spanish patient brochure botox

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Más que epidérmico

Los usos médicos de BOTOX®

Indicaciones

BOTOX® es un medicamento recetado que se inyecta en los músculos y se utiliza:

• para tratar la posición anormal de la cabeza y el dolor de cuello que ocasiona la distonía cervical (DC) en personas de 16 años y más

• para tratar ciertos tipos de problemas del músculo del ojo (estrabismo) o espasmo anormal de los párpados (blefaroespasmo) en

personas de 12 años y más

INFORMACIÓN IMPORTANTE DE SEGURIDAD

BOTOX® y BOTOX® Cosmetic pueden causar efectos secundarios graves que pueden ser una amenaza para la vida.

Llame a su doctor o busque ayuda médica de inmediato si tiene alguno de estos problemas en cualquier momento

(horas a semanas) después de la inyección con BOTOX® o BOTOX® Cosmetic:

• Problemas para tragar, hablar o respirar, debido al debilitamiento de músculos asociados, puede ser grave y causar la pérdida

de la vida. Usted está en mayor riesgo si estos problemas son preexistentes antes de la inyección. Los problemas para tragar pueden

durar varios meses

Por favor consulte las Indicaciones

adicionales e Información Importante de

Seguridad sobre BOTOX® en el interior.

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Los usos médicos de BOTOX® (onabotulinumtoxinA)

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Indicaciones (continuado)

BOTOX® también se inyecta en la piel para tratar los síntomas de la

sudoración severa en las axilas (hiperhidrosis axilar primaria severa)

cuando los medicamentos utilizados en la piel (tópicos) no funcionan lo

sufi cientamente bien en personas de 18 años y más.

No se sabe si BOTOX® es seguro o efectivo para otros tipos de espasmos

musculares o para la sudoración severa en otros lugares además de

las axilas.

BOTOX® Cosmetic es un medicamento recetado que se inyecta en los

músculos y se usa para mejorar el aspecto de arrugas moderadas a graves

del entrecejo (líneas acentuadas de expresión) en personas de 18 a 65

años de edad por un período corto de tiempo (temporal).


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Índice

¿Qué es BOTOX®?

Como funciona el tratamiento con la neurotoxina BOTOX®

Que puede esperar del tratamiento con BOTOX®

Preguntas frecuentes sobre el tratamiento con BOTOX®

Tratamiento con BOTOX® y su cobertura de seguro

Distonía cervical y el tratamiento con BOTOX® (onabotulinumtoxinA)

Historias del éxito de BOTOX®

Vivir con distonía cervical — consejos para pacientes

El blefaroespasmo y el tratamiento con BOTOX®

El estrabismo y el tratamiento con BOTOX®

Encontrar a un doctor que inyecte BOTOX®

Grupos de apoyo al paciente


4

¿Qué es BOTOX ®?

Quizá ya ha oído hablar sobre BOTOX® Cosmetic (onabotulinumtoxinA). Pero como verá en este folleto, la historia de BOTOX® no es

sólo epidérmica.

BOTOX® (onabotulinumtoxinA) es una terapia efi caz que se ha utilizado para tratar pacientes durante aproximadamente 20 años. Uno de los

medicamentos más ampliamente investigados en el mundo, el tratamiento con BOTOX® es aprobado para uso médico en aproximadamente

75 paises.

Identifi cado por primera vez en la década de 1890, BOTOX® es una proteína purifi cada

que procede de la bacteria Clostridium botulinum. En aproximadamente 100 años, nuestro

conocimiento de la toxina botulínica tipo A se ha ampliado desde la identifi cación de la bacteria

C. botulinum hasta la comercialización de BOTOX® como el primer tratamiento aprobado con

toxina botulínica en los Estados Unidos.

En 1989, la neurotoxina de BOTOX® fue aprobada por la Administración de Fármacos y

Alimentos (Food and Drug Administration, FDA, por sus siglas en inglés) para el tratamiento

del blefaroespasmo (espasmos del párpado) y estrabismo (ojos cruzados

o desalineados). En el año 2000, la FDA aprobó BOTOX® para el

tratamiento de la rigidez muscular incontrolable o el giro del cuello, que

se conococe como la distonía cervical.

Otro hito en la historia de BOTOX® fue su aprobación en 2004 para

tratar la sudoración excesiva bajo los brazos cuando los agentes

tópicos no funcionan lo sufi cientemente bien. La misma fórmula con

la dosifi cación específi ca para tratar temporalmente las líneas de

expresión moderadas a graces entre las cejas en personas de 18 a 65

años de edad fue aprobada en 2002 como BOTOX® Cosmetic.


5

Todo fármaco aprobado por la FDA viene con la información sobre seguridad para los doctores y los pacientes. Las secciones

sombreadas en azul en este folleto contienen información sobre el tratamiento con BOTOX ®, así como información detallada sobre el

fármaco en sí. Si usted tiene preguntas o preocupación sobre cualesquiera de estas secciones por favor no dude en consultar

a su doctor.

www.BOTOXMedical.com

BOTOX® (onabotulinumtoxinA) lo hace solamente Allergan—una compañía mundial especializada en dispositivos médicos y farmacéuticos que

ofrece innovadores productos en más de 100 países. El tratamiento con BOTOX® es producido bajo estrictos estándares de control de calidad

por Allergan y debe ser administrado a pacientes sólo por médicos con licencia.

INFORMACIÓN IMPORTANTE DE SEGURIDAD (continuado)


(horas a semanas) después de la inyección de BOTOX® o BOTOX® Cosmetic:

• Propagación de los efectos de la toxina. El efecto de la toxina botulínica puede afectar zonas alejadas del lugar de la

inyección y provocar síntomas graves, incluyendo: pérdida de fuerza y debilidad muscular general, visión doble, visión borrosa

y párpados caídos, ronquera o cambio o pérdida de la voz (disfonía), problemas para decir las palabras con claridad (disartria),

pérdida de control de la vejiga, difi cultad para respirar, difi cultad para tragar

No se ha confi rmado ningún caso grave de propagación del efecto de la toxina lejos del lugar de la inyección cuando se ha usado

BOTOX® a la dosis recomendada para tratar sudoración intensa en las axilas, blefaroespasmo, o estrabismo, o cuando se ha

utilizado BOTOX® Cosmetic a la dosis recomendada para el tratamiento de las arrugas del entrecejo.


6

Como funciona el tratamiento con la neurotoxina BOTOX®

Cuando usted sufre de espasmos musculares, es porque sus células nerviosas están enviando señales directamente a los músculos, lo que

causa este efecto. El tratamiento con BOTOX® (onabotulinumtoxinA) funciona mediante el bloqueo de estas señales, lo que impide la liberación

de una sustancia conocida como acetilcolina.1 Demasiada acetilcolina hace que los músculos estén demasiado activos y tensos. Con la

neurotoxina BOTOX®, los espasmos musculares pueden cesar o disminuir1 signifi cativamente, lo cual proporciona alivio.

Usted también puede experimentar dolor de cuello asociado con la distonía cervical. Se cree que el BOTOX® funciona de manera similar para

bloquear las señales nerviosas que causan el dolor de cuello, lo que produce alivio. Hay evidencia de un estudio con pacientes que muestra

que el tratamiento con BOTOX® puede reducir en gran medida el dolor de cuello incluso antes de que disminuyan los espasmos musculares.2

La forma exacta en que funciona el BOTOX® en la reducción del dolor de cuello en la distonía cervical no es conocida.

Por favor consulte con su doctor cualquier pregunta que tenga sobre su tratamiento.


La dosis de BOTOX® no es la misma que, o comparable a, otro producto de toxina botulínica.

Se ha reportado reacciones alérgicas graves o inmediatas. Estas reacciones incluyen erupción cutánea con picazón,

hinchazón y difi cultad para respirar. Dígale a su médico o procure ayuda médica de inmediato si usted experimenta cualquiera de

estos síntomas; futuras inyecciones de BOTOX® o BOTOX® Cosmetic deben evitarse.


7

Las señales que pueden causar contracciones musculares y dolor de cuello llegan a los músculos a través de los nervios.

La neurotoxina de BOTOX® actúa en el músculo donde es inyectada para bloquear las señales que le indican al músculo que se contraiga y se cree que bloquea las señales que causan el dolor de cuello.

Como resultado, los espasmos musculares pueden detenerse o reducirse en gran medida, lo que produce un alivio que puede durar hasta 3 meses.1

BOTOX® funciona al hacer que los nervios no liberen acetilcolina, que es una sustancia que transmite señales de los nervios a los músculos.



8

Que puede esperar del tratamiento con BOTOX ®

Las inyecciones de BOTOX® serán

administradas en el consultorio médico.


No use BOTOX® o BOTOX® Cosmetic si usted: es alérgico a alguno de los ingredientes de BOTOX® o BOTOX® Cosmetic (véase

la Guía de Medicación para los ingredientes); ha tenido una reacción alérgica a cualquier producto de toxina botulínica tales como

Myobloc ® o Dysport ®; tiene una infección en la piel en el sitio previsto de la inyección.

Una vez que usted y su doctor han determinado que BOTOX® (onabotulinumtoxinA) es para usted, su tratamiento consistirá en una serie

de inyecciones en los músculos seleccionados por su doctor. Las inyecciones de BOTOX® serán administradas en el consultorio médico. La

cantidad de BOTOX® y los puntos de inyección dependerán de sus necesidades. Usted podría experimentar dolor, infección, infl amación,

sensibilidad, hinchazón, enrojecimiento y/o sangrado/moretones en los puntos de inyección.

Dado que la neurotoxina BOTOX® es inyectada directamente en los músculos afectados, no se espera que esté presente en el torrente

sanguíneo después de la inyección en la dosis recomendada. Usted debería ser capaz de dejar el consultorio de su doctor después de un

período corto de recuperación.

¿Cuánto tardan en verse los resultados? No mucho. Podría empezar a ver la mejoría en los

síntomas a los pocos días (unas pocas semanas en algunas afecciones) de haber recibido el

tratamiento con BOTOX® y quizá no tenga que volver a consulta para recibir otra inyección en

hasta 3 meses.1


9

Usted puede empezar a ver efectos positivos a los pocos

días del tratamiento con BOTOX® y quizá no tenga que volver a consulta para recibir

otra inyección en hasta 3 meses.1

Por favor coméntele a su doctor sobre cualquier

medicamento con y sin receta médica que usted pueda estar

tomando para otra afección médica.



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¿Duele el tratamiento con BOTOX®?

El tratamiento con BOTOX® (onabotulinumtoxinA) se administra con agujas muy fi nas, de manera que la mayoría de la gente siente sólo un

leve malestar. No es común requerir alivio del dolor, aunque algunos doctores sugieren el uso de una crema de anestesia tópica antes

del tratamiento.

¿BOTOX® Cosmetic es igual a la neurotoxina BOTOX®?

Sí. BOTOX® Cosmetic y BOTOX® tienen la misma formulación. La neurotoxina BOTOX® es uno de los medicamentos más ampliamente

investigados en el mundo y ha sido utilizada durante aproximadamente 20 años. La misma formulación con dosis específi cas para el

tratamiento temporal de las arrugas del entrecejo de moderadas a graves (líneas acentuadas de expresión entre las cejas) para las

personas de edades comprendidas entre 18 y 65 años fue aprobada en 2002 como BOTOX® Cosmetic (onabotulinumtoxinA).

¿Es seguro recibir repetidas inyecciones de BOTOX®?

El tratamiento con BOTOX® está aprobado por la FDA para varias inyecciones. En la mayoría de los pacientes el tratamiento con BOTOX®

suele durar hasta 3 meses1—y se puede repetir siempre y cuando el paciente siente alivio de los síntomas y no tenga reaciones alérgicas

graces u otros efectos secundarios relacionados con BOTOX®. Su doctor determinará el momento apropiado para volver a aplicar la inyección.

Pacientes de todo el mundo reciben inyecciones repetidas de la neurotoxina BOTOX® para tratar con efi cacia una variedad de condiciones

médicas (distonía cervical, blefaroespasmo, y estrabismo).

Preguntas frecuentes sobre el tratamiento con BOTOX ®


Dígale a su doctor acerca de todas sus condiciones de músculos o nervios tales como la esclerosis lateral amiotrófi ca

[ALS o enfermedad de Lou Gehrig], miastenia gravis o síndrome de Lambert-Eaton, ya que podría estar en mayor riesgo de efectos

secundarios graves, incluyendo disfagia severa (difi cultad para tragar) y compromiso respiratorio (difi cultad para respirar) de dosis

típicas de BOTOX® o BOTOX® Cosmetic.


11


¿Es cierto que algunos pacientes no siempre tienen la misma respuesta a repetidas inyecciones de BOTOX®?

Hay muchos factores que impactan los resultados del tratamiento con BOTOX®. Un porcentaje muy pequeño desarrolla inmunidad

al BOTOX®. Otros factores que impactan los resultados incluyen la precisión de las inyecciones, la dosifi cación, y los cambios en las

afecciones de los pacientes con el tiempo.

Existen otras toxinas botulínicas disponibles. ¿Son iguales al tratamiento de BOTOX®?

Es importante entender que no hay dos productos de toxinas botulínicas iguales. Se diferencian en su dosis, proceso de fabricación,

potencia, y efectos adversos. Como resultado, cada producto y su unidad de dosifi cación son únicos y diferentes, y un producto no

puede reemplazar el otro.

¿Cómo se sabe que se está recibiendo el tratamiento con BOTOX® y no con un producto sucedáneo?

BOTOX® es una marca registrada de Allergan, Inc. El producto BOTOX® está empacado en una ampolla de vidrio con tapa violeta o naranja

etiquetada como BOTOX ® y tiene un holograma de Allergan a un lado. Quizá quiera usted pedirle a quien lo va a inyectar que le confi rme

que BOTOX® es el producto a usar en su tratamiento.


12

Tratamiento con BOTOX ® y su cobertura de seguro

Soluciones de Reembolsos de BOTOX®

Muchos planes de seguros, incluyendo Medicare y Medicaid, cubren el costo del tratamiento con BOTOX® (onabotulinumtoxinA) para ciertas

afecciones. Allergan, el fabricante de BOTOX®, ha puesto al alcance de usted y de su médico un servicio para determinar si su plan cubre la

mayoría de los costos del tratamiento con BOTOX®. Dicho programa se conoce como Soluciones de Reembolsos de BOTOX®

(BOTOX® Reimbursement Solutions), y nuestros representantes están especialmente capacitados para ayudar a resolver las cuestiones de

seguros de BOTOX®, responder preguntas, e introducir reclamaciones.

Para más información sobre Soluciones de Reembolso de BOTOX®, llame al 1-800-44-BOTOX, Opción 4. El horario es de lunes a viernes, 9 AM a 8 PM, horario estándar del este (ET, por sus siglas en inglés.)


Dígale a su doctor acerca de todas sus afecciones médicas, incluso si usted tiene: planes de someterse a una cirugía,

ha tenido una cirugía en el rostro; debilidad de los músculos de la frente, como problemas para levantar las cejas; párpados

caídos; cualquier otro cambio anormal del rostro; está embarazada o piensa quedar embarazada (no se sabe si BOTOX® o BOTOX®

Cosmetic puede dañar a su bebe no nacido); está dando pecho o planea dar pecho (no se sabe si BOTOX® o BOTOX® Cosmetic se

excreta en la leche materna).


13


Programa de ASISTENCIA AL PACIENTE DE BOTOX®

El Programa de ASISTENCIA AL PACIENTE DE BOTOX® (BOTOX PATIENT ASSISTANCE® Program) está dedicado a ayudar fi nancieramente a

los pacientes elegibles. Hay ciertos requisitos fi nancieros y de otro tipo que deben cumplirse para califi car para el programa pero se puede

califi car si no tiene seguro o si su seguro no es sufi ciente para satisfacer las necesidades médicas.

Para recibir ayuda del Programa de ASISTENCIA AL PACIENTE DE BOTOX® (BOTOX PATIENT ASSISTANCE® Program), usted debe:

■ Estar sin seguro o sub asegurado

■ Estar ubicado en o por debajo de un cierto nivel de ingresos económicos

■ Tener un diagnóstico apoyado por estudios clínicos que validen el uso de BOTOX®

■ Ser residente de los Estados Unidos o Puerto Rico

Si usted piensa que califi ca para el Programa de ASISTENCIA AL PACIENTE DE BOTOX®

(BOTOX PATIENT ASSISTANCE® Program), visítenos en BOTOXReimbursementSolutions.com, o llámenos al 1-800-44-BOTOX, Opción 4.


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Distonía cervical y el tratamiento con BOTOX ® (onabotulinumtoxin A)

Definición y síntomas de la distonía cervical

La distonía cervical es una afección que hace que los músculos del cuello se tensen o sufran espasmos incontrolables.3,4 Si usted tiene distonía

cervical, su cabeza puede torcerse de manera fuera de lo común, o puede ser forzada a una postura anormal. Los síntomas pueden difi cultar el

desempeño de las sencillas tareas diarias como vestirse o manejar un auto. Pero la distonía cervical puede ser tratada. El obtener tratamiento

puede ayudarle a volver a las actividades que usted disfrutaba antes que comenzaron los síntomas.

El primer paso para sentirse mejor es plantearle sus síntomas a su doctor. Las señales comunes de la distonía cervical a menudo varían de

persona a persona y pueden incluir cualquiera de las siguientes combinaciones:

■ Espasmos musculares o rigidez4,5

■ Jalones o tirantez incómoda en el cuello5,6 o voltear de la cabeza5,7

■ Dolor de cuello (reportado en hasta 91% de los pacientes)8

■ Dolor alrededor del cuello que empeora con el tiempo7

■ Temblores en la cabeza o la mano5-7

■ Síntomas que van aumentando hasta involucrar partes adyacentes del cuerpo9

Si sospecha que tiene distonía cervical, consulte a su doctor.


15


“Todo comenzó con un dolor en la base de mi cuello. Entonces mi cuello

comenzó a jalarse y sacudirse cuando traté de enderezarlo. Fue difícil.

Luchaba con esto todos los días. Estaba en guerra con mi cuello.”

Gus, paciente con distonía cervical


Dígale a su doctor acerca de todos los medicamentos que toma, incluyendo medicamentos con receta y sin receta,

vitaminas, y productos herbarios.

BOTOX® y BOTOX® Cosmetic pueden causar pérdida de fuerza o debilidad muscular general, o problemas de visión. Si estoocurre,

no conduzca un automóvil, opere maquinaria o realice otras actividades peligrosas.


16

Diagnóstico de la distonía cervical

El diagnóstico de la distonía cervical puede ser un reto, en especial en sus fases iniciales o leves. Esto es porque los síntomas pueden ser

leves al inicio y diferir de persona a persona. La distonía cervical a veces es diagnosticada incorrectamente porque se asemeja a otras

dolencias físicas como cuello rígido o estrés. En algunos casos, los pacientes podrían sufrir distonía cervical durante un año o más antes de

ser diagnosticados o tratados.7

Para el diagnóstico de la distonía cervical se pueden usar diversas pruebas como imágenes del cerebro, exámenes de sangre,

electroencefalografías (EEG, por sus siglas en inglés), electromiografías (EMG, por sus siglas en inglés), y monitoreo por video. Una evaluación

también podría incluir pruebas genéticas en algunas situaciones.4 Estas pruebas pueden ser usadas para descartar otras afecciones, dejando

la distonía cervical como el diagnóstico.

Para proporcionar información adicional que pueda ayudar a los doctores a diagnosticar la distonía cervical, los expertos en trastornos del

movimiento han desarrollado estas sencillas preguntas10:

■ ¿Siente usted que su cabeza gira, se inclina o se desplaza en alguna dirección?

■ ¿Se sacude o se agita su cabeza?

■ ¿Sus hombros se levantan o se mueven hacia arriba o hacia abajo sin control?

■ ¿Le han dicho otras personas que su cabeza se mueve hacia los lados, hacia adelante o hacia atrás?

■ ¿Le han dicho otras personas que la cabeza le tiembla?

■ ¿Tiene algún dolor o rigidez en el cuello la mayor parte del tiempo?

■ ¿Hay alguna posición en la que usted puede poner su cabeza para hacer que el movimiento o el dolor cesen?

■ ¿Alguna vez ha consultado a un doctor acerca de los giros o temblores de la cabeza?

Distonía cervical y el tratamiento con BOTOX ® (onabotulinumtoxinA) (continuado)


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La distonía cervical es una enfermedad progresiva

La distonía cervical es una enfermedad progresiva lo que signifi ca que los síntomas pueden empeorar con el tiempo. En aproximadamente

20% de las personas los síntomas de distonía cervical desaparecen completamente.9 Esto se conoce como remisión. Sin embargo, es

importante entender que los síntomas a menudo retornan.9 Normalmente para la mayoría de la gente con distonía cervical los síntomas

dejan de empeorar después 5 años9

Son muchas las causas de la distonía cervical: accidentes, herencia, o causas desconocidas. Para más información, consulte a su médico.


Otros efectos secundarios de BOTOX® y BOTOX® Cosmetic incluyen: boca seca, molestias o dolor en el sitio de la

inyección,cansancio, dolor de cabeza, dolor de cuello, y problemas oculares: visión doble, visión borrosa, disminución de la visión,

párpados caídos, hinchazón de los párpados, y sequedad en los ojos.

Para obtener información adicional consulte la Guía del Medicamento o hable con su médico.

Le animamos a que reporte efectos secundarios negativos de los medicamentos recetados a la FDA.

Visite www.fda.gov/medwatch o llame a 1-800-FDA-1088.

Se ha ofrecido a su doctor información completa sobre el producto, incluyendo la Guía del Medicamento.


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Distonía cervical y el tratamiento con BOTOX ® (onabotulinumtoxinA) (continuado)Cómo afecta a las actividades cotidianas la distonía cervical

Si usted tiene distonía cervical, podrá tener difi cultades para hacer cosas simples. Vestirse, afeitarse, hacer las tareas domésticas, conducir

un coche, o usar una computadora pueden convertirse en un desafío. Además, la distonía cervical a menudo interfi ere con la capacidad del

paciente para realizar actividades cotidianas.7

Aun cuando no hay cura para la distonía cervical, hay buenas probabilidades de que los síntomas puedan ser manejados con éxito con el

tratamiento apropiado. Podría ayudar el saber que hay profesionales de salud quienes entienden su afección y que tienen experiencia en

ayudar a que los pacientes encuentren alivio.


BOTOX® y BOTOX® Cosmetic pueden causar efectos secundarios graves que pueden ser una amenaza para la vida.


(horas a semanas) después de la inyección de BOTOX® y BOTOX® Cosmetic:

• Problemas para tragar, hablar o respirar, debido al debilitamiento de músculos asociados, puede ser grave y causar la

pérdida de la vida. Usted está en mayor riesgo si estos problemas son preexistentes antes de la inyección. Los problemas para

tragar pueden durar varios meses


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Hacia un ladoLaterócolis

Hacia adelante Anterócolis

Hacia atrásRetrócolis

RotadaTortícolis


Tipos de distonía cervical

La distonía cervical causa tensión muscular constante—ésta es la parte de la distonía—y esto ocurre principalmente en el área del cuello,

en lo que se llama la columna cervical. Los músculos tensos en el cuello jalan la cabeza con movimientos y hacia posturas anormales.

Hay 4 tipos principales de distonía cervical, defi nida por la inclinación de la cabeza:

La mayoría de los pacientes (hasta un 81%) tienen una combinación de estas tres posturas.5 Por ejemplo, la cabeza puede verse halada en

2 o más direcciones a la vez, como hacia adelante y hacia un lado.5 La distonía cervical también puede ser llamada espasmódica, si hay

contracciones musculares involuntarias repentinas, o sostenida, si la tensión muscular es contínua.4

n


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Distonía cervical y el tratamiento con BOTOX ®(onabotulinumtoxinA) (continuado)Tratamientos para la distonía cervical

Los doctores cuentan con un número de opciones para tratar la distonía cervical. El tratamiento más comúnmente escogido es con la

neurotoxina BOTOX® (onabotulinumtoxinA). BOTOX® es considerada la terapia de primera línea para la distonía cervical,11 lo cual quiere decir

que los doctores pueden escoger el usar directamente a la neurotoxina BOTOX®, sin tratar otras opciones. Su médico determina exactamente

cuáles músculos le están causando problemas y les inyecta la neurotoxina BOTOX®.

El BOTOX® se utiliza a menudo en combinación con la terapia física. También pueden usarse medicamentos orales. La cirugía en los nervios

implicados también puede ser una opción, pero se utiliza muy poco, ahora que la neurotoxina BOTOX® está disponible.4



(horas a semanas) después de la inyección de BOTOX® y BOTOX® Cosmetic:

• Propagación de los efectos de la toxina. El efecto de la toxina botulínica puede afectar zonas alejadas del lugar de la

inyección y provocar síntomas graves, incluyendo: pérdida de fuerza y debilidad musuclar general, visión doble, visión borrosa

y párpados caídos, ronquera o cambio o pérdida de la voz (disfonía), problemas para decir las palabras con claridad (disartria),

pérdida de control de la vejiga, difi cultad para respirar, difi cultad para tragar

No se ha confi rmado ningún caso grave de propagación del efecto de la toxina lejos del lugar de la inyección cuando se ha usado

BOTOX® a la dosis recomendada para tratar sudoración intensa en las axilas, blefaroespasmo, o estrabismo, o cuando se ha

utilizado BOTOX® Cosmetic a la dosis recomendada para el tratamiento de las arrugas del entrecejo.

La dosis de BOTOX® no es la misma que, o comparable a, otro producto de toxina botulínica.


21

Como puede ayudar BOTOX®

Para la mayoría de la gente con distonía cervical, las inyecciones de BOTOX® (onabotulinumtoxinA) son muy efi caces. La terapia con BOTOX®

detiene o reduce de gran manera el dolor de cuello y los espasmos musculares. Los resultados de un estudio clínico clave mostraron que

después de recibir inyecciones de la neurotoxina BOTOX®, los pacientes con

distonía cervical habían mejorado la postura de la cabeza, sentían un dolor menos

intenso y frecuente, y tenían mejor capacidad para funcionar en ciertas actividades

diarias.7 Otro estudio mostró que puede haber alivio del dolor aún antes de que los

músculos se relajen de manera signifi cativa.2

Todos estos son benefi cios importantes para personas con distonía cervical. Para

muchos, las inyecciones de BOTOX® pueden ser un tratamiento efi caz para la

distonía cervical. Después de un tratamiento con la neurotoxina BOTOX®, muchos

pacientes con distonía cervical pasan hasta 3 meses de alivio de los espasmos

musculares.1 Esto es lo que tarda a los nervios el reanudar la liberación

de acetilcolina.


Con el tratamiento con BOTOX ® muchos pacientes con distonía cervical obtienen alivio en los músculos del cuello demasiado activos

o tensos. BOTOX ® también puede disminuir el dolor de cuello asociado con la distonía cervical, incluso antes de que reduzcan

considerablemente los espasmos musculares.

Aqui encontrará lo que la neurotoxina de BOTOX® puede hacer para usted:

■ Detener o reducir en gran medida el dolor de

cuello y los espasmos musculares

■ Mejorar la postura de la cabeza

■ Reducir la intensidad y la frecuencia del dolor

de cuello

■ Mejorar su capacidad para realizar ciertas

actividades cotidianas


22

Tratamientos precedentes al

diagnóstico de la distonía cervical:

— Masaje

— Acupuntura

— Tracción

— Esteroides

— Psicotrópicos

— Ajustes quiroprácticos

Duración del tiempo desde

los síntomas iniciales hasta el

diagnóstico: 17 años

Presentando síntomas:

— Dolor de cuello

— Temblor

— Rigidez

— Rango limitado de

movimiento

Régimen de tratamiento:

Inyecciones de BOTOX®

(onabotulinumtoxinA)

Historia del éxito de BOTOX®

Kathleen, 34 años de edad


Se han reportado reacciones alérgicas graves o inmediatas. Estas reacciones incluyen erupción cutánea con picazón,

hinchazón y difi cultad para respirar. Dígale a su médico y procure ayuda médica de inmediato si usted experimenta cualquiera de

estos síntomas; futuras inyecciones de BOTOX® o BOTOX® Cosmetic deben evitarse.


Los resultados individuales pueden variar.

23

“Ocasionalmente, mi cuello

podría contraerse por

un segundo…

y entonces

sólo se relajaba.

Simplemente ya no tenía

más ese poder.”



24


Inyecciones de BOTOX® (onabotulinumtoxinA)

Historia del éxito de BOTOX®

Gus, 32 años de edad

Tratamientos precedentes al

diagnóstico de la distonía cervical:

— Analgésicos

— Anti-inflamatorios

— Fisioterapia

Duración del tiempo desde

los síntomas iniciales hasta el

diagnóstico: 1 año

Presentando síntomas:

— Dolor de cuello

— Temblor

— Tortícolis derecha


Inyecciones de BOTOX®

(onabotulinumtoxinA) y fisioterapia


No use BOTOX® o BOTOX® Cosmetic si usted: es alérgico a alguno de los ingredientes de BOTOX® o BOTOX® Cosmetic (véase

la Guía de Medicación para los ingredientes); ha tenido una reacción alérgica a cualquier producto de toxina botulínica tales com

Myobloc ® o Dysport ®; tiene una infección en la piel en el sitio previsto de la inyección.


Los resultados individuales pueden variar.

25

“Mi intención es continuar los

tratamientos mientras sean necesarios y

permanecer positivo, vivir la vida, vivirla

de forma tan normal como pueda.”


Pregunte a su doctor si los tratamientos con BOTOX ® son buenos para usted.


26

Vivir con distonía cervical—consejos para pacientes

Además de tomar sus medicamentos y seguir los consejos de su doctor, hay otras cosas que puede hacer para ayudar a aliviar los síntomas

de la distonía cervical:

■ Evite el estrés en el trabajo, en lugares públicos, o en el hogar

– Es importante entender que el estrés puede exacerbar los síntomas de distonía cervical 12

■ Asegúrese de obtener sufi ciente tiempo de relajación12

■ Coma con sensatez y nutricionalmente

– Evite los alimentos que estimulen los nervios. La cafeína, el azúcar, y el chocolate pueden a veces

activar los síntomas de la distonía cervical 12

■ Consulte a su doctor en cuanto al programa de ejercicio

– Yoga ligera, calistenia simple, ejercicio en el agua, y ejercicios de respiración profunda que puedan

ayudar a relajar tanto a la mente como al cuerpo 12

■ Conéctese con grupos de apoyo en su área para obtener recursos adicionales y educación (algunos están enumerados en la parte

posterior de este folleto)

Si su doctor decide que debe ser tratado para la distonía cervical, asegúrese de hacer un seguimiento de cualquier mejora o empeoramiento

de sus síntomas, así como su reacción al tratamiento. Comparta todas sus observaciones con su doctor y sea un colaborador activo en la

gestión de su distonía cervical.


27


He aquí un ejercicio sensorial que usted quizá quisiera probar...

La distonía cervical es la distonía focal más común que responde a trucos sensoriales. Por ejemplo: los pacientes con distonía cervical

pueden ponerse la mano a un lado de la cara, barbilla, o detrás de la cabeza. Esto puede ayudar a reducir la intensidad de los síntomas.

El tocar o aplicar leve presión en ciertas áreas de la cabeza—en el lado opuesto al cual la cabeza gira—puede temporalmente permitir

la corrección de la posición anormal de la cabeza.


Dígale a su doctor acerca de todas sus condiciones de músculos o nervios tales como la esclerosis lateral amiotrófi ca

[ALS o enfermedad de Lou Gehrig], miastenia gravis, o síndrome de Lambert-Eaton, ya que podría estar en mayor riesgo de efectos

secundarios graves, incluyendo disfagia severa (difi cultar para tragar) y compromiso respiratorio (difi cultar para respirar) de dosis

típicas de BOTOX® o BOTOX® Cosmetic.

Dígale a su doctor acerca de todas sus afecciones médicas, incluso si usted tiene: planes de someterse a una cirugía,

ha tenido una cirugía en el rostro; debilidad de los músculos de la frente, como problemas para levantar las cejas; párpados

caídos; cualquier otro cambio anormal del rostro; está embarazada o piensa quedar embarazada (no se sabe si BOTOX® o BOTOX®

Cosmetic puede dañar a su bebe no nacido); está dando pecho o planea dar pecho (no se sabe si BOTOX® o BOTOX® Cosmetic se

excreta en la leche materna).


28

El blefaroespasmo y el tratamiento con BOTOX ®

Definición y síntomas del blefaroespasmo

El blefaroespasmo es un trastorno muscular caracterizado por espasmos

musculares involuntarios de los músculos alrededor del ojo, lo que resulta

en un estrechamiento incontrolable o en el cierre del párpado.13,14 Una

consecuencia grave del blefaroespasmo es el deterioro de la visión.

En algunos pacientes, el cierre forzado de los párpados se vuelve tan

grave que hacer las cosas simples como conducir un auto o usar una

computadora se convierten en un reto. Aproximadamente 65% de la gente

con blefaroespasmo son mujeres y la edad promedio del inicio es 56 años

de edad.14


Dígale a su doctor acerca de todos los medicamentos que toma, incluyendo medicamentos con receta y sin receta,

vitaminas, y productos herbarios.

BOTOX® y BOTOX® Cosmetic pueden causar pérdida de fuerza o debilidad muscular general, o problemas de visión. Si esto

ocurre, no conduzca un automóvil, opere maquinaria o realice otras actividades peligrosas.


29


Diagnóstico del blefaroespasmo

Los doctores diagnostican el blefaroespasmo basado en signos y síntomas

claves. En los estados iniciales del blefaroespasmo, los pacientes pueden

quejarse de irritación e incomodidad de los párpados además de aumento

en el parpadeo.13,14

A medida que el blefaroespasmo progresa, el parpadeo usualmente se vuelve

más frecuente, enérgico, e incontrolable. La luz brillante, el ruido, el estrés,

el aire contaminado, o el viento pueden empeorar los síntomas.15 Sin el

tratamiento medico apropiado pocos pacientes con blefaroespasmo mejoran

por su cuenta.14

Como puede ayudar el tratamiento con BOTOX ®

La neurotoxina BOTOX® (onabotulinumtoxinA) ha sido el tratamiento principal para el blefaroespasmo desde la aprobación de la FDA en 1989.

Las inyecciones de BOTOX® se administran directamente en el sitio de acción. Cuando es inyectado directamente en los músculos afectados

alrededor del ojo, la neurotoxina afl oja el espasmo muscular y el cerrar a la fuerza involuntariamente del párpado. El tratamiento con BOTOX®

se puede repetir aproximadamente cada 3 meses mientras el paciente continúa respondiendo y no tiene una reacción alérgica.1

Entre los primeros síntomas del blefaroespasmo pueden estar 14:

■ Ojos secos o llorosos

■ Sensibilidad a la luz

■ Aumento del parpadeo

■ Dolor ocular■ Irritación


30

El estrabismo y el tratamiento con BOTOX ®

Definición y síntomas del estrabismo

Estrabismo es el nombre que los doctores le dan a un grupo de afecciones

en las cuales los músculos se tensan alrededor del ojo lo que resulta en

que se jala el globo ocular hacia un lado. También se conoce al estrabismo

como ojos cruzados. Una forma común es la esotropía, o estrabismo

convergente, que es cuando uno o ambos ojos miran hacia la nariz.15

Entre otros síntomas se encuentran el ladeo de la cabeza para ver cosas,

movimientos frecuentes de los ojos, dolor de cabeza, frotamiento de los

ojos, lagrimeo, y visión doble.

Hoy en día, el estrabismo se trata típicamente en la infancia temprana

(antes de los 4 a 6 años de edad) con entrenamiento ortóptico (ejercicios

de los ojos), anteojos, y/o lentes de contacto.15 En algunos casos en los que

las técnicas de fortalecimiento no tienen éxito, quizá se requiera realinear

los músculos oculares mediante cirugía.15


Otros efectos secundarios de BOTOX® y BOTOX® Cosmetic incluyen: boca seca, molestias o dolor en el sitio de la inyección,

cansancio, dolor de cabeza, dolor de cuello, y problemas oculares: visión doble, visión borrosa, disminución de la visión, párpados

caídos, hinchazón de los párpados, y sequedad en los ojos.

Para obtener información adicional consulte la Guía del Medicamento o hable con su médico.

Le animamos a que reporte efectos secundarios negativos de los medicamentos recetados a la FDA.

Visite www.fda.gov/medwatch o llame a 1-800-FDA-1088.

Se ha ofrecido a su doctor información completa sobre el producto, incluyendo la Guía del Medicamento.


31


El estrabismo en adultos con frecuencia se diagnostica en aquellos pacientes que no fueron tratados o que fueron tratados sin éxito durante

la infancia.16 También hay algunos adultos que desarrollan estrabismo debido a una enfermedad o un traumatismo, lo cual suele dar lugar a

visión doble o una limitación en su percepción de la profundidad o del campo de visión (visión periférica y lateral).16

Diagnóstico del estrabismo

Cuando ocurre en niños, los padres son los primeros en notarlo o los doctores porque los ojos de los niños aparecen en posición anormal. Un

examen ocular confi rma el diagnóstico e identifi ca el tipo de estrabismo.

El estrabismo nunca debe ser ignorado bajo la presunción de que al crecer el niño se le pasará. A menos que sea tratado antes de los 4 a 6

años de edad, el estrabismo puede llevar a una pérdida de la visión permanente en el ojo desviado.15

Como puede ayudar el tratamiento con BOTOX ®

En el tratamiento del estrabismo, se cree que sólo el tratamiento con BOTOX® (onabotulinumtoxinA) tiene un efecto sobre los pares de

músculos. Al ser inyectados con la neurotoxina BOTOX®, los músculos se debilitan y los espasmos se reducen ligeramente. Esto permite que

los músculos del otro lado del ojo se contraigan.1 A través de esta doble acción, el tratamiento con BOTOX® se piensa que ayuda a alinear los

ojos, o a que miren en la misma dirección.


32

Encontrar a un doctor que inyecte BOTOX ®

Si usted quiere hablar sobre su afección con un doctor que inyecte BOTOX® (onabotulinumtoxinA), usted puede encontrar uno al

visitar www.BOTOXMedical.com y usar nuestra herramienta para encontrar a un doctor Find a Doctor.

Para ubicar a un doctor que inyecte la neurotoxina BOTOX ®, simplemente visite estos sitios Web:

www.BOTOXMedical.comEl sitio Web oficial de BOTOX®:

http://doctor.webmd.com/physician_finderWebMD ® Directorio Médico:

http://webapps.ama-assn.org/doctorfinder/html/patient.htmlAMA DoctorFinder:

Por favor vea la Información Importante de Seguridad sobre BOTOX® en la cubierta delantera y el folleto interior.


33

Para más información sobre BOTOX®por favor visite nuestro sitio Web

1-800-44-BOTOX

o llame alll l



34

Grupos de apoyo al paciente

Su proveedor de atención médica es la mejor fuente de información para su afección y tratamiento. Además, hay muchas

organizaciones que ofrecen servicios de apoyo, educación, y servicios para los pacientes.

Muchas organizaciones nacionales tienen capítulos locales. Póngase en contacto con el grupo nacional para obtener más

información sobre los capítulos en su área.*

■ Benign Essential Blepharospasm Research Foundation (BEBRF) 1-409-832-0788 www.blepharospasm.org

■ Care4Dystonia, Inc. www.care4dystonia.org

■ Dystonia Medical Research Foundation (DMRF) 1-312-755-0198 1-800-377-DYST (1-800-377-3978) www.dystonia-foundation.org

■ The National Spasmodic Torticollis Association (NSTA) 1-714-378-9837 1-800-487-8385 www.torticollis.org

■ ST/Dystonia, Inc. 1-262-560-9534 1-888-445-4588 www.spasmodictorticollis.org

*Las organizaciones mencionadas se ofrecen como recursos potenciales para los pacientes y el personal médico; no están

respaldadas por Allergan.


35


Para más información sobre BOTOX®, por favor visite nuestro sitio Web


o llame al 1-800-44-BOTOX

©2010 Allergan, Inc., Irvine, CA 92612 ®marks owned by Allergan, Inc.

Dysport is a registered trademark of Ipsen Biopharm Limited. Myobloc is a registered trademark of Solstice Neurosciences, Inc.

WebMD is a registered service mark of WebMD, Inc. www.BOTOXMedical.com

www.BOTOXReimbursementSolutions.com 1-800-44-BOTOX

Re-order: APC51QX10 106489

Por favor vea la Información Importante de Seguridad sobre BOTOX® en la cubierta delantera y el folleto interior.

1. Información Para La Receta Médica de BOTOX®, marzo de 2010. 2. Relja M, Telarovic S. Toxina botulínica tipo-A y respuesta al dolor en la distonía cervical: estudio de la respuesta a una dosis. Presentado en: 9º

Congreso Internacional de Mal de Parkinson y Trastornos del Movimiento; del 5 al 8 de marzo de 2005; Nueva Orleans, LA. 3. Fahn S, Marsden CD, Calne DB. La clasificación e investigación de la distonía. Mov Disord.

1987;2(4):332-358. 4. Jankovic J. Tratamiento de distonía cervical. En: Brin MF, Comella CL, Jankovic J, eds. Dystonia: Etiology, Clinical Features, and Treatment. Philadelphia, PA: Lippincott Williams & Wilkins; 2004:159-

166. 5. Chan J, Brin MF, Fahn S. Distonía cervical idiopática: características clínicas. Mov Disord. 1991;6(2):119-126. 6. Jankovic J, Leder S, Warner D, Schwartz K. La distonía cervical: hallazgos clínicos y trastornos

asociados del movimiento. Neurology. 1991;41(7):1088-1091. 7. van Herwaarden GM, Anten HW, Hoogduin CA, et al. Tortícolis espasmódica idiopática: una encuesta de los síndromes clínicos y las experiencias de los

pacientes. Clin Neurol Neurosurg. 1994;96(3):222-225. 8. Galvez-Jimenez N, Lampuri C, Patino-Picirrillo R, Hargreave MJA, Hanson MR. Distonía y dolores de cabeza: características clínicas y respuesta a la terapia con

toxina botulínica. En: Fahn S, Hallett M, DeLong MR, eds. Dystonia 4: Advances in Neurology. Philadelphia, PA: Lippincott Williams & Wilkins; 2004;94:321-328. 9. Jahanshahi M, Marion MH, Marsden CD. Historia natural del

principio de tortícolis idiopática en los adultos. Arch Neurol. 1990;47(5):548-552. 10. Saunders-Pullman R, Soto-Valencia J, Costan-Toth C, et al. Una nueva herramienta de evaluación para la distonía cervical. Neurology.

2005;64(12):2046-2049. 11. Jankovic J, Schwartz K. Respuesta e immunoresistencia a inyecciones de la toxina botulinum. Neurology. 1995;45(9):1743-1746. 12. ST/Distonía. ¡Cómo encontrar el camino a la felicidad! Sitio

Web de ST/Dystonia. http://www.spasmodictorticollis.org/info/living.cfm. Accesado el 4 de junio de 2010. 13. Malinovsky V. Blefaroespasmo benigno esencial. J Am Optom Assoc. 1987;58(8):646-651. 14. Grandas F, Elston

J, Quinn N, Marsden CD. Blefaroespasmo: una revisión de 264 pacientes. J Neurol Neurosurg Psychiatry. 1988;51(6):767-772. 15. The Merck Manuals Online Medical Library. Estrabismo. Sitio Web de The Merck Manuals

Online Medical Library. http://www.merck.com/mmpe/print/sec19/ch293/ch293e.html. Actualizado en junio de 2007. Accesado el 4 de junio de 2010. 16. Asociación Norteamericana de Oftalmología Pediátrica y Estrabismo.

Información general sobre el estrabismo en adultos. Sitio Web de la Asociación Norteamericana de Oftalmología Pediátrica y Estrabismo. http://www.aapos.org/resources_links/adult_strabismus_info. Accesado el 4 de junio

de 2010.


HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use BOTOX® safely and effectively. See full prescribing information for BOTOX.

BOTOX (onabotulinumtoxinA) Initial U.S. Approval: 1989

RECENT MAJOR CHANGES

• BoxedWarning,DistantSpreadofToxinEffect7/2009• IndicationsandUsage,UpperLimbSpasticity(1.1)3/2010• DosageandAdministration,UpperLimbSpasticity(2.2)3/2010• WarningsandPrecautions(5.1,5.2,5.4)7/2009• WarningsandPrecautions(5.3,5.6,5.9)3/2010

INDICATIONS AND USAGE

BOTOX is an acetylcholine release inhibitor and a neuromuscular blocking agent indicated for thetreatmentof:• Upperlimbspasticityinadultpatients(1.1)• Cervicaldystoniainadultpatients,toreducetheseverityofabnormalheadpositionandneckpain(1.2)• Severeaxillaryhyperhidrosisthatisinadequatelymanagedbytopicalagentsinadultpatients(1.3)• Blepharospasmassociatedwithdystoniainpatients≥12yearsofage(1.4)• Strabismusinpatients≥12yearsofage(1.4)

Important limitations:

• SafetyandeffectivenessofBOTOXhavenotbeenestablishedforthetreatmentofupperlimbspasticityinpediatricpatients,andforthetreatmentoflowerlimbspasticityinadultandpediatricpatients.

• SafetyandeffectivenessofBOTOXforhyperhidrosisinbodyareasotherthanaxillaryhavenotbeenestablished.

DOSAGE AND ADMINISTRATION

• Indicationspecificdosageandadministrationrecommendationsshouldbefollowed;Donotexceedatotaldoseof360Unitsadministeredevery12to16weeksoratlongerintervals(2)

• See Preparation and Dilution Technique for instructions onBOTOX reconstitution, storage, andpreparationbeforeinjection(2.1)

• Upper Limb Spasticity: Select dose based onmuscles affected, severity of muscle activity, priorresponsetotreatment,andadverseeventhistory;Electromyographicguidancerecommended(2.2)

• CervicalDystonia:Basedosingonthepatient’sheadandneckposition,localizationofpain,musclehypertrophy,patientresponse,andadverseeventhistory;uselowerinitialdoseinbotulinumtoxinnaïvepatients(2.3)

• Axillaryhyperhidrosis:50Unitsperaxilla(2.4)• Blepharospasm:1.25Units-2.5Unitsintoeachof3sitesperaffectedeye(2.5)• Strabismus:1.25Units-2.5Unitsinitiallyinanyonemuscle(2.6)

DOSAGE FORMS AND STRENGTHS

Single-use, sterile 100Units or 200Units vacuum-dried powder for reconstitution onlywith sterile,non-preserved0.9%SodiumChlorideInjectionUSPpriortoinjection(3)

CONTRAINDICATIONS

• Hypersensitivitytoanybotulinumtoxinpreparationortoanyofthecomponentsintheformulation(4.1,5.3,6.2)

• Infectionattheproposedinjectionsite(4.2)

WARNINGS AND PRECAUTIONS

• PotencyUnitsofBOTOXnot interchangeablewithotherpreparationsofbotulinum toxinproducts(5.1,11)

• Spreadoftoxineffects;swallowingandbreathingdifficultiescanleadtodeath(5.2)• Immediatemedicalattentionmayberequiredincasesofrespiratory,speechorswallowingdifficulties(5.2,5.4)

• Concomitantneuromusculardisordermayexacerbateclinicaleffectsoftreatment(5.5)• Usewithcautioninpatientswithcompromisedrespiratoryfunction(5.4,5.6)• Cornealexposureandulceration(5.7)• Retrobulbarhemorrhagesandcompromisedretinalcirculation(5.8)• Bronchitisandupperrespiratorytractinfectionsinpatientstreatedforupperlimbspasticity(5.9)

ADVERSE REACTIONS

Incontrolledstudies,themostcommonlyobservedadversereactions(≥5%and>placebo)were:• Spasticity:paininextremity(6.1)• CervicalDystonia:dysphagia,upperrespiratoryinfection,neckpain,headache,increasedcough,flusyndrome,backpain,rhinitis(6.1)

• AxillaryHyperhidrosis: injection site pain and hemorrhage, non-axillary sweating, pharyngitis, flusyndrome(6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Allergan at 1-800-433-8871 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

• PatientsreceivingconcomitanttreatmentofBOTOXandaminoglycosidesorotheragentsinterferingwithneuromusculartransmission(e.g.,curare-likeagents),ormusclerelaxants,shouldbeobservedcloselybecausetheeffectofBOTOXmaybepotentiated(7)

USE IN SPECIFIC POPULATIONS

• Pregnancy:Basedonanimaldata,maycausefetalharm(8.1)• Pediatric Use: Safety and efficacy are not established in patients under 18 years of age for thetreatment of upper limb spasticity and axillary hyperhidrosis, in patients under 16 years of agefor the treatmentof cervicaldystonia,and inpatientsunder12yearsofage for the treatmentofblepharospasmandstrabismus(8.4)

See 17 for PATIENT COUNSELING INFORMATION and Medication GuideRevised: 06/2010

FULL PRESCRIBING INFORMATION: CONTENTS*1 INDICATIONS AND USAGE 1.1 UpperLimbSpasticity 1.2 CervicalDystonia 1.3 PrimaryAxillaryHyperhidrosis 1.4 BlepharospasmandStrabismus2 DOSAGE AND ADMINISTRATION 2.1 PreparationandDilutionTechnique 2.2 UpperLimbSpasticity 2.3 CervicalDystonia 2.4 PrimaryAxillaryHyperhidrosis 2.5 Blepharospasm 2.6 Strabismus3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 4.1 KnownHypersensitivitytoBotulinumToxin 4.2 InfectionattheInjectionSite(s)5 WARNINGS AND PRECAUTIONS 5.1 LackofInterchangeabilitybetweenBotulinumToxinProducts 5.2 SpreadofToxinEffect 5.3 HypersensitivityReactions 5.4 DysphagiaandBreathingDifficultiesinTreatmentofCervicalDystonia 5.5 Pre-ExistingNeuromuscularDisorders 5.6 PulmonaryEffectsofBOTOX®inPatientswithCompromisedRespiratoryStatusTreatedfor

Spasticity 5.7 CornealExposureandUlcerationinPatientsTreatedwithBOTOXforBlepharospasm 5.8 RetrobulbarHemorrhagesinPatientsTreatedwithBOTOXforStrabismus 5.9 BronchitisandUpperRespiratoryTractInfectionsinPatientsTreatedforSpasticity 5.10 HumanAlbuminandTransmissionofViralDiseases6 ADVERSE REACTIONS 6.1 ClinicalStudiesExperience 6.2 Post-MarketingExperience 6.3 Immunogenicity7 DRUG INTERACTIONS8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.3 NursingMothers 8.4 PediatricUse 8.5 GeriatricUse10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY 12.1 MechanismofAction 12.3 Pharmacokinetics13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis,Mutagenesis,ImpairmentofFertility14 CLINICAL STUDIES 14.1 UpperLimbSpasticity 14.2 CervicalDystonia 14.3 PrimaryAxillaryHyperhidrosis 14.4 Blepharospasm 14.5 Strabismus16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION 17.1 Swallowing,SpeakingorBreathingDifficulties,orOtherUnusualSymptoms 17.2 AbilitytoOperateMachineryorVehicles 17.3 MedicationGuide

*Sectionsorsubsectionsomittedfromthefullprescribinginformationarenotlisted

FULL PRESCRIBING INFORMATION

Distant Spread of Toxin EffectPostmarketing reports indicate that the effects of BOTOX and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults treated for spasticity and other conditions, particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including spasticity in children, and in approved indications, cases of spread of effect have been reported at doses comparable to those used to treat cervical dystonia and at lower doses.

1 INDICATIONS AND USAGE

1.1 Upper Limb SpasticityBOTOX (onabotulinumtoxinA) for injection is indicated for the treatment of upper limb spasticity in adultpatients,todecreasetheseverityofincreasedmuscletoneinelbowflexors(biceps),wristflexors(flexorcarpiradialisandflexorcarpiulnaris)andfingerflexors(flexordigitorumprofundusandflexordigitorumsublimis).

Important limitationsSafetyandeffectivenessofBOTOXhavenotbeenestablished for the treatmentofotherupper limbmusclegroups, or for the treatment of lower limb spasticity. Safety and effectiveness of BOTOX have not beenestablishedforthetreatmentofspasticityinpediatricpatientsunderage18years.BOTOXhasnotbeenshownto improve upper extremity functional abilities, or range ofmotion at a joint affected by a fixed contracture.TreatmentwithBOTOXisnotintendedtosubstituteforusualstandardofcarerehabilitationregimens.

1.2 Cervical Dystonia BOTOXisindicatedforthetreatmentofadultswithcervicaldystonia,toreducetheseverityofabnormalheadpositionandneckpainassociatedwithcervicaldystonia.

1.3 Primary Axillary HyperhidrosisBOTOXisindicatedforthetreatmentofsevereprimaryaxillaryhyperhidrosisthatisinadequatelymanagedwithtopicalagents.

Important limitationsThesafetyandeffectivenessofBOTOXforhyperhidrosisinotherbodyareashavenotbeenestablished.Weaknessof handmuscles andblepharoptosismayoccur in patientswho receiveBOTOX for palmarhyperhidrosisandfacialhyperhidrosis,respectively.Patientsshouldbeevaluatedforpotentialcausesofsecondaryhyperhidrosis(e.g.,hyperthyroidism)toavoidsymptomatictreatmentofhyperhidrosiswithoutthediagnosisand/ortreatmentoftheunderlyingdisease.

WARNING: Distant Spread of Toxin Effect Seefullprescribinginformationforcompleteboxedwarning.TheeffectsofBOTOXandallbotulinumtoxinproductsmayspreadfromtheareaofinjectiontoproducesymptomsconsistentwithbotulinumtoxineffects.Thesesymptomshavebeenreportedhourstoweeksafterinjection.Swallowingandbreathingdifficultiescanbelifethreateningandtherehavebeenreportsofdeath.Theriskofsymptomsisprobablygreatestinchildrentreatedforspasticitybutsymptomscanalsooccurinadults,particularlyinthosepatientswhohaveunderlyingconditionsthatwouldpredisposethemtothesesymptoms.

SafetyandeffectivenessofBOTOX®havenotbeenestablishedforthetreatmentofaxillaryhyperhidrosisinpediatricpatientsunderage18.

1.4 Blepharospasm and StrabismusBOTOXisindicatedforthetreatmentofstrabismusandblepharospasmassociatedwithdystonia,includingbenignessentialblepharospasmorVIInervedisordersinpatients12yearsofageandabove.

2 DOSAGE AND ADMINISTRATION

ThepotencyUnitsofBOTOX(onabotulinumtoxinA)forinjectionarespecifictothepreparationandassaymethodutilized.Theyarenot interchangeablewithotherpreparationsofbotulinum toxinproductsand,therefore,unitsofbiologicalactivityofBOTOXcannotbecomparedtonorconvertedintounitsofanyotherbotulinumtoxinproductsassessedwithanyotherspecificassaymethod [see Warnings and Precautions (5.1) and Description (11)].

Injection specific dosage and administration recommendations should be followed. In treating adultpatients for one ormore indications, themaximum cumulative dose should generally not exceed 360Units,ina3monthinterval.

ThesafeandeffectiveuseofBOTOXdependsuponproperstorageoftheproduct,selectionofthecorrectdose,andproper reconstitutionandadministration techniques. PhysiciansadministeringBOTOXmustunderstandtherelevantneuromuscularand/ororbitalanatomyoftheareainvolvedandanyalterationstotheanatomyduetopriorsurgicalprocedures.Anunderstandingofstandardelectromyographictechniquesis also required for treatment of strabismus and of upper limb spasticity, and may be useful for thetreatmentofcervicaldystonia.

UsecautionwhenBOTOX treatment isused in thepresenceof inflammationat theproposed injectionsite(s)orwhenexcessiveweaknessoratrophyispresentinthetargetmuscle(s).

2.1 Preparation and Dilution TechniqueBOTOX is supplied in single-use100Units and200Units per vial.Prior to injection, reconstituteeachvacuum-driedvialofBOTOXwithsterile,non-preserved0.9%SodiumChloride InjectionUSP.Drawuptheproperamountofdiluentintheappropriatesizesyringe(DilutionTable),andslowlyinjectthediluentintothevial.Discardthevialifavacuumdoesnotpullthediluentintothevial.GentlymixBOTOXwiththesalinebyrotatingthevial.Recordthedateandtimeofreconstitutiononthespaceonthelabel.BOTOXshouldbeadministeredwithin24hoursafterreconstitution.Duringthistimeperiod,reconstitutedBOTOXshouldbestoredinarefrigerator(2°to8°C).

Dilution Table: 0.9% Sodium Chloride Injection Dilution Instructions for 100 Unit and 200 Unit BOTOX Vials

Diluent*Addedto 100 Unit Vial

ResultingDoseUnitsper0.1mL

Diluent*Addedto 200 Unit Vial

ResultingDoseUnitsper0.1mL

1mL2mL4mL8mL

10Units5Units2.5Units1.25Units

1mL2mL4mL8mL10mL

20Units10Units5Units2.5Units2Units

*0.9%SodiumChlorideInjectionOnly

Note:These dilutions are calculated for an injection volume of 0.1mL.A decrease or increase in theBOTOXdoseisalsopossiblebyadministeringasmallerorlargerinjectionvolume-from0.05mL(50%decreaseindose)to0.15mL(50%increaseindose).

An injectionofBOTOX ispreparedbydrawing intoanappropriatelysizedsterilesyringeanamountoftheproperlyreconstitutedtoxinslightlygreater thanthe intendeddose.Airbubbles in thesyringebarrelareexpelledandthesyringeisattachedtoanappropriateinjectionneedle.Patencyoftheneedleshouldbeconfirmed.Anew,sterile,needleandsyringeshouldbeusedtoenter thevialoneachoccasionforremovalofBOTOX.

ReconstitutedBOTOXshouldbeclear,colorless,andfreeofparticulatematter.Parenteraldrugproductsshouldbeinspectedvisuallyforparticulatematteranddiscolorationpriortoadministrationandwheneverthesolutionandthecontainerpermit.

2.2 Upper Limb SpasticityDosingininitialandsequentialtreatmentsessionsshouldbetailoredtotheindividualbasedonthesize,numberandlocationofmusclesinvolved,severityofspasticity,thepresenceoflocalmuscleweakness,thepatient’sresponsetoprevioustreatment,oradverseeventhistorywithBOTOX.

Inclinicaltrials,dosesrangingfrom75Unitsto360Unitsweredividedamongselectedmusclesatagiventreatmentsession.

Followingarerecommendeddoserangespermuscle:

Total Dosage (Number of Sites)

Biceps Brachii 100Units-200Unitsdividedin4sites

Flexor Carpi Radialis 12.5Units-50Unitsin1site

Flexor Carpi Ulnaris 12.5Units-50Unitsin1site

Flexor Digitorum Profundus 30Units-50Unitsin1site

Flexor Digitorum Sublimis 30Units-50Unitsin1site

Therecommendeddilution is200Units/4mLor100Units/2mLwith0.9%non-preservedsterilesaline(seeDilutionTable).Thelowestrecommendedstartingdoseshouldbeused,andnomorethan50Unitspersiteshouldgenerallybeadministered.Anappropriatelysizedneedle(e.g.,25-30gauge)maybeusedforsuperficialmuscles,andalonger22gaugeneedlemaybeusedfordeepermusculature.Localizationoftheinvolvedmuscleswithelectromyographicguidanceornervestimulationtechniquesisrecommended.

RepeatBOTOXtreatmentmaybeadministeredwhentheeffectofapreviousinjectionhasdiminished,butgenerallynosoonerthan12weeksafterthepreviousinjection.Thedegreeandpatternofmusclespasticityatthetimeofre-injectionmaynecessitatealterationsinthedoseofBOTOXandmusclestobeinjected.

2.3 Cervical DystoniaThe phase 3 study enrolled patients who had extended histories of receiving and tolerating BOTOXinjections,withpriorindividualizedadjustmentofdose.ThemeanBOTOXdoseadministeredtopatientsinthephase3studywas236Units(25thto75thpercentilerangeof198Unitsto300Units).TheBOTOXdosewasdividedamongtheaffectedmuscles[see Clinical Studies (14.2)].Dosingininitialandsequentialtreatment sessions should be tailored to the individual patient based on the patient’s head and neckposition,localizationofpain,musclehypertrophy,patientresponse,andadverseeventhistory.TheinitialdoseforapatientwithoutprioruseofBOTOXshouldbeatalowerdose,withsubsequentdosingadjustedbasedonindividualresponse.Limitingthetotaldoseinjectedintothesternocleidomastoidmuscleto100Unitsorlessmaydecreasetheoccurrenceofdysphagia[see Warnings and Precautions (5.2, 5.4, 5.5)].

The recommended dilution is 200Units/2mL, 200Units/4mL, 100Units/1mL, or 100Units/2mLwith0.9%non-preservedsterilesaline,dependingonvolumeandnumberofinjectionsitesdesiredtoachievetreatmentobjectives(seeDilutionTable).Ingeneral,nomorethan50Unitspersiteshouldbeadministered.Anappropriatelysizedneedle(e.g.,25-30gauge)maybeusedforsuperficialmuscles,and a longer 22 gauge needle may be used for deeper musculature. Localization of the involvedmuscleswithelectromyographicguidancemaybeuseful.

Clinical improvement generally begins within the first two weeks after injection with maximum clinicalbenefitatapproximatelysixweekspost-injection. In thephase3studymostsubjectswereobservedtohavereturnedtopre-treatmentstatusby3monthspost-treatment.

2.4 Primary Axillary HyperhidrosisTherecommendeddose is50Unitsperaxilla.Thehyperhidroticarea tobe injectedshouldbedefinedusing standard staining techniques, e.g.,Minor’s Iodine-StarchTest.The recommended dilution is 100Units/4mLwith0.9%preservative-freesterilesaline (seeDilutionTable).Usinga30gaugeneedle,50UnitsofBOTOX®(2mL)isinjectedintradermallyin0.1to0.2mLaliquotstoeachaxillaevenlydistributedinmultiplesites(10-15)approximately1-2cmapart.

Repeatinjectionsforhyperhidrosisshouldbeadministeredwhentheclinicaleffectofapreviousinjectiondiminishes.

Instructions for the Minor’s Iodine-Starch Test Procedure:Patientsshouldshaveunderarmsandabstainfromuseofover-the-counterdeodorantsorantiperspirantsfor24hoursprior to the test.Patient shouldbe restingcomfortablywithoutexercise,hotdrinks,etc. forapproximately 30 minutes prior to the test. Dry the underarm area and then immediately paint it withiodinesolution.Allowtheareatodry,thenlightlysprinkletheareawithstarchpowder.Gentlyblowoffanyexcess starch powder. The hyperhidrotic area will develop a deep blue-black color over approximately10minutes.

Eachinjectionsitehasaringofeffectofuptoapproximately2cmindiameter.Tominimizetheareaofnoeffect,theinjectionsitesshouldbeevenlyspacedasshowninFigure1:

Eachdoseisinjectedtoadepthofapproximately2mmandata45°angletotheskinsurface,withthebevelsideuptominimize leakageandtoensurethe injectionsremain intradermal. If injectionsitesaremarkedinink,donotinjectBOTOXdirectlythroughtheinkmarktoavoidapermanenttattooeffect.

2.5 BlepharospasmFor blepharospasm, reconstituted BOTOX is injected using a sterile, 27-30 gauge needle withoutelectromyographicguidance.Theinitialrecommendeddoseis1.25Units-2.5Units(0.05mLto0.1mLvolumeateachsite) injected into themedialand lateralpre-tarsalorbicularisoculiof theupper lidandinto the lateral pre-tarsalorbicularisoculi of the lower lid.Avoiding injectionnear the levatorpalpebraesuperiorismayreducethecomplicationofptosis.Avoidingmediallowerlidinjections,andtherebyreducingdiffusion into the inferioroblique,may reduce thecomplicationofdiplopia.Ecchymosisoccurseasily inthesofteyelidtissues.Thiscanbepreventedbyapplyingpressureattheinjectionsiteimmediatelyaftertheinjection.

Therecommendeddilutiontoachieve1.25Unitsis100Units/8mL;for2.5Unitsitis100Units/4mL(seeDilutionTable).

Ingeneral,theinitialeffectoftheinjectionsisseenwithinthreedaysandreachesapeakatonetotwoweekspost-treatment.Each treatment lastsapproximately threemonths, followingwhich theprocedurecanberepeated.Atrepeattreatmentsessions,thedosemaybeincreaseduptotwo-foldiftheresponsefromthe initial treatment isconsidered insufficient-usuallydefinedasaneffect thatdoesnot last longerthantwomonths.However,thereappearstobelittlebenefitobtainablefrominjectingmorethan5Unitspersite.SometolerancemaybefoundwhenBOTOXisusedintreatingblepharospasmiftreatmentsaregivenanymorefrequentlythaneverythreemonths,andisraretohavetheeffectbepermanent.

ThecumulativedoseofBOTOX treatmentforblepharospasmina30-dayperiodshouldnotexceed200Units.

2.6 StrabismusBOTOX is intended for injection into extraocular muscles utilizing the electrical activity recorded fromthetipoftheinjectionneedleasaguidetoplacementwithinthetargetmuscle.Injectionwithoutsurgicalexposure or electromyographic guidance should not be attempted. Physicians should be familiar withelectromyographictechnique.

TopreparetheeyeforBOTOXinjection,itisrecommendedthatseveraldropsofalocalanestheticandanoculardecongestantbegivenseveralminutespriortoinjection.

Note:ThevolumeofBOTOX injectedfor treatmentofstrabismusshouldbebetween0.05-0.15mLpermuscle.

The initial listed doses of the reconstituted BOTOX [see Dosage and Administration (2.1)] typicallycreate paralysis of the injected muscles beginning one to two days after injection and increasing inintensityduringthefirstweek.Theparalysislastsfor2-6weeksandgraduallyresolvesoverasimilartimeperiod.Overcorrections lasting over sixmonths havebeen rare.About one half of patientswill requiresubsequentdosesbecauseofinadequateparalyticresponseofthemuscletotheinitialdose,orbecauseofmechanicalfactorssuchaslargedeviationsorrestrictions,orbecauseofthelackofbinocularmotorfusiontostabilizethealignment.

I.InitialdosesinUnits.Usethelowerlisteddosesfortreatmentofsmalldeviations.Usethelargerdosesonlyforlargedeviations.

A. Forverticalmuscles,andforhorizontalstrabismusoflessthan20prismdiopters:1.25Units-2.5Unitsinanyonemuscle.

B. Forhorizontalstrabismusof20prismdioptersto50prismdiopters:2.5Units-5Unitsinanyonemuscle.

C. ForpersistentVInervepalsyofonemonthorlongerduration:1.25Units-2.5Unitsinthemedialrectusmuscle.

II.Subsequentdosesforresidualorrecurrentstrabismus. A. Itisrecommendedthatpatientsbere-examined7-14daysaftereachinjectiontoassesstheeffect

ofthatdose. B. Patientsexperiencingadequateparalysisof the targetmuscle that requiresubsequent injections

shouldreceiveadosecomparabletotheinitialdose. C. Subsequent doses for patients experiencing incomplete paralysis of the target muscle may be

increaseduptotwo-foldcomparedtothepreviouslyadministereddose. D. Subsequent injections should not be administered until the effects of the previous dose have

dissipatedasevidencedbysubstantialfunctionintheinjectedandadjacentmuscles. E. Themaximumrecommendeddoseasasingleinjectionforanyonemuscleis25Units.

Therecommendeddilutiontoachieve1.25Unitsis100Units/8mL;for2.5Unitsitis100Units/4mL(seeDilutionTable).

3 DOSAGE FORMS AND STRENGTHS

Single-use,sterile100Unitsor200Unitsvacuum-driedpowder for reconstitutiononlywithsterile,non-preserved0.9%SodiumChlorideInjectionUSPpriortoinjection[see Dosage and Administration (2.1)].

4 CONTRAINDICATIONS

4.1 Known Hypersensitivity to Botulinum ToxinBOTOXiscontraindicatedinpatientswhoarehypersensitivetoanybotulinumtoxinpreparationortoanyofthecomponentsintheformulation[see Warnings and Precautions (5.3)].

Figure 1:Figure 1:

4.2 Infection at the Injection Site(s)BOTOX®iscontraindicatedinthepresenceofinfectionattheproposedinjectionsite(s).

5 WARNINGS AND PRECAUTIONS

5.1 Lack of Interchangeability between Botulinum Toxin Products The potency Units of BOTOX are specific to the preparation and assay method utilized. They are not interchangeable with other preparations of botulinum toxin products and, therefore, units of biological activity of BOTOX cannot be compared to nor converted into units of any other botulinum toxin products assessed with any other specific assay method [see Description (11)].

5.2 Spread of Toxin EffectPostmarketingsafetydatafromBOTOXandotherapprovedbotulinumtoxinssuggestthatbotulinumtoxineffectsmay,insomecases,beobservedbeyondthesiteoflocalinjection.Thesymptomsareconsistentwiththemechanismofactionofbotulinumtoxinandmayincludeasthenia,generalizedmuscleweakness,diplopia,ptosis,dysphagia,dysphonia,dysarthria,urinaryincontinence,andbreathingdifficulties.Thesesymptomshavebeen reportedhours toweeksafter injection.Swallowingandbreathingdifficulties canbe life threatening and there havebeen reports of death related to spreadof toxin effects.The risk ofthe symptoms is probably greatest in children treated for spasticity but symptoms can also occur inadultstreatedforspasticityandotherconditions,andparticularlyinthosepatientswhohaveunderlyingconditions thatwould predispose them to these symptoms. In unapproveduses, including spasticity inchildren,andinapprovedindications,symptomsconsistentwithspreadoftoxineffecthavebeenreportedatdosescomparabletoorlowerthandosesusedtotreatcervicaldystonia.

NodefinitiveseriousadverseeventreportsofdistantspreadoftoxineffectassociatedwithdermatologicuseofBOTOX/BOTOX Cosmeticat the labeleddoseof20Units (forglabellar lines)or100Units (forsevereprimaryaxillaryhyperhidrosis)havebeenreported.

Nodefinitiveseriousadverseevent reportsofdistantspreadof toxineffectassociatedwithBOTOX forblepharospasmat therecommendeddose(30Unitsandbelow)or forstrabismusat the labeleddoseshavebeenreported.

5.3 Hypersensitivity ReactionsSerious and/or immediate hypersensitivity reactions have been reported. These reactions includeanaphylaxis,serumsickness,urticaria,softtissueedema,anddyspnea.Ifsuchareactionoccurs,furtherinjectionofBOTOXshouldbediscontinuedandappropriatemedicaltherapyimmediatelyinstituted.Onefatalcaseofanaphylaxishasbeenreportedinwhichlidocainewasusedasthediluent,andconsequentlythecausalagentcannotbereliablydetermined.

5.4 Dysphagia and Breathing Difficulties in Treatment of Cervical DystoniaTreatment with BOTOX and other botulinum toxin products can result in swallowing or breathingdifficulties.Patientswithpre-existingswallowingorbreathingdifficultiesmaybemoresusceptibletothesecomplications.Inmostcases,thisisaconsequenceofweakeningofmusclesintheareaofinjectionthatareinvolvedinbreathingorswallowing.Whendistanteffectsoccur,additionalrespiratorymusclesmaybeinvolved[see Warnings and Precautions (5.2)].

Deathsasacomplicationofseveredysphagiahavebeenreportedafter treatmentwithbotulinumtoxin.Dysphagiamaypersistforseveralmonths,andrequireuseofafeedingtubetomaintainadequatenutritionandhydration.Aspirationmayresultfromseveredysphagiaandisaparticularriskwhentreatingpatientsinwhomswallowingorrespiratoryfunctionisalreadycompromised.

Treatment of cervical dystonia with botulinum toxins may weaken neck muscles that serve asaccessorymusclesofventilation.Thismayresultinacriticallossofbreathingcapacityinpatientswithrespiratorydisorderswhomayhavebecomedependentupontheseaccessorymuscles.Therehavebeenpostmarketing reportsof seriousbreathingdifficulties, including respiratory failure, in cervicaldystoniapatients.

Patients with smaller neck muscle mass and patients who require bilateral injections into thesternocleidomastoidmuscle have been reported to be at greater risk for dysphagia. Limiting the doseinjectedintothesternocleidomastoidmusclemayreducetheoccurrenceofdysphagia.Injectionsintothelevatorscapulaemaybeassociatedwithanincreasedriskofupperrespiratoryinfectionanddysphagia.

Patientstreatedwithbotulinumtoxinmayrequireimmediatemedicalattentionshouldtheydevelopproblemswithswallowing, speechor respiratorydisorders.These reactionscanoccurwithinhours toweeksafterinjectionwithbotulinumtoxin[see Warnings and Precautions (5.2) and Adverse Reactions (6.1)].

5.5 Pre-Existing Neuromuscular DisordersIndividualswith peripheralmotor neuropathic diseases, amyotrophic lateral sclerosis or neuromuscularjunctiondisorders(e.g.,myastheniagravisorLambert-Eatonsyndrome)shouldbemonitoredparticularlycloselywhengivenbotulinum toxin.Patientswithneuromusculardisordersmaybeat increased riskofclinicallysignificanteffectsincludingseveredysphagiaandrespiratorycompromisefromtypicaldosesofBOTOX[see Adverse Reactions (6.1)].

5.6 Pulmonary Effects of BOTOX in Patients with Compromised Respiratory Status Treated for Spasticity

Patients with compromised respiratory status treated withBOTOX for upper limb spasticity should bemonitoredclosely.Inadouble-blind,placebo-controlled,parallelgroupstudyinpatientswithstablereducedpulmonaryfunction(definedasFEV140-80%ofpredictedvalueandFEV1/FVC≤0.75),theeventrateinchangeofForcedVitalCapacity≥15%or≥20%wasgenerallygreaterinpatientstreatedwithBOTOXthaninpatientstreatedwithplacebo(seeTable1).

Table 1: Event rate per patient treatment cycle among patients with reduced lung function who experienced at least a 15% or 20% decrease in forced vital capacity from baseline at Week 1, 6, 12 post-injection with up to two treatment cycles with BOTOX or placebo

BOTOX 360 Units

BOTOX

240 Units Placebo

≥15% ≥20% ≥15% ≥20% ≥15% ≥20%

Week1 4% 0% 3% 0% 7% 3%

Week6 7% 4% 4% 2% 2% 2%

Week12 10% 5% 2% 1% 4% 1%

Differencesfromplacebowerenotstatisticallysignificant

Inpatientswithreducedlungfunction,upperrespiratorytractinfectionswerealsoreportedmorefrequentlyasadversereactionsinpatientstreatedwithBOTOX[see Warnings and Precautions (5.9)].

5.7 Corneal Exposure and Ulceration in Patients Treated with BOTOX for BlepharospasmReducedblinkingfromBOTOXinjectionoftheorbicularismusclecanleadtocornealexposure,persistentepithelialdefect,andcornealulceration,especiallyinpatientswithVIInervedisorders.Vigoroustreatmentofanyepithelialdefectshouldbeemployed.Thismayrequireprotectivedrops,ointment,therapeuticsoftcontactlenses,orclosureoftheeyebypatchingorothermeans.

5.8 Retrobulbar Hemorrhages in Patients Treated with BOTOX for StrabismusDuring theadministrationofBOTOX for the treatmentofstrabismus,retrobulbarhemorrhagessufficientto compromise retinal circulation have occurred. It is recommended that appropriate instruments todecompresstheorbitbeaccessible.

5.9 Bronchitis and Upper Respiratory Tract Infections in Patients Treated for SpasticityBronchitiswasreportedmorefrequentlyasanadversereactioninpatientstreatedforupperlimbspasticitywithBOTOX®(3%at251Units-360Unitstotaldose),comparedtoplacebo(1%).Inpatientswithreducedlungfunctiontreatedforupperlimbspasticity,upperrespiratorytractinfectionswerealsoreportedmorefrequentlyasadversereactionsinpatientstreatedwithBOTOX(11%at360Unitstotaldose;8%at240Unitstotaldose)comparedtoplacebo(6%).

5.10 Human Albumin and Transmission of Viral DiseasesThis product contains albumin, a derivative of human blood. Based on effective donor screening andproductmanufacturingprocesses,itcarriesanextremelyremoteriskfortransmissionofviraldiseases.AtheoreticalriskfortransmissionofCreutzfeldt-Jakobdisease(CJD)isalsoconsideredextremelyremote.NocasesoftransmissionofviraldiseasesorCJDhaveeverbeenreportedforalbumin.

6 ADVERSE REACTIONS

ThefollowingadversereactionstoBOTOX(onabotulinumtoxinA)forinjectionarediscussedingreaterdetailinothersectionsofthelabeling: • SpreadofToxinEffects[see Warnings and Precautions (5.2)] • Hypersensitivity[see Contraindications (4.1) and Warnings and Precautions (5.3)] • DysphagiaandBreathingDifficultiesinTreatmentofCervicalDystonia

[see Warnings and Precautions (5.4)] • BronchitisandUpperRespiratoryTractInfectionsinPatientsTreatedforSpasticity

[see Warnings and Precautions (5.9)]

6.1 Clinical Studies ExperienceBecauseclinical trialsareconductedunderwidelyvaryingconditions, theadversereactionratesobservedcannotbedirectlycomparedtoratesinothertrialsandmaynotreflecttheratesobservedinclinicalpractice.

BOTOXandBOTOXCosmeticcontainthesameactiveingredientinthesameformulation,butwithdifferentlabeledIndicationsandUsage.Therefore,adverseeventsobservedwiththeuseofBOTOX CosmeticalsohavethepotentialtobeobservedwiththeuseofBOTOXandvice-versa.

Ingeneral,adverseeventsoccurwithin thefirstweekfollowing injectionofBOTOXandwhilegenerallytransient, may have a duration of several months or longer. Localized pain, infection, inflammation,tenderness,swelling,erythema,and/orbleeding/bruisingmaybeassociatedwith the injection.Needle-related pain and/or anxietymay result in vasovagal responses (including e.g., syncope, hypotension),whichmayrequireappropriatemedicaltherapy.

Localweaknessof the injectedmuscle(s) represents theexpectedpharmacologicalactionofbotulinumtoxin.However,weaknessofnearbymusclesmayalsooccurduetospreadoftoxin[see Warnings and Precautions (5.2)].

Upper Limb SpasticityTable2belowliststheadversereactionsreportedby≥2%ofBOTOX-treatedpatientsandmorefrequentthaninplacebo-treatedpatientsindouble-blind,placebo-controlledclinicaltrials.

Table 2: Adverse Reactions Reported by ≥ 2% of BOTOX-treated Patients and More Frequent than in Placebo-treated Patients in Adult Spasticity Double-blind, Placebo-controlled Clinical Trials

Adverse Reactions by Body System

BOTOX 251 Units - 360 Units (N=115)

BOTOX 150 Units - 250 Units (N=188)

BOTOX < 150 Units

(N=54)

Placebo (N=182)

Gastrointestinal disorder Nausea 3 (3%) 3 (2%) 1 (2%) 1 (1%)

General disorders and administration site conditions Fatigue 4 (3%) 4 (2%) 1 (2%) 0

Infections and infestations Bronchitis 4 (3%) 4 (2%) 0 2 (1%)

Musculoskeletal and connective tissue disorders Pain in extremity Muscular weakness

7 (6%) 0

10 (5%) 7 (4%)

5 (9%) 1 (2%)

8 (4%) 2 (1%)

Cervical DystoniaIncervicaldystoniapatientsevaluatedforsafetyindouble-blindandopen-labelstudiesfollowinginjectionof BOTOX, the most frequently reported adverse reactions were dysphagia (19%), upper respiratoryinfection(12%),neckpain(11%),andheadache(11%).

Othereventsreportedin2-10%ofpatients inanyonestudyindecreasingorderof incidenceinclude:increased cough, flu syndrome, back pain, rhinitis, dizziness, hypertonia, soreness at injection site,asthenia, oral dryness, speechdisorder, fever, nausea, anddrowsiness.Stiffness, numbness, diplopia,ptosis,anddyspneahavebeenreported.

DysphagiaandsymptomaticgeneralweaknessmaybeattributabletoanextensionofthepharmacologyofBOTOXresultingfromthespreadofthetoxinoutsidetheinjectedmuscles[see Warnings and Precautions (5.2, 5.4)].

Themost common severe adverse event associatedwith the use ofBOTOX injection in patientswithcervicaldystoniaisdysphagiawithabout20%ofthesecasesalsoreportingdyspnea[see Warnings and Precautions (5.2, 5.4)].Mostdysphagia is reportedasmildormoderate inseverity.However, itmaybeassociatedwithmoreseveresignsandsymptoms [see Warnings and Precautions (5.4)].

Additionally,reportsintheliteratureincludeacaseofafemalepatientwhodevelopedbrachialplexopathytwo days after injection of 120 Units ofBOTOX for the treatment of cervical dystonia, and reports ofdysphoniainpatientswhohavebeentreatedforcervicaldystonia.

Primary Axillary HyperhidrosisThemost frequently reported adverse events (3 - 10%of adult patients) following injection ofBOTOXin double-blind studies included injection site pain and hemorrhage, non-axillary sweating, infection,pharyngitis,flusyndrome,headache,fever,neckorbackpain,pruritus,andanxiety.

Thedatareflect346patientsexposedtoBOTOX50Unitsand110patientsexposedtoBOTOX75Unitsineachaxilla.

BlepharospasmInastudyofblepharospasmpatientswhoreceivedanaveragedosepereyeof33Units (injectedat3to5sites)ofthecurrentlymanufacturedBOTOX,themostfrequentlyreportedtreatment-relatedadversereactionswereptosis(21%),superficialpunctatekeratitis(6%),andeyedryness(6%).

Othereventsreportedinpriorclinicalstudiesindecreasingorderofincidenceinclude:irritation,tearing,lagophthalmos,photophobia,ectropion,keratitis,diplopia,entropion,diffuseskinrash,andlocalswellingoftheeyelidskinlastingforseveraldaysfollowingeyelidinjection.

IntwocasesofVIInervedisorder,reducedblinkingfromBOTOX®injectionoftheorbicularismuscleledtoseriouscornealexposure,persistentepithelialdefect,cornealulcerationandacaseofcornealperforation.Focal facial paralysis, syncope, and exacerbation of myasthenia gravis have also been reported aftertreatmentofblepharospasm.

StrabismusExtraocularmusclesadjacent to the injectionsitecanbeaffected,causingverticaldeviation,especiallywithhigherdosesofBOTOX.Theincidenceratesoftheseadverseeffectsin2058adultswhoreceivedatotalof3650injectionsforhorizontalstrabismuswas17%.

The incidence of ptosis has been reported to be dependent on the location of the injected muscles,1% after inferior rectus injections, 16% after horizontal rectus injections and 38% after superior rectusinjections.

Inaseriesof5587injections,retrobulbarhemorrhageoccurredin0.3%ofcases.

6.2 Post-Marketing ExperienceThere have been spontaneous reports of death, sometimes associated with dysphagia, pneumonia,and/or other significant debility or anaphylaxis, after treatmentwithbotulinum toxin [see Warnings and Precautions (5.3, 5.4)].

Therehavealsobeenreportsofadverseeventsinvolvingthecardiovascularsystem,includingarrhythmiaandmyocardial infarction, somewith fatal outcomes.Someof thesepatientshad risk factors includingcardiovascular disease.The exact relationship of these events to the botulinum toxin injection has notbeenestablished.

Newonsetor recurrent seizureshavealsobeen reported, typically inpatientswhoarepredisposed toexperiencingtheseevents.Theexactrelationshipoftheseeventstothebotulinumtoxininjectionhasnotbeenestablished.

Thefollowingevents,notalreadyaddressedelsewhereinthepackageinsert,havebeenreportedsincethedrughasbeenmarketed:abdominalpain;anorexia;brachialplexopathy;diarrhea;facialpalsy;facialparesis; hyperhidrosis; hypoacusis; hypoaesthesia; localized numbness; malaise; myalgia; paresthesia;pyrexia; radiculopathy; skin rash (including erythema multiforme, and psoriasiform eruption); tinnitus;vertigo;visualdisturbances;andvomiting.

Becausetheseeventsarereportedvoluntarilyfromapopulationofuncertainsize,itisnotalwayspossibletoreliablyestimatetheirfrequencyorestablishacausalrelationshiptobotulinumtoxin.

6.3 ImmunogenicityAswithalltherapeuticproteins,thereisapotentialforimmunogenicity.FormationofneutralizingantibodiestobotulinumtoxintypeAmayreducetheeffectivenessofBOTOXtreatmentbyinactivatingthebiologicalactivityofthetoxin.

In a long term, open-label study evaluating 326 cervical dystonia patients treated for an average of 9treatmentsessionswiththecurrentformulationofBOTOX,4(1.2%)patientshadpositiveantibodytests.All4ofthesepatientsrespondedtoBOTOXtherapyatthetimeofthepositiveantibodytest.However,3ofthesepatientsdevelopedclinicalresistanceaftersubsequenttreatment,whilethefourthpatientcontinuedtorespondtoBOTOXtherapyfortheremainderofthestudy.

Onepatientamongthe445hyperhidrosispatients(0.2%)andtwopatientsamongthe380adultupperlimbspasticitypatients(0.5%)withanalyzedspecimensshowedthepresenceofneutralizingantibodies.

ThedatareflectthepatientswhosetestresultswereconsideredpositiveornegativeforneutralizingactivitytoBOTOXinamouseprotectionassay.Theresultsofthesetestsarehighlydependentonthesensitivityand specificity of the assay. For these reasons, comparison of the incidence of neutralizing activity toBOTOXwiththeincidencereportedtootherproductsmaybemisleading.

Thecriticalfactorsforneutralizingantibodyformationhavenotbeenwellcharacterized.Theresultsfromsomestudiessuggest thatBOTOX injectionsatmorefrequent intervalsorathigherdosesmay leadtogreaterincidenceofantibodyformation.Thepotentialforantibodyformationmaybeminimizedbyinjectingwiththelowesteffectivedosegivenatthelongestfeasibleintervalsbetweeninjections.

7 DRUG INTERACTIONS

NoformaldruginteractionstudieshavebeenconductedwithBOTOX(onabotulinumtoxinA)forinjection.

Co-administration of BOTOX and aminoglycosides or other agents interfering with neuromusculartransmission(e.g.,curare-likecompounds)shouldonlybeperformedwithcautionastheeffectofthetoxinmaybepotentiated.

UseofanticholinergicdrugsafteradministrationofBOTOXmaypotentiatesystemicanticholinergiceffects.

The effect of administering different botulinum neurotoxin products at the same time or within severalmonths of each other is unknown. Excessive neuromuscular weakness may be exacerbated byadministrationofanotherbotulinumtoxinpriortotheresolutionoftheeffectsofapreviouslyadministeredbotulinumtoxin.

Excessive weaknessmay also be exaggerated by administration of a muscle relaxant before or afteradministrationofBOTOX.

8 USE IN SPECIFIC POPULATIONS

8.1 PregnancyPregnancyCategoryC.Therearenoadequateandwell-controlledstudies inpregnantwomen.BOTOXshouldbeusedduringpregnancyonlyifthepotentialbenefitjustifiesthepotentialrisktothefetus.

WhenBOTOX(4,8,or16Units/kg)wasadministeredintramuscularlytopregnantmiceorratstwotimesduring the period of organogenesis (on gestation days 5 and 13), reductions in fetal bodyweight anddecreased fetal skeletal ossification were observed at the two highest doses. The no-effect dose fordevelopmental toxicity in thesestudies(4Units/kg) isapproximately1½times theaveragehighhumandoseforupperlimbspasticityof360Unitsonabodyweightbasis(Units/kg).

WhenBOTOXwasadministeredintramuscularlytopregnantrats(0.125,0.25,0.5,1,4,or8Units/kg)orrabbits (0.063,0.125,0.25,or0.5Units/kg)dailyduring theperiodoforganogenesis (totalof12dosesin rats, 13doses in rabbits), reduced fetal bodyweightsanddecreased fetal skeletal ossificationwereobserved at the two highest doses in rats and at the highest dose in rabbits.These doseswere alsoassociatedwithsignificantmaternaltoxicity,includingabortions,earlydeliveries,andmaternaldeath.Thedevelopmentalno-effectdosesinthesestudiesof1Unit/kginratsand0.25Units/kginrabbitsarelessthantheaveragehighhumandosebasedonUnits/kg.

When pregnant rats received single intramuscular injections (1, 4, or 16 Units/kg) at three differentperiodsofdevelopment(priortoimplantation,implantation,ororganogenesis),noadverseeffectsonfetaldevelopmentwereobserved.Thedevelopmentalno-effectlevelforasinglematernaldoseinrats(16Units/kg)isapproximately3timestheaveragehighhumandosebasedonUnits/kg.

8.3 Nursing MothersItisnotknownwhetherBOTOXisexcretedinhumanmilk.Becausemanydrugsareexcretedinhumanmilk,cautionshouldbeexercisedwhenBOTOXisadministeredtoanursingwoman.

8.4 Pediatric UseSpasticitySafetyandeffectivenessofBOTOX®forthetreatmentofspasticityhavenotbeenestablishedinpatientsbelowtheageof18years.

Cervical DystoniaSafetyandeffectivenessinpediatricpatientsbelowtheageof16yearshavenotbeenestablished.

Blepharospasm and StrabismusSafetyandeffectivenessinpediatricpatientsbelowtheageof12yearshavenotbeenestablished.

Axillary HyperhidrosisSafetyandeffectivenessinpediatricpatientsbelowtheageof18yearshavenotbeenestablished.

8.5 Geriatric UseClinicalstudiesofBOTOXdidnotincludesufficientnumbersofsubjectsaged65andovertodeterminewhether they respond differently from younger subjects. Other reported clinical experience has notidentifieddifferencesinresponsesbetweentheelderlyandyoungerpatients.Thereweretoofewpatientsovertheageof75toenableanycomparisons.Ingeneral,doseselectionforanelderlypatientshouldbecautious,usuallystartingatthelowendofthedosingrange,reflectingthegreaterfrequencyofdecreasedhepatic,renal,orcardiacfunction,andofconcomitantdiseaseorotherdrugtherapy.

10 OVERDOSAGE

ExcessivedosesofBOTOX(onabotulinumtoxinA)forinjectionmaybeexpectedtoproduceneuromuscularweakness with a variety of symptoms. Respiratory support may be required where excessivedoses cause paralysis of respiratory muscles. In the event of overdose, the patient should bemedically monitored for symptoms of excessive muscle weakness or muscle paralysis [see Boxed Warning and Warnings and Precautions (5.2, 5.4)].Symptomatictreatmentmaybenecessary.

Symptoms of overdose are likely not to be present immediately following injection. Should accidentalinjectionororal ingestionoccur, thepersonshouldbemedicallysupervisedforseveralweeksforsignsandsymptomsofexcessivemuscleweaknessorparalysis.

Intheeventofoverdose,antitoxinraisedagainstbotulinumtoxinisavailablefromtheCentersforDiseaseControlandPrevention(CDC)inAtlanta,GA.However,theantitoxinwillnotreverseanybotulinumtoxin-inducedeffectsalreadyapparentbythetimeofantitoxinadministration.Intheeventofsuspectedoractualcasesofbotulinum toxinpoisoning,pleasecontactyour localorstateHealthDepartment toprocessarequestforantitoxinthroughtheCDC.Ifyoudonotreceivearesponsewithin30minutes,pleasecontactthe CDC directly at 1-770-488-7100. More information can be obtained at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5232a8.htm.

11 DESCRIPTION

BOTOX (onabotulinumtoxinA) for injection is a sterile, vacuum-dried purified botulinum toxin type A,produced from fermentationofHallstrainClostridiumbotulinum typeA,and intended for intramuscularandintradermaluse.Itispurifiedfromtheculturesolutionbydialysisandaseriesofacidprecipitationstoacomplexconsistingoftheneurotoxin,andseveralaccessoryproteins.ThecomplexisdissolvedinsterilesodiumchloridesolutioncontainingAlbuminHumanandissterilefiltered(0.2microns)priortofillingandvacuum-drying.

OneUnitofBOTOXcorrespondstothecalculatedmedianintraperitoneallethaldose(LD50)inmice.ThemethodutilizedforperformingtheassayisspecifictoAllergan’sproduct,BOTOX.Duetospecificdetailsof thisassaysuchas thevehicle,dilutionscheme,and laboratoryprotocols for thevariousmouseLD50assays, Units of biological activity ofBOTOX cannot be compared to nor converted into Units of anyotherbotulinumtoxinoranytoxinassessedwithanyotherspecificassaymethod.Therefore,differencesinspeciessensitivitiestodifferentbotulinumneurotoxinserotypesprecludeextrapolationofanimal-doseactivityrelationshipstohumandoseestimates.ThespecificactivityofBOTOXisapproximately20Units/nanogramofneurotoxinproteincomplex.

EachvialofBOTOXcontainseither100UnitsofClostridiumbotulinumtypeAneurotoxincomplex,0.5mgofAlbuminHuman,and0.9mgofsodiumchloride;or200UnitsofClostridiumbotulinumtypeAneurotoxincomplex,1mgofAlbuminHuman,and1.8mgofsodiumchlorideinasterile,vacuum-driedformwithoutapreservative.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of ActionBOTOXblocksneuromuscular transmissionbybindingtoacceptorsitesonmotororsympatheticnerveterminals,enteringthenerveterminals,andinhibitingthereleaseofacetylcholine.ThisinhibitionoccursastheneurotoxincleavesSNAP-25,aproteinintegraltothesuccessfuldockingandreleaseofacetylcholinefromvesiclessituatedwithinnerveendings.Wheninjectedintramuscularlyattherapeuticdoses,BOTOXproducespartialchemicaldenervationofthemuscleresultinginalocalizedreductioninmuscleactivity.Inaddition,themusclemayatrophy,axonalsproutingmayoccur,andextrajunctionalacetylcholinereceptorsmaydevelop.Thereisevidencethatreinnervationofthemusclemayoccur,thusslowlyreversingmuscledenervation produced byBOTOX.When injected intradermally,BOTOX produces temporary chemicaldenervationofthesweatglandresultinginlocalreductioninsweating.

12.3 Pharmacokinetics Usingcurrentlyavailableanalyticaltechnology,itisnotpossibletodetectBOTOXintheperipheralbloodfollowingintramuscularinjectionattherecommendeddoses.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility CarcinogenesisLongtermstudiesinanimalshavenotbeenperformedtoevaluatethecarcinogenicpotentialofBOTOX.

MutagenesisBOTOXwasnegativeinabatteryofinvitro(microbialreversemutationassay,mammaliancellmutationassay,andchromosomalaberrationassay)andinvivo(micronucleusassay)genetictoxicologicassays.

Impairment of FertilityInfertilitystudiesofBOTOX(4,8,or16Units/kg)inwhicheithermaleorfemaleratswereinjectedintramuscularlypriortomatingandonthedayofmating(3doses,2weeksapartformales,2doses,2weeksapartforfemales)tountreatedanimals,reducedfertilitywasobservedinmalesattheintermediateandhighdosesandinfemalesatthehighdose.Theno-effectdosesforreproductivetoxicity(4Units/kginmales,8Units/kginfemales)areapproximatelyequaltotheaveragehighhumandoseforupperlimbspasticityof360Unitsonabodyweightbasis(Units/kg).

14 CLINICAL STUDIES

14.1 Upper Limb SpasticityThe efficacy and safety ofBOTOX for the treatment of upper limb spasticity were evaluated in threerandomized,multi-center,double-blind,placebo-controlledstudies.

Study1included126patients(64BOTOX®and62placebo)withupper limbspasticity(Ashworthscoreofat least3 forwristflexor toneandat least2 forfingerflexor tone)whowereat least6monthspost-stroke.BOTOX (a totaldoseof200Units to240Units)andplacebowere injected intramuscularly (IM)into the flexor digitorum profundus, flexor digitorum sublimis, flexor carpi radialis, flexor carpi ulnaris,andifnecessaryintotheadductorpollicisandflexorpollicislongus(seeTable3).UseofanEMG/nervestimulatorwasrecommendedtoassistinpropermusclelocalizationforinjection.Patientswerefollowedfor12weeks.

Table 3: Study Medication Dose and Injection Sites in Study 1

Muscles Injected Volume (mL)

BOTOX (Units)

Number of Injection Sites

Wrist Flexor Carpi Radialis 1 50 1Flexor Carpi Ulnaris 1 50 1

Finger Flexor Digitorum Profundus 1 50 1

Flexor Digitorum Sublimis 1 50 1

Thumb Adductor Pollicisa 0.4 20 1

Flexor Pollicis Longusa 0.4 20 1ainjectedonlyifspasticityispresentinthismuscle

Theprimaryefficacyvariablewaswristflexorsmuscletoneatweek6,asmeasuredbytheAshworthscore.TheAshworthScaleisaclinicalmeasureoftheforcerequiredtomoveanextremityaroundajoint,withareductioninscoreclinicallyrepresentingareductionintheforceneededtomoveajoint(i.e.,improvementinspasticity).

Possiblescoresrangefrom0to4:0=Noincreaseinmuscletone(none)1=Slight increase in muscle tone, giving a ‘catch’ when the limb was moved in flexion or extension

(mild)2=Moremarkedincreaseinmuscletonebutaffectedlimbiseasilyflexed(moderate)3=Considerableincreaseinmuscletone-passivemovementdifficult(severe)4=Limbrigidinflexionorextension(verysevere).

KeysecondaryendpointsincludedPhysicianGlobalAssessment,fingerflexorsmuscletone,andthumbflexorstoneatWeek6.ThePhysicianGlobalAssessmentevaluatedtheresponsetotreatment intermsofhowthepatientwasdoinginhis/herlifeusingascalefrom-4=verymarkedworseningto+4=verymarked improvement. Study 1 results on the primary endpoint and the key secondary endpoints areshowninTable4.

Table 4: Primary and Key Secondary Endpoints by Muscle Group at Week 6 in Study 1

BOTOX (N=64)

Placebo (N=62)

Median Change from Baseline in Wrist Flexor Muscle Tone on the Ashworth Scale†a -2.0* 0.0

Median Change from Baseline in Finger Flexor Muscle Tone on the Ashworth Scale††b -1.0* 0.0

Median Change from Baseline in Thumb Flexor Muscle Tone on the Ashworth Scale††c -1.0 -1.0

Median Physician Global Assessment of Response to Treatment†† 2.0* 0.0

†PrimaryendpointatWeek6††SecondaryendpointsatWeek6*Significantlydifferentfromplacebo(p≤0.05)aBOTOXinjectedintoboththeflexorcarpiradialisandulnarismusclesbBOTOXinjectedintotheflexordigitorumprofundusandflexordigitorumsublimismusclescBOTOXinjectedintotheadductorpollicisandflexorpollicislongusmuscles

Study2compared3dosesofBOTOXwithplaceboandincluded91patients[BOTOX360Units(N=21),BOTOX 180 Units (N=23), BOTOX 90 Units (N=21), and placebo (N=26)] with upper limb spasticity(expandedAshworth score of at least 2 for elbow flexor tone and at least 3 forwrist flexor tone)whowereatleast6weekspost-stroke.BOTOXandplacebowereinjectedwithEMGguidanceintotheflexordigitorumprofundus,flexordigitorumsublimis,flexorcarpiradialis,flexorcarpiulnaris,andbicepsbrachii(seeTable5).

Table 5: Study Medication Dose and Injection Sites in Study 2 and Study 3

Total Dosage

Muscles InjectedBOTOX

low dose (90 Units)

BOTOX mid dose

(180 Units)

BOTOX high dose (360 Units)

Volume (mL)

per site

Injection Sites (n)

Wrist Flexor Carpi Ulnaris 10 Units 20 Units 40 Units 0.4 1

Flexor Carpi Radialis 15 Units 30 Units 60 Units 0.6 1

Finger Flexor Digitorum Profundus 7.5 Units 15 Units 30 Units 0.3 1

Flexor Digitorum Sublimis 7.5 Units 15 Units 30 Units 0.3 1

Elbow Biceps Brachii 50 Units 100 Units 200 Units 0.5 4

TheprimaryefficacyvariableinStudy2wasthewristflexortoneatWeek6asmeasuredbytheexpandedAshworthScale.TheexpandedAshworthScaleuses thesamescoringsystemas theAshworthScale,butallowsforhalf-pointincrements.

Keysecondaryendpoints inStudy2 includedPhysicianGlobalAssessment,fingerflexorsmuscletone,andelbowflexorsmuscletoneatWeek6.Study2resultsontheprimaryendpointandthekeysecondaryendpointsatWeek6areshowninTable6.

Table 6: Primary and Key Secondary Endpoints by Muscle Group and BOTOX® Dose at Week 6 in Study 2

BOTOX low dose (90 Units)

(N=21)

BOTOX mid dose

(180 Units) (N=23)


(N=21)

Placebo (N=26)

Median Change from Baseline in Wrist Flexor Muscle Tone on the Ashworth Scale†b

-1.5* -1.0* -1.5* -1.0

Median Change from Baseline in Finger Flexor Muscle Tone on the Ashworth Scale††c

-0.5 -0.5 -1.0 -0.5

Median Change from Baseline in Elbow Flexor Muscle Tone on the Ashworth Scale††d

-0.5 -1.0* -0.5a -0.5

Median Physician Global Assessment of Response to Treatment

1.0* 1.0* 1.0* 0.0

†PrimaryendpointatWeek6††SecondaryendpointsatWeek6*Significantlydifferentfromplacebo(p≤0.05)ap=0.053bTotaldoseofBOTOXinjectedintoboththeflexorcarpiradialisandulnarismusclescTotaldoseofBOTOXinjectedintotheflexordigitorumprofundusandflexordigitorumsublimismusclesdDoseofBOTOXinjectedintobicepsbrachiimuscle

Study3compared3dosesofBOTOXwithplaceboandenrolled88patients[BOTOX360Units(N=23),BOTOX 180 Units (N=23), BOTOX 90 Units (N=23), and placebo (N=19)] with upper limb spasticity(expandedAshworthscoreofatleast2forelbowflexortoneandatleast3forwristflexortoneand/orfingerflexortone)whowereatleast6weekspost-stroke.BOTOXandplacebowereinjectedwithEMGguidanceintotheflexordigitorumprofundus,flexordigitorumsublimis,flexorcarpiradialis,flexorcarpiulnaris,andbicepsbrachii(seeTable5).

TheprimaryefficacyvariableinStudy3waswristandelbowflexortoneasmeasuredbytheexpandedAshworthscore.Akeysecondaryendpointwasassessmentoffingerflexorsmuscletone.Study3resultsontheprimaryendpointatWeek4areshowninTable7.

Table 7: Primary and Key Secondary Endpoints by Muscle Group and BOTOX Dose at Week 4 in Study 3

BOTOX low dose (90 Units)

(N=23)

BOTOX mid dose

(180 Units) (N=21)


(N=22)

Placebo (N=19)

Median Change from Baseline in Wrist Flexor Muscle Tone on the Ashworth Scale†b

-1.0 -1.0 -1.5* -0.5

Median Change from Baseline in Finger Flexor Muscle Tone on the Ashworth Scale††c

-1.0 -1.0 -1.0* -0.5

Median Change from Baseline in Elbow Flexor Muscle Tone on the Ashworth Scale†d

-0.5 -0.5 -1.0* -0.5

†PrimaryendpointatWeek4††SecondaryendpointsatWeek4*Significantlydifferentfromplacebo(p≤0.05)bTotaldoseofBOTOXinjectedintoboththeflexorcarpiradialisandulnarismusclescTotaldoseofBOTOXinjectedintotheflexordigitorumprofundusandflexordigitorumsublimismuscles

dDoseofBOTOXinjectedintobicepsbrachiimuscle

14.2 Cervical DystoniaAphase3 randomized,multi-center,double-blind,placebo-controlledstudyof the treatmentofcervicaldystoniawasconducted.ThisstudyenrolledadultpatientswithcervicaldystoniaandahistoryofhavingreceivedBOTOXinanopenlabelmannerwithperceivedgoodresponseandtolerablesideeffects.Patientswereexcludediftheyhadpreviouslyreceivedsurgicalorotherdenervationtreatmentfortheirsymptomsorhadaknownhistoryofneuromusculardisorder.SubjectsparticipatedinanopenlabelenrichmentperiodwheretheyreceivedtheirpreviouslyemployeddoseofBOTOX.Onlypatientswhowereagainperceivedasshowingaresponsewereadvancedtotherandomizedevaluationperiod.Themusclesinwhichtheblindedstudyagentinjectionsweretobeadministeredweredeterminedonanindividualpatientbasis.

Therewere214subjectsevaluatedfortheopenlabelperiod,ofwhich170progressedintotherandomized,blindedtreatmentperiod(88intheBOTOXgroup,82intheplacebogroup).Patientevaluationscontinuedforat least10weekspost-injection.Theprimaryoutcome for thestudywasadualendpoint, requiringevidence of both a change in the Cervical Dystonia Severity Scale (CDSS) and an increase in thepercentageofpatientsshowinganyimprovementonthePhysicianGlobalAssessmentScaleat6weeksaftertheinjectionsession.TheCDSSquantifiestheseverityofabnormalheadpositioningandwasnewlydevisedforthisstudy.CDSSallots1pointforeach5degrees(orpartthereof)ofheaddeviationineachofthethreeplanesofheadmovement(rangeofscoresuptotheoreticalmaximumof54).ThePhysicianGlobalAssessmentScaleisa9categoryscalescoringthephysician’sevaluationofthepatients’statuscompared to baseline, ranging from–4 to +4 (verymarkedworsening to complete improvement),with0 indicatingnochangefrombaselineand+1slight improvement.Pain isalsoan importantsymptomofcervicaldystoniaandwasevaluatedbyseparateassessmentsofpainfrequencyandseverityonscalesof0(nopain)to4(constantinfrequencyorextremelysevereinintensity).Studyresultsontheprimaryendpointsandthepain-relatedsecondaryendpointsareshowninTable8.

Table 8: Efficacy Outcomes of the Phase 3 Cervical Dystonia Study (Group Means)

Placebo N=82

BOTOX® N=88

95% CI on Difference

Baseline CDSS 9.3 9.2

Change in CDSS at Week 6 -0.3 -1.3 (-2.3, 0.3)[a,b]

% Patients with Any Improvement on Physician Global Assessment

31% 51% (5%, 34%)[a]

Pain Intensity Baseline 1.8 1.8

Change in Pain Intensity at Week 6 -0.1 -0.4 (-0.7, -0.2)[c]

Pain Frequency Baseline 1.9 1.8

Change in Pain Frequency at Week 6 -0.0 -0.3 (-0.5, -0.0)[c]

[a] Confidence intervals are constructed from the analysis of covariance table with treatment andinvestigationalsiteasmaineffects,andbaselineCDSSasacovariate.[b]Thesevalues represent theprospectivelyplannedmethod formissingdata imputationandstatisticaltest.Sensitivityanalyses indicatedthat the95%confidence intervalexcludedthevalueofnodifferencebetweengroupsandthep-valuewaslessthan0.05.Theseanalysesincludedseveralalternativemissingdataimputationmethodsandnon-parametricstatisticaltests.[c]Confidenceintervalsarebasedonthet-distribution.

Exploratoryanalysesof this studysuggested that themajorityofpatientswhohadshownabeneficialresponsebyweek6hadreturnedtotheirbaselinestatusby3monthsaftertreatment.Exploratoryanalysesofsubsetsbypatientsexandagesuggestthatbothsexesreceivebenefit,althoughfemalepatientsmayreceivesomewhatgreateramountsthanmalepatients.Thereisaconsistenttreatment-associatedeffectbetweensubsetsgreaterthanandlessthanage65.Thereweretoofewnon-Caucasianpatientsenrolledtodrawanyconclusionsregardingrelativeefficacyinracialsubsets.

Therewereseveralrandomizedstudiesconductedpriortothephase3study,whichweresupportivebutnotadequatelydesignedtoassessorquantitativelyestimatetheefficacyofBOTOX.

Inthephase3studythemediantotalBOTOXdoseinpatientsrandomizedtoreceiveBOTOX(N=88)was236Units,with25thto75thpercentilerangesof198Unitsto300Units.Ofthese88patients,mostreceivedinjectionsto3or4muscles;38receivedinjectionsto3muscles,28to4muscles,5to5muscles,and5to2muscles.ThedosewasdividedamongsttheaffectedmusclesinquantitiesshowninTable9.Thetotaldoseandmusclesselectedweretailoredtomeetindividualpatientneeds.

Table 9: Number of Patients Treated per Muscle and Fraction of Total Dose Injected into Involved Muscles

Muscle

Number of Patients Treated in this Muscle

(N=88)

Mean % Dose per Muscle

Mid-Range of % Dose per Muscle*

Splenius capitis/cervicis 83 38 25-50

Sternocleidomastoid 77 25 17-31

Levator scapulae 52 20 16-25

Trapezius 49 29 18-33

Semispinalis 16 21 13-25

Scalene 15 15 6-21

Longissimus 8 29 17-41

*Themid-rangeofdoseiscalculatedasthe25thto75thpercentiles.

14.3 Primary Axillary HyperhidrosisTheefficacyandsafetyofBOTOXforthetreatmentofprimaryaxillaryhyperhidrosiswereevaluatedintworandomized,multi-center, double-blind, placebo-controlled studies.Study1 includedadult patientswithpersistentprimaryaxillaryhyperhidrosiswhoscored3or4onaHyperhidrosisDiseaseSeverityScale(HDSS)andwhoproducedatleast50mgofsweatineachaxillaatrestover5minutes.HDSSisa4-pointscalewith1=“underarmsweatingisnevernoticeableandneverinterfereswithmydailyactivities”;to4=“underarmsweatingisintolerableandalwaysinterfereswithmydailyactivities”.Atotalof322patientswererandomizedina1:1:1ratiototreatmentinbothaxillaewitheither50UnitsofBOTOX,75UnitsofBOTOX,orplacebo.Patientswereevaluatedat4-weekintervals.Patientswhorespondedtothefirstinjectionwerere-injectedwhentheyreportedare-increaseinHDSSscoreto3or4andproducedatleast50mgsweatineachaxillabygravimetricmeasurement,butnosoonerthan8weeksaftertheinitialinjection.

Study respondersweredefinedaspatientswhoshowedat leasta2-grade improvement frombaselinevalueontheHDSS4weeksafterbothof thefirst twotreatmentsessionsorhadasustainedresponseaftertheirfirsttreatmentsessionanddidnotreceivere-treatmentduringthestudy.Spontaneousrestingaxillarysweatproductionwasassessedbyweighingafilterpaperheld in theaxillaoveraperiodof5minutes(gravimetricmeasurement).Sweatproductionresponderswerethosepatientswhodemonstratedareductioninaxillarysweatingfrombaselineofatleast50%atweek4.

InthethreestudygroupsthepercentageofpatientswithbaselineHDSSscoreof3rangedfrom50%to54%andfrom46%to50%forascoreof4.Themedianamountofsweatproduction(averagedforeachaxilla)was102mg,123mg,and114mgfortheplacebo,50Unitsand75Unitsgroupsrespectively.

Thepercentageof respondersbasedonat leasta2-gradedecrease frombaseline inHDSSorbasedona>50%decreasefrombaselineinaxillarysweatproductionwasgreaterinbothBOTOXgroupsthanintheplacebogroup(p<0.001),butwasnotsignificantlydifferentbetweenthetwoBOTOXdoses(seeTable10).

Durationofresponsewascalculatedasthenumberofdaysbetweeninjectionandthedateofthefirstvisitatwhichpatientsreturnedto3or4ontheHDSSscale.ThemediandurationofresponsefollowingthefirsttreatmentinBOTOX-treatedpatientswitheitherdosewas201days.AmongthosewhoreceivedasecondBOTOXinjection,themediandurationofresponsewassimilartothatobservedafterthefirsttreatment.

In study 2, 320 adults with bilateral axillary primary hyperhidrosis were randomized to receive either50UnitsofBOTOX(n=242)orplacebo(n=78).Treatmentrespondersweredefinedassubjectsshowingat leasta50%reductionfrombaseline inaxillarysweatingmeasuredbygravimetricmeasurementat4weeks.Atweek4post-injection,thepercentagesofresponderswere91%(219/242)intheBOTOXgroupand36%(28/78) in theplacebogroup,p<0.001.Thedifference inpercentageof respondersbetweenBOTOXandplacebowas55%(95%CI=43.3,65.9).

Table 10: Study 1 - Study Outcomes

Treatment Response

BOTOX® 50 Units N=104

BOTOX® 75 Units N=110

Placebo N=108

BOTOX® 50-placebo

(95% CI)

BOTOX® 75-placebo

(95% CI)

HDSS Score change ≥2 (n)a

55% (57) 49% (54) 6% (6) 49.3% (38.8, 59.7)

43% (33.2, 53.8)

>50% decrease in axillary sweat production % (n)

81% (84) 86% (94) 41% (44) 40% (28.1, 52.0)

45% (33.3, 56.1)

aPatientswhoshowedat leasta2-gradeimprovementfrombaselinevalueontheHDSS4weeksafterbothofthefirsttwotreatmentsessionsorhadasustainedresponseaftertheirfirsttreatmentsessionanddidnotreceivere-treatmentduringthestudy.

14.4 BlepharospasmBotulinumtoxinhasbeeninvestigatedforuseinpatientswithblepharospasminseveralstudies.Inanopenlabel, historically controlledstudy,27patientswithessential blepharospasmwere injectedwith2UnitsofBOTOXateachofsixsitesoneachside.Twenty-fiveof the27patients treatedwithbotulinumtoxinreportedimprovementwithin48hours.Onepatientwascontrolledwithahigherdosageat13weekspostinitialinjectionandonepatientreportedmildimprovementbutremainedfunctionallyimpaired.

In another study, 12 patientswith blepharospasmwere evaluated in a double-blind, placebo-controlledstudy. Patients receiving botulinum toxin (n=8) improved compared with the placebo group (n=4).Theeffectsofthetreatmentlastedameanof12weeks.

Onethousandsixhundredeighty-fourpatientswithblepharospasmwhowereevaluatedinanopenlabeltrialshowedclinicalimprovementasevaluatedbymeasuredeyelidforceandclinicallyobservedintensityoflidspasm,lastinganaverageof12weekspriortotheneedforre-treatment.

14.5 StrabismusSixhundredseventy-sevenpatientswithstrabismustreatedwithoneormoreinjectionsofBOTOXwereevaluatedinanopenlabeltrial.Fifty-fivepercentofthesepatientsimprovedtoanalignmentof10prismdioptersorlesswhenevaluatedsixmonthsormorefollowinginjection.

16 HOW SUPPLIED/STORAGE AND HANDLING

BOTOXissuppliedinasingle-usevialinthefollowingsizes:100UnitsNDC0023-1145-01200UnitsNDC0023-3921-02

VialsofBOTOXhaveaholographicfilmontheviallabelthatcontainsthename“Allergan”withinhorizontallinesofrainbowcolor. Inordertoseethehologram,rotatethevialbackandforthbetweenyourfingersunderadesklamporfluorescentlightsource.(Note:theholographicfilmonthelabelisabsentinthedate/lotarea.)Ifyoudonotseethelinesofrainbowcolororthename“Allergan”,donotusetheproductandcontactAllerganforadditionalinformationat1-800-890-4345from7:00AMto3:00PMPacificTime.

StorageUnopenedvialsofBOTOXshouldbestoredinarefrigerator(2°to8°C)forupto36monthsforthe100Unitvialorupto24monthsforthe200Unitvial.Donotuseaftertheexpirationdateonthevial.AdministerBOTOXwithin24hoursofreconstitution;duringthisperiodreconstitutedBOTOXshouldbestored inarefrigerator(2°to8°C).ReconstitutedBOTOXshouldbeclear,colorless,andfreeofparticulatematter.

Allvials, includingexpiredvials,orequipmentusedwiththedrugshouldbedisposedofcarefully,as isdonewithallmedicalwaste.

Rx Only

17 PATIENT COUNSELING INFORMATION

ProvideacopyoftheMedicationGuideandreviewthecontentswiththepatient.

17.1 Swallowing, Speaking or Breathing Difficulties, or Other Unusual SymptomsPatientsshouldbeadvised to inform theirdoctororpharmacist if theydevelopanyunusualsymptoms(including difficulty with swallowing, speaking, or breathing), or if any existing symptom worsens [see Boxed Warning and Warnings and Precautions (5.2, 5.4)].

17.2 Ability to Operate Machinery or VehiclesPatientsshouldbecounseledthatiflossofstrength,muscleweakness,blurredvision,ordroopingeyelidsoccur,theyshouldavoiddrivingacarorengaginginotherpotentiallyhazardousactivities.

17.3 Medication Guide

MEDICATION GUIDEBOTOX® and BOTOX® Cosmetic (Boe-tox)

(onabotulinumtoxinA) for Injection

ReadtheMedicationGuidethatcomeswithBOTOXorBOTOXCosmeticbeforeyoustartusingitandeachtimeitisgiventoyou.Theremaybenewinformation.Thisinformationdoesnottaketheplaceoftalkingwithyourdoctoraboutyourmedicalconditionoryourtreatment.Youshouldsharethisinformationwithyourfamilymembersandcaregivers.

What is the most important information I should know about BOTOX and BOTOX Cosmetic?

BOTOX® and BOTOX® Cosmetic may cause serious side effects that can be life threatening. Call your doctor or get medical help right away if you have any of these problems after treatment with BOTOX or BOTOX Cosmetic:

• Problems swallowing, speaking, or breathing. These problems can happen hours to weeks after an injection of BOTOX or BOTOX Cosmetic usuallybecausethemusclesthatyouusetobreatheandswallowcanbecomeweakaftertheinjection.DeathcanhappenasacomplicationifyouhavesevereproblemswithswallowingorbreathingaftertreatmentwithBOTOXorBOTOXCosmetic.

• Peoplewithcertainbreathingproblemsmayneedtousemusclesintheirnecktohelpthembreathe.ThesepatientsmaybeatgreaterriskforseriousbreathingproblemswithBOTOXorBOTOXCosmetic.

• Swallowingproblemsmaylastforseveralmonths.Peoplewhocannotswallowwellmayneedafeedingtubetoreceivefoodandwater.Ifswallowingproblemsaresevere,foodorliquidsmaygointoyourlungs.PeoplewhoalreadyhaveswallowingorbreathingproblemsbeforereceivingBOTOXorBOTOXCosmetichavethehighestriskofgettingtheseproblems.

• Spread of toxin effects.Insomecases,theeffectofbotulinumtoxinmayaffectareasofthebodyawayfromtheinjectionsiteandcausesymptomsofaseriousconditioncalledbotulism.Thesymptomsofbotulisminclude:

• lossofstrengthandmuscleweaknessalloverthebody

• doublevision

• blurredvisionanddroopingeyelids

• hoarsenessorchangeorlossofvoice(dysphonia)

• troublesayingwordsclearly(dysarthria)

• lossofbladdercontrol

• troublebreathing

• troubleswallowing

ThesesymptomscanhappenhourstoweeksafteryoureceiveaninjectionofBOTOXorBOTOXCosmetic.

Theseproblemscouldmakeitunsafeforyoutodriveacarordootherdangerousactivities.See“WhatshouldIavoidwhilereceivingBOTOXorBOTOXCosmetic?”

TherehasnotbeenaconfirmedseriouscaseofspreadoftoxineffectawayfromtheinjectionsitewhenBOTOXhasbeenusedattherecommendeddosetotreatsevereunderarmsweating,blepharospasm,orstrabismus,orwhenBOTOX Cosmetichasbeenusedattherecommendeddosetotreatfrownlines.

What are BOTOX and BOTOX Cosmetic?

BOTOXisaprescriptionmedicinethatisinjectedintomusclesandused:

• totreatincreasedmusclestiffnessinelbow,wrist,andfingermusclesinadultswithupperlimbspasticity.

• totreattheabnormalheadpositionandneckpainthathappenswithcervicaldystonia(CD)inadults.

• totreatcertaintypesofeyemuscleproblems(strabismus)orabnormalspasmoftheeyelids(blepharospasm)inpeople12yearsandolder.

BOTOXisalsoinjectedintotheskintotreatthesymptomsofsevereunderarmsweating(severeprimaryaxillaryhyperhidrosis)whenmedicinesusedontheskin(topical)donotworkwellenough.

BOTOX®Cosmeticisaprescriptionmedicinethatisinjectedintomusclesandusedtoimprovethelookofmoderatetoseverefrownlinesbetweentheeyebrows(glabellarlines)inadultsyoungerthan65yearsofageforashortperiodoftime(temporary).

ItisnotknownwhetherBOTOXissafeoreffectiveinchildrenyoungerthan:

• 18yearsofagefortreatmentofspasticity

• 16yearsofagefortreatmentofcervicaldystonia

• 18yearsofagefortreatmentofhyperhidrosis

• 12yearsofagefortreatmentofstrabismusorblepharospasm

BOTOXCosmeticisnotrecommendedforuseinchildrenyoungerthan18yearsofage.

ItisnotknownwhetherBOTOXandBOTOXCosmeticaresafeoreffectiveforothertypesofmusclespasmsorforseveresweatinganywhereotherthanyourarmpits.

Who should not take BOTOX or BOTOX Cosmetic?

DonottakeBOTOXorBOTOXCosmeticifyou:

• areallergictoanyoftheingredientsinBOTOXorBOTOXCosmetic.SeetheendofthisMedicationGuideforalistofingredientsinBOTOXandBOTOXCosmetic.

• hadanallergicreactiontoanyotherbotulinumtoxinproductsuchasMyobloc®orDysport®

• haveaskininfectionattheplannedinjectionsite

What should I tell my doctor before taking BOTOX or BOTOX Cosmetic?

Tell your doctor about all your medical conditions, including if you have:

• adiseasethataffectsyourmusclesandnerves(suchasamyotrophiclateralsclerosis[ALSorLouGehrig’sdisease],myastheniagravisorLambert-Eatonsyndrome).See“WhatisthemostimportantinformationIshouldknowaboutBOTOXandBOTOXCosmetic?”

• allergiestoanybotulinumtoxinproduct

• hadanysideeffectfromanybotulinumtoxinproductinthepast

• abreathingproblem,suchasasthmaoremphysema

• swallowingproblems

• bleedingproblems

• planstohavesurgery

• hadsurgeryonyourface

• weaknessofyourforeheadmuscles,suchastroubleraisingyoureyebrows

• droopingeyelids

• anyotherchangeinthewayyourfacenormallylooks

• arepregnantorplantobecomepregnant.ItisnotknownifBOTOXorBOTOXCosmeticcanharmyourunbornbaby.

• arebreast-feedingorplantobreastfeed.ItisnotknownifBOTOXorBOTOXCosmeticpassesintobreastmilk.

Tell your doctor about all the medicines you take,includingprescriptionandnonprescriptionmedicines,vitaminsandherbalproducts.UsingBOTOXorBOTOXCosmeticwithcertainothermedicinesmaycauseserioussideeffects.Do not start any new medicines until you have told your doctor that you have received BOTOX or BOTOX Cosmetic in the past.

Especiallytellyourdoctorifyou:

• havereceivedanyotherbotulinumtoxinproductinthelastfourmonths

• havereceivedinjectionsofbotulinumtoxin,suchasMyobloc®(rimabotulinumtoxinB)orDysport®(abobotulinumtoxinA)inthepast.Besureyourdoctorknowsexactlywhichproductyoureceived.

• haverecentlyreceivedanantibioticbyinjection

• takemusclerelaxants

• takeanallergyorcoldmedicine

• takeasleepmedicine

Ask your doctor if you are not sure if your medicine is one that is listed above.

Knowthemedicinesyoutake.Keepalistofyourmedicineswithyoutoshowyourdoctorandpharmacisteachtimeyougetanewmedicine.

How should I take BOTOX®orBOTOX®Cosmetic?

• BOTOXorBOTOXCosmeticisaninjectionthatyourdoctorwillgiveyou.

• BOTOXisinjectedintoyouraffectedmusclesorskin.

• BOTOXCosmeticisinjectedintoyouraffectedmuscles.

• YourdoctormaychangeyourdoseofBOTOXorBOTOXCosmetic,untilyouandyourdoctorfindthebestdoseforyou.

What should I avoid while taking BOTOX or BOTOX Cosmetic?

BOTOXandBOTOXCosmeticmaycauselossofstrengthorgeneralmuscleweakness,orvisionproblemswithinhourstoweeksoftakingBOTOXorBOTOXCosmetic.If this happens, do not drive a car, operate machinery, or do other dangerous activities. See“WhatisthemostimportantinformationIshouldknowaboutBOTOXandBOTOXCosmetic?”

What are the possible side effects of BOTOX and BOTOX Cosmetic?

BOTOX and BOTOXCosmetic can cause serious side effects. See“WhatisthemostimportantinformationIshouldknowaboutBOTOXandBOTOXCosmetic?”

Other side effects of BOTOX and BOTOX Cosmetic include:

• drymouth

• discomfortorpainattheinjectionsite

• tiredness

• headache

• neckpain

• eyeproblems:doublevision,blurredvision,decreasedeyesight,droopingeyelids,swellingofyoureyelids,anddryeyes.

• allergicreactions.SymptomsofanallergicreactiontoBOTOXorBOTOX Cosmeticmayinclude:itching,rash,reditchywelts,wheezing,asthmasymptoms,ordizzinessorfeelingfaint.Tellyourdoctororgetmedicalhelprightawayifyouarewheezingorhaveasthmasymptoms,orifyoubecomedizzyorfaint.

Tellyourdoctorifyouhaveanysideeffectthatbothersyouorthatdoesnotgoaway.

ThesearenotallthepossiblesideeffectsofBOTOX®andBOTOX®Cosmetic.Formoreinformation,askyourdoctororpharmacist.

Callyourdoctorformedicaladviceaboutsideeffects.YoumayreportsideeffectstoFDAat1-800-FDA-1088.

General information about BOTOX and BOTOX Cosmetic:MedicinesaresometimesprescribedforpurposesotherthanthoselistedinaMedicationGuide.

ThisMedicationGuidesummarizesthemostimportantinformationaboutBOTOXandBOTOX Cosmetic.Ifyouwouldlikemoreinformation,talkwithyourdoctor.YoucanaskyourdoctororpharmacistforinformationaboutBOTOXandBOTOX Cosmeticthatiswrittenforhealthcareprofessionals.FormoreinformationaboutBOTOXandBOTOX CosmeticcallAllerganat1-800-433-8871orgotowww.botox.com.

What are the ingredients in BOTOX and BOTOX Cosmetic?Activeingredient:botulinumtoxintypeAInactiveingredients:humanalbuminandsodiumchloride

Issued: 06/2010

ThisMedicationGuidehasbeenapprovedbytheU.S.FoodandDrugAdministration.

Manufacturedby:AllerganPharmaceuticalsIrelandasubsidiaryof:Allergan,Inc.2525DupontDr.Irvine,CA92612©2010Allergan,Inc.®markownedbyAllergan,Inc.U.S.Patents6,974,578;6,683,049;and6,896,886

Myobloc®isaregisteredtrademarkofSolsticeNeurosciences,Inc.Dysport®isaregisteredtrademarkofIpsenBiopharmLimitedCompany.

71829US11A72284US11B

APC96LY10

BOTOX® Cosmetic (onabotulinumtoxinA)for injection

Manufacturedby:AllerganPharmaceuticalsIreland asubsidiaryof:Allergan,Inc.2525DupontDr.,Irvine,CA92612

Distant Spread of Toxin EffectPostmarketingreportsindicatethattheeffectsofBOTOX® Cosmetic and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These symptoms havebeenreportedhourstoweeksafterinjection.Swallowingandbreathingdifficultiescanbelife threatening and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults treated for spasticity and other conditions, particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including spasticity in children and adults, and in approved indications, cases of spread of effect have occurred at doses comparable to those used to treat cervical dystonia and at lower doses.

DESCRIPTION

BOTOX® Cosmetic (onabotulinumtoxinA) for injection, is a sterile, vacuum-dried purified botulinum toxin type A, produced from fermentation of Hall strain Clostridium botulinum type A grown in a medium containing casein hydrolysate, glucose, and yeast extract, intended for intramuscular use. It is purified from the culture solution by dialysis and a series of acid precipitations to a complex consisting of the neurotoxin, and several accessory proteins. The complex is dissolved in sterile sodium chloride solution containing Albumin Human and is sterile filtered(0.2microns)priortofillingandvacuum-drying.

One Unit of BOTOX® Cosmetic corresponds to the calculated median intraperitoneal lethal dose (LD50)inmice.ThemethodutilizedforperformingtheassayisspecifictoAllergan’sproduct, BOTOX® Cosmetic. Due to specific details of this assay such as the vehicle, dilution scheme and laboratory protocols for the various mouse LD50 assays, Units of biological activity of BOTOX® Cosmetic cannot be compared to nor converted into Units of any other botulinum toxin or any toxin assessed with any other specific assay method. In addition, differences in species sensitivities to different botulinum neurotoxin serotypes precludes extrapolation of animal-dose activity relationships to human dose estimates. The specific activity of BOTOX® Cosmetic isapproximately20Units/nanogramofneurotoxin protein complex.

Each vial of BOTOX® Cosmetic containseither100UnitsofClostridium botulinum type A neurotoxincomplex,0.5mgofAlbuminHuman,and0.9mgofsodiumchlorideor50Unitsof Clostridium botulinumtypeAneurotoxincomplex,0.25mgofAlbuminHuman,and0.45mgof sodium chloride in a sterile, vacuum-dried form without a preservative.

CLINICAL PHARMACOLOGY

BOTOX® Cosmetic blocks neuromuscular transmission by binding to acceptor sites on motor nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine. This inhibitionoccursastheneurotoxincleavesSNAP-25,aproteinintegraltothesuccessful dockingandreleaseofacetylcholinefromvesiclessituatedwithinnerveendings.Wheninjectedintramuscularly at therapeutic doses, BOTOX® Cosmetic produces partial chemical denervation of the muscle resulting in a localized reduction in muscle activity. In addition, the muscle may atrophy, axonal sprouting may occur, and extrajunctional acetylcholine receptors may develop. There is evidence that reinnervation of the muscle may occur, thus slowly reversing muscle denervation produced by BOTOX® Cosmetic.

Pharmacokinetics

Using currently available analytical technology, it is not possible to detect BOTOX® Cosmetic in the peripheral blood following intramuscular injection at the recommended doses.

CLINICAL STUDIES

Glabellar Lines

Twophase3randomized,multi-center,double-blind,placebo-controlledstudiesofidentical design were conducted to evaluate BOTOX® Cosmetic for use in the temporary improvement of the appearance of moderate to severe glabellar facial lines. The studies enrolled healthy adults (ages18to75)withglabellarlinesofatleastmoderateseverityatmaximumfrown.Patients were excluded if they had ptosis, deep dermal scarring, or an inability to substantially lessen glabellarlinesevenbyphysicallyspreadingthemapart.SubjectsreceivedasingletreatmentwithBOTOX® Cosmetic(N=405,combinedstudies)orplacebo(N=132,combinedstudies).Injection volumewas0.1mL/injectionsite,foradose/injectionsiteintheactivetreatmentgroupsof4 Units.Subjectswereinjectedintramuscularlyinfivesites,1intheprocerusmuscleand2ineachcorrugatorsuperciliimuscle,foratotaldoseintheactivetreatmentgroupsof20Units.

Theco-primaryefficacyendpointsweretheinvestigator’sratingofglabellarlineseverityat maximumfrownandthesubject’sglobalassessmentofchangeinappearanceofglabellarlines, bothatDay30post-injection.Fortheinvestigatorrating,usinga4-pointgradingscale(0=none,3=severe)aresponderwasdefinedashavingaseveritygradeof0or1.Forthesubject’sglobalassessmentofchange,theratingswerefrom+4(completeimprovement)to-4(verymarkedworsening).Aresponderwasdefinedashavingagradeofatleast+2(moderateimprovement). After completion of the randomized studies, subjects were offered participation in an open label, repeat treatment study to assess the safety of repeated treatment sessions.

Thecombinedresultsofthesetwoefficacytrialsarepresentedhere.Themeanagewas46years, with32patients(6%)≥65yearsofage.Mostofthesubjects(82%)werewomen,andCaucasian (84%).Atbaseline,210patients(39%)hadglabellarlineseverityscoresatrestofmoderate or severe.

Inthesestudies,theseverityofglabellarlineswasreducedforupto120daysinthe BOTOX® Cosmetic group compared to the placebo group as measured both by investigator ratingofglabellarlineseverityatmaximumfrown(Table1),andbysubject’sglobalassessment ofchangeinappearanceofglabellarlines(Table2).

TABLE 1.Investigator’s Assessment of Glabellar Line Severity at Maximum Frown – Responder Rates (% and Number of Subjects with Severity of None or Mild)

Day BOTOX® Cosmetic

Placebo Differencea

7 74% 299/405

6% 8/132

68% (62,74)

30b 80% 325/405

3% 4/132

77% (72,82)

60 70% 283/403

2% 2/130

69% (64,74)

90 48% 192/403

2% 3/128

45% (40,51)

120 25% 102/403

2% 2/128

24% (19,29)

a95%confidenceintervalsareshowninparenthesis bDay30:Co-PrimaryEfficacyTimepoint,P<0.001

TABLE 2.Subject’s Assessment of Change in Appearance of Glabellar Lines – Responder Rates (% and Number of Subjects with at Least Moderate Improvement)

Day BOTOX® Cosmetic

Placebo Differencea

7 82% 334/405

9% 12/132

73% (68,80)

30b 89% 362/405

7% 9/132

83% (77,88)

60 82% 330/403

4% 5/130

78% (73,83)

90 63% 254/403

3% 4/128

60% (54,66)

120 39% 157/403

1% 1/128

38% (33,43)

a95%confidenceintervalsareshowninparenthesis bDay30:Co-PrimaryEfficacyTimepoint,P<0.001

In the subset of patients with resting severity scores of moderate or severe, the investigator assessmentofarestingseverityofmildornoneatday30wasalsoachievedbymore BOTOX® Cosmetictreatedpatients(74%,119/161)thanplacebotreatedpatients(20%,10/49).

Analysisofthelimitednumberofpatients65yearsoroldersuggestedalowertreatment-associatedresponsecomparedtopatientslessthan65yearsofage.(Table3).

TABLE 3.Investigator’s and Subject’s Assessment – Responder Rates for Subjects < 65 and ≥ 65 Years of Age at Day 30

Assessment Age Group BOTOX® Cosmetic

N=405

Placebo N=132

Differencea

Investigators (maximal frown)

<65 83% 316/382

2% 2/123

81% (77,86)

Subjects <65 91% 346/382

7% 8/123

84% (79,90)

Investigators (maximal frown)

≥65 39% 9/23

22% 2/9

17% (-17,51)

Subjects ≥65 70% 16/23

11% 1/9

58% (31,86)

a95%confidenceintervalsareshowninparenthesis

Exploratory analyses by gender suggested that responder rates in the BOTOX® Cosmetic treated groupwerehigherforwomenthanformenforboththeinvestigatorassessment(day30;85%of 334women,59%of71men)andtheSubjectAssessment(day30;93%ofwomen,72%ofmen). Inthelimitednumberofnon-Caucasianpatients(n=64intheBOTOX® Cosmetictreatedgroup) theresponderratesweresimilartothoseobservedintheCaucasianpatients.

INDICATIONS AND USAGE

BOTOX® Cosmetic is indicated for the temporary improvement in the appearance of moderate to severe glabellarlinesassociatedwithcorrugatorand/orprocerusmuscleactivityinadultpatients ≤65yearsofage.

CONTRAINDICATIONS

BOTOX® Cosmeticiscontraindicatedinthepresenceofinfectionattheproposedinjectionsite(s) and in individuals with known hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation.

WARNINGS

BOTOX® and BOTOX® Cosmetic contain the same active ingredient in the same formulation. Therefore, adverse events observed with the use of BOTOX® also have the potential to be associated with the use of BOTOX® Cosmetic.

The recommended dosage and frequency of administration for BOTOX® Cosmetic should not be exceeded. Risks resulting from administration at higher dosages are not known.

Lack of Interchangeability between Botulinum Toxin Products

The potency Units of BOTOX® Cosmetic are specific to the preparation and assay method utilized. They are not interchangeable with other preparations of botulinum toxin products and, therefore, units of biological activity of BOTOX® Cosmetic cannot be compared to or converted into units of any other botulinum toxin products assessed with any other specific assay method (see DESCRIPTION).

Spread of Toxin Effect

PostmarketingsafetydatafromBOTOX® Cosmetic and other approved botulinum toxins suggest that botulinum toxin effects may, in some cases, be observed beyond the site of local injection. The symptoms are consistent with the mechanism of action of botulinum toxin and may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These symptoms have been reported hourstoweeksafterinjection.Swallowingandbreathingdifficultiescanbelifethreatening and there have been reports of death related to spread of toxin effects. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults treated for spasticity and other conditions, and particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including spasticity in children and adults, and in approved indications, symptoms consistent with spread of toxin effect have been reported at doses comparable to or lower than doses used to treat cervical dystonia.

Nodefinitiveseriousadverseeventreportsofdistantspreadoftoxineffectassociatedwithdermatologicuse of BOTOX®/BOTOX® Cosmeticatthelabeleddoseof20Units(forglabellarlines)or100Units(forsevereprimaryaxillaryhyperhidrosis)havebeenreported.

Nodefinitiveseriousadverseeventreportsofdistantspreadoftoxineffectassociatedwith BOTOX®forblepharospasmattherecommendeddose(30Unitsandbelow)orforstrabismusat the labeled doses have been reported.

Hypersensitivity Reactions

Seriousand/orimmediatehypersensitivityreactionshavebeenreported.Thesereactionsincludeanaphylaxis, urticaria, soft tissue edema, and dyspnea. If such a reaction occurs, further injection of BOTOX® Cosmetic should be discontinued and appropriate medical therapy immediately instituted. One fatal case of anaphylaxis has been reported in which lidocaine was used as the diluent, and consequently the causal agent cannot be reliably determined.

Pre-Existing Neuromuscular Disorders

Individuals with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscularjunctionaldisorders(e.g.,myastheniagravisorLambert-Eatonsyndrome)should bemonitoredparticularlycloselywhengivenbotulinumtoxin.Patientswithneuromuscular disorders may be at increased risk of clinically significant effects including severe dysphagia and respiratory compromise from typical doses of BOTOX® Cosmetic(seeADVERSE REACTIONS).

Dysphagia and Breathing Difficulties in Treatment of Cervical Dystonia

Treatment with BOTOX® and other botulinum toxin products can result in swallowing or breathing difficulties.Patientswithpre-existingswallowingorbreathingdifficultiesmaybemoresusceptibleto these complications. In most cases, this is a consequence of weakening of muscles in the area of injectionthatareinvolvedinbreathingorswallowing.Whendistanteffectsoccur,additionalrespiratorymusclesmaybeinvolved(seeWARNINGS).

Deaths as a complication of severe dysphagia have been reported after treatment with botulinum toxin. Dysphagia may persist for several months, and require use of a feeding tube to maintain adequate nutrition and hydration. Aspiration may result from severe dysphagia and is a particular risk when treating patients in whom swallowing or respiratory function is already compromised.

Treatment of cervical dystonia with botulinum toxins may weaken neck muscles that serve as accessory muscles of ventilation. This may result in a critical loss of breathing capacity in patients with respiratory disorders who may have become dependent upon these accessory muscles. There have been postmarketing reports of serious breathing difficulties, including respiratory failure, in cervical dystonia patients.

Patientstreatedwithbotulinumtoxinmayrequireimmediatemedicalattentionshouldthey develop problems with swallowing, speech, or respiratory disorders. These reactions can occurwithinhourstoweeksafterinjectionwithbotulinumtoxin(seeWARNINGS, ADVERSE REACTIONS, CLINICAL PHARMACOLOGY).

Cardiovascular System

There have been reports following administration of BOTOX® of adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes. Someofthesepatientshadriskfactorsincludingpre-existingcardiovasculardisease.

Human Albumin

Thisproductcontainsalbumin,aderivativeofhumanblood.Basedoneffectivedonorscreening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases.AtheoreticalriskfortransmissionofCreutzfeldt-Jakobdisease(CJD)alsoisconsideredextremelyremote.NocasesoftransmissionofviraldiseasesorCJDhaveeverbeenidentified for albumin.

PRECAUTIONS

The safe and effective use of BOTOX® Cosmetic depends upon proper storage of the product, selectionofthecorrectdose,andproperreconstitutionandadministrationtechniques.Physiciansadministering BOTOX® Cosmeticmustunderstandtherelevantneuromuscularand/ororbital anatomy of the area involved, as well as any alterations to the anatomy due to prior surgical procedures and avoid injection into vulnerable anatomic areas.

CautionshouldbeusedwhenBOTOX® Cosmetic treatment is used in the presence of inflammationattheproposedinjectionsite(s)orwhenexcessiveweaknessoratrophyispresent inthetargetmuscle(s).

Reduced blinking from BOTOX® Cosmetic injection of the orbicularis muscle can lead to corneal exposure, persistent epithelial defect and corneal ulceration, especially in patients with VII nerve disorders. In the use of BOTOX® for the treatment of blepharospasm, one case of corneal perforation in an aphakic eye requiring corneal grafting has occurred because of this effect. Carefultestingofcornealsensationineyespreviouslyoperatedupon,avoidanceofinjectioninto the lower lid area to avoid ectropion, and vigorous treatment of any epithelial defect should be employed. This may require protective drops, ointment, therapeutic soft contact lenses, or closure of the eye by patching or other means.

Inducing paralysis in one or more extraocular muscles may produce spatial disorientation, double visionorpastpointing.Coveringtheaffectedeyemayalleviatethesesymptoms.

CautionshouldbeusedwhenBOTOX® Cosmetic treatment is used in patients who have an inflammatory skin problem at the injection site, marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin or the inability to substantially lessen glabellarlinesbyphysicallyspreadingthemapartasthesepatientswereexcludedfromthePhase 3safetyandefficacytrials.

Needle-relatedpainand/oranxietymayresultinvasovagalresponses(includinge.g.,syncope,hypotension),whichmayrequireappropriatemedicaltherapy.

Injection intervals of BOTOX® Cosmetic should be no more frequent than every three months andshouldbeperformedusingthelowesteffectivedose(seeADVERSE REACTIONS, IMMUNOGENICITY).

Information for Patients

ThephysicianshouldprovideacopyoftheFDA-ApprovedPatientMedicationGuideandreview thecontentswiththepatient.Patientsshouldbeadvisedtoinformtheirdoctororpharmacistif theydevelopanyunusualsymptoms(includingdifficultywithswallowing,speaking,orbreathing), or if any existing symptom worsens.

Patientsshouldbecounseledthatiflossofstrength,muscleweakness,orimpairedvisionoccur, they should avoid driving a car or engaging in other potentially hazardous activities.

Drug Interactions

Co-administrationofBOTOX® Cosmetic and aminoglycosides1 or other agents interfering withneuromusculartransmission(e.g.,curare-likenondepolarizingblockers,lincosamides, polymyxins,quinidine,magnesiumsulfate,anticholinesterases,succinylcholinechloride)should only be performed with caution as the effect of the toxin may be potentiated.

The effect of administering different botulinum neurotoxin serotypes at the same time or within several months of each other is unknown. Excessive neuromuscular weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin.

Pregnancy: Pregnancy Category C

Administration of BOTOX® Cosmetic is not recommended during pregnancy. There are no adequate and well-controlled studies of BOTOX® Cosmeticinpregnantwomen.When pregnant mice and rats were injected intramuscularly during the period of organogenesis, the developmentalNOEL(NoObservedEffectLevel)ofBOTOX® Cosmeticwas4Units/kg.Higher doses(8Units/kgor16Units/kg)wereassociatedwithreductionsinfetalbodyweightsand/or delayed ossification.

Inarangefindingstudyinrabbits,dailyinjectionof0.125Units/kg/day(days6to18ofgestation) and2Units/kg(days6and13ofgestation)producedseverematernaltoxicity,abortionsand/or fetal malformations. Higher doses resulted in death of the dams. The rabbit appears to be a very sensitive species to BOTOX® Cosmetic.

If the patient becomes pregnant after the administration of this drug, the patient should be apprised of the potential risks, including abortion or fetal malformations that have been observed in rabbits.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term studies in animals have not been performed to evaluate carcinogenic potential of BOTOX® Cosmetic.

ThereproductiveNOELfollowingintramuscularinjectionof0,4,8,and16Units/kgwas4Units/kg inmaleratsand8Units/kginfemalerats.Higherdoseswereassociatedwithdose-dependentreductionsinfertilityinmalerats(wherelimbweaknessresultedintheinabilitytomate),and testicular atrophy or an altered estrous cycle in female rats. There were no adverse effects on the viability of the embryos.

Nursing Mothers

Itisnotknownwhetherthisdrugisexcretedinhumanmilk.Becausemanydrugsareexcreted in human milk, caution should be exercised when BOTOX® Cosmetic is administered to a nursing woman.

Pediatric Use

Use of BOTOX® Cosmetic is not recommended in children.

Geriatric Use

The two clinical studies of BOTOX® Cosmeticdidnotincludesufficientnumbersofsubjectsaged65and over to determine whether they respond differently from younger subjects. However, the responder ratesappearedtobehigherforpatientsyoungerthanage65thanforpatients65yearsorolder(see CLINICAL STUDIES).

Thereweretoofewpatients(N=3)overtheageof75toallowanymeaningfulcomparisons.

ADVERSE REACTIONS

General

BOTOX® and BOTOX® Cosmetic contain the same active ingredient in the same formulation. Therefore adverse events observed with the use of BOTOX® also have the potential to be associated with the use of BOTOX® Cosmetic.

The most serious adverse events reported after treatment with botulinum toxin include spontaneous reports of death, sometimes associated with anaphylaxis, dysphagia, pneumonia, and/orothersignificantdebility.

There have also been reports of adverse events involving the cardiovascular system, including arrhythmiaandmyocardialinfarction,somewithfataloutcomes.Someofthesepatientshad riskfactorsincludingpre-existingcardiovasculardisease(seeWARNINGS).

Newonsetorrecurrentseizureshavealsobeenreported,typicallyinpatientswhoarepredisposed to experiencing these events. The exact relationship of these events to the botulinum toxin injection has not been established. Additionally, a report of acute angle closure glaucoma one day after receiving an injection of botulinum toxin for blepharospasm was received, with recovery four months later after laser iridotomy and trabeculectomy. Focal facial paralysis, syncope and exacerbation of myasthenia gravis have also been reported after treatment of blepharospasm.

In general, adverse events occur within the first week following injection of BOTOX® Cosmetic and while generally transient may have a duration of several months or longer. Localized pain, infection,inflammation,tenderness,swelling,erythemaand/orbleeding/bruisingmaybe associatedwiththeinjection.Localweaknessoftheinjectedmuscle(s)representstheexpectedpharmacological action of botulinum toxin. However, weakness of adjacent muscles may also occur due to spread of toxin.

Glabellar Lines

In clinical trials of BOTOX® Cosmetic the most frequently reported adverse events following injection of BOTOX® Cosmetic were headache*, respiratory infection*, flu syndrome*, blepharoptosis and nausea.

Lessfrequentlyoccurring(<3%)adversereactionsincludedpainintheface,erythemaatthe injectionsite*,paresthesia*andmuscleweakness.Whilelocalweaknessoftheinjectedmuscle(s) is representative of the expected pharmacological action of botulinum toxin, weakness of adjacent muscles may occur as a result of the spread of toxin. These events are thought to be associated with the injection and occurred within the first week. The events were generally transient but may last several months or longer. (*incidencenotdifferentfromPlacebo)

ThedatadescribedinTable4reflectexposuretoBOTOX® Cosmeticin405subjectsaged18to 75whowereevaluatedintherandomized,placebo-controlledclinicalstudiestoassesstheuse of BOTOX® Cosmeticintheimprovementoftheappearanceofglabellarlines(seeCLINICAL STUDIES).Adverseeventsofanycausewerereportedfor44%oftheBOTOX® Cosmetic treated subjectsand42%oftheplacebotreatedsubjects.Theincidenceofblepharoptosiswashigherin the BOTOX® Cosmetictreatedarmthaninplacebo(3%vs.0).

Intheopen-label,repeatinjectionstudy,blepharoptosiswasreportedfor2%(8/373)ofsubjects inthefirsttreatmentcycleand1%(4/343)ofsubjectsinthesecondtreatmentcycle.Adverse eventsofanytypewerereportedfor49%(183/373)ofsubjectsoverall.Themostfrequently reported of these adverse events in the open-label study included respiratory infection, headache, flu syndrome, blepharoptosis, pain and nausea.

Becauseclinicaltrialsareconductedunderwidelyvaryingconditions,adversereactionrates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not be predictive of rates observed in practice.

TABLE 4.Adverse Events Reported at Higher Frequency (>1%) in the BOTOX® Cosmetic Group Compared to the Placebo Group

Percent of Patients Reporting Adverse Events

Adverse Events by Body System BOTOX® Cosmetic (N=405)

%

Placebo (N=130)

%

Overall 44 42

BodyasaWhole PaininFace

2 1

SkinandAppendages SkinTightness

1 0

DigestiveSystem Nausea

Dyspepsia Tooth Disorder

3 1 1

2 0 0

SpecialSenses Blepharoptosis

3 0

MusculoskeletalSystem MuscleWeakness

2 0

Cardiovascular Hypertension

1 0

Immunogenicity

Treatment with BOTOX® Cosmetic may result in the formation of neutralizing antibodies that may reduce the effectiveness of subsequent treatments with BOTOX® Cosmetic by inactivating the biological activity of the toxin. The rate of formation of neutralizing antibodies in patients receiving BOTOX® Cosmetic has not been well studied.

The critical factors for neutralizing antibody formation have not been well characterized. The results from some studies suggest that botulinum toxin injections at more frequent intervals or at higher doses may lead to greater incidence of antibody formation. The potential for antibody formation may be minimized by injecting the lowest effective dose given at the longest feasible intervals between injections.

Postmarketing Experience

Transient ptosis, the most frequently reported complication, has been reported in the literature inapproximately5%ofpatients.Therehasbeenasinglereportofdiplopia,whichresolved completely in three weeks.

The following other adverse reactions have been identified since the drug has been marketed: abdominalpain;blurredvision;brachialplexopathy;decreasedhearing;diarrhea;earnoise; erythemamultiforme;fever;focalfacialparalysis;glaucoma;localizednumbness;lossofappetite;malaise;myalgia;myastheniagravis;pruritus;psoriasiformeruption;retinalveinocclusion; sweating;syncope;vertigowithnystagmus;andvomiting.

Becausethesereactionsarereportedvoluntarilyfromapopulationofuncertainsize,itisnot always possible to reliably estimate their frequency or establish a causal relationship to botulinum toxin.

Reporting Adverse Events

Adverse events following use of BOTOX® CosmeticshouldbereportedtothePharmacovigilanceDepartment,AllerganInc.(1-800-433-8871).AdverseeventsmayalsobereportedtotheU.S. DepartmentofHealthandHumanServices(DHHS)AdverseEventReportingSystem.Report forms and reporting requirement information can be obtained from Adverse Event Reporting System(AERS)throughatollfreenumber1-800-822-7967.

Overdosage

Excessive doses of BOTOX® Cosmetic may be expected to produce neuromuscular weakness with a variety of symptoms. Respiratory support may be required where excessive doses cause paralysis of respiratory muscles. In the event of overdose, the patient should be medically monitoredforsymptomsofexcessivemuscleweaknessormuscleparalysis(seeWARNINGS and PRECAUTIONS).Symptomatictreatmentmaybenecessary.

Symptomsofoverdosearelikelynottobepresentimmediatelyfollowinginjection.Should accidental injection or oral ingestion occur, the person should be medically supervised for several weeks for signs and symptoms of excessive muscle weakness or muscle paralysis.

Intheeventofoverdose,antitoxinraisedagainstbotulinumtoxinisavailablefromtheCentersforDiseaseControlandPrevention(CDC)inAtlanta,GA.However,theantitoxinwillnotreverseanybotulinum toxin-induced effects already apparent by the time of antitoxin administration. In the event of suspected or actual cases of botulinum toxin poisoning, please contact your local or state HealthDepartmenttoprocessarequestforantitoxinthroughtheCDC.Ifyoudonotreceivea responsewithin30minutes,pleasecontacttheCDCdirectlyat1-770-488-7100.Moreinformation canbeobtainedathttp://www.cdc.gov/ncidod/srp/drugs/drug-service.html.

DOSAGE AND ADMINISTRATION

For Intramuscular Injection Only

BOTOX® Cosmeticistobereconstitutedonlywith0.9%sterile,non-preservedsalinepriortointramuscularinjection.Perthedilutiontablebelow,drawuptherequiredamountof0.9%sterile non-preserved sodium chloride solution into a syringe to obtain a reconstituted solution at a concentrationof4Units/0.1mLandatotaltreatmentdoseof20Unitsin0.5mL.Thedurationofactivityof BOTOX® Cosmeticforglabellarlinesisapproximately3-4months.Thesafetyandeffectivenessofmore frequent dosing with BOTOX® Cosmetic has not been clinically evaluated and is not recommended.

Dilution Table

Diluent Added to 100 Unit Vial (0.9% Sodium

Chloride Injection Only)

Resulting Dose Units per 0.1 mL

Diluent Added to 50 Unit Vial (0.9% Sodium

Chloride Injection Only)

Resulting Dose Units per 0.1 mL

2.5mL 4Units 1.25mL 4Units

Reconstituted BOTOX® Cosmetic should be clear, colorless, and free of particulate matter.

BOTOX® Cosmetic is supplied as a single use vial. The product and diluent do not contain a preservative.Onceopenedandreconstituteditshouldbestoredinarefrigerator(2°to8°C) andusedwithin24hours.Discardanyremainingsolution.Parenteraldrugproductsshould be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not freeze reconstituted BOTOX® Cosmetic.

Dilution Technique

Usinga21-gaugeneedleandanappropriatelysizedsyringedrawupatotalof2.5mL/100Unit vialor1.25mL/50Unitvialof0.9%sterilesalinewithoutapreservative.Inserttheneedleata45° angle and slowly inject into the BOTOX® Cosmetic vial. Discard the vial if a vacuum does not pull the diluent into the vial. Gently rotate the vial and record the date and time of reconstitution on the space on the label.

Drawatleast0.5mLoftheproperlyreconstitutedtoxinintothesterilesyringe,preferablya tuberculin syringe and expel any air bubbles in the syringe barrel. Remove the needle used to reconstitutetheproductandattacha30-33gaugeneedle.Confirmthepatencyoftheneedle.

Injection Technique

Glabellar facial lines arise from the activity of the corrugator and orbicularis oculi muscles. These muscles move the brow medially, and the procerus and depressor supercilii pull the brow inferiorly. Thiscreatesafrownor“furrowedbrow”.Thelocation,size,anduseofthemusclesvarymarkedlyamong individuals. Lines induced by facial expression occur perpendicular to the direction of action of contracting facial muscles. An effective dose for facial lines is determined by gross observation of the patient’sabilitytoactivatethesuperficialmusclesinjected.

In order to reduce the complication of ptosis the following steps should be taken:

Avoid injection near the levator palpebrae superioris, particularly in patients with larger brow •depressor complexes.

Lateralcorrugatorinjectionsshouldbeplacedatleast1cmabovethebonysupraorbitalridge.•

Ensuretheinjectedvolume/doseisaccurateandwherefeasiblekepttoaminimum.•

Donotinjecttoxincloserthan1cmabovethecentraleyebrow.•

Usinga30-33gaugeneedle,injectadoseof0.1mLintoeachof5sites,2ineachcorrugator muscleand1intheprocerusmuscleforatotaldoseof20Units.Typicallytheinitialdosesofreconstituted BOTOX® Cosmetic induce chemical denervation of the injected muscles one to two days after injection, increasing in intensity during the first week.

HOW SUPPLIED

BOTOX® Cosmetic is supplied in a single use vial in the following sizes:

50Units:NDC0023-3919-50 100Units:NDC0023-9232-01

Vials of BOTOX® Cosmetic have a holographic film on the vial label that contains the name “Allergan”withinhorizontallinesofrainbowcolor.Inordertoseethehologram,rotatethevial backandforthbetweenyourfingersunderadesklamporfluorescentlightsource.(Note:theholographicfilmonthelabelisabsentinthedate/batcharea.)Ifyoudonotseethelinesof rainbowcolororthename“Allergan,”donotusetheproductandcontactAllerganforadditionalinformationat1-800-890-4345from7:00AMto3:00PMPacificTime.

Rx Only Single use vial.

Storage

Unopened vials of BOTOX® Cosmeticshouldbestoredinarefrigerator(2°to8°C)forupto 36monthsforthe100Unitvialorupto24monthsforthe50Unitvial.

Administer BOTOX® Cosmeticwithin24hoursofreconstitution;duringthisperiodreconstituted BOTOX® Cosmeticshouldbestoredinarefrigerator(2°to8°C).ReconstitutedBOTOX® Cosmetic should be clear, colorless and free of particulate matter.

Do not use after the expiration date on the vial. All vials, including expired vials, or equipment used with the drug should be disposed of carefully as is done with all medical waste.

Revised: 08/2009

©2010Allergan,Inc. ® mark owned by Allergan, Inc. U.S.Patents6,974,578;6,683,049and6,896,886

Manufacturedby:AllerganPharmaceuticalsIreland asubsidiaryof:Allergan,Inc.,2525DupontDr.,Irvine,CA92612

REFERENCE

1.WangYC,BurrDH,KorthalsGJ,SugiyamaH.Acutetoxicityofaminoglycosideantibioticsasan aidindetectingbotulism.ApplEnvironMicrobiol1984;48:951-955.

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MEDICATION GUIDEBOTOX®

BOTOX® Cosmetic(Boe-tox)(onabotulinumtoxinA)for Injection

Read the Medication Guide that comes with BOTOX or BOTOX Cosmetic before you start using it and each time it is given to you. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. You should share this information with your family members and caregivers.

What is the most important information I should know about BOTOX and BOTOX Cosmetic?

BOTOX and BOTOX Cosmetic may cause serious side effects that can be life threatening. Call your doctor or get medical help right away if you have any of these problems after treatment with BOTOX or BOTOX Cosmetic:

• Problems swallowing, speaking, or breathing. These problems can happen hours to weeks after an injection of BOTOX or BOTOX Cosmetic usually because the muscles that you use to breathe and swallow can become weak after the injection. Death can happen as a complication if you have severe problems with swallowing or breathing after treatment with BOTOX or BOTOX Cosmetic.

• Peoplewithcertainbreathingproblemsmayneedtousemusclesintheir neck to help them breathe. These patients may be at greater risk for serious breathing problems with BOTOX or BOTOX Cosmetic.

• Swallowingproblemsmaylastforseveralmonths.Peoplewhocannotswallow well may need a feeding tube to receive food and water. If swallowing problems are severe, food or liquids may go into your lungs.Peoplewhoalreadyhaveswallowingorbreathingproblemsbefore receiving BOTOX or BOTOX Cosmetic have the highest risk of getting these problems.

• Spread of toxin effects. In some cases, the effect of botulinum toxin may affect areas of the body away from the injection site and cause symptoms of a serious condition called botulism. The symptoms of botulism include:

• lossofstrengthandmuscleweaknessalloverthebody

• doublevision

• blurredvisionanddroopingeyelids

• hoarsenessorchangeorlossofvoice(dysphonia)

• troublesayingwordsclearly(dysarthria)

• lossofbladdercontrol

• troublebreathing

• troubleswallowing

These symptoms can happen hours to weeks after you receive an injection of BOTOX or BOTOX Cosmetic.

These problems could make it unsafe for you to drive a car or do other dangerousactivities.See“WhatshouldIavoidwhilereceivingBOTOX or BOTOX Cosmetic?”

There has not been a confirmed serious case of spread of toxin effect away from the injection site when BOTOX has been used at the recommended dose to treat severe underarm sweating, blepharospasm, or strabismus, or when BOTOX Cosmetic has been used at the recommended dose to treat frown lines.

What are BOTOX and BOTOX Cosmetic?

BOTOX is a prescription medicine that is injected into muscles and used:

• totreatincreasedmusclestiffnessinelbow,wrist,andfingermusclesin adults with upper limb spasticity.

• totreattheabnormalheadpositionandneckpainthathappenswithcervicaldystonia(CD)inadults.

• totreatcertaintypesofeyemuscleproblems(strabismus)orabnormalspasmoftheeyelids(blepharospasm)inpeople12yearsandolder.

BOTOX is also injected into the skin to treat the symptoms of severe underarmsweating(severeprimaryaxillaryhyperhidrosis)whenmedicinesusedontheskin(topical)donotworkwellenough.

BOTOX Cosmetic is a prescription medicine that is injected into muscles and used to improve the look of moderate to severe frown lines between theeyebrows(glabellarlines)inadultsyoungerthan65yearsofageforashortperiodoftime(temporary).

It is not known whether BOTOX is safe or effective in children younger than:

• 18yearsofagefortreatmentofspasticity

• 16yearsofagefortreatmentofcervicaldystonia

• 18yearsofagefortreatmentofhyperhidrosis

• 12yearsofagefortreatmentofstrabismusorblepharospasm

BOTOX Cosmetic is not recommended for use in children younger than18yearsofage.

It is not known whether BOTOX and BOTOX Cosmetic are safe or effective for other types of muscle spasms or for severe sweating anywhere other than your armpits.

Who should not take BOTOX or BOTOX Cosmetic?

Do not take BOTOX or BOTOX Cosmetic if you:

• areallergictoanyoftheingredientsinBOTOX or BOTOX Cosmetic. SeetheendofthisMedicationGuideforalistofingredientsinBOTOX and BOTOX Cosmetic.

• hadanallergicreactiontoanyotherbotulinumtoxinproductsuchasMyobloc® or Dysport ®

• haveaskininfectionattheplannedinjectionsite

What should I tell my doctor before taking BOTOX or BOTOX Cosmetic?

Tell your doctor about all your medical conditions, including if you have:

• adiseasethataffectsyourmusclesandnerves(suchasamyotrophiclateralsclerosis[ALSorLouGehrig’sdisease],myastheniagravisorLambert-Eatonsyndrome).See“Whatisthemostimportantinformation I should know about BOTOX and BOTOX Cosmetic?”

• allergiestoanybotulinumtoxinproduct

• hadanysideeffectfromanybotulinumtoxinproductinthepast

• abreathingproblem,suchasasthmaoremphysema

• swallowingproblems

• bleedingproblems

• planstohavesurgery

• hadsurgeryonyourface

• weaknessofyourforeheadmuscles,suchastroubleraising your eyebrows

• droopingeyelids

• anyotherchangeinthewayyourfacenormallylooks

• arepregnantorplantobecomepregnant.ItisnotknownifBOTOX or BOTOX Cosmetic can harm your unborn baby.

• arebreast-feedingorplantobreastfeed.ItisnotknownifBOTOX or BOTOX Cosmetic passes into breast milk.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal products. Using BOTOX or BOTOX Cosmetic with certain other medicines may cause serious side effects. Do not start any new medicines until you have told your doctor that you have received BOTOX or BOTOX Cosmetic in the past.

Especially tell your doctor if you:

• havereceivedanyotherbotulinumtoxinproductinthelast four months

• havereceivedinjectionsofbotulinumtoxin,suchasMyobloc® (rimabotulinumtoxinB)orDysport ®(abobotulinumtoxinA)inthepast.Besureyourdoctorknowsexactlywhichproductyoureceived.

• haverecentlyreceivedanantibioticbyinjection

• takemusclerelaxants

• takeanallergyorcoldmedicine

• takeasleepmedicine

Ask your doctor if you are not sure if your medicine is one that is listed above.

Know the medicines you take. Keep a list of your medicines with you to show your doctor and pharmacist each time you get a new medicine.

How should I take BOTOX or BOTOX Cosmetic?

•BOTOX or BOTOX Cosmetic is an injection that your doctor will give you.

•BOTOX is injected into your affected muscles or skin.

•BOTOX Cosmetic is injected into your affected muscles.

• YourdoctormaychangeyourdoseofBOTOX or BOTOX Cosmetic, until you and your doctor find the best dose for you.

What should I avoid while taking BOTOX or BOTOX Cosmetic?

BOTOX and BOTOX Cosmetic may cause loss of strength or general muscle weakness, or vision problems within hours to weeks of taking BOTOX and BOTOX Cosmetic. If this happens, do not drive a car, operate machinery, or do other dangerous activities.See“What is the most important information I should know about BOTOX and BOTOX Cosmetic?”

What are the possible side effects of BOTOX and BOTOX Cosmetic?

BOTOX and BOTOX Cosmetic can cause serious side effects.See “WhatisthemostimportantinformationIshouldknowaboutBOTOX and BOTOX Cosmetic?”

Other side effects of BOTOX and BOTOX Cosmetic include:

• drymouth

• discomfortorpainattheinjectionsite

• tiredness

• headache

• neckpain

• eyeproblems:doublevision,blurredvision,decreasedeyesight,drooping eyelids, swelling of your eyelids, and dry eyes.

• allergicreactions.SymptomsofanallergicreactiontoBOTOX or BOTOX Cosmetic may include: itching, rash, red itchy welts, wheezing, asthma symptoms, or dizziness or feeling faint. Tell your doctor or get medical help right away if you are wheezing or have asthma symptoms, or if you become dizzy or faint.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of BOTOX and BOTOX Cosmetic. For more information, ask your doctor or pharmacist.

Callyourdoctorformedicaladviceaboutsideeffects.YoumayreportsideeffectstoFDAat1-800-FDA-1088.

General information about BOTOX and BOTOX Cosmetic:

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

This Medication Guide summarizes the most important information about BOTOX and BOTOX Cosmetic. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about BOTOX and BOTOX Cosmetic that is written for healthcare professionals. For more information about BOTOX and BOTOX Cosmetic call Allergan at 1-800-433-8871orgotowww.botox.com.

What are the ingredients in BOTOX and BOTOX Cosmetic?

Active ingredient: botulinum toxin type A Inactive ingredients: human albumin and sodium chloride

Issued: 03/2010

ThisMedicationGuidehasbeenapprovedbytheU.S.FoodandDrugAdministration.

Manufacturedby:AllerganPharmaceuticalsIreland a subsidiary of: Allergan, Inc. 2525DupontDr. Irvine,CA92612

©2010Allergan,Inc. ® mark owned by Allergan, Inc. U.S.Patents6,974,578;6,683,049and6,896,886 Myobloc®isaregisteredtrademarkofSolsticeNeurosciences,Inc. Dysport ®isaregisteredtrademarkofIpsenBiopharmLimitedCompany.

72284US11BAPC47IU10

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