Abobotulinumtoxin A Injection

Cervical Dystonia

DYSPORT® is indicated for the treatment of adults with cervical dystonia.

Glabellar Lines

DYSPORT® is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with procerus and corrugator muscle activity in adult patients less than 65 years of age.

Upper Limb Spasticity

DYSPORT® is indicated for the treatment of upper limb spasticity in adult patients, to decrease the severity of increased muscle tone in elbow flexors, wrist flexors and finger flexors.

Included as part of the PRECAUTIONS section.

DYSPORT®
(DIS-port)
(abobotulinumtoxinA) for Injection

What is the most important information I should know about DYSPORT®?

DYSPORT® may cause serious side effects that can be life threatening including:

• Problems breathing or swallowing
• Spread of toxin effects

These problems can happen within hours, or days to weeks after an injection of DYSPORT®. Call your doctor or get medical help right away if you have any of these problems after treatment with DYSPORT®

1. Problems swallowing, speaking, or breathing. These problems can happen within hours, or days to weeks after an injection of DYSPORT® 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 DYSPORT®.

• People with certain breathing problems may need to use muscles in their neck to help them breathe. These patients may be at greater risk for serious breathing problems with DYSPORT®.
  • Swallowing problems may last for several weeks. 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 DYSPORT® have the highest risk of getting these problems.

2. 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 within hours, or days to weeks after you receive an injection of DYSPORT®. These problems could make it unsafe for you to drive a car or do other dangerous activities. See “What should I avoid while receiving DYSPORT®?”

What is DYSPORT®?

DYSPORT® is a prescription medicine that is injected into muscles and used:

• to treat cervical dystonia (CD) in adults
• to improve the look of moderate to severe frown lines between the eyebrows (glabellar lines) in adults younger than 65 years of age for a short period of time (temporary)
• to treat increased muscle stiffness in, elbow, wrist, and finger muscles in adults with upper limb spasticity.

CD is caused by muscle spasms in the neck. These spasms cause abnormal position of the head and often neck pain. After DYSPORT® is injected into muscles; those muscles are weakened for up to 12 to 16 weeks or longer. This may help lessen your symptoms.

Frown lines (wrinkles) happen because the muscles that control facial expression are used often (muscle tightening over and over). After DYSPORT® is injected into the muscles that control facial expression, the medicine stops the tightening of these muscles for up to 4 months.

• It is not known whether DYSPORT® is safe or effective in children under 18 years of age.
• It is not known whether DYSPORT® is safe or effective for the treatment of other types of muscle spasms.
• It is not known whether DYSPORT® is safe or effective for the treatment of other wrinkles.

Who should not take DYSPORT®?

Do not take DYSPORT® if you:

• are allergic to DYSPORT® or any of the ingredients in DYSPORT®. See the end of this Medication Guide for a list of ingredients in DYSPORT®
• are allergic to cow's milk protein
• had an allergic reaction to any other botulinum toxin product such as Myobloc® (rimabotulinumtoxinB), Botox® (onabotulinumtoxinA), or Xeomin® (incobotulinumtoxinA).
• have a skin infection at the planned injection site

What should I tell my doctor before taking DYSPORT®?

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 DYSPORT®?”
• 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 diabetes
• have or have had a slow heart beat or other problem with your heart rate or rhythm
• 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
• are pregnant or plan to become pregnant. It is not known if DYSPORT® can harm your unborn baby
• are breast-feeding or planning to breast-feed. It is not known if DYSPORT® passes into breast milk

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal products. Using DYSPORT® with certain other medicines may cause serious side effects. Do not start any newmedicines until you have told your doctor that you have received DYSPORT® 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), Botox® (onabotulinumtoxinA) or Xeomin® (incobotulinumtoxinA) in the past; 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

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 should I take DYSPORT®?

• DYSPORT® is an injection that your doctor will give you
• DYSPORT® is injected into the affected muscles
• Your doctor may give you another dose of DYSPORT® after 12 weeks or longer, if it is needed
• If you are being treated for CD or upper limb spasticity, your doctor may change your dose of DYSPORT®, until you andyour doctor find the best dose for you
• The dose of DYSPORT® is not the same as the dose of any other botulinum toxin product

What should I avoid while taking DYSPORT®?

DYSPORT® may cause loss of strength or general muscle weakness, blurred vision, or drooping eyelids within hours toweeks of taking DYSPORT®. If this happens, do not drive a car, operate machinery, or do other dangerousactivities. See “What is the most important information I should know about DYSPORT®?”

What are the possible side effects of DYSPORT®?

DYSPORT®can cause serious side effects. See “What is the most important information I should know about DYSPORT®?”

The most common side effects of DYSPORT® in people with cervical dystonia include:

• muscle weakness
• neck pain or muscle pain
• difficulty swallowing
• dry mouth
• problems speaking
• injection site pain
• feeling of tiredness
• eye problems
• headache

The most common side effects of DYSPORT® in people with glabellar lines include:

• stuffy or runny nose and sore throat
• headache
• drooping eyelids
• injection site pain
• injection site reaction
• sinus infection
• upper respiratory infection
• swelling of eyelids
• nausea

The most common side effects of DYSPORT® in people with upper limb spasticity include:

• urinary tract infection
• fall
• stuffy or runny nose and sore throat
• muscle weakness
• depression
• dizziness
• musculoskeletal pain

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 DYSPORT®. For more information, ask your doctor 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 DYSPORT®:

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.

This Medication Guide summarizes the most important information about DYSPORT®. If you would like more information,talk with your doctor. You can ask your doctor or pharmacist for information about DYSPORT® that is written for healthcareprofessionals. For more information about DYSPORT® call 877-397-7671 or go to www.dysport.com orwww.DysportUSA.com.

What are the ingredients in DYSPORT®?

Active ingredient: (botulinum toxin Type A)

Inactive ingredients: human albumin and lactose. DYSPORT® may contain cow's milk protein.

Your doctor or pharmacist can provide more information about Dysport (abobotulinumtoxinA).

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 3.01. Revision date: 8/24/2012.

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The following serious adverse reactions are discussed below and elsewhere in labeling:

• Distant Spread of Toxin Effect [see BOXED WARNING]
• Lack of Interchangeability between Botulinum Toxin Products [see WARNINGS AND PRECAUTIONS]
• Spread of Effects from Toxin [see WARNINGS AND PRECAUTIONS]
• Dysphagia and Breathing Difficulties [see WARNINGS AND PRECAUTIONS]
• Facial Anatomy in the Treatment of Glabellar Lines [see WARNINGS AND PRECAUTIONS]
• Pre-existing Neuromuscular Disorders [see WARNINGS AND PRECAUTIONS]
• Human Albumin [see WARNINGS AND PRECAUTIONS]
• Intradermal Immune Reaction [see WARNINGS AND PRECAUTIONS]

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.

Cervical Dystonia

The data described below reflect exposure to DYSPORT® in 357 cervical dystonia patients in 6 studies. Of these, two studies were randomized, double-blind, single treatment, placebo controlled studies with subsequent optional open label treatment in which dose optimization (250 to 1000 Units per treatment) over the course of 5 treatment cycles was allowed.

The population was almost entirely Caucasian (99%) with a median age of 51 years (range 18-82 years). Most patients (87%) were less than 65 years of age; 58.4% were women.

The most commonly reported adverse reactions (occurring in more than 5% of patients who received 500 Units of DYSPORT® in the placebo controlled clinical trials) in cervical dystonia patients were: muscular weakness, dysphagia, dry mouth, injection site discomfort, fatigue, headache, neck pain, musculoskeletal pain, dysphonia, injection site pain, and eye disorders (consisting of blurred vision, diplopia, and reduced visual acuity and accommodation). Other than injection site reactions, most adverse reactions became noticeable about one week after treatment and lasted several weeks.

The rates of adverse reactions were higher in the combined controlled and open-label experience than in the placebo-controlled trials. During the clinical studies, two patients ( < 1%) experienced adverse reactions leading to withdrawal. One patient experienced disturbance in attention, eyelid disorder, feeling abnormal and headache, and one patient experienced dysphagia.

Table 3 compares the incidence of the most frequent adverse reactions from a single treatment cycle of 500 Units of DYSPORT® compared to placebo [see Clinical Studies].

Table 3: Most Common Adverse Reactions (>5%) and Greater than Placebo in the Pooled, Double-blind Phase of Clinical Trials in Patients with Cervical Dystonia

Dose-response relationships for common adverse reactions in a randomized multiple fixed-dose study in which the total dose was divided between two muscles (the sternocleidomastoid and splenius capitis) are shown in Table 4.

Table 4: Common Adverse Reactions by Dose in Fixed-dose Study in Patients with Cervical Dystonia

Injection site discomfort and injection site pain were common adverse reactions following DYSPORT® administration.

The following adverse reactions were reported less frequently ( < 5%).

Breathing difficulties were reported by approximately 3% of patients following DYSPORT® administration and in 1% of placebo patients in clinical trials during the double-blind phase. These consisted mainly of dyspnea. The median time to onset from last dose of DYSPORT® was approximately one week, and the median duration was approximately three weeks.

Other adverse reactions with incidences of less than 5% in the DYSPORT® 500 Units group in the double-blind phase of clinical trials included dizziness in 3.5% of DYSPORT®-treated patients and 1% of placebo-treated patients, and muscle atrophy in 1% of DYSPORT®-treated patients and in none of the placebo-treated patients.

Patients treated with DYSPORT® exhibited a small increase from baseline (0.23 mol/L) in mean blood glucose relative to placebo- treated patients. This was not clinically significant among patients in the development program but could be a factor in patients whose diabetes is difficult to control.

ECG measurements were only recorded in a limited number of patients in an open-label study without a placebo or active control. This study showed a statistically significant reduction in heart rate compared to baseline, averaging about three beats per minute, observed thirty minutes after injection.

Glabellar Lines

In placebo-controlled clinical trials of DYSPORT®, the most common adverse reactions( ≥ 2%) following injection of DYSPORT® were nasopharyngitis, headache, injection site pain, injection site reaction, upper respiratory tract infection, eyelid edema, eyelid ptosis, sinusitis, and nausea.

Table 5 reflects exposure to DYSPORT® in 398 patients 19 to 75 years of age who were evaluated in the randomized, placebo- controlled clinical studies that assessed the use of DYSPORT® for the temporary improvement in the appearance of glabellar lines [see Clinical Studies]. Adverse reactions of any cause occurred in 48% of the DYSPORT®-treated patients and 33% of the placebo- treated patients.

Table 5: Most Common Adverse Reactions with > 1% Incidence in Pooled, Placebo-Controlled Trials for Glabellar Lines

In the overall safety database, where some patients received up to twelve treatments with DYSPORT®, adverse reactions were reported for 57% (1425/2491) of patients. The most frequently reported of these adverse reactions were headache, nasopharyngitis, injection site pain, sinusitis, URI, injection site bruising, and injection site reaction (numbness, discomfort, erythema, tenderness, tingling, itching, stinging, warmth, irritation, tightness, swelling).

Adverse reactions that occurred after repeated injections in 2-3% of the population included bronchitis, influenza, pharyngolaryngeal pain, cough, contact dermatitis, injection site swelling, and injection site discomfort.

The incidence of eyelid ptosis did not increase in the long-term safety studies with multiple re-treatments at intervals ≥ three months. The majority of the reports of eyelid ptosis were mild to moderate in severity and resolved over several weeks. [see DOSAGE AND ADMINISTRATION].

Upper Limb Spasticity

Table 6 lists the most frequently reported adverse reactions ( ≥ 2%) in any DYSPORT® dose group and more frequent than placebo in double blind studies evaluating the treatment of upper limb spasticity in adults with DYSPORT®.

Table 6: Most Common Adverse Reactions Observed in at Least 2% of Patients Treated in Pooled, Double-Blind Trials of Patients with Upper Limb Spasticity Reported More Frequently than with Placebo

Injection site reactions (e.g. pain, bruising, haemorrhage, injection site erythema/haematoma etc.) have occurred following administration of DYSPORT®.

In a pooled analysis of clinical studies, adverse reactions with an incidence of less than 2% reported in DYSPORT® treatment groups included dysphagia 0.5%, gait disturbance 0.5%, hypertonia 0.5%, and sensation of heaviness 0.3%.

Postmarketing Experience

Because adverse 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.

The following adverse reactions have been identified during post-approval use of DYSPORT®: vertigo, photophobia, influenza-like illness, amyotrophy, burning sensation, facial paresis, hypoesthesia, erythema, and excessive granulation tissue.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity.

The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. In addition, the observed incidence of 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 across products in this class may be misleading.

About 3% of subjects developed antibodies (binding or neutralizing) over time with DYSPORT® treatment.

Testing for antibodies to DYSPORT® was performed for 1554 subjects who had up to nine cycles of treatment. Two subjects (0.13%) tested positive for binding antibodies at baseline. Three additional subjects tested positive for binding antibodies after receiving DYSPORT® treatment. None of the subjects tested positive for neutralizing antibodies.

From 230 subjects treated with DYSPORT® and tested for the presence of binding antibodies, 5 subjects were positive at baseline and 17 developed antibodies after treatment. Among those 17 subjects, 10 subjects developed neutralizing antibodies. An additional 51 subjects from a separate repeat dose study were tested for the presence of neutralizing antibodies only. None of the subjects tested positive.

In total, from the 281 subjects treated in the long-term studies and tested for the presence of neutralizing antibodies, 3.6% developed neutralizing antibodies after treatment.

In the presence of binding and neutralizing antibodies to DYSPORT® some patients continue to experience clinical benefit.

Read the entire FDA prescribing information for Dysport (Abobotulinumtoxin A Injection)

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