BOTOX Billing and Coding for Chronic Migraine

Transcription

1 S T R E A M L I N E Billing nd Coding for Chronic Migrine Indiction Chronic Migrine for injection is indicted for the prophylxis of hedches in dult ptients with chronic migrine ( 15 dys per month with hedche lsting 4 hours dy or longer). Importnt Limittions Sfety nd effectiveness hve not been estblished for the prophylxis of episodic migrine (14 hedche dys or fewer per month) in 7 plcebo-controlled studies. IMPORTANT SAFETY INFORMATION, INCLUDING BOXED WARNING WARNING: DISTANT SPREAD OF TOXIN EFFECT Postmrketing reports indicte tht the effects of nd ll botulinum toxin products my spred from the re of injection to produce symptoms consistent with botulinum toxin effects. These my include stheni, generlized muscle wekness, diplopi, ptosis, dysphgi, dysphoni, dysrthri, urinry incontinence, nd brething difficulties. These symptoms hve been reported hours to weeks fter injection. Swllowing nd brething difficulties cn be life thretening, nd there hve been reports of deth. The risk of symptoms is probbly gretest in children treted for spsticity, but symptoms cn lso occur in dults treted for spsticity nd other conditions, prticulrly in those ptients who hve n underlying condition tht would predispose them to these symptoms. In unpproved uses, including spsticity in children, nd in pproved indictions, cses of spred of effect hve been reported t doses comprble to those used to tret cervicl dystoni nd spsticity nd t lower doses. Plese see dditionl Importnt Sfety Informtion bout on following pges.

2 Common codes for (onbotulinumtoxina) indictions DRUG CODES CODE TYPE CODE CODE DEFINITION HCPCS II J0585 INJECTION, ONABOTULINUMTOXINA, 1 UNIT NDC Unit vil CPT * PROCEDURE CODE Chemodenervtion of muscle(s); muscle(s) innervted by fcil, trigeminl, cervicl spinl nd ccessory nerves, bilterl (eg, for chronic migrine) DIAGNOSIS CODES Plese see full Indictions nd Importnt Limittions on following pges. Dignosis ICD-10-CM G G G G Chronic migrine without ur, not intrctble, without sttus migrinosus Chronic migrine without ur, intrctble, without sttus migrinosus Chronic migrine without ur, not intrctble, with sttus migrinosus Chronic migrine without ur, intrctble, with sttus migrinosus Note: For electronic billing, pyers require n 11-digit NDC number [5-4-2 configurtion] on the clim form. Therefore, n dditionl zero should be dded to the beginning of the 10-digit NDC code listed on the box [eg, ]. Contct pyers to confirm their reporting preferences nd determine which procedure code to use. Check pyer guidelines regrding the definition of site, coding, nd use of modifiers. *CPT codes nd descriptors re copyrighted by the AMA. These include uses tht re outside lbeled indictions. The procedure codes nd dignosis codes re for illustrtive purposes only, s the prctitioner must determine the proper coding for the tretment provided. This piece is being provided in response to inquiries reltive to the identifiction of drug codes, dignosis codes, nd procedure codes. ICD-10-CM codes submitted to the pyer must ccurtely describe the dignosis for which the ptient receives tretment, represent codes t the highest level of specificity (up to 3-7 chrcter codes) nd reflect the contents of ny clinicl notes nd/or chrt documenttion nd be included in Letter of Medicl Necessity (LOMN) or prior uthoriztion (PA). CPT codes submitted to the pyer must describe the service(s) preformed. The coding informtion contined herein is gthered from vrious resources nd is subject to chnge. This document is intended for reference only. Nothing in this document is intended to serve s reimbursement dvice, gurntee of coverge, or gurntee of pyment for. Third-prty pyment for medicl products nd services is ffected by numerous fctors. The decision bout which code to report must be mde by the provider/physicin considering the clinicl fcts, circumstnces, nd pplicble coding rules, including the requirement to code to the highest level of specificity. Plese refer to your Medicre policy/other pyer policies for specific guidnce. IMPORTANT SAFETY INFORMATION (continued) CONTRAINDICATIONS is contrindicted in the presence of infection t the proposed injection site(s) nd in individuls with known hypersensitivity to ny botulinum toxin preprtion or to ny of the components in the formultion. WARNINGS AND PRECAUTIONS Lck of Interchngebility Between Botulinum Toxin Products The potency Units of re specific to the preprtion nd ssy method utilized. They re not interchngeble with other preprtions of botulinum toxin products nd, therefore, Units of biologicl ctivity of cnnot be compred to nor converted into Units of ny other botulinum toxin products ssessed with ny other specific ssy method. Spred of Toxin Effect See Boxed Wrning. No definitive serious dverse event reports of distnt spred of toxin effect ssocited with for chronic migrine t the lbeled dose hve been reported. Plese see dditionl Importnt Sfety Informtion bout on following pge.

3 IMPORTANT SAFETY INFORMATION (continued) WARNINGS AND PRECAUTIONS (continued) Serious Adverse Rections With Unpproved Use Serious dverse rections, including excessive wekness, dysphgi, nd spirtion pneumoni, with some dverse rections ssocited with ftl outcomes, hve been reported in ptients who received (onbotulinumtoxina) injections for unpproved uses. In these cses, the dverse rections were not necessrily relted to distnt spred of toxin, but my hve resulted from the dministrtion of to the site of injection nd/or djcent structures. In severl of the cses, ptients hd pre-existing dysphgi or other significnt disbilities. There is insufficient informtion to identify fctors ssocited with n incresed risk for dverse rections ssocited with the unpproved uses of. The sfety nd effectiveness of for unpproved uses hve not been estblished. Hypersensitivity Rections Serious nd/or immedite hypersensitivity rections hve been reported. These rections include nphylxis, serum sickness, urticri, soft-tissue edem, nd dyspne. If such rection occurs, further injection of should be discontinued nd pproprite medicl therpy immeditely instituted. One ftl cse of nphylxis hs been reported in which lidocine ws used s the diluent, nd consequently the cusl gent cnnot be relibly determined. Incresed Risk of Cliniclly Significnt Effects With Pre-Existing Neuromusculr Disorders Individuls with peripherl motor neuropthic diseses, myotrophic lterl sclerosis, or neuromusculr junction disorders (eg, mystheni grvis or Lmbert-Eton syndrome) should be monitored when given botulinum toxin. Ptients with known or unrecognized neuromusculr disorders or neuromusculr junction disorders my be t incresed risk of cliniclly significnt effects including generlized muscle wekness, diplopi, ptosis, dysphoni, dysrthri, severe dysphgi, nd respirtory compromise from therpeutic doses of (see Wrnings nd Precutions). Dysphgi nd Brething Difficulties with nd other botulinum toxin products cn result in swllowing or brething difficulties. Ptients with pre-existing swllowing or brething difficulties my be more susceptible to these complictions. In most cses, this is consequence of wekening of muscles in the re of injection tht re involved in brething or orophryngel muscles tht control swllowing or brething (see Boxed Wrning). Humn Albumin nd Trnsmission of Virl Diseses This product contins lbumin, derivtive of humn blood. Bsed on effective donor screening nd product mnufcturing processes, it crries n extremely remote risk for trnsmission of virl diseses nd vrint Creutzfeldt-Jkob disese (vcjd). There is theoreticl risk for trnsmission of Creutzfeldt-Jkob disese (CJD), but if tht risk ctully exists, the risk of trnsmission would lso be considered extremely remote. No cses of trnsmission of virl diseses, CJD, or vcjd hve ever been identified for licensed lbumin or lbumin contined in other licensed products. ADVERSE REACTIONS Adverse rections to (onbotulinumtoxina) for injection re discussed in greter detil in the following sections: Boxed Wrning, Contrindictions, nd Wrnings nd Precutions. Chronic Migrine The most frequently reported dverse rections following injection of for chronic migrine include neck pin (9%), hedche (5%), eyelid ptosis (4%), migrine (4%), musculr wekness (4%), musculoskeletl stiffness (4%), bronchitis (3%), injection-site pin (3%), musculoskeletl pin (3%), mylgi (3%), fcil presis (2%), hypertension (2%), nd muscle spsms (2%). Postmrketing Experience There hve been spontneous reports of deth, sometimes ssocited with dysphgi, pneumoni, nd/or other significnt debility or nphylxis, fter tretment with botulinum toxin. There hve lso been reports of dverse events involving the crdiovsculr system, including rrhythmi nd myocrdil infrction, some with ftl outcomes. Some of these ptients hd risk fctors including crdiovsculr disese. The exct reltionship of these events to the botulinum toxin injection hs not been estblished. DRUG INTERACTIONS Co-dministrtion of or other gents interfering with neuromusculr trnsmission (eg, minoglycosides, curre-like compounds) should only be performed with cution s the effect of the toxin my be potentited. Use of nticholinergic drugs fter dministrtion of my potentite systemic nticholinergic effects. The effect of dministering different botulinum neurotoxin products t the sme time or within severl months of ech other is unknown. Excessive neuromusculr wekness my be excerbted by dministrtion of nother botulinum toxin prior to the resolution of the effects of previously dministered botulinum toxin nd lso by dministrtion of muscle relxnt before or fter dministrtion of. For more informtion on, plese see the ccompnying full Prescribing Informtion, including Boxed Wrning nd Mediction Guide Allergn. All rights reserved. All trdemrks re the property of their respective owners BRE70215_v2 07/17

4 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use sfely nd effectively. See full prescribing informtion for. (onbotulinumtoxina) for injection, for intrmusculr, intrdetrusor, or intrderml use Initil U.S. Approvl: 1989 WARNING: DISTANT SPREAD OF TOXIN EFFECT See full prescribing informtion for complete boxed wrning. The effects of nd ll botulinum toxin products my spred from the re of injection to produce symptoms consistent with botulinum toxin effects. These symptoms hve been reported hours to weeks fter injection. Swllowing nd brething difficulties cn be life thretening nd there hve been reports of deth. The risk of symptoms is probbly gretest in children treted for spsticity but symptoms cn lso occur in dults, prticulrly in those ptients who hve n underlying condition tht would predispose them to these symptoms. (5.2) RECENT MAJOR CHANGES Wrnings nd Precutions (5.5, 5.7, 5.13, 5.14) 4/2017 INDICATIONS AND USAGE is n cetylcholine relese inhibitor nd neuromusculr blocking gent indicted for: of overctive bldder (OAB) with symptoms of urge urinry incontinence, urgency, nd frequency, in dults who hve n indequte response to or re intolernt of n nticholinergic mediction (1.1) of urinry incontinence due to detrusor overctivity ssocited with neurologic condition [e.g., spinl cord injury (SCI), multiple sclerosis (MS)] in dults who hve n indequte response to or re intolernt of n nticholinergic mediction (1.1) Prophylxis of hedches in dult ptients with chronic migrine ( 15 dys per month with hedche lsting 4 hours dy or longer) (1.2) of spsticity in dult ptients (1.3) of cervicl dystoni in dult ptients, to reduce the severity of bnorml hed position nd neck pin (1.4) of severe xillry hyperhidrosis tht is indequtely mnged by topicl gents in dult ptients (1.5) of blephrospsm ssocited with dystoni in ptients 12 yers of ge (1.6) of strbismus in ptients 12 yers of ge (1.6) Importnt Limittions: Sfety nd effectiveness of hve not been estblished for: Prophylxis of episodic migrine (14 hedche dys or fewer per month) (1.2) of upper or lower limb spsticity in peditric ptients (1.3) of hyperhidrosis in body res other thn xillry (1.5) DOSAGE AND ADMINISTRATION Follow indiction-specific dosge nd dministrtion recommendtions; Do not exceed totl dose of 400 Units dministered in 3 month intervl (2.1) See Preprtion nd Dilution Technique for instructions on reconstitution, storge, nd preprtion before injection (2.2) Overctive Bldder: Recommended totl dose, s 0.5 ml (5 Units) injections cross 20 sites into the detrusor (2.3) Detrusor Overctivity ssocited with Neurologic Condition: Recommended totl dose 200 Units, s 1 ml (~6.7 Units) injections cross 30 sites into the detrusor (2.3) Chronic Migrine: Recommended totl dose 155 Units, s 0.1 ml (5 Units) injections per ech site divided cross 7 hed/neck muscles (2.4) Upper Limb Spsticity: Select dose bsed on muscles ffected, severity of muscle ctivity, prior response to tretment, nd dverse event history; Electromyogrphic guidnce recommended (2.5) Lower Limb Spsticity: Recommended totl dose 300 Units to 400 Units divided cross nkle nd toe muscles (2.5) Cervicl Dystoni: Bse dosing on the ptient s hed nd neck position, locliztion of pin, muscle hypertrophy, ptient response, nd dverse event history; use lower initil dose in botulinum toxin nïve ptients (2.6) FULL PRESCRIBING INFORMATION: CONTENTS* WARNING: DISTANT SPREAD OF TOXIN EFFECT 1 INDICATIONS AND USAGE 1.1 Bldder Dysfunction 1.2 Chronic Migrine 1.3 Spsticity 1.4 Cervicl Dystoni 1.5 Primry Axillry Hyperhidrosis 1.6 Blephrospsm nd Strbismus Axillry Hyperhidrosis: 50 Units per xill (2.7) Blephrospsm: 1.25 Units-2.5 Units into ech of 3 sites per ffected eye (2.8) Strbismus: The dose is bsed on prism diopter correction or previous response to tretment with (2.9) DOSAGE FORMS AND STRENGTHS Single-use, sterile or 200 Units vcuum-dried powder for reconstitution only with sterile, preservtive-free 0.9% Sodium Chloride Injection USP prior to injection (3) CONTRAINDICATIONS Hypersensitivity to ny botulinum toxin preprtion or to ny of the components in the formultion (4.1, 5.4, 6) Infection t the proposed injection site (4.2) Intrdetrusor Injections: Urinry Trct Infection or Urinry Retention (4.3) WARNINGS AND PRECAUTIONS Potency Units of re not interchngeble with other preprtions of botulinum toxin products (5.1, 11) Spred of toxin effects; swllowing nd brething difficulties cn led to deth. Seek immedite medicl ttention if respirtory, speech or swllowing difficulties occur (5.2, 5.6) Potentil serious dverse rections fter injections for unpproved uses (5.3) Concomitnt neuromusculr disorder my excerbte clinicl effects of tretment (5.5) Use with cution in ptients with compromised respirtory function (5.6, 5.7, 5.10) Cornel exposure nd ulcertion due to reduced blinking my occur with tretment of blephrospsm (5.8) Retrobulbr hemorrhges nd compromised retinl circultion my occur with tretment of strbismus (5.9) Bronchitis nd upper respirtory trct infections in ptients treted for spsticity (5.10) Urinry trct infections in ptients treted for OAB (5.12) Urinry retention: Post-void residul urine volume should be monitored in ptients treted for OAB or detrusor overctivity ssocited with neurologic condition who do not ctheterize routinely, prticulrly ptients with multiple sclerosis or dibetes mellitus. (5.13) ADVERSE REACTIONS The most common dverse rections ( 5% nd >plcebo) re (6.1): OAB: urinry trct infection, dysuri, urinry retention Detrusor Overctivity ssocited with neurologic condition: urinry trct infection, urinry retention Chronic Migrine: neck pin, hedche Spsticity: pin in extremity Cervicl Dystoni: dysphgi, upper respirtory infection, neck pin, hedche, incresed cough, flu syndrome, bck pin, rhinitis Axillry Hyperhidrosis: injection site pin nd hemorrhge, non-xillry sweting, phryngitis, flu syndrome To report SUSPECTED ADVERSE REACTIONS, contct Allergn t or FDA t FDA-1088 or DRUG INTERACTIONS Ptients receiving concomitnt tretment of nd minoglycosides or other gents interfering with neuromusculr trnsmission (e.g., curre-like gents), or muscle relxnts, should be observed closely becuse the effect of my be potentited (7) USE IN SPECIFIC POPULATIONS Pregnncy: Bsed on niml dt, my cuse fetl hrm. (8.1) Peditric Use: Sfety nd efficcy re not estblished in ptients under 18 yers of ge for the prophylxis of hedches in chronic migrine, tretment of OAB, detrusor overctivity ssocited with neurologic condition, spsticity, nd xillry hyperhidrosis; in ptients under 16 yers of ge for tretment of cervicl dystoni; nd in ptients under 12 yers of ge for tretment of blephrospsm nd strbismus (8.4) See 17 for PATIENT COUNSELING INFORMATION nd Mediction Guide 2 DOSAGE AND ADMINISTRATION 2.1 Instructions for Sfe Use 2.2 Preprtion nd Dilution Technique 2.3 Bldder Dysfunction 2.4 Chronic Migrine 2.5 Spsticity 2.6 Cervicl Dystoni 2.7 Primry Axillry Hyperhidrosis 2.8 Blephrospsm 2.9 Strbismus Revised: 4/2017

5 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 4.1 Known Hypersensitivity to Botulinum Toxin 4.2 Infection t the Injection Site(s) 4.3 Urinry Trct Infection or Urinry Retention 5 WARNINGS AND PRECAUTIONS 5.1 Lck of Interchngebility between Botulinum Toxin Products 5.2 Spred of Toxin Effect 5.3 Serious Adverse Rections with Unpproved Use 5.4 Hypersensitivity Rections 5.5 Incresed Risk of Cliniclly Significnt Effects with Pre-Existing Neuromusculr Disorders 5.6 Dysphgi nd Brething Difficulties 5.7 Pulmonry Effects of in Ptients with Compromised Respirtory Sttus Treted for Spsticity or for Detrusor Overctivity ssocited with Neurologic Condition 5.8 Cornel Exposure nd Ulcertion in Ptients Treted with for Blephrospsm 5.9 Retrobulbr Hemorrhges in Ptients Treted with for Strbismus 5.10 Bronchitis nd Upper Respirtory Trct Infections in Ptients Treted for Spsticity 5.11 Autonomic Dysreflexi in Ptients Treted for Detrusor Overctivity ssocited with Neurologic Condition 5.12 Urinry Trct Infections in Ptients with Overctive Bldder 5.13 Urinry Retention in Ptients Treted for Bldder Dysfunction 5.14 Humn Albumin nd Trnsmission of Virl Diseses 6 ADVERSE REACTIONS 6.1 Clinicl Trils Experience 6.2 Immunogenicity 6.3 Post-Mrketing Experience 7 DRUG INTERACTIONS 7.1 Aminoglycosides nd Other Agents Interfering with Neuromusculr Trnsmission 7.2 Anticholinergic Drugs 7.3 Other Botulinum Neurotoxin Products 7.4 Muscle Relxnts 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnncy 8.2 Lcttion 8.4 Peditric Use 8.5 Geritric Use 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechnism of Action 12.3 Phrmcokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Crcinogenesis, Mutgenesis, Impirment of Fertility 13.2 Animl Toxicology nd/or Phrmcology 14 CLINICAL STUDIES 14.1 Overctive Bldder (OAB) 14.2 Detrusor Overctivity ssocited with Neurologic Condition 14.3 Chronic Migrine 14.4 Spsticity 14.5 Cervicl Dystoni 14.6 Primry Axillry Hyperhidrosis 14.7 Blephrospsm 14.8 Strbismus 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION * Sections or subsections omitted from the full prescribing informtion re not listed. FULL PRESCRIBING INFORMATION WARNING: DISTANT SPREAD OF TOXIN EFFECT Postmrketing reports indicte tht the effects of nd ll botulinum toxin products my spred from the re of injection to produce symptoms consistent with botulinum toxin effects. These my include stheni, generlized muscle wekness, diplopi, ptosis, dysphgi, dysphoni, dysrthri, urinry incontinence nd brething difficulties. These symptoms hve been reported hours to weeks fter injection. Swllowing nd brething difficulties cn be life thretening nd there hve been reports of deth. The risk of symptoms is probbly gretest in children treted for spsticity but symptoms cn lso occur in dults treted for spsticity nd other conditions, prticulrly in those ptients who hve n underlying condition tht would predispose them to these symptoms. In unpproved uses, including spsticity in children, nd in pproved indictions, cses of spred of effect hve been reported t doses comprble to those used to tret cervicl dystoni nd spsticity nd t lower doses. [See Wrnings nd Precutions (5.2)] 1 INDICATIONS AND USAGE 1.1 Bldder Dysfunction Overctive Bldder (onbotulinumtoxina) for injection is indicted for the tretment of overctive bldder with symptoms of urge urinry incontinence, urgency, nd frequency, in dults who hve n indequte response to or re intolernt of n nticholinergic mediction. Detrusor Overctivity ssocited with Neurologic Condition is indicted for the tretment of urinry incontinence due to detrusor overctivity ssocited with neurologic condition (e.g., SCI, MS) in dults who hve n indequte response to or re intolernt of n nticholinergic mediction. 1.2 Chronic Migrine is indicted for the prophylxis of hedches in dult ptients with chronic migrine ( 15 dys per month with hedche lsting 4 hours dy or longer). Importnt Limittions Sfety nd effectiveness hve not been estblished for the prophylxis of episodic migrine (14 hedche dys or fewer per month) in seven plcebo-controlled studies. 1.3 Spsticity Upper Limb Spsticity is indicted for the tretment of upper limb spsticity in dult ptients, to decrese the severity of incresed muscle tone in elbow flexors (biceps), wrist flexors (flexor crpi rdilis nd flexor crpi ulnris), finger flexors (flexor digitorum profundus nd flexor digitorum sublimis), nd thumb flexors (dductor pollicis nd flexor pollicis longus). Lower Limb Spsticity is indicted for the tretment of lower limb spsticity in dult ptients to decrese the severity of incresed muscle tone in nkle nd toe flexors (gstrocnemius, soleus, tibilis posterior, flexor hllucis longus, nd flexor digitorum longus). Importnt Limittions Sfety nd effectiveness of hve not been estblished for the tretment of other upper or lower limb muscle groups. Sfety nd effectiveness of hve not been estblished for the tretment of spsticity in peditric ptients under ge 18 yers. hs not been shown to improve upper extremity functionl bilities, or rnge of motion t joint ffected by fixed contrcture. with is not intended to substitute for usul stndrd of cre rehbilittion regimens. 1.4 Cervicl Dystoni is indicted for the tretment of dults with cervicl dystoni, to reduce the severity of bnorml hed position nd neck pin ssocited with cervicl dystoni. 1.5 Primry Axillry Hyperhidrosis is indicted for the tretment of severe primry xillry hyperhidrosis tht is indequtely mnged with topicl gents. Importnt Limittions The sfety nd effectiveness of for hyperhidrosis in other body res hve not been estblished. Wekness of hnd muscles nd blephroptosis my occur in ptients who receive for plmr hyperhidrosis nd fcil hyperhidrosis, respectively. Ptients should be evluted for potentil cuses of secondry hyperhidrosis (e.g., hyperthyroidism) to void symptomtic tretment of hyperhidrosis without the dignosis nd/or tretment of the underlying disese. Sfety nd effectiveness of hve not been estblished for the tretment of xillry hyperhidrosis in peditric ptients under ge Blephrospsm nd Strbismus is indicted for the tretment of strbismus nd blephrospsm ssocited with dystoni, including benign essentil blephrospsm or VII nerve disorders in ptients 12 yers of ge nd bove. 2 DOSAGE AND ADMINISTRATION 2.1 Instructions for Sfe Use The potency Units of (onbotulinumtoxina) for injection re specific to the preprtion nd ssy method utilized. They re not interchngeble with other preprtions of botulinum toxin products nd, therefore, units of biologicl ctivity of cnnot be compred to nor converted into units of ny other botulinum toxin products ssessed with ny other specific ssy method [see Wrnings nd Precutions (5.1) nd Description (11)]. Indiction specific dosge nd dministrtion recommendtions should be followed. When inititing tretment, the lowest recommended dose should be used. In treting dult ptients for one or more indictions, the mximum cumultive dose should not exceed 400 Units, in 3 month intervl. The sfe nd effective use of depends upon proper storge of the product, selection of the correct dose, nd proper reconstitution nd dministrtion techniques. An understnding of stndrd electromyogrphic techniques is lso required for tretment of strbismus, upper or lower limb spsticity, nd my be useful for the tretment of cervicl dystoni. Physicins dministering must understnd the relevnt neuromusculr nd structurl ntomy of the re involved nd ny ltertions to the ntomy due to prior surgicl procedures nd disese, especilly when injecting ner the lungs.

6 2.2 Preprtion nd Dilution Technique Prior to injection, reconstitute ech vcuum-dried vil of with only sterile, preservtive-free 0.9% Sodium Chloride Injection USP. Drw up the proper mount of diluent in the pproprite size syringe (see Tble 1, or for specific instructions for detrusor overctivity ssocited with neurologic condition see Section 2.3), nd slowly inject the diluent into the vil. Discrd the vil if vcuum does not pull the diluent into the vil. Gently mix with the sline by rotting the vil. Record the dte nd time of reconstitution on the spce on the lbel. should be dministered within 24 hours fter reconstitution. During this time period, reconstituted should be stored in refrigertor (2 to 8 C). Tble 1: Dilution Instructions for Vils ( nd 200 Units)** Diluent* Added to 100 Unit Vil 1 ml 2 ml 4 ml 8 ml 10 ml Resulting Dose Units per 0.1 ml 10 Units 5 Units 2.5 Units 1.25 Units 1 Unit Diluent* Added to 200 Unit Vil 1 ml 2 ml 4 ml 8 ml 10 ml Resulting Dose Units per 0.1 ml 20 Units 10 Units 5 Units 2.5 Units 2 Units * Preservtive-free 0.9% Sodium Chloride Injection, USP Only ** For Detrusor Overctivity ssocited with Neurologic Condition Dilution see Section 2.3 Note: These dilutions re clculted for n injection volume of 0.1 ml. A decrese or increse in the dose is lso possible by dministering smller or lrger injection volume - from 0.05 ml (50% decrese in dose) to 0.15 ml (50% increse in dose). An injection of is prepred by drwing into n ppropritely sized sterile syringe n mount of the properly reconstituted toxin slightly greter thn the intended dose. Air bubbles in the syringe brrel re expelled nd the syringe is ttched to n pproprite injection needle. Ptency of the needle should be confirmed. A new, sterile needle nd syringe should be used to enter the vil on ech occsion for removl of. Reconstituted should be cler, colorless, nd free of prticulte mtter. Prenterl drug products should be inspected visully for prticulte mtter nd discolortion prior to dministrtion nd whenever the solution nd the continer permit. 2.3 Bldder Dysfunction Generl Ptients must not hve urinry trct infection (UTI) t the time of tretment. Prophylctic ntibiotics, except minoglycosides, [see Drug Interctions (7.1)] should be dministered 1-3 dys pre-tretment, on the tretment dy, nd 1-3 dys posttretment to reduce the likelihood of procedure-relted UTI. Ptients should discontinue nti-pltelet therpy t lest 3 dys before the injection procedure. Ptients on nti-cogulnt therpy need to be mnged ppropritely to decrese the risk of bleeding. Approprite cution should be exercised when performing cystoscopy. Overctive Bldder An intrvesicl instilltion of diluted locl nesthetic with or without sedtion my be used prior to injection, per locl site prctice. If locl nesthetic instilltion is performed, the bldder should be drined nd irrigted with sterile sline before injection. The recommended dose is of, nd is the mximum recommended dose. The recommended dilution is /10 ml with preservtive-free 0.9% Sodium Chloride Injection, USP (see Tble 1). Dispose of ny unused sline. Reconstituted (/10 ml) is injected into the detrusor muscle vi flexible or rigid cystoscope, voiding the trigone. The bldder should be instilled with enough sline to chieve dequte visuliztion for the injections, but over-distension should be voided. The injection needle should be filled (primed) with pproximtely 1 ml of reconstituted prior to the strt of injections (depending on the needle length) to remove ny ir. The needle should be inserted pproximtely 2 mm into the detrusor, nd 20 injections of 0.5 ml ech (totl volume of 10 ml) should be spced pproximtely 1 cm prt (see Figure 1). For the finl injection, pproximtely 1 ml of sterile norml sline should be injected so tht the remining in the needle is delivered to the bldder. After the injections re given, ptients should demonstrte their bility to void prior to leving the clinic. The ptient should be observed for t lest 30 minutes post-injection nd until spontneous void hs occurred. Ptients should be considered for reinjection when the clinicl effect of the previous injection hs diminished (medin time until ptients qulified for the second tretment of in double-blind, plcebo-controlled clinicl studies ws 169 dys [~24 weeks]), but no sooner thn 12 weeks from the prior bldder injection. Figure 1: Injection Pttern for Intrdetrusor Injections for of Overctive Bldder nd Detrusor Overctivity ssocited with Neurologic Condition Detrusor Overctivity ssocited with Neurologic Condition An intrvesicl instilltion of diluted locl nesthetic with or without sedtion, or generl nesthesi my be used prior to injection, per locl site prctice. If locl nesthetic instilltion is performed, the bldder should be drined nd irrigted with sterile sline before injection. The recommended dose is 200 Units of per tretment, nd should not be exceeded. 200 Unit Vil of Reconstitute 200 Unit vil of with 6 ml of preservtive-free 0.9% Sodium Chloride Injection, USP nd mix the vil gently. Drw 2 ml from the vil into ech of three 10 ml syringes. Complete the reconstitution by dding 8 ml of preservtive-free 0.9% Sodium Chloride Injection, USP into ech of the 10 ml syringes, nd mix gently. This will result in three 10 ml syringes ech contining 10 ml (~67 Units in ech), for totl of 200 Units of reconstituted. Use immeditely fter reconstitution in the syringe. Dispose of ny unused sline. 100 Unit Vil of Reconstitute two 100 Unit vils of, ech with 6 ml of preservtive-free 0.9% Sodium Chloride Injection, USP nd mix the vils gently. Drw 4 ml from ech vil into ech of two 10 ml syringes. Drw the remining 2 ml from ech vil into third 10 ml syringe for totl of 4 ml in ech syringe. Complete the reconstitution by dding 6 ml of preservtive-free 0.9% Sodium Chloride Injection, USP into ech of the 10 ml syringes, nd mix gently. This will result in three 10 ml syringes ech contining 10 ml (~67 Units in ech), for totl of 200 Units of reconstituted. Use immeditely fter reconstitution in the syringe. Dispose of ny unused sline. Reconstituted (200 Units/30 ml) is injected into the detrusor muscle vi flexible or rigid cystoscope, voiding the trigone. The bldder should be instilled with enough sline to chieve dequte visuliztion for the injections, but over-distension should be voided. The injection needle should be filled (primed) with pproximtely 1 ml of reconstituted prior to the strt of injections (depending on the needle length) to remove ny ir. The needle should be inserted pproximtely 2 mm into the detrusor, nd 30 injections of 1 ml (~6.7 Units) ech (totl volume of 30 ml) should be spced pproximtely 1 cm prt (see Figure 1). For the finl injection, pproximtely 1 ml of sterile norml sline should be injected so tht the remining in the needle is delivered to the bldder. After the injections re given, the sline used for bldder wll visuliztion should be drined. The ptient should be observed for t lest 30 minutes post-injection. Ptients should be considered for re-injection when the clinicl effect of the previous injection diminishes (medin time to qulifiction for re-tretment in the double-blind, plcebo-controlled clinicl studies ws dys [42-48 weeks] for 200 Units), but no sooner thn 12 weeks from the prior bldder injection. 2.4 Chronic Migrine The recommended dilution is 200 Units/4 ml or /2 ml, with finl concentrtion of 5 Units per 0.1 ml (see Tble 1). The recommended dose for treting chronic migrine is 155 Units dministered intrmusculrly using sterile 30-guge, 0.5 inch needle s 0.1 ml (5 Units) injections per ech site. Injections should be divided cross 7 specific hed/neck muscle res s specified in the digrms nd Tble 2 below. A one inch needle my be needed in the neck region for ptients with thick neck muscles. With the exception of the procerus muscle, which should be injected t one site (midline), ll muscles should be injected bilterlly with hlf the number of injection sites dministered to the left, nd hlf to the right side of the hed nd neck. The recommended re-tretment schedule is every 12 weeks.

7 Digrms 1-4: Recommended Injection Sites (A through G) for Chronic Migrine Figure 2: Injection Sites for Upper Limb Spsticity 4 Biceps brchii Flexor crpi ulnris Flexor crpi rdilis A. Corrugtor: 5 U ech side D. Temporlis: 20 U ech side E. Occipitlis: 15 U ech side B. Procerus: 5 U (one site) F. Cervicl prspinl: 10 U ech side Flexor digitorum sublimis (flexor digitorum superficilis) Flexor digitorum profundus G. Trpezius: 15 U ech side Flexor pollicis longus C. Frontlis: 10 U ech side Adductor pollicis Tble 2: Dosing by Muscle for Chronic Migrine Hed/Neck Are Recommended Dose (Number of Sites) Frontlis 20 Units divided in 4 sites Corrugtorb 10 Units divided in 2 sites b Procerus 5 Units in 1 site Lower Limb Spsticity The recommended dose for treting lower limb spsticity is 300 Units to 400 Units divided mong 5 muscles (gstrocnemius, soleus, tibilis posterior, flexor hllucis longus nd flexor digitorum longus) (see Tble 4 nd Figure 3). Tble 4: Dosing by Muscle for Lower Limb Spsticity Occipitlisb 30 Units divided in 6 sites Temporlisb 40 Units divided in 8 sites Muscle Trpeziusb 30 Units divided in 6 sites Gstrocnemius medil hed 75 Units divided in 3 sites Cervicl Prspinl Muscle Groupb 20 Units divided in 4 sites Gstrocnemius lterl hed 75 Units divided in 3 sites Soleus 75 Units divided in 3 sites Tibilis Posterior 75 Units divided in 3 sites Flexor hllucis longus 50 Units divided in 2 sites Flexor digitorum longus 50 Units divided in 2 sites Totl Dose: 155 Units divided in 31 sites Ech IM injection site = 0.1 ml = 5 Units Dose distributed bilterlly 2.5 Spsticity Dosing in initil nd sequentil tretment sessions should be tilored to the individul bsed on the size, number nd loction of muscles involved, severity of spsticity, the presence of locl muscle wekness, the ptient s response to previous tretment, or dverse event history with. The recommended dilution is 200 Units/4 ml or /2 ml with preservtivefree 0.9% Sodium Chloride Injection, USP (see Tble 1). The lowest recommended strting dose should be used, nd no more thn 50 Units per site should generlly be dministered. An ppropritely sized needle (e.g., guge) my be used for superficil muscles, nd longer 22 guge needle my be used for deeper musculture. Locliztion of the involved muscles with techniques such s needle electromyogrphic guidnce or nerve stimultion is recommended. Repet tretment my be dministered when the effect of previous injection hs diminished, but generlly no sooner thn 12 weeks fter the previous injection. The degree nd pttern of muscle spsticity t the time of re-injection my necessitte ltertions in the dose of nd muscles to be injected. Upper Limb Spsticity In clinicl trils, doses rnging from 75 Units to 400 Units were divided mong selected muscles (see Tble 3 nd Figure 2) t given tretment session. Tble 3: Dosing by Muscle for Upper Limb Spsticity b Muscle Biceps Brchii Recommended Dose Totl Dosge (Number of Sites) -200 Units divided in 4 sites Flexor Crpi Rdilis 12.5 Units-50 Units in 1 site Flexor Crpi Ulnris 12.5 Units-50 Units in 1 site Flexor Digitorum Profundus 30 Units-50 Units in 1 site Flexor Digitorum Sublimis 30 Units-50 Units in 1 site Adductor Pollicis 20 Units in 1 site Flexor Pollicis Longus 20 Units in 1 site Recommended Dose Totl Dosge (Number of Sites) Figure 3: Injection Sites for Lower Limb Spsticity Medil hed of gstrocnemius Lterl hed of gstrocnemius Soleus Tibilis posterior Flexor digitorum longus nd Flexor hllucis longus 2.6 Cervicl Dystoni A double-blind, plcebo-controlled study enrolled ptients who hd extended histories of receiving nd tolerting injections, with prior individulized djustment of dose. The men dose dministered to ptients in this study ws 236 Units (25th to 75th percentile rnge of 198 Units to 300 Units). The dose ws divided mong the ffected muscles [see Clinicl Studies (14.5)]. Dosing in initil nd sequentil tretment sessions should be tilored to the individul ptient bsed on the ptient s hed nd neck position, locliztion of pin, muscle hypertrophy, ptient response, nd dverse event history. The initil dose for ptient without prior use of should be t lower dose, with subsequent dosing djusted bsed on individul response. Limiting the totl dose injected into the sternocleidomstoid muscle to or less my decrese the occurrence of dysphgi [see Wrnings nd Precutions (5.2, 5.5, 5.6)]. The recommended dilution is 200 Units/2 ml, 200 Units/4 ml, /1 ml, or /2 ml with preservtive-free 0.9% Sodium Chloride Injection, USP, depending on volume nd number of injection sites desired to chieve tretment objectives (see Tble 1). In generl, no more thn 50 Units per site should be dministered using sterile needle (e.g., guge) of n pproprite length. Locliztion of the involved muscles with electromyogrphic guidnce my be useful.

8 Clinicl improvement generlly begins within the first two weeks fter injection with mximum clinicl benefit t pproximtely six weeks post-injection. In the doubleblind, plcebo-controlled study most subjects were observed to hve returned to pretretment sttus by 3 months post-tretment. 2.7 Primry Axillry Hyperhidrosis The recommended dose is 50 Units per xill. The hyperhidrotic re to be injected should be defined using stndrd stining techniques, e.g., Minor s Iodine-Strch Test. The recommended dilution is /4 ml with 0.9% preservtive-free sterile sline (see Tble 1). Using sterile 30 guge needle, 50 Units of (2 ml) is injected intrdermlly in 0.1 to 0.2 ml liquots to ech xill evenly distributed in multiple sites (10-15) pproximtely 1-2 cm prt. Repet injections for hyperhidrosis should be dministered when the clinicl effect of previous injection diminishes. Instructions for the Minor s Iodine-Strch Test Procedure: Ptients should shve underrms nd bstin from use of over-the-counter deodornts or ntiperspirnts for 24 hours prior to the test. Ptient should be resting comfortbly without exercise, hot drinks for pproximtely 30 minutes prior to the test. Dry the underrm re nd then immeditely pint it with iodine solution. Allow the re to dry, then lightly sprinkle the re with strch powder. Gently blow off ny excess strch powder. The hyperhidrotic re will develop deep blue-blck color over pproximtely 10 minutes. Ech injection site hs ring of effect of up to pproximtely 2 cm in dimeter. To minimize the re of no effect, the injection sites should be evenly spced s shown in Figure 4. Figure 4: Injection Pttern for Primry Axillry Hyperhidrosis Ech dose is injected to depth of pproximtely 2 mm nd t 45 ngle to the skin surfce, with the bevel side up to minimize lekge nd to ensure the injections remin intrderml. If injection sites re mrked in ink, do not inject directly through the ink mrk to void permnent tttoo effect. 2.8 Blephrospsm For blephrospsm, reconstituted is injected using sterile, guge needle without electromyogrphic guidnce. The initil recommended dose is 1.25 Units-2.5 Units (0.05 ml to 0.1 ml volume t ech site) injected into the medil nd lterl pretrsl orbiculris oculi of the upper lid nd into the lterl pre-trsl orbiculris oculi of the lower lid. Avoiding injection ner the levtor plpebre superioris my reduce the compliction of ptosis. Avoiding medil lower lid injections, nd thereby reducing diffusion into the inferior oblique, my reduce the compliction of diplopi. Ecchymosis occurs esily in the soft eyelid tissues. This cn be prevented by pplying pressure t the injection site immeditely fter the injection. The recommended dilution to chieve 1.25 Units is /8 ml; for 2.5 Units it is /4 ml (see Tble 1). In generl, the initil effect of the injections is seen within three dys nd reches pek t one to two weeks post-tretment. Ech tretment lsts pproximtely three months, following which the procedure cn be repeted. At repet tretment sessions, the dose my be incresed up to two-fold if the response from the initil tretment is considered insufficient, usully defined s n effect tht does not lst longer thn two months. However, there ppers to be little benefit obtinble from injecting more thn 5 Units per site. Some tolernce my be found when is used in treting blephrospsm if tretments re given ny more frequently thn every three months, nd is rre to hve the effect be permnent. The cumultive dose of tretment for blephrospsm in 30-dy period should not exceed 200 Units. 2.9 Strbismus is intended for injection into extroculr muscles utilizing the electricl ctivity recorded from the tip of the injection needle s guide to plcement within the trget muscle. Injection without surgicl exposure or electromyogrphic guidnce should not be ttempted. Physicins should be fmilir with electromyogrphic technique. To prepre the eye for injection, it is recommended tht severl drops of locl nesthetic nd n oculr decongestnt be given severl minutes prior to injection. The volume of injected for tretment of strbismus should be between ml per muscle. The initil listed doses of the reconstituted [see Dosge nd Administrtion (2.2)] typiclly crete prlysis of the injected muscles beginning one to two dys fter injection nd incresing in intensity during the first week. The prlysis lsts for 2-6 weeks nd grdully resolves over similr time period. Overcorrections lsting over six months hve been rre. About one hlf of ptients will require subsequent doses becuse of indequte prlytic response of the muscle to the initil dose, or becuse of mechnicl fctors such s lrge devitions or restrictions, or becuse of the lck of binoculr motor fusion to stbilize the lignment. Initil Doses in Units Use the lower listed doses for tretment of smll devitions. Use the lrger doses only for lrge devitions. For verticl muscles, nd for horizontl strbismus of less thn 20 prism diopters: 1.25 Units-2.5 Units in ny one muscle. For horizontl strbismus of 20 prism diopters to 50 prism diopters: 2.5 Units- 5 Units in ny one muscle. For persistent VI nerve plsy of one month or longer durtion: 1.25 Units-2.5 Units in the medil rectus muscle. Subsequent Doses for Residul or Recurrent Strbismus It is recommended tht ptients be re-exmined 7-14 dys fter ech injection to ssess the effect of tht dose. Ptients experiencing dequte prlysis of the trget muscle tht require subsequent injections should receive dose comprble to the initil dose. Subsequent doses for ptients experiencing incomplete prlysis of the trget muscle my be incresed up to two-fold compred to the previously dministered dose. Subsequent injections should not be dministered until the effects of the previous dose hve dissipted s evidenced by substntil function in the injected nd djcent muscles. The mximum recommended dose s single injection for ny one muscle is 25 Units. The recommended dilution to chieve 1.25 Units is /8 ml; for 2.5 Units it is /4 ml (see Tble 1). 3 DOSAGE FORMS AND STRENGTHS Single-use, sterile or 200 Units vcuum-dried powder for reconstitution only with sterile, preservtive-free 0.9% Sodium Chloride Injection USP prior to injection. 4 CONTRAINDICATIONS 4.1 Known Hypersensitivity to Botulinum Toxin is contrindicted in ptients who re hypersensitive to ny botulinum toxin preprtion or to ny of the components in the formultion [see Wrnings nd Precutions (5.4)]. 4.2 Infection t the Injection Site(s) is contrindicted in the presence of infection t the proposed injection site(s). 4.3 Urinry Trct Infection or Urinry Retention Intrdetrusor injection of is contrindicted in ptients with overctive bldder or detrusor overctivity ssocited with neurologic condition who hve urinry trct infection. Intrdetrusor injection of is lso contrindicted in ptients with urinry retention nd in ptients with post-void residul (PVR) urine volume >200 ml, who re not routinely performing clen intermittent self-ctheteriztion (CIC). 5 WARNINGS AND PRECAUTIONS 5.1 Lck of Interchngebility between Botulinum Toxin Products The potency Units of re specific to the preprtion nd ssy method utilized. They re not interchngeble with other preprtions of botulinum toxin products nd, therefore, units of biologicl ctivity of cnnot be compred to nor converted into units of ny other botulinum toxin products ssessed with ny other specific ssy method [see Description (11)]. 5.2 Spred of Toxin Effect Postmrketing sfety dt from nd other pproved botulinum toxins suggest tht botulinum toxin effects my, in some cses, be observed beyond the site of locl injection. The symptoms re consistent with the mechnism of ction of botulinum toxin nd my include stheni, generlized muscle wekness, diplopi, ptosis, dysphgi, dysphoni, dysrthri, urinry incontinence, nd brething difficulties. These symptoms hve been reported hours to weeks fter injection. Swllowing nd brething difficulties cn be life thretening nd there hve been reports of deth relted to spred of toxin effects. The risk of symptoms is probbly gretest in children treted for spsticity but symptoms cn lso occur in dults treted for spsticity nd other conditions, nd prticulrly in those ptients who hve n underlying condition tht would predispose them to these symptoms. In unpproved uses, including spsticity in children, nd in pproved indictions, symptoms consistent with spred of toxin effect hve been reported t doses comprble to or lower thn doses used to tret cervicl dystoni nd spsticity. Ptients or cregivers should be dvised to seek immedite medicl cre if swllowing, speech or respirtory disorders occur. No definitive serious dverse event reports of distnt spred of toxin effect ssocited with for blephrospsm t the recommended dose (30 Units nd below), severe primry xillry hyperhidrosis t the recommended dose (), strbismus, or for chronic migrine t the lbeled doses hve been reported. 5.3 Serious Adverse Rections with Unpproved Use Serious dverse rections, including excessive wekness, dysphgi, nd spirtion pneumoni, with some dverse rections ssocited with ftl outcomes, hve been reported in ptients who received injections for unpproved uses. In these cses, the dverse rections were not necessrily relted to distnt spred of toxin, but my hve resulted from the dministrtion of to the site of injection nd/or djcent structures. In severl of the cses, ptients hd pre-existing dysphgi or other significnt disbilities. There is insufficient informtion to identify fctors ssocited with n incresed risk for dverse rections ssocited with the unpproved uses of. The sfety nd effectiveness of for unpproved uses hve not been estblished.

9 5.4 Hypersensitivity Rections Serious nd/or immedite hypersensitivity rections hve been reported. These rections include nphylxis, serum sickness, urticri, soft tissue edem, nd dyspne. If such rection occurs, further injection of should be discontinued nd pproprite medicl therpy immeditely instituted. One ftl cse of nphylxis hs been reported in which lidocine ws used s the diluent, nd consequently the cusl gent cnnot be relibly determined. 5.5 Incresed Risk of Cliniclly Significnt Effects with Pre-Existing Neuromusculr Disorders Individuls with peripherl motor neuropthic diseses, myotrophic lterl sclerosis or neuromusculr junction disorders (e.g., mystheni grvis or Lmbert-Eton syndrome) should be monitored when given botulinum toxin. Ptients with known or unrecognized neuromusculr disorders or neuromusculr junction disorders my be t incresed risk of cliniclly significnt effects including generlized muscle wekness, diplopi, ptosis, dysphoni, dysrthri, severe dysphgi nd respirtory compromise from therpeutic doses of [see Wrnings nd Precutions (5.2, 5.6)]. 5.6 Dysphgi nd Brething Difficulties with nd other botulinum toxin products cn result in swllowing or brething difficulties. Ptients with pre-existing swllowing or brething difficulties my be more susceptible to these complictions. In most cses, this is consequence of wekening of muscles in the re of injection tht re involved in brething or orophryngel muscles tht control swllowing or brething [see Wrnings nd Precutions (5.2)]. Deths s compliction of severe dysphgi hve been reported fter tretment with botulinum toxin. Dysphgi my persist for severl months, nd require use of feeding tube to mintin dequte nutrition nd hydrtion. Aspirtion my result from severe dysphgi nd is prticulr risk when treting ptients in whom swllowing or respirtory function is lredy compromised. with botulinum toxins my weken neck muscles tht serve s ccessory muscles of ventiltion. This my result in criticl loss of brething cpcity in ptients with respirtory disorders who my hve become dependent upon these ccessory muscles. There hve been postmrketing reports of serious brething difficulties, including respirtory filure. Ptients with smller neck muscle mss nd ptients who require bilterl injections into the sternocleidomstoid muscle for the tretment of cervicl dystoni hve been reported to be t greter risk for dysphgi. Limiting the dose injected into the sternocleidomstoid muscle my reduce the occurrence of dysphgi. Injections into the levtor scpule my be ssocited with n incresed risk of upper respirtory infection nd dysphgi. Ptients treted with botulinum toxin my require immedite medicl ttention should they develop problems with swllowing, speech or respirtory disorders. These rections cn occur within hours to weeks fter injection with botulinum toxin [see Wrnings nd Precutions (5.2)]. 5.7 Pulmonry Effects of in Ptients with Compromised Respirtory Sttus Treted for Spsticity or for Detrusor Overctivity ssocited with Neurologic Condition Ptients with compromised respirtory sttus treted with for spsticity should be monitored closely. In double-blind, plcebo-controlled, prllel group study in ptients treted for upper limb spsticity with stble reduced pulmonry function (defined s FEV % of predicted vlue nd FEV 1 /FVC 0.75), the event rte in chnge of Forced Vitl Cpcity (FVC) 15% or 20% ws generlly greter in ptients treted with thn in ptients treted with plcebo (see Tble 5). Tble 5: Event Rte Per Ptient Cycle Among Ptients with Reduced Lung Function Who Experienced t Lest 15% or 20% Decrese in FVC From Bseline t Week 1, 6, 12 Post-injection with Up to Two Cycles with or 360 Units 240 Units 15% 20% 15% 20% 15% 20% Week 1 4% 0% 3% 0% 7% 3% Week 6 7% 4% 4% 2% 2% 2% Week 12 10% 5% 2% 1% 4% 1% Differences from plcebo were not sttisticlly significnt In spsticity ptients with reduced lung function, upper respirtory trct infections were lso reported more frequently s dverse rections in ptients treted with thn in ptients treted with plcebo [see Wrnings nd Precutions (5.10)]. In double-blind, plcebo-controlled, prllel group study in dult ptients with detrusor overctivity ssocited with neurologic condition nd restrictive lung disese of neuromusculr etiology [defined s FVC 50-80% of predicted vlue in ptients with spinl cord injury between C5 nd C8, or MS] the event rte in chnge of Forced Vitl Cpcity 15% or 20% ws generlly greter in ptients treted with thn in ptients treted with plcebo (see Tble 6). Tble 6: Number nd Percent of Ptients Experiencing t Lest 15% or 20% Decrese in FVC From Bseline t Week 2, 6, 12 Post-injection with or 200 Units 15% 20% 15% 20% Week 2 0/15 (0%) 0/15 (0%) 1/11 (9%) 0/11 (0%) Week 6 2/13 (15%) 1/13 (8%) 0/12 (0%) 0/12 (0%) Week 12 0/12 (0%) 0/12 (0%) 0/7 (0%) 0/7 (0%) 5.8 Cornel Exposure nd Ulcertion in Ptients Treted with for Blephrospsm Reduced blinking from injection of the orbiculris muscle cn led to cornel exposure, persistent epithelil defect, nd cornel ulcertion, especilly in ptients with VII nerve disorders. Vigorous tretment of ny epithelil defect should be employed. This my require protective drops, ointment, therpeutic soft contct lenses, or closure of the eye by ptching or other mens. 5.9 Retrobulbr Hemorrhges in Ptients Treted with for Strbismus During the dministrtion of for the tretment of strbismus, retrobulbr hemorrhges sufficient to compromise retinl circultion hve occurred. It is recommended tht pproprite instruments to decompress the orbit be ccessible Bronchitis nd Upper Respirtory Trct Infections in Ptients Treted for Spsticity Bronchitis ws reported more frequently s n dverse rection in ptients treted for upper limb spsticity with (3% t 251 Units-360 Units totl dose), compred to plcebo (1%). In ptients with reduced lung function treted for upper limb spsticity, upper respirtory trct infections were lso reported more frequently s dverse rections in ptients treted with (11% t 360 Units totl dose; 8% t 240 Units totl dose) compred to plcebo (6%). In dult ptients treted for lower limb spsticity, upper respirtory trct infections were reported more frequently s n dverse event in ptients treted with (2% t 300 Units to 400 Units totl dose) compred to plcebo (1%) Autonomic Dysreflexi in Ptients Treted for Detrusor Overctivity ssocited with Neurologic Condition Autonomic dysreflexi ssocited with intrdetrusor injections of could occur in ptients treted for detrusor overctivity ssocited with neurologic condition nd my require prompt medicl therpy. In clinicl trils, the incidence of utonomic dysreflexi ws greter in ptients treted with 200 Units compred with plcebo (1.5% versus 0.4%, respectively) Urinry Trct Infections in Ptients with Overctive Bldder increses the incidence of urinry trct infection [see Adverse Rections (6.1)]. Clinicl trils for overctive bldder excluded ptients with more thn 2 UTIs in the pst 6 months nd those tking ntibiotics chroniclly due to recurrent UTIs. Use of for the tretment of overctive bldder in such ptients nd in ptients with multiple recurrent UTIs during tretment should only be considered when the benefit is likely to outweigh the potentil risk Urinry Retention in Ptients Treted for Bldder Dysfunction Due to the risk of urinry retention, tret only ptients who re willing nd ble to initite ctheteriztion post-tretment, if required, for urinry retention. In ptients who re not ctheterizing, post-void residul (PVR) urine volume should be ssessed within 2 weeks post-tretment nd periodiclly s mediclly pproprite up to 12 weeks, prticulrly in ptients with multiple sclerosis or dibetes mellitus. Depending on ptient symptoms, institute ctheteriztion if PVR urine volume exceeds 200 ml nd continue until PVR flls below 200 ml. Instruct ptients to contct their physicin if they experience difficulty in voiding s ctheteriztion my be required. The incidence nd durtion of urinry retention is described below for ptients with overctive bldder nd detrusor overctivity ssocited with neurologic condition who received or plcebo injections. Overctive Bldder In double-blind, plcebo-controlled trils in ptients with OAB, the proportion of subjects who initited clen intermittent ctheteriztion (CIC) for urinry retention following tretment with or plcebo is shown in Tble 7. The durtion of post-injection ctheteriztion for those who developed urinry retention is lso shown.