MECHANISMOFACTION

BOTOXcontainsaproteincomplexpurifiedfromthebacteriumClostridiumbotulinum.Acomponentofthiscomplex,
BotulinumToxinTypeAistheimportantactiveingredient.TypeAisoneofthesevendistinctbotulinumtoxinsproduced
bydifferentstrainsofthebacterium.BOTOXdecreasesmuscleactivitybyblockingoveractivenerveimpulsesthattrigger
excessivemusclecontractionsorglandularactivity.iInaddition,BOTOXisbelievedtoreduceneckpainassociatedwith
cervicaldystoniathroughatemporaryreductioninmuscleactivityandpossiblythroughitsinfluenceonthepainsensory
system(e.g.,inhibitingthereleaseofneurotransmittersinvolvedinthetransmissionofpainfulsensations),althoughthe
exactmechanismofactionisunknown.

MechanismofAction
PhaseINerveMuscleCommunicationisBlocked
BOTOXblocksthetransmissionofoveractivenerveimpulsestothetargetedmusclebyselectivelypreventingtherelease
oftheneurotransmitteracetylcholine(ACh)attheneuromuscularjunction,temporarilypreventingmusclecontraction.i
Thisisprimarilyalocaleffect.Incervicaldystonia,BOTOXmayalsopreventthereleaseofpainstimulatingneuropeptides
inperipheralnerves.

Indications
BOTOXisaprescriptionmedicinethatisinjectedintomuscles
andused:

totreatincreasedmusclestiffnessinelbow,wrist,and
fingermuscleswithupperlimbspasticityinpeople18
yearsandolder.

totreattheabnormalheadpositionandneckpainthat
happenswithcervicaldystonia(CD)inpeople18yearsand
older.

totreatcertaintypesofeyemuscleproblems(strabismus)
orabnormalspasmoftheeyelids(blepharospasm)in
people12yearsandolder.
BOTOXisalsoinjectedintotheskintotreatthesymptomsof
severeunderarmsweating(severeprimaryaxillary
hyperhidrosis)whenmedicinesusedontheskin(topical)do
notworkwellenoughinpeople18yearsandolder.
ItisnotknownwhetherBOTOXissafeoreffectiveforother
typesofmusclespasmsorforseveresweatinganywhereother
thanyourarmpits.
BOTOXCosmeticisaprescriptionmedicinethatisinjectedinto
musclesandusedtoimprovethelookofmoderatetosevere

frownlinesbetweentheeyebrows(glabellarlines)inpeople18
to65yearsofageforashortperiodoftime(temporary).
IMPORTANTSAFETYINFORMATION
BOTOXandBOTOXCosmeticmaycauseserioussideeffects
thatcanbelifethreatening.Callyourdoctororgetmedical
helprightawayifyouhaveanyoftheseproblemsanytime
(hourstoweeks)afterinjectionofBOTOXorBOTOX
Cosmetic:
Problemsswallowing,speaking,orbreathing,dueto
weakeningofassociatedmuscles,canbesevereandresultin
lossoflife.Youareatthehighestriskiftheseproblemsare
preexistingbeforeinjection.Swallowingproblemsmaylast
forseveralmonths.
Spreadoftoxineffects.Theeffectofbotulinumtoxinmay
affectareasawayfromtheinjectionsiteandcauseserious
symptomsincluding:lossofstrengthandallovermuscle
weakness,doublevision,blurredvisionanddroopingeyelids,
hoarsenessorchangeorlossofvoice(dysphonia),trouble
sayingwordsclearly(dysarthria),lossofbladdercontrol,
troublebreathing,troubleswallowing.
Pleaseseenextpageforadditional
ImportantSafetyInformation

A) Binding:
TheheavychainportionoftheactiveingredientinBOTOX
(onabotulinumtoxinA)neurotoxinbindstothecellmembrane
ofthemotornerveviaanunidentifiedhighaffinityacceptor
molecule.Thishighaffinitybindingactionallowsforefficient
uptakeofBOTOXbythemotornerveandfacilitatesselective,
targetedtreatmentattheinjectionsite.

B)Internalizing:
Afterbinding,theBOTOXproteinmoleculepassesthrough
thecellmembraneofthemotornerveandintoitscytoplasm
viaaprocesscalledendocytosis.Itisherethattheenzymatic
component(lightchain)oftheBOTOXproteinmoleculeis
activated.

IMPORTANTSAFETYINFORMATION(continued)

Therehasnotbeenaconfirmedseriouscaseofspreadof
toxineffectawayfromtheinjectionsitewhenBOTOX
hasbeenusedattherecommendeddosetotreatsevere
underarmsweating,blepharospasm,orstrabismusor
whenBOTOXCosmetichasbeenusedatthe
recommendeddosetotreatfrownlines.

suchasMyoblocorDysport;haveaskininfectionatthe
plannedinjectionsite.

ThedoseofBOTOXisnotthesameas,orcomparable
to,anotherbotulinumtoxinproduct.
Seriousandorimmediateallergicreactionshavebeen
reported.Thesereactionsincludeitchyrash,swelling,
andshortnessofbreath.Tellyourdoctororgetmedical
helprightawayifyouexperienceanysuchsymptoms,
furtherinjectionofBOTOXorBOTOXCosmeticshould
bediscontinued.
DonottakeBOTOXorBOTOXCosmeticifyou:are
allergictoanyoftheingredientsinBOTOXorBOTOX
Cosmetic(seeMedicationGuideforingredients);hadan
allergicreactiontoanyotherbotulinumtoxinproduct

Tellyourdoctoraboutallyourmuscleornerve
conditionssuchasamyotrophiclateralsclerosis[ALSor
LouGehrigsdisease],myastheniagravisorLambert
Eatonsyndromeasyoumaybeatincreasedriskof
serioussideeffectsincludingseveredysphagia(difficulty
swallowing)andrespiratorycompromise(difficulty
breathing)fromtypicaldosesofBOTOXorBOTOX
Cosmetic.
Tellyourdoctoraboutallyourmedicalconditions,
includingifyouhave:planstohavesurgery;hadsurgery
onyourface;weaknessofforeheadmuscles,suchas
troubleraisingyoureyebrows;droopingeyelids;any
otherabnormalfacialchange;arepregnantorplanto
becomepregnant(ItisnotknownifBOTOXorBOTOX
Cosmeticcanharmyourunbornbaby);arebreastfeeding
orplantobreastfeed(ItisnotknownifBOTOXor
BOTOXCosmeticpassesintobreastmilk).

Pleaseseenextpageforadditional
ImportantSafetyInformation

C) Blocking:
Insidethemotornerve,thelightchainoftheBOTOX
(onabotulinumtoxinA)proteinmoleculecleavesaparta
protein(calledSNAP25)thatenablesvesicleswhichstorethe
neurotransmitteracetylcholinetoattachtothecell
membrane.CleavingSNAP25preventsthesevesiclesfrom
fusingwiththemembraneandpreventsthereleaseof
acetylcholineintotheneuromuscularjunction(thespace
betweenthemotornerveandthemuscle).Thus,nerve
impulsesthatcontrolmusclecontractionsareblockeddecreasingmuscleactivity.

CleavingSNAP25alsoblocksreleaseofneuropeptidesinvolvedinthetransmissionofpainfulsensations
(includingsubstanceP,glutamateandcalcitoningenerelatedpeptide,orCGRP),theoreticallyreducingpain
sensitizationofperipheralnerves.ThismaybehowBOTOXreducestheneckpainassociatedwithcervical
dystonia,althoughtheexactmechanismofactionisunknown.

PhaseIINerveMuscleCommunicationisRestored
TheeffectofBOTOXisgenerallytemporary.Previousnerveimpulseactivityandassociatedmusclecontractions
resumeoverthecourseofafewtoseveralmonths,dependingontheindividualpatientandtheindicationforwhich
theyarebeingtreated.

A) NerveSprouting:
Newnerveendingssproutandconnecttothe
muscleaftertheoriginalnerveendingis
blocked,renewingtheabilityofthenerveto
causemusclecontractions.

IMPORTANTSAFETYINFORMATION(continued)
Tellyourdoctoraboutallthemedicinesyoutake,
includingprescriptionandnonprescriptionmedicines,
vitaminsandherbalproducts.

BOTOXandBOTOXCosmeticmaycauselossof
strengthorgeneralmuscleweakness,orvision
problems.Ifthishappens,donotdriveacar,operate
machinery,ordootherdangerousactivities.

OthersideeffectsofBOTOXandBOTOXCosmetic
include:drymouth,discomfortorpainattheinjection
site,tiredness,headache,neckpain,andeyeproblems:
doublevision,blurredvision,decreasedeyesight,
droopingeyelids,swellingofyoureyelids,anddryeyes.
FormoreinformationrefertotheMedicationGuideor
talkwithyourdoctor.
Pleaseseenextpageforadditional
ImportantSafetyInformation

B) OriginalNerveConnectionReestablished:
Eventually,thenewnervesproutsretractandtheoriginal
nerveendingregainsitsfunction,suggestingthattreatment
withBOTOX(onabotulinumtoxinA)neurotoxindoesnot
permanentlyaltertheneuromuscularjunction.

IMPORTANTSAFETYINFORMATION(continued)

YouareencouragedtoreportnegativesideeffectsofprescriptiondrugstotheFDA.Visitwww.fda.gov/medwatch,or
call1800FDA1088.

PleaseseetheaccompanyingfullProductInformation,includingMedicationGuide,forBOTOX.

PleaseseetheaccompanyingfullProductInformation,includingMedicationGuide,forBOTOXCosmetic.

ForfurtherinformationpleasecontactAllergan,Inc.:
CarolineVanHove:

7142465134
CrystalMuilenburg:
7142465842
KellieLao:

7142462278

2010Allergan,Inc.Irvine,CA92612.marksownedbyAllergan,Inc.
DysportisaregisteredtrademarkofIpsenBiopharmLimited
MyoblocisaregisteredtrademarkofElanPharmaceuticals,Inc.

APC17PF10

BOTOXPrescribingInformation,March2010