More than skin deep. The medical uses of BOTOX

Transcription

1 The medical uses of More tha ski deep Idicatios is a prescriptio medicie that is ijected ito muscles ad used: to treat the abormal head positio ad eck pai that happes with cervical dystoia (CD) i people 16 years ad older to treat certai types of eye muscle problems (strabismus) or abormal spasm of the eyelids (blepharospasm) i people 12 years ad older IMPORTANT SAFETY INFORMATION ad Cosmetic may cause serious side effects that ca be life threateig. Call your doctor or get medical help right away if you have ay of these problems ay time (hours to weeks) after ijectio of or Cosmetic: Problems swallowig, speakig, or breathig, due to weakeig of associated muscles, ca be severe ad result i loss of life. You are at the highest risk if these problems are pre-existig before ijectio. Swallowig problems may last for several moths Please see additioal Idicatios ad Importat Safety Iformatio about iside. 1

2 The medical uses of (oabotuliumtoxia) Table of cotets Page 4 Page 6 What is? How eurotoxi treatmet works Idicatios (cotiued) is also ijected ito the ski to treat the symptoms of severe uderarm sweatig (severe primary axillary hyperhidrosis) whe medicies used o the ski (topical) do ot work well eough i people 18 years ad older. It is ot kow whether is safe or effective for other types of muscle spasms or for severe sweatig aywhere other tha your armpits. Cosmetic is a prescriptio medicie that is ijected ito muscles ad used to improve the look of moderate to severe frow lies betwee the eyebrows (glabellar lies) i people 18 to 65 years of age for a short period of time (temporary). Page 8 Page 10 Page 12 Page 14 Page 22 Page 26 Page 28 Page 30 Page 32 Page 34 What to expect from your treatmet Frequetly asked questios about treatmet treatmet ad your isurace coverage Cervical dystoia ad (oabotuliumtoxia) treatmet success stories Livig with cervical dystoia tips for patiets Blepharospasm ad treatmet Strabismus ad treatmet Fidig a doctor who ijects Patiet support groups 2 3

3 What is? You may have heard of Cosmetic (oabotuliumtoxia). But as you will lear i this brochure, the story is more tha ski deep. (oabotuliumtoxia) is a effective therapy that has bee used to treat patiets for approximately 20 years. Oe of the most researched medicies i the world, treatmet is approved for medical use i approximately 75 coutries. First idetified i the 1890s, is a purified protei that comes from the bacterium Clostridium botulium. I approximately 100 years, our kowledge of Botulium Toxi Type A has expaded from the idetificatio of the bacterium C. botulium to the commercializatio of as the first approved botulium toxi therapy i the Uited States. I 1989, eurotoxi was approved by the Food ad Drug Admiistratio (FDA) for the treatmet of blepharospasm (eyelid spasms) ad strabismus (crossed or misaliged eyes). I 2000, the FDA approved for the treatmet of ucotrollable muscle tighteig or turig i the eck, kow as cervical dystoia. Aother milestoe i the history of was its approval i 2004 to treat symptoms of severe uderarm sweatig whe topical medicies do t work well eough. The same formulatio with dosig specific to temporarily treat moderate to severe frow lies betwee the brows for people ages 18 to 65 was approved i 2002 as Cosmetic. (oabotuliumtoxia) is made oly by Allerga a global specialty pharmaceutical ad medical device compay offerig iovative products i approximately 100 coutries. treatmet is produced uder strict quality cotrol stadards by Allerga ad is to be admiistered to patiets oly by licesed doctors. Every drug approved by the FDA has product safety iformatio for doctors ad for patiets. The highlighted blue sectios i this brochure cotai iformatio about treatmet, as well as detailed iformatio about the drug itself. If you have ay questios or cocers about ay of the iformatio cotaied i these sectios, please do ot hesitate to ask your doctor. IMPORTANT SAFETY INFORMATION (cotiued) Call your doctor or get medical help right away if you have ay of these problems ay time (hours to weeks) after ijectio of or Cosmetic: Spread of toxi effects. The effect of botulium toxi may affect areas away from the ijectio site ad cause serious symptoms icludig: loss of stregth ad all-over muscle weakess, double visio, blurred visio ad droopig eyelids, hoarseess or chage or loss of voice (dysphoia), trouble sayig words clearly (dysarthria), loss of bladder cotrol, trouble breathig, trouble swallowig There has ot bee a cofirmed serious case of spread of toxi effect away from the ijectio site whe has bee used at the recommeded dose to treat severe uderarm sweatig, blepharospasm, or strabismus, or whe Cosmetic has bee used at the recommeded dose to treat frow lies. 4 5

4 How eurotoxi treatmet works Whe you experiece muscle spasms, it is because your erve cells are sedig sigals directly to your muscles, which causes this effect. (oabotuliumtoxia) treatmet works by blockig these sigals, which prevets the release of a substace kow as acetylcholie. 1 Too much acetylcholie causes your muscles to become overactive ad tese up. With eurotoxi, muscle spasms may stop or become greatly reduced, 1 resultig i relief. You may also experiece eck pai associated with cervical dystoia. is believed to work i a similar way to block the erve sigals that cause eck pai, resultig i relief. There is evidece from a study of patiets that shows treatmet may sigificatly reduce eck pai eve before muscle spasms are reduced. 2 The exact way works to reduce eck pai i cervical dystoia is ot kow. works by stoppig erves from releasig acetylcholie, a substace that trasmits sigals from erves to muscles. Please discuss with your doctor ay questios you may have about your treatmet. IMPORTANT SAFETY INFORMATION (cotiued) The dose of is ot the same as, or comparable to, aother botulium toxi product. Serious ad or immediate allergic reactios have bee reported. These reactios iclude itchy rash, swellig, ad shortess of breath. Tell your doctor or get medical help right away if you experiece ay such symptoms; further ijectio of or Cosmetic should be discotiued. The sigals that ca cause muscle cotractios ad eck pai reach muscles through the erves. eurotoxi works i the muscle where it is ijected to block sigals that tell the muscle to cotract ad is believed to block sigals that cause eck pai. As a result, muscle spasms may stop or be greatly reduced, resultig i relief, which may last up to 3 moths

5 What to expect from your treatmet Oce you ad your doctor have determied that (oabotuliumtoxia) is right for you, your treatmet will cosist of a umber of ijectios ito the muscles selected by your doctor. ijectios will be give right i your doctor s office. The amout of ad the locatios of the ijectios will deped o your idividual eeds. You may experiece pai, ifectio, iflammatio, tederess, swellig, redess ad/or bleedig/bruisig at the ijectio sites. Because eurotoxi is ijected directly ito your affected muscles, it is ot expected to be preset i your bloodstream after ijectio at the recommeded dosage. You should be able to leave your doctor s office after a brief recovery period. How log does it take to see results? Not log at all. You may begi seeig a improvemet i your symptoms withi a few days (a few weeks for some coditios) of treatmet, ad you may ot have to visit your doctor for aother ijectio for up to 3 moths. 1 You may begi seeig positive effects withi a few days of treatmet, ad you may ot have to visit the doctor for aother ijectio for up to 3 moths. 1 ijectios are give right i your doctor s office. Please talk to your doctor about ay prescriptio ad over-the-couter medicatios you may be takig for your medical coditios. IMPORTANT SAFETY INFORMATION (cotiued) Do ot take or Cosmetic if you: are allergic to ay of the igrediets i or Cosmetic (see Medicatio Guide for igrediets); had a allergic reactio to ay other botulium toxi product such as Myobloc or Dysport ; have a ski ifectio at the plaed ijectio site. 8 9

6 Frequetly asked questios about treatmet Does treatmet hurt? The eedles used to admiister (oabotuliumtoxia) treatmet are very fie, so most people experiece oly mild discomfort. It is ucommo for pai relief to be required, although some doctors suggest the use of a topical aesthetic cream before treatmet. Is Cosmetic the same as eurotoxi? Yes. Cosmetic ad are the same formulatio. eurotoxi is oe of the most widely researched medicies i the world ad has bee used for approximately 20 years. The same formulatio with dosig specific to temporarily treat moderate to severe glabellar lies (moderate to severe frow lies betwee the brows) for people ages 18 to 65 was approved i 2002 as Cosmetic (oabotuliumtoxia). Is it safe to get repeated ijectios of? treatmet is approved by the FDA for repeat ijectios. I most patiets, treatmet typically lasts for up to 3 moths 1 ad ca be repeated as log as the patiet experieces symptom relief ad does ot have ay serious allergic reactios or other side effects related to. Your physicia will determie the appropriate time for re-ijectio. Patiets aroud the world receive repeated ijectios of eurotoxi to effectively treat a variety of medical coditios (cervical dystoia, blepharospasm, ad strabismus). IMPORTANT SAFETY INFORMATION (cotiued) Tell your doctor about all your muscle or erve coditios such as amyotrophic lateral sclerosis [ALS or Lou Gehrig s disease], myastheia gravis, or Lambert-Eato sydrome, as you may be at icreased risk of serious side effects icludig severe dysphagia (difficulty swallowig) ad respiratory compromise (difficulty breathig) from typical doses of or Cosmetic. Is it true that some patiets do ot always have the same respose to repeated ijectios? There are may factors that ca impact the results of treatmet. A small percetage of people develop immuity to. Other factors that impact results iclude the accuracy of ijectios, dosig, ad chages i patiets coditios over time. There are other botulium toxis available. Are they the same as treatmet? It is importat to uderstad that o two botulium toxi products are the same. They differ i dosig, maufacturig process, potecy, ad adverse evets. As a result, each product ad its Uit dosig is uique ad differet, ad oe product caot take the place of aother. How do I kow that I am receivig treatmet ad ot a differet product? eurotoxi is a registered trademark of Allerga, Ic. The product is packaged i a glass vial with a purple or orage lid, labeled as, ad has a Allerga hologram o the side. You may wat to ask your ijector to see the vial to cofirm that this is the product he or she is usig for your treatmet

7 treatmet ad your isurace coverage Reimbursemet Solutios May isurace plas, icludig Medicare ad Medicaid, cover the cost of (oabotuliumtoxia) treatmet for certai coditios. Allerga, the maker of, has made a service available to you ad your doctor to determie if your pla covers the cost of treatmet. The program is called Reimbursemet Solutios, ad our represetatives are specially traied to help resolve isurace issues, aswer questios, ad file claims. For more iformatio about Reimbursemet Solutios, call , Optio 4. The hours are Moday through Friday, 9 am to 8 pm, ET. PATIENT ASSISTANCE Program The PATIENT ASSISTANCE Program is dedicated to helpig fiacially eligible patiets receive the (oabotuliumtoxia) treatmet they eed. There are certai fiacial ad other requiremets that you must meet i order to qualify for the program. You may qualify if you do ot have isurace or if your isurace is ot sufficiet to meet your medical eeds. To receive help from the PATIENT ASSISTANCE Program, you must: Be uisured or uderisured Meet or be below a certai household icome level Have a diagosis supported by cliical studies that validate the use of Be a residet of the Uited States or Puerto Rico If you thik you may be eligible for the PATIENT ASSISTANCE Program, visit us at ReimbursemetSolutios.com, or call us at , Optio 4. IMPORTANT SAFETY INFORMATION (cotiued) Tell your doctor about all your medical coditios, icludig if you have: plas to have surgery; had surgery o your face; weakess of forehead muscles, such as trouble raisig your eyebrows; droopig eyelids; ay other abormal facial chage; are pregat or pla to become pregat (it is ot kow if or Cosmetic ca harm your ubor baby); are breast-feedig or pla to breastfeed (it is ot kow if or Cosmetic passes ito breast milk)

8 Cervical dystoia ad (oabotuliumtoxia) treatmet Cervical dystoia defiitio ad symptoms Cervical dystoia is a coditio that causes the muscles i your eck to tighte or spasm without your cotrol. 3,4 If you have cervical dystoia, your head may tur i a uusual way, or it may be forced ito a abormal posture. The symptoms ca make it hard to do simple daily tasks, such as dressig yourself or drivig a car. But cervical dystoia ca be treated. Gettig treatmet may help you retur to activities you ejoyed before your symptoms started. The first step to feelig better is talkig to your doctor about your symptoms. Commo sigs of cervical dystoia ofte vary from perso to perso ad may iclude ay combiatio of the followig: Muscle spasms or tightess 4,5 Ucomfortable pullig or drawig i the eck 6 or head turig 5,7 It all started with a pai i the base of my eck. The my eck started to pull ad shake whe I tried to pull it back. It was tough. I was fightig it every day. I was at war with my eck. Gus, cervical dystoia patiet Neck pai (reported i up to 91% of patiets) 8 Aches ad pais aroud the eck that worse over time 7 Head or had tremors 5-7 Symptoms that progress to ivolve adjacet body parts 9 If you suspect that you have cervical dystoia, be sure to talk to your doctor. IMPORTANT SAFETY INFORMATION (cotiued) Tell your doctor about all the medicies you take, icludig prescriptio ad oprescriptio medicies, vitamis, ad herbal products. ad Cosmetic may cause loss of stregth or geeral muscle weakess, or visio problems. If this happes, do ot drive a car, operate machiery, or do other dagerous activities

9 Cervical dystoia ad (oabotuliumtoxia) treatmet (cotiued) Diagosig cervical dystoia Diagosig cervical dystoia ca be a challege, especially i its early or mild stages. This is because the symptoms may be subtle, or slight at first, ad differ from perso to perso. Cervical dystoia is sometimes diagosed icorrectly because it resembles other physical complaits such as stiff eck or stress. I some cases, patiets may suffer with cervical dystoia for a year or more before beig diagosed ad treated. 7 I testig for cervical dystoia, may differet tests may be used icludig brai imagigs, blood tests, EEGs, EMGs, ad video moitorig, amog others. A evaluatio may also iclude geetic testig i some situatios. 4 These tests may be used to rule out other coditios, leavig cervical dystoia as the diagosis. To provide additioal iformatio that ca help doctors diagose cervical dystoia, movemet disorder experts have developed these simple screeig questios 10 : Do you fid your head turig, tiltig, or shiftig i ay directio? Does your head shake or jerk? Do your shoulders lift or pull up or dow without your cotrol? Have other people told you that your head pulls to either side, forward, or backward? Have other people told you that you have head tremors? Do you have ay pai or stiffess i your eck most of the time? Is there a positio you ca put your head i to make the movemet or pai stop? Did you ever see a doctor about head turig or shakig? Cervical dystoia is a progressive disease Cervical dystoia is a progressive disease, meaig that the symptoms may get worse with time. I up to approximately 20% of patiets, cervical dystoia symptoms go away completely. 9 This is kow as remissio. However, it is importat to uderstad that the symptoms ofte retur. 9 For most people with cervical dystoia, their symptoms usually stop worseig after 5 years. 9 There are may causes of cervical dystoia through a accidet, through iherited gees, or through some ukow cause. If you are iterested i more iformatio, please talk to your doctor. IMPORTANT SAFETY INFORMATION (cotiued) Other side effects of ad Cosmetic iclude: dry mouth, discomfort or pai at the ijectio site, tiredess, headache, eck pai, ad eye problems: double visio, blurred visio, decreased eyesight, droopig eyelids, swellig of your eyelids, ad dry eyes. For more iformatio refer to the Medicatio Guide or talk with your doctor. You are ecouraged to report egative side effects of prescriptio drugs to the FDA. Visit or call FDA Full Product Iformatio, icludig Medicatio Guide, has bee provided to your doctor

10 Cervical dystoia ad (oabotuliumtoxia) treatmet (cotiued) How cervical dystoia impacts daily activities If you have cervical dystoia, you may fid it hard to do simple thigs. Dressig, shavig, housework, drivig a car, or usig a computer ca become a challege. Also, cervical dystoia ofte iterferes with a patiet s ability to perform activities of daily livig. 7 Although there is o cure for cervical dystoia, there is a good chace that your symptoms ca be successfully maaged with proper treatmet. It may help to kow that there are healthcare professioals who uderstad your coditio ad are experieced i helpig patiets fid relief. Types of cervical dystoia Cervical dystoia causes costat muscle tesio that s the dystoia part ad it occurs maily i the eck area, i what is called the cervical spie. Tese muscles i the eck pull the head i abormal movemets ad postures. There are 4 mai types of cervical dystoia, defied by which way the head is tiltig: Forward Aterocollis To the side Laterocollis Backward Retrocollis Rotated Torticollis IMPORTANT SAFETY INFORMATION (cotiued) ad Cosmetic may cause serious side effects that ca be life threateig. Call your doctor or get medical help right away if you have ay of these problems ay time (hours to weeks) after ijectio of or Cosmetic: Problems swallowig, speakig, or breathig, due to weakeig of associated muscles, ca be severe ad result i loss of life. You are at the highest risk if these problems are pre-existig before ijectio. Swallowig problems may last for several moths Most patiets (up to 81%) have a combiatio of these postures. 5 For example, the head may be pulled i 2 or more directios at the same time, such as forward ad to the side. 5 Cervical dystoia may also be called spasmodic, if there are sudde, ivolutary muscle cotractios, or sustaied, if the muscle tesio is cotiuous

11 Cervical dystoia ad (oabotuliumtoxia) treatmet (cotiued) Treatmets for cervical dystoia Doctors have a umber of optios for treatig cervical dystoia. The most commoly chose treatmet is (oabotuliumtoxia) eurotoxi. is cosidered a first-lie therapy for cervical dystoia, 11 which meas that doctors may choose to go straight to eurotoxi, without tryig other optios. Your physicia determies exactly which muscles are troublig you ad ijects eurotoxi ito them. is ofte used i combiatio with physical therapy. Oral prescriptio drugs may also be used. Surgery o the ivolved erves may also be a optio, but surgery is rarely used, ow that eurotoxi is available. 4 IMPORTANT SAFETY INFORMATION (cotiued) Call your doctor or get medical help right away if you have ay of these problems ay time (hours to weeks) after ijectio of or Cosmetic: Spread of toxi effects. The effect of botulium toxi may affect areas away from the ijectio site ad cause serious symptoms icludig: loss of stregth ad all-over muscle weakess, double visio, blurred visio ad droopig eyelids, hoarseess or chage or loss of voice (dysphoia), trouble sayig words clearly (dysarthria), loss of bladder cotrol, trouble breathig, trouble swallowig There has ot bee a cofirmed serious case of spread of toxi effect away from the ijectio site whe has bee used at the recommeded dose to treat severe uderarm sweatig, blepharospasm, or strabismus, or whe Cosmetic has bee used at the recommeded dose to treat frow lies. The dose of is ot the same as, or comparable to, aother botulium toxi product. How ca help For the vast majority of people with cervical dystoia, (oabotuliumtoxia) ijectios are very effective. therapy may stop or greatly reduce eck pai ad muscle spasms. Results from a key cliical study showed that after receivig eurotoxi ijectios, patiets with cervical dystoia had improved head posture, pai that was less itese ad occurred less ofte, ad a improved ability to fuctio i certai daily activities. 7 Aother study showed that eck pai relief may happe eve before muscle spasms are sigificatly reduced. 2 These are all importat beefits for people with cervical dystoia. For may of them, ijectios ca be a effective cervical dystoia treatmet. After a eurotoxi treatmet, may cervical dystoia patiets experiece up to 3 moths of relief from muscle spasms. 1 That is how log it takes the erves to resume the release of acetylcholie. Here s what eurotoxi ca do for you: Stop or greatly reduce eck pai ad muscle spasms Improve head posture Reduce itesity ad frequecy of eck pai Improve your ability to perform certai daily activities With treatmet, may cervical dystoia patiets get relief from their overly active or tese eck muscles. may also decrease their eck pai associated with cervical dystoia eve before muscle spasms are sigificatly reduced

12 success story Treatmets precedig cervical dystoia diagosis: Massage Acupucture Tractio Steroids Psychotropics Chiropractic adjustmet Kathlee, age 34 Duratio of time from iitial symptoms to diagosis: 17 years Presetig symptoms: Neck pai Tremor Stiffess Limited rage of motio Treatmet regime: (oabotuliumtoxia) ijectios Occasioally, my eck might grab for a secod ad the it just releases. It just does t have that power aymore. Idividual results may vary. IMPORTANT SAFETY INFORMATION (cotiued) Serious ad or immediate allergic reactios have bee reported. These reactios iclude itchy rash, swellig, ad shortess of breath. Tell your doctor or get medical help right away if you experiece ay such symptoms; further ijectio of or Cosmetic should be discotiued

13 success story Treatmets precedig cervical dystoia diagosis: Aalgesics Ati-iflammatories Physical therapy Gus, age 32 Duratio of time from iitial symptoms to diagosis: 1 year Presetig symptoms: Neck pai Tremor Right torticollis Treatmet regime: (oabotuliumtoxia) ijectios ad physical therapy My outlook is to cotiue my treatmets as log as they re eeded ad stay positive, live life, just live as much of a ormal life as I ca. Idividual results may vary. Ask your doctor if treatmet is right for you. IMPORTANT SAFETY INFORMATION (cotiued) Do ot take or Cosmetic if you: are allergic to ay of the igrediets i or Cosmetic (see Medicatio Guide for igrediets); had a allergic reactio to ay other botulium toxi product such as Myobloc or Dysport ; have a ski ifectio at the plaed ijectio site

14 Livig with cervical dystoia tips for patiets I additio to takig your medicatios ad followig your doctor s advice, there is more you ca do to help relieve your cervical dystoia symptoms: Avoid stress ad stressful situatios, whether they occur i the workplace, i public places, or at home It is importat to uderstad that stress ca exacerbate the symptoms of cervical dystoia 12 Here is a sesory exercise you may wat to try... Cervical dystoia is the most commo focal dystoia that respods to sesory tricks. For example, patiets with cervical dystoia may place their had o the side of their face, chi, or back of the head. This may help reduce the itesity of the symptoms. Lightly touchig or applyig pressure to certai areas of the head o the side that is opposite to that which the head is tured may temporarily allow correctio of abormal head positio. Make sure you get eough relaxatio time 12 Eat sesibly ad utritioally Avoid those foods that stimulate the erves. Caffeie, sugar, ad chocolate ca sometimes activate cervical dystoia symptoms 12 Cosult with your doctor regardig a exercise program Light yoga, simple calistheics, water exercises, ad deep breathig exercises ca help relax both mid ad body 12 Coect with support groups i your area for additioal resources ad educatio (some are listed at the back of this brochure) If your doctor decides you should be treated for cervical dystoia, be sure to keep track of ay improvemets or worseig of your symptoms as well as how you react to treatmet. Share all your observatios with your doctor be a active parter i maagig your cervical dystoia. IMPORTANT SAFETY INFORMATION (cotiued) Tell your doctor about all your muscle or erve coditios such as amyotrophic lateral sclerosis [ALS or Lou Gehrig s disease], myastheia gravis, or Lambert-Eato sydrome, as you may be at icreased risk of serious side effects icludig severe dysphagia (difficulty swallowig) ad respiratory compromise (difficulty breathig) from typical doses of or Cosmetic. Tell your doctor about all your medical coditios, icludig if you have: plas to have surgery; had surgery o your face; weakess of forehead muscles, such as trouble raisig your eyebrows; droopig eyelids; ay other abormal facial chage; are pregat or pla to become pregat (it is ot kow if or Cosmetic ca harm your ubor baby); are breast-feedig or pla to breastfeed (it is ot kow if or Cosmetic passes ito breast milk)

15 Blepharospasm ad treatmet Blepharospasm defiitio ad symptoms Blepharospasm is a muscle disorder characterized by ivolutary spasm of the muscles aroud the eye, resultig i ucotrolled arrowig or closig of the eyelid. 13,14 Oe serious cosequece of blepharospasm is impairmet of visio. I some patiets, forced closure of the eyelid becomes so severe that doig simple thigs such as drivig a car or usig a computer becomes a challege. Approximately 65% of people with blepharospasm are female, ad the average age of oset is 56 years. 14 Diagosig blepharospasm Doctors diagose blepharospasm based o key sigs ad symptoms. I the early stages of blepharospasm, patiets may complai of irritatio ad discomfort of the eyelids as well as icreased blikig. 13,14 As blepharospasm progresses, blikig usually becomes more frequet, forceful, ad ucotrollable. Bright light, oise, stress, polluted air, or wid ca make the symptoms worse. 13 Without proper medical treatmet, few blepharospasm patiets get better o their ow. 14 How treatmet ca help Early symptoms of blepharospasm may iclude 14 : Dry eyes or waterig eyes Light sesitivity Icreased blikig Ocular pai Soreess (oabotuliumtoxia) eurotoxi has bee the pricipal treatmet for blepharospasm sice FDA approval i ijectios are admiistered directly ito the site of actio. Whe ijected directly i the affected muscles aroud the eyes, the eurotoxi relieves the muscle spasm ad the forceful ivolutary closig of the eyelid. treatmet ca be repeated approximately every 3 moths as log as the patiet cotiues to respod ad does ot have a allergic reactio. 1 IMPORTANT SAFETY INFORMATION (cotiued) Tell your doctor about all the medicies you take, icludig prescriptio ad oprescriptio medicies, vitamis, ad herbal products. ad Cosmetic may cause loss of stregth or geeral muscle weakess, or visio problems. If this happes, do ot drive a car, operate machiery, or do other dagerous activities

16 Strabismus ad treatmet Strabismus defiitio ad symptoms Strabismus is the ame doctors give a group of disorders i which muscles tighte aroud the eye, resultig i pullig of the eyeball to the side. Strabismus is also kow as crossed eyes. A commo form is esotropia, or coverget strabismus, which is whe oe or both eyes tur toward the ose. 15 Other symptoms iclude squitig, tiltig the head to look at thigs, frequet eye movemets, headache, rubbig the eyes, tearig, ad double visio. Today, strabismus is typically treated early i childhood (before 4 to 6 years of age) by orthoptic traiig (eye exercises), eyeglasses, ad/or cotact leses. 15 I some cases where stregtheig techiques are ot successful, surgery may be required to realig the eye muscles. 15 IMPORTANT SAFETY INFORMATION (cotiued) Other side effects of ad Cosmetic iclude: dry mouth, discomfort or pai at the ijectio site, tiredess, headache, eck pai, ad eye problems: double visio, blurred visio, decreased eyesight, droopig eyelids, swellig of your eyelids, ad dry eyes. For more iformatio refer to the Medicatio Guide or talk with your doctor. You are ecouraged to report egative side effects of prescriptio drugs to the FDA. Visit or call FDA Full Product Iformatio, icludig Medicatio Guide, has bee provided to your doctor. Strabismus i adults is ofte diagosed i those who were utreated or usuccessfully treated durig childhood. 16 There are also some adults who develop strabismus due to illess or trauma, which usually results i double visio or a limitatio i their depth perceptio or field of visio (peripheral ad side). 16 Diagosig strabismus Whe it occurs i childre, strabismus is usually oticed first by parets or a doctor because the child s eyes appear to be positioed abormally. A eye examiatio cofirms the diagosis ad idetifies the type of strabismus. Strabismus should ever be igored o the assumptio that a child will outgrow it. Uless treated before age 4 to 6, strabismus ca lead to permaet loss of sight i the deviatig eye. 15 How treatmet ca help I treatig strabismus, oly (oabotuliumtoxia) treatmet is believed to have a effect o pairs of muscles. Upo beig ijected with eurotoxi, the muscles weake ad spasms are slightly reduced. This allows the muscles o the other side of the eye to cotract. 1 Through this dual actio, treatmet is thought to help the eyes alig, or look i the same directio

17 Fidig a doctor who ijects If you would like to discuss your coditio with a doctor who ijects (oabotuliumtoxia), you ca fid oe by visitig ad usig our Fid a Doctor tool. To locate a doctor who ijects eurotoxi, simply visit these websites: The official website: WebMD Physicia Directory: For more iformatio o, visit our website at or call AMA DoctorFider: Please see Importat Safety Iformatio about o frot cover ad throughout brochure

18 Patiet support groups Your healthcare provider is the best source of iformatio for your coditio ad its treatmet. I additio, there are may orgaizatios that offer support, educatio, ad services for patiets. May atioal orgaizatios have local chapters. Please cotact the atioal group for more iformatio o chapters i your area.* Beig Essetial Blepharospasm Research Foudatio (BEBRF) Care4Dystoia, Ic. Dystoia Medical Research Foudatio (DMRF) DYST ( ) The Natioal Spasmodic Torticollis Associatio (NSTA) ST/Dystoia, Ic * The orgaizatios listed are provided as potetial resources for patiets ad caregivers; they are ot edorsed by Allerga

19 For more iformatio o, visit our website at or call Please see Importat Safety Iformatio about o frot cover ad iside brochure. 1. Prescribig Iformatio, March Relja M, Telarovic S. Botulium toxi type-a ad pai resposiveess i cervical dystoia: a dose respose study. Preseted at: 9th Iteratioal Cogress of Parkiso s Disease ad Movemet Disorders; March 5-8, 2005; New Orleas, LA. 3. Fah S, Marsde CD, Cale DB. Classificatio ad ivestigatio of dystoia. Mov Disord. 1987;2(4): Jakovic J. Treatmet of cervical dystoia. I: Bri MF, Comella CL, Jakovic J, eds. Dystoia: Etiology, Cliical Features, ad Treatmet. Philadelphia, PA: Lippicott Williams & Wilkis; 2004: Cha J, Bri MF, Fah S. Idiopathic cervical dystoia: cliical characteristics. Mov Disord. 1991;6(2): Jakovic J, Leder S, Warer D, Schwartz K. Cervical dystoia: cliical fidigs ad associated movemet disorders. Neurology. 1991;41(7): va Herwaarde GM, Ate HW, Hoogdui CA, et al. Idiopathic spasmodic torticollis: a survey of the cliical sydromes ad patiets experieces. Cli Neurol Neurosurg. 1994;96(3): Galvez-Jimeez N, Lampuri C, Patio- Picirrillo R, Hargreave MJA, Haso MR. Dystoia ad headaches: cliical features ad respose to botulium toxi therapy. I: Fah S, Hallett M, DeLog MR, eds. Dystoia 4: Advaces i Neurology. Philadelphia, PA: Lippicott Williams & Wilkis; 2004;94: Jahashahi M, Mario MH, Marsde CD. Natural history of adult-oset idiopathic torticollis. Arch Neurol. 1990;47(5): Sauders-Pullma R, Soto-Valecia J, Costa-Toth C, et al. A ew screeig tool for cervical dystoia. Neurology. 2005;64(12): Jakovic J, Schwartz K. Respose ad immuoresistace to botulium toxi ijectios. Neurology. 1995;45(9): ST/Dystoia. Fidig your road to happiess! ST/Dystoia website. Accessed Jue 4, Maliovsky V. Beig essetial blepharospasm. J Am Optom Assoc. 1987;58(8): Gradas F, Elsto J, Qui N, Marsde CD. Blepharospasm: a review of 264 patiets. J Neurol Neurosurg Psychiatry. 1988;51(6): The Merck Mauals Olie Medical Library. Strabismus. The Merck Mauals Olie Medical Library website. Updated Jue Accessed Jue 4, The America Associatio for Pediatric Ophthalmology ad Strabismus. Adult strabismus geeral iformatio. The America Associatio for Pediatric Ophthalmology ad Strabismus website. Accessed Jue 4, Allerga, Ic., Irvie, CA marks owed by Allerga, Ic. Dysport is a registered trademark of Ipse Biopharm Limited. Myobloc is a registered trademark of Solstice Neuroscieces, Ic. WebMD is a registered service mark of WebMD, Ic Re-order: APC55HM

20 Cosmetic (oabotuliumtoxia) for ijectio Maufactured by: Allerga Pharmaceuticals Irelad a subsidiary of: Allerga, Ic Dupot Dr., Irvie, CA Distat Spread of Toxi Effect Postmarketig reports idicate that the effects of Cosmetic ad all botulium toxi products may spread from the area of ijectio to produce symptoms cosistet with botulium toxi effects. These may iclude astheia, geeralized muscle weakess, diplopia, blurred visio, ptosis, dysphagia, dysphoia, dysarthria, uriary icotiece, ad breathig difficulties. These symptoms have bee reported hours to weeks after ijectio. Swallowig ad breathig difficulties ca be life threateig ad there have bee reports of death. The risk of symptoms is probably greatest i childre treated for spasticity but symptoms ca also occur i adults treated for spasticity ad other coditios, particularly i those patiets who have uderlyig coditios that would predispose them to these symptoms. I uapproved uses, icludig spasticity i childre ad adults, ad i approved idicatios, cases of spread of effect have occurred at doses comparable to those used to treat cervical dystoia ad at lower doses. DESCRIPTION Cosmetic (oabotuliumtoxia) for ijectio, is a sterile, vacuum-dried purified botulium toxi type A, produced from fermetatio of Hall strai Clostridium botulium type A grow i a medium cotaiig casei hydrolysate, glucose, ad yeast extract, iteded for itramuscular use. It is purified from the culture solutio by dialysis ad a series of acid precipitatios to a complex cosistig of the eurotoxi, ad several accessory proteis. The complex is dissolved i sterile sodium chloride solutio cotaiig Albumi Huma ad is sterile filtered (0.2 micros) prior to fillig ad vacuum-dryig. Oe Uit of Cosmetic correspods to the calculated media itraperitoeal lethal dose (LD50) i mice. The method utilized for performig the assay is specific to Allerga s product, Cosmetic. Due to specific details of this assay such as the vehicle, dilutio scheme ad laboratory protocols for the various mouse LD50 assays, Uits of biological activity of Cosmetic caot be compared to or coverted ito Uits of ay other botulium toxi or ay toxi assessed with ay other specific assay method. I additio, differeces i species sesitivities to differet botulium eurotoxi serotypes precludes extrapolatio of aimal-dose activity relatioships to huma dose estimates. The specific activity of Cosmetic is approximately 20 Uits/aogram of eurotoxi protei complex. Each vial of Cosmetic cotais either 100 Uits of Clostridium botulium type A eurotoxi complex, 0.5 mg of Albumi Huma, ad 0.9 mg of sodium chloride or 50 Uits of Clostridium botulium type A eurotoxi complex, 0.25 mg of Albumi Huma, ad 0.45 mg of sodium chloride i a sterile, vacuum-dried form without a preservative. CLINICAL PHARMACOLOGY Cosmetic blocks euromuscular trasmissio by bidig to acceptor sites o motor erve termials, eterig the erve termials, ad ihibitig the release of acetylcholie. This ihibitio occurs as the eurotoxi cleaves SNAP-25, a protei itegral to the successful dockig ad release of acetylcholie from vesicles situated withi erve edigs. Whe ijected itramuscularly at therapeutic doses, Cosmetic produces partial chemical deervatio of the muscle resultig i a localized reductio i muscle activity. I additio, the muscle may atrophy, axoal sproutig may occur, ad extrajuctioal acetylcholie receptors may develop. There is evidece that reiervatio of the muscle may occur, thus slowly reversig muscle deervatio produced by Cosmetic. Pharmacokietics Usig curretly available aalytical techology, it is ot possible to detect Cosmetic i the peripheral blood followig itramuscular ijectio at the recommeded doses. Cliical Studies Glabellar Lies Two phase 3 radomized, multi-ceter, double-blid, placebo-cotrolled studies of idetical desig were coducted to evaluate Cosmetic for use i the temporary improvemet of the appearace of moderate to severe glabellar facial lies. The studies erolled healthy adults (ages 18 to 75) with glabellar lies of at least moderate severity at maximum frow. Patiets were excluded if they had ptosis, deep dermal scarrig, or a iability to substatially lesse glabellar lies eve by physically spreadig them apart. Subjects received a sigle treatmet with Cosmetic (N=405, combied studies) or placebo (N=132, combied studies). Ijectio volume was 0.1 ml/ijectio site, for a dose/ijectio site i the active treatmet groups of 4 Uits. Subjects were ijected itramuscularly i five sites, 1 i the procerus muscle ad 2 i each corrugator supercilii muscle, for a total dose i the active treatmet groups of 20 Uits. The co-primary efficacy edpoits were the ivestigator s ratig of glabellar lie severity at maximum frow ad the subject s global assessmet of chage i appearace of glabellar lies, both at Day 30 post-ijectio. For the ivestigator ratig, usig a 4-poit gradig scale (0=oe, 3=severe) a respoder was defied as havig a severity grade of 0 or 1. For the subject s global assessmet of chage, the ratigs were from +4 (complete improvemet) to -4 (very marked worseig). A respoder was defied as havig a grade of at least +2 (moderate improvemet). After completio of the radomized studies, subjects were offered participatio i a ope label, repeat treatmet study to assess the safety of repeated treatmet sessios. The combied results of these two efficacy trials are preseted here. The mea age was 46 years, with 32 patiets (6%) 65 years of age. Most of the subjects (82%) were wome, ad Caucasia (84%). At baselie, 210 patiets (39%) had glabellar lie severity scores at rest of moderate or severe. I these studies, the severity of glabellar lies was reduced for up to 120 days i the Cosmetic group compared to the placebo group as measured both by ivestigator ratig of glabellar lie severity at maximum frow (Table 1), ad by subject s global assessmet of chage i appearace of glabellar lies (Table 2). TABLE 1. Ivestigator s Assessmet of Glabellar Lie Severity at Maximum Frow Respoder Rates (% ad Number of Subjects with Severity of Noe or Mild) Day Cosmetic 7 74% 299/ b 80% 325/ % 283/ % 192/ % 102/403 a 95% cofidece itervals are show i parethesis b Day 30: Co-Primary Efficacy Time poit, P<0.001 Placebo 6% 8/132 3% 4/132 2% 2/130 2% 3/128 2% 2/128 Differece a 68% (62, 74) 77% (72, 82) 69% (64, 74) 45% (40, 51) 24% (19, 29) TABLE 2. Subject s Assessmet of Chage i Appearace of Glabellar Lies Respoder Rates (% ad Number of Subjects with at Least Moderate Improvemet) Day Cosmetic 7 82% 334/ b 89% 362/ % 330/ % 254/ % 157/403 a 95% cofidece itervals are show i parethesis b Day 30: Co-Primary Efficacy Time poit, P<0.001 Placebo 9% 12/132 7% 9/132 4% 5/130 3% 4/128 1% 1/128 Differece a 73% (68, 80) 83% (77, 88) 78% (73, 83) 60% (54, 66) 38% (33, 43) I the subset of patiets with restig severity scores of moderate or severe, the ivestigator assessmet of a restig severity of mild or oe at day 30 was also achieved by more Cosmetic treated patiets (74%, 119/161) tha placebo treated patiets (20%, 10/49). Aalysis of the limited umber of patiets 65 years or older suggested a lower treatmet-associated respose compared to patiets less tha 65 years of age. (Table 3). TABLE 3. Ivestigator s ad Subject s Assessmet Respoder Rates for Subjects < 65 ad 65 Years of Age at Day 30 Assessmet Age Group Ivestigators (maximal frow) Cosmetic N=405 < 65 83% 316/382 Subjects < 65 91% 346/382 Ivestigators (maximal frow) 65 39% 9/23 Subjects 65 70% 16/23 a 95% cofidece itervals are show i parethesis Placebo N=132 2% 2/123 7% 8/123 22% 2/9 11% 1/9 Differece a 81% (77, 86) 84% (79, 90) 17% (-17, 51) 58% (31, 86) Exploratory aalyses by geder suggested that respoder rates i the Cosmetic treated group were higher for wome tha for me for both the ivestigator assessmet (day 30; 85% of 334 wome, 59% of 71 me) ad the Subject Assessmet (day 30; 93% of wome, 72% of me). I the limited umber of o-caucasia patiets (=64 i the Cosmetic treated group) the respoder rates were similar to those observed i the Caucasia patiets BtxCos Full Combo PI_MG_ST.idd 3 6/28/10 5:05:43 PM

21 INDICATIONS AND USAGE Cosmetic is idicated for the temporary improvemet i the appearace of moderate to severe glabellar lies associated with corrugator ad/or procerus muscle activity i adult patiets 65 years of age. CONTRAINDICATIONS Cosmetic is cotraidicated i the presece of ifectio at the proposed ijectio site(s) ad i idividuals with kow hypersesitivity to ay botulium toxi preparatio or to ay of the compoets i the formulatio. WARNINGS ad Cosmetic cotai the same active igrediet i the same formulatio. Therefore, adverse evets observed with the use of also have the potetial to be associated with the use of Cosmetic. The recommeded dosage ad frequecy of admiistratio for Cosmetic should ot be exceeded. Risks resultig from admiistratio at higher dosages are ot kow. Lack of Iterchageability betwee Botulium Toxi Products The potecy Uits of Cosmetic are specific to the preparatio ad assay method utilized. They are ot iterchageable with other preparatios of botulium toxi products ad, therefore, uits of biological activity of Cosmetic caot be compared to or coverted ito uits of ay other botulium toxi products assessed with ay other specific assay method (see DESCRIPTION). Spread of Toxi Effect Postmarketig safety data from Cosmetic ad other approved botulium toxis suggest that botulium toxi effects may, i some cases, be observed beyod the site of local ijectio. The symptoms are cosistet with the mechaism of actio of botulium toxi ad may iclude astheia, geeralized muscle weakess, diplopia, blurred visio, ptosis, dysphagia, dysphoia, dysarthria, uriary icotiece, ad breathig difficulties. These symptoms have bee reported hours to weeks after ijectio. Swallowig ad breathig difficulties ca be life threateig ad there have bee reports of death related to spread of toxi effects. The risk of symptoms is probably greatest i childre treated for spasticity but symptoms ca also occur i adults treated for spasticity ad other coditios, ad particularly i those patiets who have uderlyig coditios that would predispose them to these symptoms. I uapproved uses, icludig spasticity i childre ad adults, ad i approved idicatios, symptoms cosistet with spread of toxi effect have bee reported at doses comparable to or lower tha doses used to treat cervical dystoia. No defiitive serious adverse evet reports of distat spread of toxi effect associated with dermatologic use of / Cosmetic at the labeled dose of 20 Uits (for glabellar lies) or 100 Uits (for severe primary axillary hyperhidrosis) have bee reported. No defiitive serious adverse evet reports of distat spread of toxi effect associated with for blepharospasm at the recommeded dose (30 Uits ad below) or for strabismus at the labeled doses have bee reported. Hypersesitivity Reactios Serious ad/or immediate hypersesitivity reactios have bee reported. These reactios iclude aaphylaxis, urticaria, soft tissue edema, ad dyspea. If such a reactio occurs, further ijectio of Cosmetic should be discotiued ad appropriate medical therapy immediately istituted. Oe fatal case of aaphylaxis has bee reported i which lidocaie was used as the diluet, ad cosequetly the causal aget caot be reliably determied. Pre-Existig Neuromuscular Disorders Idividuals with peripheral motor europathic diseases, amyotrophic lateral sclerosis, or euromuscular juctioal disorders (e.g., myastheia gravis or Lambert-Eato sydrome) should be moitored particularly closely whe give botulium toxi. Patiets with euromuscular disorders may be at icreased risk of cliically sigificat effects icludig severe dysphagia ad respiratory compromise from typical doses of Cosmetic (see ADVERSE REACTIONS). Dysphagia ad Breathig Difficulties i Treatmet of Cervical Dystoia Treatmet with ad other botulium toxi products ca result i swallowig or breathig difficulties. Patiets with pre-existig swallowig or breathig difficulties may be more susceptible to these complicatios. I most cases, this is a cosequece of weakeig of muscles i the area of ijectio that are ivolved i breathig or swallowig. Whe distat effects occur, additioal respiratory muscles may be ivolved (see WARNINGS). Deaths as a complicatio of severe dysphagia have bee reported after treatmet with botulium toxi. Dysphagia may persist for several moths, ad require use of a feedig tube to maitai adequate utritio ad hydratio. Aspiratio may result from severe dysphagia ad is a particular risk whe treatig patiets i whom swallowig or respiratory fuctio is already compromised. Treatmet of cervical dystoia with botulium toxis may weake eck muscles that serve as accessory muscles of vetilatio. This may result i a critical loss of breathig capacity i patiets with respiratory disorders who may have become depedet upo these accessory muscles. There have bee postmarketig reports of serious breathig difficulties, icludig respiratory failure, i cervical dystoia patiets. Patiets treated with botulium toxi may require immediate medical attetio should they develop problems with swallowig, speech, or respiratory disorders. These reactios ca occur withi hours to weeks after ijectio with botulium toxi (see WARNINGS, ADVERSE REACTIONS, CLINICAL PHARMACOLOGY). Cardiovascular System There have bee reports followig admiistratio of of adverse evets ivolvig the cardiovascular system, icludig arrhythmia ad myocardial ifarctio, some with fatal outcomes. Some of these patiets had risk factors icludig pre-existig cardiovascular disease. Huma Albumi This product cotais albumi, a derivative of huma blood. Based o effective door screeig ad product maufacturig processes, it carries a extremely remote risk for trasmissio of viral diseases. A theoretical risk for trasmissio of Creutzfeldt-Jakob disease (CJD) also is cosidered extremely remote. No cases of trasmissio of viral diseases or CJD have ever bee idetified for albumi. PRECAUTIONS The safe ad effective use of Cosmetic depeds upo proper storage of the product, selectio of the correct dose, ad proper recostitutio ad admiistratio techiques. Physicias admiisterig Cosmetic must uderstad the relevat euromuscular ad/or orbital aatomy of the area ivolved, as well as ay alteratios to the aatomy due to prior surgical procedures ad avoid ijectio ito vulerable aatomic areas. Cautio should be used whe Cosmetic treatmet is used i the presece of iflammatio at the proposed ijectio site(s) or whe excessive weakess or atrophy is preset i the target muscle(s). Reduced blikig from Cosmetic ijectio of the orbicularis muscle ca lead to coreal exposure, persistet epithelial defect ad coreal ulceratio, especially i patiets with VII erve disorders. I the use of for the treatmet of blepharospasm, oe case of coreal perforatio i a aphakic eye requirig coreal graftig has occurred because of this effect. Careful testig of coreal sesatio i eyes previously operated upo, avoidace of ijectio ito the lower lid area to avoid ectropio, ad vigorous treatmet of ay epithelial defect should be employed. This may require protective drops, oitmet, therapeutic soft cotact leses, or closure of the eye by patchig or other meas. Iducig paralysis i oe or more extraocular muscles may produce spatial disorietatio, double visio or past poitig. Coverig the affected eye may alleviate these symptoms. Cautio should be used whe Cosmetic treatmet is used i patiets who have a iflammatory ski problem at the ijectio site, marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarrig, thick sebaceous ski or the iability to substatially lesse glabellar lies by physically spreadig them apart as these patiets were excluded from the Phase 3 safety ad efficacy trials. Needle-related pai ad/or axiety may result i vasovagal resposes (icludig e.g., sycope, hypotesio), which may require appropriate medical therapy. Ijectio itervals of Cosmetic should be o more frequet tha every three moths ad should be performed usig the lowest effective dose (see ADVERSE REACTIONS, IMMUNOGENICITY). Iformatio for Patiets The physicia should provide a copy of the FDA-Approved Patiet Medicatio Guide ad review the cotets with the patiet. Patiets should be advised to iform their doctor or pharmacist if they develop ay uusual symptoms (icludig difficulty with swallowig, speakig, or breathig), or if ay existig symptom worses. Patiets should be couseled that if loss of stregth, muscle weakess, or impaired visio occur, they should avoid drivig a car or egagig i other potetially hazardous activities. Drug Iteractios Co-admiistratio of Cosmetic ad amioglycosides 1 or other agets iterferig with euromuscular trasmissio (e.g., curare-like odepolarizig blockers, licosamides, polymyxis, quiidie, magesium sulfate, aticholiesterases, succiylcholie chloride) should oly be performed with cautio as the effect of the toxi may be potetiated. The effect of admiisterig differet botulium eurotoxi serotypes at the same time or withi several moths of each other is ukow. Excessive euromuscular weakess may be exacerbated by admiistratio of aother botulium toxi prior to the resolutio of the effects of a previously admiistered botulium toxi. Pregacy: Pregacy Category C Admiistratio of Cosmetic is ot recommeded durig pregacy. There are o adequate ad well-cotrolled studies of Cosmetic i pregat wome. Whe pregat mice ad rats were ijected itramuscularly durig the period of orgaogeesis, the developmetal NOEL (No Observed Effect Level) of Cosmetic was 4 Uits/kg. Higher doses (8 Uits/kg or 16 Uits/kg) were associated with reductios i fetal body weights ad/or delayed ossificatio. I a rage fidig study i rabbits, daily ijectio of Uits/kg/day (days 6 to 18 of gestatio) ad 2 Uits/kg (days 6 ad 13 of gestatio) produced severe materal toxicity, abortios ad/or fetal malformatios. Higher doses resulted i death of the dams. The rabbit appears to be a very sesitive species to Cosmetic BtxCos Full Combo PI_MG_ST.idd 4 6/28/10 5:05:44 PM