full prescribing information for complete boxed warning. The effects of XEOMIN 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 underlying conditions that would predispose them to these symptoms. ( 5.1 )

5 WARNINGS AND PRECAUTIONS Respiratory, speech, or swallowing difficulties: increased risk if bilateral neck muscle injections are needed, or with pre-existing muscular disorders; immediate medical attention may be required ( 5.1 , 5.4 ) The potency Units of XEOMIN cannot be compared to or converted into Units of any other preparations of botulinum toxin products ( 5.2 ) Corneal exposure and ulceration: protective measures may be required ( 5.5 ) 5.1 Spread of Toxin Effect Postmarketing safety data from XEOMIN and other approved botulinum toxins suggest that botulinum toxin effects may, in some cases, 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 probably greatest in children treated for spasticity 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 lower limb spasticity in children, and in approved indications, symptoms consistent with spread of toxin effect have been reported at doses comparable to or lower than doses used to treat cervical dystonia. Patients or caregivers should be advised to seek immediate medical care if swallowing, speech, or respiratory disorders occur. 5.2 Lack of Unit Equivalency Between Botulinum Toxin Products The potency Units of XEOMIN are specific to the preparation and assay method utilized. Units of biological activity of XEOMIN cannot be compared to or converted into Units of any other botulinum toxin products assessed with any other specific assay method [see Description (11) ] . 5.3 Hypersensitivity Reactions Serious hypersensitivity reactions have been reported with botulinum toxin products. Hypersensitivity reactions include anaphylaxis, serum sickness, urticaria, soft tissue edema, and dyspnea. If serious and/or immediate hypersensitivity reactions occur, discontinue further injection of XEOMIN and institute appropriate medical therapy immediately. The use of XEOMIN in patients with a known hypersensitivity to any botulinum neurotoxin or to any of the excipients (human albumin, sucrose), could lead to a life-threatening allergic reaction [see Contraindications (4) ]. 5.4 Dysphagia and Breathing Difficulties Treatment with XEOMIN and other botulinum toxin products can result in swallowing or breathing difficulties. 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 muscles may be involved [see Warnings and Precautions (5.4) ] . Deaths as a complication of severe dysphagia have been reported after treatment with botulinum toxin. Dysphagia may persist for several months, and require use of a feeding tube to maintain adequate nutrition and hydration. Aspiration may result from severe dysphagia, and is a particular risk when treating patients in whom swallowing or respiratory function is already compromised. Treatment of cervical dystonia with botulinum toxins may weaken neck muscles that serve as accessory muscles of ventilation. This may result in critical loss of breathing capacity in patients with respiratory disorders who may have become dependent upon these accessory muscles. There have been post-marketing reports of serious breathing difficulties, including respiratory failure, in patients with cervical dystonia treated with botulinum toxin products. Patients with smaller neck muscle mass and patients who require bilateral injections into the sternocleidomastoid muscles have been reported to be at greater risk of dysphagia. In general, limiting the dose injected into the sternocleidomastoid muscle may decrease the occurrence of dysphagia. Patients treated with botulinum toxin may require immediate medical attention should they develop problems with swallowing, speech or respiratory disorders. These reactions can occur within hours to weeks after injection with botulinum toxin [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ] . Patients with neuromuscular disorders with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscular junctional disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome) may be at increased risk for severe dysphagia and respiratory compromise from typical doses of XEOMIN. 5.5 Corneal Exposure, Corneal Ulceration, and Ectropion in Patients Treated for Blepharospasm Reduced blinking from injection of botulinum toxin products in the orbicularis muscle can lead to corneal exposure, persistent epithelial defect, and corneal ulceration, especially in patients with VII nerve disorders. As patients with previous eye surgery may have reduced corneal sensation, carefully assess corneal sensation before treatment. Vigorous treatment of any corneal epithelial defect should be employed. This may require protective drops, ointment, therapeutic soft contact lenses, or closure of the eye by patching or other means. Because of its anticholinergic effects, XEOMIN should be used with caution in patients at risk of developing narrow angle glaucoma. To decrease the risk for ectropion, XEOMIN should not be injected into the medial lower eyelid area. Ecchymosis easily occurs in the soft tissues of the eyelid. Immediate gentle pressure at the injection site can limit the size. 5.6 Risk of Ptosis in Patients Treated for Glabellar Lines Do not exceed the recommended dosage and frequency of administration of XEOMIN. In order to reduce the complication of ptosis the following steps should be taken: Avoid injection near the levator palpebrae superioris, particularly in patients with larger brow depressor complexes. Corrugator injections should be placed at least 1 cm above the bony supraorbital ridge. 5.7 Human Albumin and Transmission of Viral Diseases This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases and variant Creutzfeldt-Jakob disease (vCJD). There is a theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD), but if that risk actually exists, the risk of transmission would also be considered extremely remote. No cases of transmission of viral diseases, CJD, or vCJD have ever been identified for licensed albumin or albumin contained in other licensed products. 5.8 Pre-existing Conditions at the Injection Site Use caution when XEOMIN is used where the targeted muscle shows excessive weakness or atrophy. Use caution when XEOMIN is used in patients who have marked facial asymmetry, with surgical alterations to the facial anatomy, pre-existing eyelid or eyebrow ptosis, when excessive weakness or atrophy is present in the target muscles, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin (e.g., the inability to substantially lessen glabellar lines even by physically spreading them apart).

6 ADVERSE REACTIONS The following adverse reactions to XEOMIN are discussed in greater detail in other sections of the labeling: Spread of Effects from Toxin [see Warnings and Precautions (5.1) ] Lack of Unit Equivalency between Botulinum Toxin Products [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Dysphagia and Breathing Difficulties [see Warnings and Precautions (5.4) ] Corneal Exposure, Corneal Ulceration, and Ectropion in Patients Treated with XEOMIN for Blepharospasm [see Warnings and Precautions (5.5) ] Risk of Ptosis in Patients Treated for Glabellar Lines [see Warnings and Precautions (5.6) ] Human Albumin and Transmission of Viral Diseases [see Warnings and Precautions (5.7) ] The most commonly observed adverse reactions at rates specified below and greater than placebo are: Chronic Sialorrhea: Chronic Sialorrhea in Adults (≥4% of patients) : tooth extraction, dry mouth, diarrhea, and hypertension ( 6.1 ) Chronic Sialorrhea in Pediatric Patients (≥1% of patients): bronchitis, headache, and nausea/vomiting ( 6.1 ) Spasticity: Upper Limb Spasticity in Adults (≥2% of patients) : seizure, nasopharyngitis, dry mouth, and upper respiratory tract infection ( 6.1 ) Upper Limb Spasticity in Pediatric Patients (≥3% of patients) : nasopharyngitis and bronchitis ( 6.1 ) Cervical Dystonia (≥5% of patients) : dysphagia, neck pain, muscle weakness, injection site pain, and musculoskeletal pain ( 6.1 ) Blepharospasm (≥10% of patients) : eyelid ptosis, dry eye, visual impairment, and dry mouth ( 6.1 ) Upper facial lines (Glabellar Lines, Horizontal Forehead Lines, and Lateral Canthal Lines): (>1% of patients) : injection site bruising ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Merz Pharmaceuticals, LLC at 888-493-6646 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, 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. Chronic Sialorrhea Chronic Sialorrhea in Adult Patients Table 6 lists the adverse reactions that occurred in ≥3% of XEOMIN-treated patients in the double-blind, placebo-controlled phase of the study in adult patients with chronic sialorrhea [see Clinical Studies (14.1) ] . The most common adverse reactions (≥4%) were tooth extraction, dry mouth, diarrhea, and hypertension. In the controlled portion of this study, 74 patients received 100 Units of XEOMIN, and 36 patients received placebo. XEOMIN-treated patients were 21-80 years old (mean 65 years), and were predominantly male (71%) and White (99.5%). Table 6: Adverse Reactions (≥3%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Adult Chronic Sialorrhea Study Adverse Reaction XEOMIN 100 Units (N = 74) % Placebo (N = 36) % Tooth extraction 5 0 Dry mouth 4 0 Diarrhea 4 3 Hypertension 4 3 Fall 3 0 Bronchitis 3 0 Dysphonia 3 0 Back pain 3 0 Dry eye 3 0 Chronic Sialorrhea in Pediatric Patients Table 7 lists the adverse reactions that occurred in ≥1% of XEOMIN-treated patients 6-17 years of age in the double-blind, placebo-controlled portion of the study in pediatric patients with chronic sialorrhea [see Clinical Studies (14.1) ] . Of the patients 6-17 years of age, 148 patients received a dose of XEOMIN according to body weight, and 72 patients received placebo. Thirty-five patients 2-5 years of age received an open-label dose of XEOMIN according to body weight. XEOMIN-treated patients were 2-17 years of age (mean 10 years), predominately male (63%) and White (100%). Table 7: Adverse Reactions (≥1%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Pediatric Chronic Sialorrhea Study Adverse Reaction XEOMIN (6-17 years) (N = 148) % Placebo (6-17 years) (N = 72) % Bronchitis 1 0 Headache 1 0 Nausea/Vomiting 1 0 The most frequently reported adverse reaction in patients ages 2-5 years after XEOMIN injections was nasopharyngitis (6%). In the open-label extension period, 222 patients 2-17 years of age received up to three additional treatments with XEOMIN every 16±2 weeks. The safety profile of XEOMIN during the open-label extension period was similar to that observed in the double-blind phase of the placebo-controlled pediatric chronic sialorrhea study. Upper Limb Spasticity Upper Limb Spasticity in Adult Patients Table 8 lists the adverse reactions that occurred in ≥2% of XEOMIN-treated patients in two placebo-controlled studies in adult patients with upper limb spasticity. Study 1 and Study 2 were both double-blind, placebo-controlled studies, with an open-label extension [see Clinical Studies (14.2) ] . In the controlled portion of these studies, 283 patients received ≥120 Units to 400 Units, of which 217 patients received at least 400 Units of XEOMIN, and 182 patients received placebo. XEOMIN-treated patients were 20-79 years of age (mean 56 years), and were predominantly male (58%), and White (84%). Table 8: Adverse Reactions (≥2%) and Greater for XEOMIN than Placebo: Double-Blind Phase of Placebo-Controlled Adult Upper Limb Spasticity Study 1 and Study 2 Adverse Reaction XEOMIN 400 Units (N = 217) % Placebo (N = 182) % Seizure 3 0 Nasopharyngitis 2 0 Dry mouth 2 1 Upper respiratory tract infection 2 1 Upper Limb Spasticity in Pediatric Patients Table 9 lists the adverse reactions that occurred in ≥2% of XEOMIN-treated patients in Study 1 in pediatric patients 2 years of age and older with upper limb spasticity. In the controlled portion of Study 1, 350 patients were randomized to one of three doses of XEOMIN: 87 received 2 Units/kg per affected upper limb, 87 received 6 Units/kg per affected upper limb, and 176 received 8 Units/kg per affected upper limb [ see Clinical Studies (14.2) ] . XEOMIN-treated patients were 2 to 17 years of age (mean 7 years), 63% were male, and 90% were White. No relationship between increased dose and increased occurrence of adverse reactions was observed. The most common adverse reactions (≥3% of XEOMIN-treated patients) at the recommended dose of XEOMIN (8 Units/kg) were nasopharyngitis and bronchitis. Table 9: Adverse Reactions (≥2%) in Patients Treated with XEOMIN 2 Units/kg or 8 Units/kg: Double-Blind Phase of Study 1 in Pediatric Upper Limb Spasticity Adverse Reactions XEOMIN 2 Units/kg N=87 % XEOMIN 8 Units/kg N=176 % Infections and infestations Nasopharyngitis 6 3 Bronchitis 2 3 Pharyngotonsillitis Includes pharyngotonsillitis, pharyngitis and tonsillitis 2 2 Upper respiratory tract infection 2 2 Respiratory tract infection viral 1 2 Injury, poisoning and procedural complications Fall 0 2 Musculoskeletal and connective tissue disorders Pain in extremity 0 2 Cervical Dystonia The data described below reflect exposure to a single intramuscular dose of XEOMIN in a placebo-controlled, Phase 3 trial in patients with cervical dystonia [ see Clinical Studies (14.3) ]. In this study, 159 patients received XEOMIN (78 were randomized to receive a total dose of 120 Units, and 81 were randomized to receive a total dose of 240 Units). XEOMIN-treated patients were 18 to 79 years old (mean 53 years), and were predominantly female (66%) and Caucasian (91%). At study baseline, approximately 25% had mild, 50% had moderate, and 25% had severe cervical dystonia. Approximately 61% of XEOMIN-treated patients had previously received another botulinum toxin type A product. Table 10 lists adverse reactions that occurred in ≥5% of XEOMIN-treated patients (in any treatment group) and greater than placebo. Table 10: Adverse Reactions (≥5%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Cervical Dystonia Study Adverse Reaction XEOMIN 120 Units (N=77) % XEOMIN 240 Units (N=82) % Placebo (N=74) % Musculoskeletal and connective tissue disorders 23 32 11 Neck pain 7 15 4 Muscular weakness 7 11 1 Musculoskeletal pain 7 4 1 Gastrointestinal disorders 18 24 4 Dysphagia 13 18 3 Nervous system disorders 16 17 7 General disorders and administration site conditions 16 11 11 Injection site pain 9 4 7 Infections and infestations 14 13 11 Respiratory, thoracic and mediastinal disorders 13 10 3 Blepharospasm Study 1 was a randomized, double-blind, placebo-controlled study that only included treatment-naïve patients [see Clinical Studies (14.4) ] . In the controlled portion, 22 patients received XEOMIN 25 Units, 19 patients received 50 Units, and 20 patients received placebo. XEOMIN-treated patients were 23 to 78 years of age (mean 55 years). Fifty-nine percent of the patients were women, 77% were Asian, and 23% White. No patients withdrew prematurely because of an adverse event. Table 11 lists the adverse reactions that occurred in ≥6% of XEOMIN-treated patients and greater than placebo. Table 11: Adverse Reactions (≥6%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Blepharospasm Study 1 Adverse Reaction XEOMIN 50 U (N=19) % Placebo (N=20) % Eye disorders 21 10 Eyelid ptosis 16 0 Study 2 was a double-blind, placebo-controlled, flexible dose study with an open-label extension (OLEX) period. The study only included patients previously treated with onabotulinumtoxinA (Botox) [see Clinical Studies (14.4) ] . In the controlled portion, 74 patients received XEOMIN at a mean dose of approximately 33 Units per eye (minimum 10 Units, maximum 50 Units). XEOMIN-treated patients were 22 to 79 years of age (mean 62 years), predominantly female (65%) and Caucasian (60%). Table 12 lists the adverse reactions that occurred in ≥5% of XEOMIN-treated patients and greater than placebo. Table 12: Adverse Reactions (≥5%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Blepharospasm Study 2 Adverse Reaction XEOMIN (N=74) % Placebo (N=34) % Eye disorders 38 21 Eyelid ptosis 19 9 Dry eye 16 12 Visual impairment including vision blurred 12 6 Gastrointestinal disorders 30 15 Dry mouth 16 3 Diarrhea 8 0 Infections and infestations 20 15 Nasopharyngitis 5 3 Respiratory tract infection 5 3 Nervous system disorders 14 9 Headache 7 3 General disorders and administration site conditions 11 9 Respiratory, thoracic and mediastinal disorders 11 3 Dyspnea 5 3 Upper Facial Lines [Glabellar Lines (GL), Horizontal Forehead Lines (HFL), and Lateral Canthal Lines (LCL)] In two placebo-controlled trials in 730 adult subjects with upper facial lines (GL, HFL, and LCL), 545 subjects received up to 64 Units of XEOMIN and 185 subjects received placebo. XEOMIN-treated subjects were 19 to 76 years old and were predominantly female (82%). Adverse reactions were reported for 62 of the 545 XEOMIN-treated subjects (11%) and for 14 of the 185 placebo-treated subjects (8%). The most frequent adverse reactions ≥1% and greater for XEOMIN than placebo are presented in Table 13. Table 13: Adverse Reactions (≥1%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Upper Facial Lines (GL, HFL, and LCL) Trials Upper Facial Lines (GL, HFL, and LCL) Adverse Reaction XEOMIN N=545 % Placebo N=185 % Injection site bruising 2 1 In the placebo-controlled trials, brow ptosis (0.7%) and injection site discomfort (0.6%) were also reported more frequently for XEOMIN than placebo-treated subjects. In the two repeated dose upper facial lines (GL, HFL, and LCL) trials with up to three treatments of XEOMIN, adverse reactions were reported for 123 of the 720 subjects (17%). Injection site hematoma was the most common adverse reaction, reported in 8% of subjects, followed by headache (3%), injection site bruising (3%) and brow ptosis (1%). The incidence of these adverse reactions tended to decrease with subsequent treatments. In both trials, all randomized subjects were followed up for 120 days before they could enter the open-label extension (OLEX) period which comprised two additional treatment cycles, with durations of 120 days each plus up to 30 days for eligibility reassessments per cycle. During OLEX period, eligible subjects received simultaneous upper facial lines injections of XEOMIN at a total dose of 64 U in all three facial areas (20 U in GL, 20 U in HFL, and 24 U in LCL area). Glabellar Lines In three placebo-controlled trials in 803 adult subjects with glabellar lines, 535 subjects received a single dose of 20 Units of XEOMIN and 268 subjects received placebo. XEOMIN-treated subjects were 24 to 74 years old, and were predominantly female (88%). The most frequent adverse reactions ≥1% and greater for XEOMIN than Placebo are presented in Table 14. Table 14: Adverse Reactions (≥1%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Glabellar Lines Trials Adverse Reaction XEOMIN N=535 % Placebo N=263 % Nervous system disorders Headache 5 2 In the placebo-controlled trials, facial paresis (0.7%), injection site hematoma (0.6%) and eyelid edema (0.4%) were also reported more frequently for XEOMIN than placebo-treated subjects. In open-label, multiple-dose trials, adverse reactions were reported for 105 of the 800 subjects (13%). Headache was the most common adverse reaction, reported in 7% of subjects, followed by injection site hematoma (1%). Adverse reactions reported in less than 1% of subjects were: facial paresis (brow ptosis), muscle disorder (elevation of eyebrow), injection site pain, and eyelid edema. 6.2 Postmarketing Experience The following adverse reactions have been reported during post-approval use of XEOMIN. 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: allergic dermatitis, dysarthria, dysphagia, eye swelling, eyelid edema, flu-like symptoms, herpes zoster, hypersensitivity, injection site pain, injection site reaction, localized allergic reactions (e.g., swelling, edema, erythema, pruritus or rash), muscle spasm, muscular weakness, myalgia, nausea, and persistent dry mouth (> 110 days).

<table width="60%"><caption>Table 6: Adverse Reactions (&#x2265;3%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Adult Chronic Sialorrhea Study</caption><col width="34%" align="left" valign="middle"/><col width="33%" align="center" valign="middle"/><col width="33%" align="center" valign="middle"/><thead><tr><th styleCode="Lrule Rrule" align="left" valign="middle">Adverse Reaction</th><th styleCode="Rrule">XEOMIN 100 Units (N = 74) %</th><th styleCode="Rrule">Placebo (N = 36) %</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Tooth extraction</td><td styleCode="Rrule">5</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Dry mouth</td><td styleCode="Rrule">4</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Diarrhea</td><td styleCode="Rrule">4</td><td styleCode="Rrule">3</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypertension</td><td styleCode="Rrule">4</td><td styleCode="Rrule">3</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Fall</td><td styleCode="Rrule">3</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Bronchitis</td><td styleCode="Rrule">3</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Dysphonia</td><td styleCode="Rrule">3</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Back pain</td><td styleCode="Rrule">3</td><td styleCode="Rrule">0</td></tr><tr><td styleCode="Lrule Rrule"> Dry eye</td><td styleCode="Rrule">3</td><td styleCode="Rrule">0</td></tr></tbody></table>

<table width="60%"><caption>Table 7: Adverse Reactions (&#x2265;1%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Pediatric Chronic Sialorrhea Study</caption><col width="36%" align="left" valign="top"/><col width="30%" align="center" valign="top"/><col width="34%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule" valign="middle">Adverse Reaction</th><th styleCode="Rrule">XEOMIN (6-17 years) (N = 148) %</th><th styleCode="Rrule">Placebo (6-17 years) (N = 72) %</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Bronchitis</td><td styleCode="Rrule">1</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Headache</td><td styleCode="Rrule">1</td><td styleCode="Rrule">0</td></tr><tr><td styleCode="Lrule Rrule"> Nausea/Vomiting</td><td styleCode="Rrule">1</td><td styleCode="Rrule">0</td></tr></tbody></table>

<table width="65%"><caption>Table 8: Adverse Reactions (&#x2265;2%) and Greater for XEOMIN than Placebo: Double-Blind Phase of Placebo-Controlled Adult Upper Limb Spasticity Study 1 and Study 2</caption><col width="50%" align="left" valign="bottom"/><col width="30%" align="center" valign="bottom"/><col width="20%" align="center" valign="bottom"/><thead><tr><th styleCode="Lrule Rrule" align="left" valign="middle">Adverse Reaction</th><th styleCode="Rrule">XEOMIN 400 Units (N = 217) %</th><th styleCode="Rrule">Placebo (N = 182) %</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Seizure</td><td styleCode="Rrule">3</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Nasopharyngitis</td><td styleCode="Rrule">2</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Dry mouth</td><td styleCode="Rrule">2</td><td styleCode="Rrule">1</td></tr><tr><td styleCode="Lrule Rrule"> Upper respiratory tract infection</td><td styleCode="Rrule">2</td><td styleCode="Rrule">1</td></tr></tbody></table>