293Us08Bc02405 Understandtherapybro Spanish PDF

Comprenda su
Terapia con COUMADIN
Consulte las Indicaciones y la Información importante de seguridad en las

páginas 14-15 y “¿Cuál es la información más importante que debo
saber sobre COUMADIN?” para obtener información sobre el recuadro
de ADVERTENCIA sobre el riesgo de sangrado, que se encuentra en la
Guía del medicamento y la Información de prescripción completa al final de
este folleto.
COUMADIN ®
(Tabletas de warfarina sódica, USP) cristalina
ESTE FOLLETO CONTIENE EN EL INTERIOR ENCONTRARÁ...

INFORMACIÓN SOBRE UN Guía del medicamento
MEDICAMENTO DENOMINADO ¿Cuál es la información más importante que debo
COUMADIN conocer sobre COUMADIN?..........................................3
Lea este folleto, ya que responde muchas preguntas ¿Qué es COUMADIN?...................................................4
que puede tener sobre este medicamento. ¿Quiénes no deben tomar COUMADIN?.......................4
La primera mitad de este folleto es la Guía del ¿Qué debo informarle a mi proveedor de atención
medicamento. Es la misma Guía del medicamento de la salud antes de tomar COUMADIN?......................5
que viene con su receta de COUMADIN (warfarina ¿Cómo debo tomar COUMADIN?.................................5
sódica). Es importante que lo lea antes de comenzar
¿Qué debo evitar mientras tomo COUMADIN?............6
a tomar COUMADIN. Cuando resurta su receta de
COUMADIN, asegúrese de leer la Guía del medica- ¿Cuáles son los posibles efectos secundarios
mento que recibirá cada vez que resurta su receta. Es de COUMADIN?.................................................................. 6
posible que contenga nueva información. ¿Cómo debo almacenar COUMADIN?..........................7
La segunda mitad de este folleto, Más información Información general sobre COUMADIN........................7
sobre COUMADIN, contiene información adicional en Más información sobre COUMADIN (warfarina
formato de preguntas y respuestas para ayudarle a sódica)
beneficiarse de su tratamiento.
¿Cómo actúa COUMADIN?.......................................... 8
Este folleto no reemplaza la consulta con su provee- ¿Qué cantidad de COUMADIN debo tomar?................ 9
dor de atención de la salud acerca de su afección
médica o tratamiento. Usted y su proveedor de aten- ¿Por qué son tan importantes los análisis de sangre
ción de la salud deben hablar sobre COUMADIN regulares?.....................................................................9
cuando comience a tomarlo y en los chequeos regu- ¿Cuáles son algunas de las cosas que pueden afectar
lares. los resultados de mi PT/INR?......................................10
La información incluida en este folleto se ha desar- ¿Qué sucede si...?.......................................................12
rollado y obtenido a partir de más de 50 años de ¿Debo prestar atención a la cantidad de vitamina K que
experiencia con COUMADIN (warfarina sódica), la incluye mi dieta?.................................................................13
marca de warfarina sódica de Bristol-Myers Squibb. Indicaciones e Información importante de
Nuestra intención es que este material sirva de ayuda seguridad....................................................................14
para el manejo de los pacientes que usan Calendario de administración de la dosis del
COUMADIN. paciente.......................................................................16
Consulte las Indicaciones y la Información importante de seguridad en las páginas 14-15 y “¿Cuál es la información más importante que debo saber sobre
COUMADIN?” para obtener información sobre el recuadro de ADVERTENCIA sobre el riesgo de sangrado, que se encuentra en la Guía del medicamento y la
Información de prescripción completa al final de este folleto. 2
COUMADIN ®
(Tabletas de warfarina sódica, USP) cristalina Guía del medicamento
¿CUÁL ES LA INFORMACIÓN MÁS • Llame a su proveedor de atención de la

IMPORTANTE QUE DEBO CONOCER salud de inmediato si experimenta alguno
SOBRE COUMADIN (warfarina sódica)? de los siguientes signos o síntomas de
problemas de sangrado:
n Tome su COUMADIN exactamente como se le
– dolor, hinchazón o molestias
indique, a fin de reducir la probabilidad de que
– dolores de cabeza, mareos
se formen coágulos de sangre en el cuerpo. o debilidad
(Consulte “¿Qué es COUMADIN?” en la página 4) – formación inusual de
n COUMADIN es sumamente importante para su hematomas (hematomas
salud, pero puede provocar problemas de san- que aparecen sin causa
grado graves y que representen un riesgo para conocida o aumentan de
la vida. A fin de beneficiarse del uso de tamaño)
COUMADIN y también disminuir su probabilidad de – sangrado nasal
experimentar problemas de sangrado, debe: – sangrado de las encías
– sangrado debido a cortes que tarda mucho en
• Realizarse análisis de sangre en forma detenerse
regular para vigilar su respuesta a – sangrado menstrual o vaginal más abundante
COUMADIN. Este análisis de sangre se de lo normal
denomina prueba de Tiempo de Protrombina – orina de color rosado o marrón
(Prothrombin Time, PT)/Relación Normalizada – deposiciones de color negro o rojo
Internacional (International Normalized Ratio, – tos con sangre
INR). La prueba de PT/INR examina la velocidad – vómitos con sangre o material con aspecto de
de coagulación de su sangre. Su proveedor de granos de café
atención de la salud decidirá cuáles son los n Muchos otros medicamentos, incluidos los
mejores valores de PT/INR para usted. Su dosis medicamentos recetados y no recetados, las
de COUMADIN (warfarina vitaminas y los suplementos a base de
sódica) se ajustará para hierbas, pueden interactuar con
mantener su PT/INR COUMADIN (warfarina sódica) y:
en un rango • afectar la dosis que usted necesita o
objetivo • aumentar los efectos secundarios de
para usted. COUMADIN.
Guía del medicamento y la Información de prescripción completa al final
de este folleto.
3
COUMADIN ®
Informe a su proveedor de atención de la salud ¿QUÉ ES COUMADIN (warfarina sódica)?

sobre todos los medicamentos, vitaminas y
COUMADIN es un medicamento anticoagulante. Se utiliza
suplementos a base de hierbas que esté tomando.
para reducir la probabilidad de que se formen coágulos de
No interrumpa medicamentos ni tome nada nuevo,
sangre en el cuerpo. Los coágulos de sangre pueden producir
a menos que haya hablado con su proveedor de
un accidente cerebrovascular, ataque cardíaco u otras
atención de la salud al respecto. Tenga una lista de
afecciones graves, como coágulos de sangre en las piernas o
sus medicamentos con usted en todo momento
en los pulmones.
para mostrársela a su proveedor de atención de la
salud y a su farmacéutico.
¿QUIÉNES NO DEBEN TOMAR COUMADIN?
n No tome otros medicamentos que contengan
warfarina. La warfarina es el principio activo de No tome COUMADIN si:
COUMADIN (warfarina sódica). n sus probabilidades de experimentar problemas de
sangrado son mayores que el posible beneficio del
n Algunos alimentos pueden interactuar con tratamiento. Su proveedor de atención de la salud
COUMADIN y afectar su tratamiento y su dosis. decidirá si COUMADIN es adecuado para usted. Hable con
• Haga una dieta balanceada normal. Hable con su proveedor de atención de la salud sobre todas sus
su médico antes de hacer cualquier cambio en su afecciones de salud.
dieta. No coma grandes cantidades de
vegetales de hojas verdes. Los vegetales de n si está embarazada o planea quedar embarazada.
hojas verdes contienen vitamina K. Determinados COUMADIN (warfarina sódica) puede provocar la muerte
aceites vegetales también contienen grandes can- o anomalías congénitas en bebés no nacidos. Utilice un
tidades de vitamina K. Consumir demasiada vitam- método anticonceptivo efectivo si puede quedar
ina K puede reducir el efecto de COUMADIN. embarazada.
• Evite tomar jugo de arándano rojo o comer n es alérgico a la warfarina o a cualquier otro
productos con arándanos rojos. ingrediente de COUMADIN.
• Evite tomar alcohol.
n Siempre informe a sus proveedores de atención
de la salud que está tomando COUMADIN
(warfarina sódica).
n Use o lleve con usted algo que indique que está
tomando COUMADIN.
COUMADIN ®
¿QUÉ DEBO INFORMARLE A MI Informe a su proveedor de atención de la salud

PROVEEDOR DE ATENCIÓN DE LA todos los medicamentos que esté tomando, tanto
SALUD ANTES DE TOMAR COUMADIN? recetados como no recetados, vitaminas y
suplementos a base de hierbas. (Consulte “¿Cuál
Informe a su proveedor de atención de la salud es la información más importante que debo saber
acerca de todas sus afecciones de salud, entre sobre COUMADIN?” en las páginas 3-4)
otras, si usted:
• tiene problemas de sangrado.
¿CÓMO DEBO TOMAR COUMADIN?
• se cae a menudo.
• tiene problemas hepáticos n Tome COUMADIN (warfarina sódica)
o renales. exactamente como se le indique. Su proveedor
• tiene presión arterial alta. de atención de la salud ajustará su dosis
periódicamente en función de su respuesta a
• tiene un problema
COUMADIN.
cardíaco denominado
insuficiencia n Debe realizarse análisis de sangre regulares y
cardíaca congestiva. realizar visitas a su proveedor de atención de
• tiene diabetes. la salud, a fin de monitorear su afección.
• toma alcohol o tiene n Tome COUMADIN a la misma
problemas de abuso de alcohol. El alcohol hora todos los días. Puede
puede afectar su dosis de COUMADIN y debe tomar COUMADIN con alimentos
evitarse. o con el estómago vacío.
• está embarazada o planea quedar
embarazada. (Consulte “¿Quiénes no deben
tomar COUMADIN (warfarina sódica)?” en la
página 4).
• está amamantando. COUMADIN puede aumen-
tar el sangrado en su bebé. Hable con su médico
sobre la mejor forma de alimentar a su bebé. Si
decide amamantar mientras está tomando
COUMADIN (warfarina sódica), tanto usted como
su bebé deben ser monitoreados atentamente
por si experimentaran problemas de sangrado.
COUMADIN ®
n Si olvida tomar una dosis de COUMADIN, llame n No cambie de peso realizando una dieta, sin
a su proveedor de atención de la salud. Tome la consultar primero a su proveedor de atención de
dosis lo antes posible el mismo día. No tome una la salud.
dosis doble de COUMADIN el día siguiente para
n Evite tomar alcohol.
compensar una dosis que olvidó tomar.
n No haga ninguna actividad o deporte que
n Llame a su proveedor de
puedan causar una lesión grave.
atención de la salud de
inmediato si toma una cantidad
excesiva de COUMADIN. ¿CUÁLES SON LOS POSIBLES EFECTOS
SECUNDARIOS DE COUMADIN
n Llame a su proveedor de atención (warfarina sódica)?
de la salud si tiene diarrea, una
infección o fiebre. n COUMADIN es sumamente importante para su
salud, pero puede provocar problemas de sangrado
n Informe a su proveedor de atención de la graves y que representen un riesgo para la vida.
salud sobre cualquier cirugía, o procedimiento (Consulte “¿Cuál es la información más
médico u odontológico que tenga previstos. Es importante que debo saber sobre
posible que se deba interrumpir la administración COUMADIN?” en las páginas 3-4)
de COUMADIN (warfarina sódica) durante un
período breve o que se deba ajustar su dosis. n Los efectos secundarios graves de COUMADIN
también incluyen:
n Llame a su proveedor de atención de la salud
de inmediato si sufre una caída o se lesiona, • muerte del tejido cutáneo (necrosis cutánea
especialmente si se golpea la cabeza. Es posible o gangrena): Esto puede ocurrir poco después
que su proveedor de atención de la salud deba de comenzar la administración de COUMADIN.
revisarle. Esto se produce por la formación de coágulos de
sangre que bloquean el flujo sanguíneo a un
¿QUÉ DEBO EVITAR MIENTRAS TOMO área del cuerpo. Llame a su proveedor de aten-
COUMADIN (warfarina sódica)? ción de la salud de inmediato si experimenta
n No comience a tomar, interrumpa ni cambie ningún dolor o un cambio de temperatura o color en
medicamento sin hablar con su proveedor de alguna parte del cuerpo. Es posible que necesite
atención de la salud. atención médica inmediata para evitar la muerte
o la pérdida (amputación) de la parte del cuerpo
n No haga ningún cambio en su dieta, como comer afectada.
grandes cantidades de vegetales de hojas verdes.
COUMADIN ®
• “síndrome de los dedos del pie morados”: ¿CÓMO DEBO ALMACENAR

Llame a su proveedor de atención de la salud de COUMADIN?
inmediato si experimenta dolor en los dedos del
pie y estos tienen un color morado u oscuro. n Almacene COUMADIN a temperatura ambiente de
entre 59° y 86 °F. Protéjalo de la luz.
Otros efectos secundarios con COUMADIN
n Mantenga COUMADIN (warfarina sódica) y
incluyen reacciones alérgicas, problemas hepáticos,
todos los medicamentos fuera del alcance de
presión arterial baja, hinchazón, recuentos bajos de
los niños.
glóbulos rojos, palidez, fiebre y erupción. Llame a su
proveedor de atención de la salud si experimenta INFORMACIÓN GENERAL SOBRE
cualquier efecto secundario que le resulte molesto. COUMADIN
Estos no son todos los efectos secundarios de A veces, los medicamentos se recetan para fines que
COUMADIN (warfarina sódica). Para obtener más no se mencionan en la Guía del medicamento. No
información, consulte a su proveedor de atención de utilice COUMADIN para una afección para la que no
la salud o a su farmacéutico. fuera recetado. No suministre COUMADIN a otras
personas, incluso si tienen la misma afección. Hacer
esto puede causarles daño.
Esta Guía del medicamento resume la información más
importante sobre COUMADIN. Si desea obtener más
información, hable con su proveedor de atención de la
salud. Puede pedirles a su proveedor de atención de la
salud o a su farmacéutico información sobre
COUMADIN (warfarina sódica) escrita para
profesionales de la salud.
Si desea obtener más información, llame al
1-800-321-1335
Continúe leyendo este folleto para obtener más

información sobre COUMADIN (warfarina sódica).
Guía del medicamento y la Información de prescripción completa al final 7
de este folleto.
COUMADIN ®
(Tabletas de warfarina sódica, USP) cristalina Más información sobre COUMADIN
P ¿CÓMO ACTÚA COUMADIN?

R Su hígado produce factores de coagulación
que contribuyen a la coagulación de la sangre
MÁS y evitan el sangrado. Sin embargo, algunos
coágulos de sangre pueden causar problemas
INFORMACIÓN médicos graves. COUMADIN (warfarina sódica)
bloquea la formación de factores de
SOBRE coagulación en el hígado que dependen de la
vitamina K; en consecuencia, evitan la forma-
COUMADIN (Tabletas de warfarina sódica, USP) cristalina ción de coágulos de sangre.
Lea las siguientes Preguntas y respuestas para

obtener información útil sobre la terapia con
COUMADIN (warfarina sódica).
COUMADIN ®
P ¿QUÉ CANTIDAD DE COUMADIN P ¿Con qué frecuencia debo realizarme análi-

DEBO TOMAR? sis de sangre?
R Su proveedor de atención de la salud
R Su médico determina qué cantidad de determinará con qué
COUMADIN necesita (la dosis y el
cronograma) realizándole análisis de sangre frecuencia deberá realizarse
regulares. Su dosis puede cambiar con el análisis de sangre. Es posible
tiempo, en función de los resultados de estos que su dosis de
análisis de sangre. Independientemente de COUMADIN (warfarina sódica)
qué dosis de COUMADIN esté tomando, sea ajustada cuidadosamente
asegúrese de siempre tomar la dosis que su (aumentada o disminuida) para
proveedor de atención de la salud le indique, mantener su nivel de PT/INR adecuado para su
y asegúrese de siempre tomar la dosis afección. Generalmente, los resultados están
indicada todos los días. disponibles el mismo día. Cuando obtenga estos
resultados, pregunte a su proveedor de atención
¿POR QUÉ SON TAN IMPORTANTES de la salud si deberá cambiar su dosis de
LOS ANÁLISIS DE SANGRE COUMADIN.
REGULARES?
Cuando se realice un análisis de sangre,
P ¿Qué es este análisis de sangre y para qué se
utiliza? asegúrese de:
El análisis de sangre se denomina prueba de • Asistir al laboratorio en la fecha y a la hora
R PT/INR. PT/INR significa Tiempo de Protrombina y
programadas.
Relación Normalizada Internacional. Estos
• Asistir al mismo laboratorio todas las veces,
análisis se utilizan para determinar la velocidad
dado que los resultados que obtenga pueden
de coagulación de la sangre y si está recibiendo
diferir de un laboratorio a otro.
la cantidad adecuada de COUMADIN. Se extrae
solamente una pequeña cantidad de sangre • Consultar a su proveedor de atención de la
por vez. salud qué dosis debe tomar ese día y cada día
hasta el siguiente análisis de sangre.
El resultado le indica a su proveedor de atención
de la salud si COUMADIN (warfarina sódica) le • Si se cambia su dosis, registrar la nueva dosis
está ayudando a mantener el nivel de PT/INR en su calendario o en un lugar que pueda ver
adecuado para su afección. Su proveedor de con facilidad.
atención de la salud le indicará qué nivel de
PT/INR es adecuado para usted.
COUMADIN ®
P ¿CUÁLES SON ALGUNAS DE LAS sobre esta información y sus medicamentos específicos.
Esto es muy importante ya que su proveedor de
COSAS QUE PUEDEN AFECTAR LOS atención de la salud puede necesitar ajustar la dosis de
RESULTADOS DE MI PT/INR? estos medicamentos, así como de COUMADIN.
R Muchos medicamentos de venta libre o No tome otros fármacos que contengan
recetados, vitaminas y suplementos a base de warfarina. La warfarina es el principio activo de
hierbas, determinados alimentos y determinadas COUMADIN. Si toma otro medicamento que contenga
afecciones médicas pueden interactuar con warfarina mientras está tomando
COUMADIN (warfarina sódica) y afectar su COUMADIN (warfarina sódica), es posible que
PT/INR. (Consulte “¿Cuál es la información experimente una sobredosis de warfarina. Recuerde
más importante que debo saber sobre que la tabletas de COUMADIN tienen un aspecto
COUMADIN?” de las páginas 3-4). diferente del de otras tabletas de warfarina y tienen
Para obtener una lista de las posibles inscripciones diferentes; por lo tanto, es posible tomar
interacciones con COUMADIN, consulte la ambas por error.
Información de prescripción completa (escrita
para proveedores de atención de la salud).
Asimismo, debe analizar sus medicamentos,
suplementos a base de hierbas, dieta y
afecciones médicas específicas con su proveedor
de atención de la salud.
Medicamentos recetados
Muchos medicamentos diferentes, usados para
tratar muchas afecciones diferentes, pueden
afectar la respuesta de su cuerpo a COUMADIN.
Pueden aumentar o disminuir su nivel de
PT/INR.
Algunos medicamentos recetados comunes
pueden interactuar con
COUMADIN (warfarina sódica). Consulte la
Información de prescripción completa (escrita
para proveedores de atención de la salud), y
hable con su proveedor de atención de la salud
COUMADIN ®
Medicamentos no recetados Vitaminas

Muchos medicamentos no recetados o de venta libre, Las vitaminas también pueden afectar la forma en la
incluida la aspirina y otros analgésicos, pueden afectar que responde su cuerpo a COUMADIN y el cambio en
la respuesta de su cuerpo a COUMADIN (warfarina su nivel de PT/INR. Consumir demasiada vitamina K, en
sódica). Asegúrese de analizar sus medicamentos no particular, puede disminuir el efecto anticoagulante de
recetados específicos con su proveedor de atención de COUMADIN. Debe informar a su proveedor de atención
la salud. de la salud si está tomando cualquier suplemento
Medicamentos a base de hierbas vitamínico, incluido un suplemento de vitamina K.
Muchos medicamentos diferentes a base de hierbas o P ¿Qué otros procedimientos y afecciones
productos a base de plantas pueden afectar la médicos debo informar a mi proveedor de
respuesta de su cuerpo a COUMADIN. Pueden aumen- atención de la salud?
tar o disminuir su nivel de PT/INR.
R Antes de comenzar a tomar
Para obtener una lista completa de estos medicamen- COUMADIN (warfarina sódica), informe a su
tos a base de hierbas, consulte la Información de proveedor de atención de la salud sobre todas
prescripción completa (escrita para los proveedores de sus afecciones de salud. Si prevé someterse a
atención de la salud), y analícelos con su proveedor de una cirugía, incluida cirugía odontológica,
atención de la salud. Muchos medicamentos a base de informe a su proveedor de atención de la salud
hierbas tienen varios nombres comunes y científicos. que realizará el procedimiento que está
Asimismo, su potencia (o concentración) puede variar tomando COUMADIN. Es posible que su
de una marca a otra. proveedor de atención de la salud le indique
que deje de tomar COUMADIN antes del
procedimiento. Asimismo, es posible que deba
realizarse un análisis de sangre antes de que se
le realice el procedimiento. Para obtener
información sobre el control de su PT/INR,
consulte “¿Por qué los análisis de sangre
regulares son tan importantes?” de la
página 9.
Ginkgo Biloba Ginseng
COUMADIN ®
¿QUÉ SUCEDE SI...? P Qué sucede si me corto o comienzo a

P Dejo de tomar COUMADIN. ¿Durante cuánto sangrar?
tiempo continuarán los efectos
anticoagulantes de R Dado que COUMADIN (warfarina sódica) afecta
COUMADIN (warfarina sódica)? la coagulación, es posible que el sangrado tarde
más en detenerse si se corta o se lesiona.
R Si su proveedor de atención de la salud
interrumpe su terapia con COUMADIN, es posible n Si el corte es pequeño, aplique presión constante
que el efecto anticoagulante dure, aproximada- hasta que el sangrado se detenga. Esto puede
mente, de 2 a 5 días más. tardar hasta 10 minutos. Si el sangrado no se
detiene, continúe aplicando presión y busque a
P Quiero viajar. ¿Debo hacer algo en especial? tención médica.
R Hable con su proveedor de atención de la salud n Si el corte es grande, aplique presión constante y
primero. Es posible que le pida que se realice busque ayuda de inmediato dirigiéndose a la sala
una prueba de PT/INR antes de su viaje o haga de emergencias o llamando para obtener ayuda
los arreglos para que pueda realizarse el análisis médica.
mientras está de viaje. A fin de evitar cortarse cuando se afeite:
Debe tener en cuenta dos cosas: n En lugar de utilizar una afeitadora con hojas de
n Al viajar, tenga en cuenta que debe tomar su afeitar, utilice una afeitadora eléctrica o crema
COUMADIN a la misma hora todos los días. Es muy depilatoria.
importante mantener un cantidad uniforme de A fin de reducir el sangrado de las encías al cepillarse
vitamina K en su dieta. Evite los cambios drásticos los dientes:
en sus hábitos de alimentación.
n Utilice un cepillo de dientes suave, y cepíllese los
n Asegúrese de llevar suficiente dientes y utilice el hilo dental con cuidado.
COUMADIN (warfarina sódica) para todo su viaje.
Asimismo, debe llevar sus medicamentos con usted
en todo momento; no los coloque en el equipaje
que despachará ni los deje en el auto.
COUMADIN ®
¿DEBO PRESTAR ATENCIÓN A LA P ¿Cómo sé cuánta vitamina K contienen los

CANTIDAD DE VITAMINA K QUE alimentos que consumo?
INCLUYE MI DIETA?
R Muchos alimentos contienen bajas cantidades de
P ¿Los alimentos que consumo pueden vitamina K, incluidas bebidas,
afectar mi respuesta a
COUMADIN (warfarina sódica)? productos lácteos, pan, cereales
y carne. Los vegetales de
R Los alimentos que contienen vitamina K pueden hojas verdes, como la col
interferir en los efectos anticoagulantes de rizada, el perejil, las
COUMADIN. Es muy importante mantener una espinacas y las hojas de
cantidad uniforme de vitamina K en su dieta. nabo, así como el brócoli y
Evite los cambios drásticos en sus hábitos de ali- las coles de Bruselas, contiene
mentación. Por ejemplo, la ingesta de grandes grandes cantidades de vitamina
cantidades de vegetales de hojas verdes, cuando K. Hable con su proveedor de atención de la
normalmente no lo hace, puede aumentar la salud si tiene alguna pregunta sobre el contenido
cantidad de vitamina K en su organismo. de vitamina K de sus alimentos.
P ¿Debo mantener la misma dieta general P ¿Cuánto alcohol puedo tomar?
todos los días?
R No realice grandes cambios en su dieta sin hablar R Tomar alcohol puede afectar su PT/INR.
con su proveedor de atención de la salud primero. Asegúrese de hablar con su proveedor de
Si cambia sus hábitos de alimentación, es posible atención de la salud sobre la cantidad de alcohol
que su proveedor de atención de la salud le que consume.
realice un análisis de sangre con más
frecuencia para determinar si su
COUMADIN (warfarina sódica)
está actuando de
manera eficaz.

Guía del medicamento y la Información de prescripción completa al final
de este folleto.
13
COUMADIN ®
INDICACIONES: • No tome COUMADIN si está embarazada o planea quedar
• COUMADIN (warfarina sódica) se usa para ayudar a prevenir
®
embarazada. COUMADIN puede provocar la muerte o
y tratar los coágulos de sangre en las piernas, los pulmones y anomalías congénitas en bebés no nacidos. Utilice un método
los coágulos asociados con reemplazos de válvulas cardíacas o anticonceptivo efectivo si puede quedar embarazada.
los latidos cardíacos irregulares y rápidos, una afección • Hable con su proveedor de atención de la salud antes de
denominada fibrilación auricular. amamantar mientras tome COUMADIN (warfarina sódica).
• Si usted ha tenido un ataque cardíaco, COUMADIN puede • Informe a su proveedor de atención de la salud sobre todas las
usarse para reducir el riesgo de muerte, otro ataque cardíaco, afecciones médicas que pueda tener, incluidas las cirugías o
un accidente cerebrovascular y el desplazamiento de coágulos procedimientos médicos u odontológicos recientes o
de sangre a otras partes del cuerpo. planificados.
INFORMACIÓN IMPORTANTE DE SEGURIDAD: • Los pacientes sin supervisión que tengan una disminución de
la función mental debido al envejecimiento o a una enfer-
• COUMADIN puede provocar sangrado serio y que puede representar
un riesgo para la vida. Es más probable que el sangrado se medad mental, y los pacientes con alcoholismo o con un
produzca cuando comienza a tomar COUMADIN y con una dosis mayor riesgo de sangrado no deben tomar COUMADIN (war-
más alta. farina sódica).
• Los factores que pueden aumentar su riesgo de sangrado durante la
terapia con COUMADIN (warfarina sódica) incluyen: tener 65 años o
• La muerte del tejido cutáneo (necrosis cutánea o gangrena) es
más; Relaciones Normalizadas Internacionales (International un efecto secundario grave de COUMADIN. Esto se produce
Normalized Ratio, INR) mayores que 4; INR altamente variables; por la formación de coágulos de sangre que bloquean el flujo
antecedentes de sangrado que involucran el estómago o el sanguíneo a un área del cuerpo. Llame a su proveedor de
intestino; presión arterial alta; determinadas enfermedades del
cerebro, del corazón o de los riñones; anemia; cáncer; lesión física; atención de la salud de inmediato si experimenta dolor o un
tomar otros fármacos, y duración prolongada de la terapia. cambio de temperatura o color en alguna parte del cuerpo. Es
• La prueba de Tiempo de Protrombina (Prothrombin Time, PT)/INR posible que necesite atención médica inmediata para evitar la
comprueba la velocidad de coagulación de su sangre. Su
proveedor de atención de la salud decidirá cuáles son los mejores
muerte o la pérdida (amputación) de la parte del cuerpo
valores de PT/INR para usted. Su dosis de COUMADIN se ajustará afectada.
para mantener su PT/INR en un rango objetivo para usted. • Llame a su proveedor de atención de la salud de inmediato si
• Informe a su proveedor de atención de la salud de inmediato si experimenta dolor en los dedos del pie y estos tienen un color
experimenta signos o síntomas de problemas de sangrado, tales
como los siguientes: dolor, hinchazón o molestias, dolor de cabeza, morado u oscuro. Es posible que esté experimentando una
mareos o debilidad, formación inusual de hematomas, sangrado afección grave denominada síndrome de los dedos del pie
nasal, sangrado de las encías, sangrado debido a cortes que tarda morados.
mucho en detenerse, flujo menstrual o hemorragia vaginal más
abundante de lo normal, orina de color marrón o rosado,
deposiciones de color negro o rojo, tos con sangre, o vómitos con (CONTINUACIÓN)
sangre o material con aspecto de borra del café.
COUMADIN ®
INFORMACIÓN IMPORTANTE DE SEGURIDAD

(CONTINUACIÓN):
• Muchos factores aislados o en combinación, tales como
cambios en la dieta y medicamentos, incluidos los
suplementos a base de hierbas, pueden afectar su
respuesta a COUMADIN (warfarina sódica). Informe a su
proveedor de atención de la salud sobre su dieta, todos los
medicamentos recetados y de venta libre, las vitaminas y
los productos a base de hierbas que esté tomando o que
planee tomar. Hable con su proveedor de atención de la
salud antes de comenzar a consumir cualquiera de estos
productos, o de cambiar o interrumpir la administración de
estos productos. Muchos fármacos, incluida la aspirina u
otros analgésicos, pueden interactuar con COUMADIN.
• Haga una dieta balanceada normal. No haga cambios en
su dieta, tales como ingerir cantidades grandes de
vegetales de hojas verdes, que contienen vitamina K, sin
hablar antes con su proveedor de atención de la salud.
• Evite consumir alcohol, jugo de arándano rojo y productos
con arándanos rojos mientras tome COUMADIN.
• Informe a su médico si tiene alguna enfermedad como
diarrea, infección o fiebre.
• Tenga en cuenta que COUMADIN y las tabletas de
warfarina genéricas representan el mismo medicamento y
no deben tomarse juntos, dado que pueden provocar
sobredosis.
• Si usted toma una cantidad excesiva de COUMADIN u
olvida tomar una dosis, llame a su proveedor de atención
de la salud. Tome la dosis que olvidó tomar lo antes
posible el mismo día. No tome una dosis doble de
COUMADIN (warfarina sódica) el día siguiente para
compensar una dosis que olvidó tomar.
• Si tiene alguna otra pregunta sobre COUMADIN y su
afección, comuníquese con su proveedor de atención de
la salud.
COUMADIN ®
CALENDARIO DE ADMINISTRACIÓN DE LA DOSIS DEL PACIENTE

Mes:
Dosis diaria de Hora de
Fecha/día COUMADIN® (warfarina sódica) toma de la dosis PT/INR Próxima cita
NOTAS:
Mes:
NOTAS:
COUMADIN ®

Mes:
NOTAS:
Mes:
NOTAS:
COUMADIN ®

Mes:
NOTAS:
Mes:
NOTAS:
Consulte las Indicaciones y la Información importante de seguridad en las páginas 14-15 y
“¿Cuál es la información más importante que debo saber sobre COUMADIN?” para
obtener información sobre el recuadro de ADVERTENCIA sobre el riesgo de sangrado,
que se encuentra en la Guía del medicamento y la Información de prescripción completa al
18
final de este folleto. ©2009 Bristol-Myers Squibb, Princeton, NJ 08543 293US08BC02405 04/09
Anticoagulant Rx only Table 1: Relationship Between S-Warfarin Clearance and CYP2C9 Genotype in Caucasian Patients
COUMADIN® TABLETS CYP2C9 Genotype N S-Warfarin Clearance/Lean Body Weight

(mL/min/kg)
(Warfarin Sodium Tablets, USP) Crystalline Mean (SD)a
*1/*1 118 0.065 (0.025)b
COUMADIN® FOR INJECTION *1/*2 or *1/*3 59 0.041 (0.021)b
(Warfarin Sodium for Injection, USP) *2/*2, *2/*3, or *3/*3 11 0.020 (0.011)b
Total 188
WARNING: BLEEDING RISK a SD=Standard deviation.
b p<0.001. Pairwise comparisons indicated significant differences among all 3 genotypes.
Warfarin sodium can cause major or fatal bleeding. Bleeding is more likely to occur during the starting period and
with a higher dose (resulting in a higher INR). Risk factors for bleeding include high intensity of anticoagulation Other CYP2C9 alleles associated with reduced enzymatic activity occur at lower frequencies, including *5, *6, and
(INR >4.0), age ≥65, highly variable INRs, history of gastrointestinal bleeding, hypertension, cerebrovascular *11 alleles in populations of African ancestry and *5, *9, and *11 alleles in Caucasians.
disease, serious heart disease, anemia, malignancy, trauma, renal insufficiency, concomitant drugs (see
Excretion: The terminal half-life of warfarin after a single dose is approximately 1 week; however, the effective half-
PRECAUTIONS), and long duration of warfarin therapy. Regular monitoring of INR should be performed on all
life ranges from 20 to 60 hours, with a mean of about 40 hours. The clearance of R-warfarin is generally half that
treated patients. Those at high risk of bleeding may benefit from more frequent INR monitoring, careful dose of S-warfarin, thus as the volumes of distribution are similar, the half-life of R-warfarin is longer than that of
adjustment to desired INR, and a shorter duration of therapy. Patients should be instructed about prevention S-warfarin. The half-life of R-warfarin ranges from 37 to 89 hours, while that of S-warfarin ranges from 21 to
measures to minimize risk of bleeding and to report immediately to physicians signs and symptoms of bleeding 43 hours. Studies with radiolabeled drug have demonstrated that up to 92% of the orally administered dose
(see PRECAUTIONS: Information for Patients). is recovered in urine. Very little warfarin is excreted unchanged in urine. Urinary excretion is in the form of
metabolites.
DESCRIPTION
Pharmacogenomics: A meta-analysis of 9 qualified studies including 2775 patients (99% Caucasian) was
COUMADIN (crystalline warfarin sodium) is an anticoagulant which acts by inhibiting vitamin K-dependent
performed to examine the clinical outcomes associated with CYP2C9 gene variants in warfarin-treated patients.3
coagulation factors. Chemically, it is 3-(␣-acetonylbenzyl)-4-hydroxycoumarin and is a racemic mixture of the
In this meta-analysis, 3 studies assessed bleeding risks and 8 studies assessed daily dose requirements. The
R- and S-enantiomers. Crystalline warfarin sodium is an isopropanol clathrate. The crystallization of warfarin
analysis suggested an increased bleeding risk for patients carrying either the CYP2C9*2 or CYP2C9*3 alleles.
sodium virtually eliminates trace impurities present in amorphous warfarin. Its empirical formula is C19 H15 NaO4,
Patients carrying at least one copy of the CYP2C9*2 allele required a mean daily warfarin dose that was 17% less
and its structural formula may be represented by the following:
than the mean daily dose for patients homozygous for the CYP2C9*1 allele. For patients carrying at least one
O copy of the CYP2C9*3 allele, the mean daily warfarin dose was 37% less than the mean daily dose for patients
O homozygous for the CYP2C9*1 allele.
In an observational study, the risk of achieving INR >3 during the first 3 weeks of warfarin therapy was determined
H in 219 Swedish patients retrospectively grouped by CYP2C9 genotype. The relative risk of overanticoagulation as
measured by INR >3 during the first 2 weeks of therapy was approximately doubled for those patients classified
C
as *2 or *3 compared to patients who were homozygous for the *1 allele.4
ONa CH2COCH3
Warfarin reduces the regeneration of vitamin K from vitamin K epoxide in the vitamin K cycle, through inhibition of
vitamin K epoxide reductase (VKOR), a multiprotein enzyme complex. Certain single nucleotide polymorphisms in
Crystalline warfarin sodium occurs as a white, odorless, crystalline powder, is discolored by light and is very the VKORC1 gene (especially the –1639G>A allele) have been associated with lower dose requirements for
soluble in water; freely soluble in alcohol; very slightly soluble in chloroform and in ether. warfarin. In 201 Caucasian patients treated with stable warfarin doses, genetic variations in the VKORC1 gene were
associated with lower warfarin doses. In this study, about 30% of the variance in warfarin dose could be attributed
COUMADIN Tablets for oral use also contain: to variations in the VKORC1 gene alone; about 40% of the variance in warfarin dose could be attributed to variations
All strengths: Lactose, starch and magnesium stearate in VKORC1 and CYP2C9 genes combined.5 About 55% of the variability in warfarin dose could be explained by the
1 mg: D&C Red No. 6 Barium Lake combination of VKORC1 and CYP2C9 genotypes, age, height, body weight, interacting drugs, and indication for
2 mg: FD&C Blue No. 2 Aluminum Lake and FD&C Red No. 40 Aluminum Lake warfarin therapy in Caucasian patients.5 Similar observations have been reported in Asian patients.6,7
2-1/2 mg: D&C Yellow No. 10 Aluminum Lake and FD&C Blue No. 1 Aluminum Lake Elderly: Patients 60 years or older appear to exhibit greater than expected PT/INR response to the anticoagulant
3 mg: FD&C Yellow No. 6 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake and FD&C effects of warfarin. The cause of the increased sensitivity to the anticoagulant effects of warfarin in this age group
Red No. 40 Aluminum Lake is unknown. This increased anticoagulant effect from warfarin may be due to a combination of pharmacokinetic
4 mg: FD&C Blue No. 1 Aluminum Lake and pharmacodynamic factors. Racemic warfarin clearance may be unchanged or reduced with increasing age.
5 mg: FD&C Yellow No. 6 Aluminum Lake Limited information suggests there is no difference in the clearance of S-warfarin in the elderly versus young
6 mg: FD&C Yellow No. 6 Aluminum Lake and FD&C Blue No. 1 Aluminum Lake subjects. However, there may be a slight decrease in the clearance of R-warfarin in the elderly as compared to the
7-1/2 mg: D&C Yellow No. 10 Aluminum Lake and FD&C Yellow No. 6 Aluminum Lake young. Therefore, as patient age increases, a lower dose of warfarin is usually required to produce a therapeutic
10 mg: Dye Free level of anticoagulation.
COUMADIN for Injection is supplied as a sterile, lyophilized powder, which, after reconstitution with 2.7 mL sterile Asians: Asian patients may require lower initiation and maintenance doses of warfarin. One non-controlled study
Water for Injection, contains: conducted in 151 Chinese outpatients reported a mean daily warfarin requirement of 3.3±1.4 mg to achieve an INR
Warfarin Sodium 2 mg/mL of 2 to 2.5. These patients were stabilized on warfarin for various indications. Patient age was the most important
Sodium Phosphate, Dibasic, Heptahydrate 4.98 mg/mL determinant of warfarin requirement in Chinese patients with a progressively lower warfarin requirement with
Sodium Phosphate, Monobasic, Monohydrate 0.194 mg/mL increasing age.
Sodium Chloride 0.1 mg/mL Renal Dysfunction: Renal clearance is considered to be a minor determinant of anticoagulant response to warfarin.
Mannitol 38.0 mg/mL No dosage adjustment is necessary for patients with renal failure.
Sodium Hydroxide, as needed for pH adjustment to 8.1 to 8.3
Hepatic Dysfunction: Hepatic dysfunction can potentiate the response to warfarin through impaired synthesis of
CLINICAL PHARMACOLOGY clotting factors and decreased metabolism of warfarin.
COUMADIN and other coumarin anticoagulants act by inhibiting the synthesis of vitamin K dependent clotting The administration of COUMADIN (Warfarin Sodium) via the intravenous (IV) route should provide the patient with
factors, which include Factors II, VII, IX and X, and the anticoagulant proteins C and S. Half-lives of these clotting the same concentration of an equal oral dose, but maximum plasma concentration will be reached earlier. However,
factors are as follows: Factor II - 60 hours, VII - 4 to 6 hours, IX - 24 hours, and X - 48 to 72 hours. The half-lives the full anticoagulant effect of a dose of warfarin may not be achieved until 72 to 96 hours after dosing, indicating
of proteins C and S are approximately 8 hours and 30 hours, respectively. The resultant in vivo effect is a sequential that the administration of IV COUMADIN should not provide any increased biological effect or earlier onset of action.
depression of Factor VII, Protein C, Factor IX, Protein S, and Factor X and II activities. Vitamin K is an essential
cofactor for the post ribosomal synthesis of the vitamin K dependent clotting factors. The vitamin promotes the CLINICAL TRIALS
biosynthesis of ␥-carboxyglutamic acid residues in the proteins which are essential for biological activity. Atrial Fibrillation (AF): In five prospective randomized controlled clinical trials involving 3711 patients with non-
rheumatic AF, warfarin significantly reduced the risk of systemic thromboembolism including stroke (see Table 2).
Mechanism of Action: Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit The risk reduction ranged from 60% to 86% in all except one trial (CAFA: 45%) which stopped early due to published
of the vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K1 positive results from two of these trials. The incidence of major bleeding in these trials ranged from 0.6% to 2.7%
epoxide. The degree of depression is dependent upon the dosage administered and, in part, by the patient’s VKORC1 (see Table 2). Meta-analysis findings of these studies revealed that the effects of warfarin in reducing
genotype. Therapeutic doses of warfarin decrease the total amount of the active form of each vitamin K dependent thromboembolic events including stroke were similar at either moderately high INR (2.0-4.5) or low INR (1.4-3.0).
clotting factor made by the liver by approximately 30% to 50%. There was a significant reduction in minor bleeds at the low INR. Similar data from clinical studies in valvular atrial
An anticoagulation effect generally occurs within 24 hours after drug administration. However, peak anticoagulant fibrillation patients are not available.
effect may be delayed 72 to 96 hours. The duration of action of a single dose of racemic warfarin is 2 to 5 days.
The effects of COUMADIN may become more pronounced as effects of daily maintenance doses overlap. Table 2: Clinical Studies of Warfarin in Non-Rheumatic AF Patients*
Anticoagulants have no direct effect on an established thrombus, nor do they reverse ischemic tissue damage.
However, once a thrombus has occurred, the goal of anticoagulant treatment is to prevent further extension of the N Thromboembolism % Major Bleeding
formed clot and prevent secondary thromboembolic complications which may result in serious and possibly fatal
sequelae. Warfarin- Warfarin-
Treated Control PT % Risk Treated Control
Pharmacokinetics: COUMADIN is a racemic mixture of the R- and S-enantiomers. The S-enantiomer exhibits 2 to Study Patients Patients Ratio INR Reduction p-value Patients Patients
5 times more anticoagulant activity than the R-enantiomer in humans, but generally has a more rapid clearance.
Absorption: COUMADIN is essentially completely absorbed after oral administration with peak concentration AFASAK 335 336 1.5-2.0 2.8-4.2 60 0.027 0.6 0.0
generally attained within the first 4 hours. SPAF 210 211 1.3-1.8 2.0-4.5 67 0.01 1.9 1.9
Distribution: There are no differences in the apparent volumes of distribution after intravenous and oral BAATAF 212 208 1.2-1.5 1.5-2.7 86 <0.05 0.9 0.5
administration of single doses of warfarin solution. Warfarin distributes into a relatively small apparent volume of
CAFA 187 191 1.3-1.6 2.0-3.0 45 0.25 2.7 0.5
distribution of about 0.14 liter/kg. A distribution phase lasting 6 to 12 hours is distinguishable after rapid
intravenous or oral administration of an aqueous solution. Using a one compartment model, and assuming SPINAF 260 265 1.2-1.5 1.4-2.8 79 0.001 2.3 1.5
complete bioavailability, estimates of the volumes of distribution of R- and S-warfarin are similar to each other and
to that of the racemate. Concentrations in fetal plasma approach the maternal values, but warfarin has not been *All study results of warfarin vs. control are based on intention-to-treat analysis and include ischemic stroke and
found in human milk (see WARNINGS: Lactation). Approximately 99% of the drug is bound to plasma proteins. systemic thromboembolism, excluding hemorrhage and transient ischemic attacks.
Metabolism: The elimination of warfarin is almost entirely by metabolism. COUMADIN is stereoselectively Myocardial Infarction: WARIS (The Warfarin Re-Infarction Study) was a double-blind, randomized study of 1214
metabolized by hepatic microsomal enzymes (cytochrome P-450) to inactive hydroxylated metabolites patients 2 to 4 weeks post-infarction treated with warfarin to a target INR of 2.8 to 4.8. [But note that a lower INR
(predominant route) and by reductases to reduced metabolites (warfarin alcohols). The warfarin alcohols have was achieved and increased bleeding was associated with INRs above 4.0; (see DOSAGE AND ADMINISTRATION).]
minimal anticoagulant activity. The metabolites are principally excreted into the urine; and to a lesser extent into The primary endpoint was a combination of total mortality and recurrent infarction. A secondary endpoint of cere-
the bile. The metabolites of warfarin that have been identified include dehydrowarfarin, two diastereoisomer brovascular events was assessed. Mean follow-up of the patients was 37 months. The results for each endpoint
alcohols, 4'-, 6-, 7-, 8- and 10-hydroxywarfarin. The cytochrome P-450 isozymes involved in the metabolism of separately, including an analysis of vascular death, are provided in the following table:
warfarin include 2C9, 2C19, 2C8, 2C18, 1A2, and 3A4. 2C9 is likely to be the principal form of human liver P-450
which modulates the in vivo anticoagulant activity of warfarin.
The S-enantiomer of warfarin is mainly metabolized to 7-hydroxywarfarin by CYP2C9, a polymorphic enzyme. The
variant alleles CYP2C9*2 and CYP2C9*3 result in decreased in vitro CYP2C9 enzymatic 7-hydroxylation of S-warfarin.
The frequencies of these alleles in Caucasians are approximately 11% and 7% for CYP2C9*2 and CYP2C9*3, respec-
tively.1 Patients with one or more of these variant CYP2C9 alleles have decreased S-warfarin clearance (Table 1).2
Table 3: Spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding.
% Risk Miscellaneous: major regional, lumbar block anesthesia, malignant hypertension and known hypersensitivity to
Warfarin Placebo Reduction warfarin or to any other components of this product.
Event (N=607) (N=607) RR (95% CI) (p-value) WARNINGS
Total Patient Years The most serious risks associated with anticoagulant therapy with warfarin sodium are hemorrhage in any tissue
of Follow-up 2018 1944 or organ12 (see BLACK BOX WARNING) and, less frequently (<0.1%), necrosis and/or gangrene of skin and other
tissues. Hemorrhage and necrosis have in some cases been reported to result in death or permanent disability.
Total Mortality 94 (4.7/100 py) 123 (6.3/100 py) 0.76 (0.60, 0.97) 24 (p=0.030)
Necrosis appears to be associated with local thrombosis and usually appears within a few days of the start of anti-
Vascular Death 82 (4.1/100 py) 105 (5.4/100 py) 0.78 (0.60, 1.02) 22 (p=0.068) coagulant therapy. In severe cases of necrosis, treatment through debridement or amputation of the affected
tissue, limb, breast or penis has been reported. Careful diagnosis is required to determine whether necrosis is
Recurrent MI 82 (4.1/100 py) 124 (6.4/100 py) 0.66 (0.51, 0.85) 34 (p=0.001)
caused by an underlying disease. Warfarin therapy should be discontinued when warfarin is suspected to be the
Cerebrovascular Event 20 (1.0/100 py) 44 (2.3/100 py) 0.46 (0.28, 0.75) 54 (p=0.002) cause of developing necrosis and heparin therapy may be considered for anticoagulation. Although various treat-
RR=Relative risk; Risk reduction=(1 - RR); CI=Confidence interval; MI=Myocardial infarction; py=patient years ments have been attempted, no treatment for necrosis has been considered uniformly effective. See below for
information on predisposing conditions. These and other risks associated with anticoagulant therapy must be
WARIS II (The Warfarin, Aspirin, Re-Infarction Study) was an open-label, randomized study of 3630 patients weighed against the risk of thrombosis or embolization in untreated cases.
hospitalized for acute myocardial infarction treated with warfarin target INR 2.8 to 4.2, aspirin 160 mg/day, or
warfarin target INR 2.0 to 2.5 plus aspirin 75 mg/day prior to hospital discharge. There were approximately four It cannot be emphasized too strongly that treatment of each patient is a highly individualized matter. COUMADIN
times as many major bleeding episodes in the two groups receiving warfarin than in the group receiving aspirin (Warfarin Sodium), a narrow therapeutic range (index) drug, may be affected by factors such as other drugs and
alone. Major bleeding episodes were not more frequent among patients receiving aspirin plus warfarin than among dietary vitamin K. Dosage should be controlled by periodic determinations of prothrombin time (PT)/International
those receiving warfarin alone, but the incidence of minor bleeding episodes was higher in the combined therapy Normalized Ratio (INR). Determinations of whole blood clotting and bleeding times are not effective measures for
group. The primary endpoint was a composite of death, nonfatal reinfarction, or thromboembolic stroke. The mean control of therapy. Heparin prolongs the one-stage PT. When heparin and COUMADIN are administered
duration of observation was approximately 4 years. The results for WARIS II are provided in the following table.8 concomitantly, refer below to Conversion From Heparin Therapy for recommendations.
Increased caution should be observed when COUMADIN is administered in the presence of any predisposing
condition where added risk of hemorrhage, necrosis, and/or gangrene is present.
Table 4: WARIS II - Distribution of Separate Events According to Treatment Group
Anticoagulation therapy with COUMADIN may enhance the release of atheromatous plaque emboli, thereby increasing
Aspirin plus
the risk of complications from systemic cholesterol microembolization, including the “purple toes syndrome.”
Aspirin Warfarin Warfarin Rate Ratio Discontinuation of COUMADIN therapy is recommended when such phenomena are observed.
Event (N=1206) (N=1216) (N=1208) (95% CI)* p-value
No. of Events Systemic atheroemboli and cholesterol microemboli can present with a variety of signs and symptoms including
Reinfarction 117 90 69 0.56 (0.41-0.78)a <0.001 purple toes syndrome, livedo reticularis, rash, gangrene, abrupt and intense pain in the leg, foot, or toes, foot ulcers,
0.74 (0.55-0.98)b 0.03 myalgia, penile gangrene, abdominal pain, flank or back pain, hematuria, renal insufficiency, hypertension, cerebral
ischemia, spinal cord infarction, pancreatitis, symptoms simulating polyarteritis, or any other sequelae of vascular
Thromboembolic 32 17 17 0.52 (0.28-0.98)a 0.03 compromise due to embolic occlusion. The most commonly involved visceral organs are the kidneys followed by
Stroke 0.52 (0.28-0.97)b 0.03 the pancreas, spleen, and liver. Some cases have progressed to necrosis or death.
Major Bleedingc 8 33 28 3.35a (ND) ND
Purple toes syndrome is a complication of oral anticoagulation characterized by a dark, purplish or mottled color
4.00b (ND) ND
of the toes, usually occurring between 3 to 10 weeks, or later, after the initiation of therapy with warfarin or related
Minor Bleedingd 39 103 133 3.21a (ND) ND compounds. Major features of this syndrome include purple color of plantar surfaces and sides of the toes that
2.55b (ND) ND blanches on moderate pressure and fades with elevation of the legs; pain and tenderness of the toes; waxing and
Death 92 96 95 0.82 waning of the color over time. While the purple toes syndrome is reported to be reversible, some cases progress
* CI denotes confidence interval. to gangrene or necrosis which may require debridement of the affected area, or may lead to amputation.
a The rate ratio is for aspirin plus warfarin as compared with aspirin. COUMADIN should be used with caution in patients with heparin-induced thrombocytopenia and deep venous thrombosis.
b The rate ratio is for warfarin as compared with aspirin. Cases of venous limb ischemia, necrosis, and gangrene have occurred in patients with heparin-induced thrombo-
c Major bleeding episodes were defined as nonfatal cerebral hemorrhage or bleeding necessitating surgical intervention cytopenia and deep venous thrombosis when heparin treatment was discontinued and warfarin therapy was started
or blood transfusion. or continued. In some patients sequelae have included amputation of the involved area and/or death.13
d Minor bleeding episodes were defined as non-cerebral hemorrhage not necessitating surgical intervention or blood
The decision to administer anticoagulants in the following conditions must be based upon clinical judgment in
transfusion.
which the risks of anticoagulant therapy are weighed against the benefits:
ND=not determined
Lactation: Based on very limited published data, warfarin has not been detected in the breast milk of mothers
Mechanical and Bioprosthetic Heart Valves: In a prospective, randomized, open-label, positive-controlled study9
treated with warfarin. The same limited published data report that some breast-fed infants, whose mothers were
in 254 patients, the thromboembolic-free interval was found to be significantly greater in patients with mechanical
treated with warfarin, had prolonged prothrombin times, although not as prolonged as those of the mothers. The
prosthetic heart valves treated with warfarin alone compared with dipyridamole-aspirin (p<0.005) and pentoxi-
decision to breast-feed should be undertaken only after careful consideration of the available alternatives.
fylline-aspirin (p<0.05) treated patients. Rates of thromboembolic events in these groups were 2.2, 8.6, and
Women who are breast-feeding and anticoagulated with warfarin should be very carefully monitored so that
7.9/100 patient years, respectively. Major bleeding rates were 2.5, 0.0, and 0.9/100 patient years, respectively.
recommended PT/INR values are not exceeded. It is prudent to perform coagulation tests and to evaluate vitamin
In a prospective, open label, clinical trial comparing moderate (INR 2.65) vs. high intensity (INR 9.0) warfarin therapies K status in infants before advising women taking warfarin to breast-feed. Effects in premature infants have not
in 258 patients with mechanical prosthetic heart valves, thromboembolism occurred with similar frequency in the been evaluated.
two groups (4.0 and 3.7 events/100 patient years, respectively). Major bleeding was more common in the high
Severe to moderate hepatic or renal insufficiency.
intensity group (2.1 events/100 patient years) vs. 0.95 events/100 patient years in the moderate intensity group.10
Infectious diseases or disturbances of intestinal flora: sprue, antibiotic therapy.
In a randomized trial in 210 patients comparing two intensities of warfarin therapy (INR 2.0-2.25 vs. INR 2.5-4.0)
for a three-month period following tissue heart valve replacement, thromboembolism occurred with similar Trauma which may result in internal bleeding.
frequency in the two groups (major embolic events 2.0% vs. 1.9%, respectively, and minor embolic events 10.8% Surgery or trauma resulting in large exposed raw surfaces.
vs. 10.2%, respectively). Major bleeding complications were more frequent with the higher intensity (major
hemorrhages 4.6%) vs. none in the lower intensity.11 Indwelling catheters.
INDICATIONS AND USAGE Severe to moderate hypertension.
COUMADIN (Warfarin Sodium) is indicated for the prophylaxis and/or treatment of venous thrombosis and its Known or suspected deficiency in protein C mediated anticoagulant response: Hereditary or acquired deficiencies of
extension, and pulmonary embolism. protein C or its cofactor, protein S, have been associated with tissue necrosis following warfarin administration. Not all
COUMADIN is indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with patients with these conditions develop necrosis, and tissue necrosis occurs in patients without these deficiencies.
atrial fibrillation and/or cardiac valve replacement. Inherited resistance to activated protein C has been described in many patients with venous thromboembolic
disorders but has not yet been evaluated as a risk factor for tissue necrosis. The risk associated with these
COUMADIN is indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events conditions, both for recurrent thrombosis and for adverse reactions, is difficult to evaluate since it does not appear
such as stroke or systemic embolization after myocardial infarction. to be the same for everyone. Decisions about testing and therapy must be made on an individual basis. It has been
CONTRAINDICATIONS reported that concomitant anticoagulation therapy with heparin for 5 to 7 days during initiation of therapy with
Anticoagulation is contraindicated in any localized or general physical condition or personal circumstance in which COUMADIN may minimize the incidence of tissue necrosis. Warfarin therapy should be discontinued when warfarin
the hazard of hemorrhage might be greater than the potential clinical benefits of anticoagulation, such as: is suspected to be the cause of developing necrosis, and heparin therapy may be considered for anticoagulation.
Pregnancy: COUMADIN is contraindicated in women who are or may become pregnant because the drug passes Miscellaneous: polycythemia vera, vasculitis, and severe diabetes.
through the placental barrier and may cause fatal hemorrhage to the fetus in utero. Furthermore, there have been PRECAUTIONS
reports of birth malformations in children born to mothers who have been treated with warfarin during pregnancy. Periodic determination of PT/INR is essential. (See DOSAGE AND ADMINISTRATION: Laboratory Control.) Numerous
Embryopathy characterized by nasal hypoplasia with or without stippled epiphyses (chondrodysplasia punctata) factors, alone or in combination including changes in diet, medications, botanicals, and genetic variations in the
has been reported in pregnant women exposed to warfarin during the first trimester. Central nervous system CYP2C9 and VKORC1 enzymes (see CLINICAL PHARMACOLOGY: Pharmacogenomics) may influence the response
abnormalities also have been reported, including dorsal midline dysplasia characterized by agenesis of the corpus of the patient to warfarin.
callosum, Dandy-Walker malformation, and midline cerebellar atrophy. Ventral midline dysplasia, characterized by Drug-Drug and Drug-Disease Interactions: It is generally good practice to monitor the patient’s response with
optic atrophy, and eye abnormalities have been observed. Mental retardation, blindness, and other central nervous additional PT/INR determinations in the period immediately after discharge from the hospital, and whenever
system abnormalities have been reported in association with second and third trimester exposure. Although rare, other medications, including botanicals, are initiated, discontinued or taken irregularly. The following factors
teratogenic reports following in utero exposure to warfarin include urinary tract anomalies such as single kidney, are listed for reference; however, other factors may also affect the anticoagulant response.
asplenia, anencephaly, spina bifida, cranial nerve palsy, hydrocephalus, cardiac defects and congenital heart dis-
ease, polydactyly, deformities of toes, diaphragmatic hernia, corneal leukoma, cleft palate, cleft lip, schizencephaly, Drugs may interact with COUMADIN through pharmacodynamic or pharmacokinetic mechanisms. Pharmaco-
and microcephaly. dynamic mechanisms for drug interactions with COUMADIN are synergism (impaired hemostasis, reduced
clotting factor synthesis), competitive antagonism (vitamin K), and altered physiologic control loop for vitamin
Spontaneous abortion and stillbirth are known to occur and a higher risk of fetal mortality is associated with the K metabolism (hereditary resistance). Pharmacokinetic mechanisms for drug interactions with COUMADIN are
use of warfarin. Low birth weight and growth retardation have also been reported. mainly enzyme induction, enzyme inhibition, and reduced plasma protein binding. It is important to note that
Women of childbearing potential who are candidates for anticoagulant therapy should be carefully evaluated and some drugs may interact by more than one mechanism.
the indications critically reviewed with the patient. If the patient becomes pregnant while taking this drug, she
should be apprised of the potential risks to the fetus, and the possibility of termination of the pregnancy should be The following factors, alone or in combination, may be responsible for INCREASED PT/INR response:
discussed in light of those risks. ENDOGENOUS FACTORS:
Hemorrhagic tendencies or blood dyscrasias. blood dyscrasias — diarrhea hyperthyroidism
Recent or contemplated surgery of: (1) central nervous system; (2) eye; (3) traumatic surgery resulting in large see CONTRAINDICATIONS elevated temperature poor nutritional state
open surfaces. cancer hepatic disorders steatorrhea
collagen vascular disease infectious hepatitis vitamin K deficiency
Bleeding tendencies associated with active ulceration or overt bleeding of: (1) gastrointestinal, genitourinary or
congestive heart failure jaundice
respiratory tracts; (2) cerebrovascular hemorrhage; (3) aneurysms-cerebral, dissecting aorta; (4) pericarditis and
pericardial effusions; (5) bacterial endocarditis.
Threatened abortion, eclampsia and preeclampsia.
Inadequate laboratory facilities.
Unsupervised patients with senility, alcoholism, or psychosis or other lack of patient cooperation.
EXOGENOUS FACTORS:
Potential drug interactions with COUMADIN (Warfarin Sodium) are listed below by drug class and by specific drugs. Specific Drugs Reported
alcohol† COUMADIN underdosage phenobarbital
Classes of Drugs aminoglutethimide cyclophosphamide† phenytoin†
5-lipoxygenase Inhibitor Antiplatelet Drugs/Effects Leukotriene Receptor amobarbital dicloxacillin pravastatin†
Adrenergic Stimulants, Central Antithyroid Drugs† Antagonist atorvastatin† ethchlorvynol prednisone†
Alcohol Abuse Reduction Beta-Adrenergic Blockers Monoamine Oxidase azathioprine glutethimide primidone
Preparations Cholelitholytic Agents Inhibitors butabarbital griseofulvin propylthiouracil†
Analgesics Diabetes Agents, Oral Narcotics, prolonged butalbital haloperidol raloxifene
Anesthetics, Inhalation Diuretics† Nonsteroidal Anti-Inflammatory carbamazepine meprobamate ranitidine†
Antiandrogen Fungal Medications, Agents chloral hydrate† 6-mercaptopurine rifampin
Antiarrhythmics† Intravaginal, Systemic† Proton Pump Inhibitors chlordiazepoxide methimazole† secobarbital
Antibiotics† Gastric Acidity and Peptic Psychostimulants chlorthalidone moricizine hydrochloride† spironolactone
Aminoglycosides (oral) Ulcer Agents† Pyrazolones cholestyramine† nafcillin sucralfate
Cephalosporins, parenteral Gastrointestinal Salicylates clozapine paraldehyde trazodone
Macrolides Prokinetic Agents Selective Serotonin corticotropin pentobarbital vitamin C (high dose)
Miscellaneous Ulcerative Colitis Agents Reuptake Inhibitors cortisone vitamin K
Penicillins, intravenous, Gout Treatment Agents Steroids, Adrenocortical†
high dose Hemorrheologic Agents Steroids, Anabolic (17-Alkyl also: diet high in vitamin K
Quinolones Hepatotoxic Drugs Testosterone Derivatives) unreliable PT/INR determinations
†Increased and decreased PT/INR responses have been reported.
(fluoroquinolones) Hyperglycemic Agents Thrombolytics
Sulfonamides, long acting Hypertensive Emergency Thyroid Drugs Because a patient may be exposed to a combination of the above factors, the net effect of COUMADIN (Warfarin Sodium)
Tetracyclines Agents Tuberculosis Agents† on PT/INR response may be unpredictable. More frequent PT/INR monitoring is therefore advisable. Medications of
Anticoagulants Hypnotics† Uricosuric Agents unknown interaction with coumarins are best regarded with caution. When these medications are started or
Anticonvulsants† Hypolipidemics† Vaccines stopped, more frequent PT/INR monitoring is advisable.
Antidepressants† Bile Acid-Binding Resins† Vitamins†
Antimalarial Agents Fibric Acid Derivatives It has been reported that concomitant administration of warfarin and ticlopidine may be associated with cholestatic
Antineoplastics† HMG-CoA Reductase hepatitis.
Antiparasitic/Antimicrobials Inhibitors† Botanical (Herbal) Medicines: Caution should be exercised when botanical medicines (botanicals) are taken con-
comitantly with COUMADIN. Few adequate, well-controlled studies exist evaluating the potential for metabolic and/or
Specific Drugs Reported pharmacologic interactions between botanicals and COUMADIN. Due to a lack of manufacturing standardization with
botanical medicinal preparations, the amount of active ingredients may vary. This could further confound the ability
acetaminophen fenoprofen pantoprazole to assess potential interactions and effects on anticoagulation. It is good practice to monitor the patient’s response
alcohol† fluconazole paroxetine with additional PT/INR determinations when initiating or discontinuing botanicals.
allopurinol fluorouracil penicillin G, intravenous
aminosalicylic acid fluoxetine pentoxifylline Specific botanicals reported to affect COUMADIN therapy include the following:
amiodarone HCl flutamide phenylbutazone • Bromelains, danshen, dong quai (Angelica sinensis), garlic, Ginkgo biloba, ginseng, and cranberry products are
argatroban fluvastatin phenytoin† associated most often with an INCREASE in the effects of COUMADIN.
aspirin fluvoxamine piperacillin • Coenzyme Q10 (ubidecarenone) and St. John’s wort are associated most often with a DECREASE in the effects of
atenolol gefitinib piroxicam COUMADIN.
atorvastatin† gemfibrozil pravastatin† Some botanicals may cause bleeding events when taken alone (eg, garlic and Ginkgo biloba) and may have
azithromycin glucagon prednisone† anticoagulant, antiplatelet, and/or fibrinolytic properties. These effects would be expected to be additive to the
bivalirudin halothane propafenone anticoagulant effects of COUMADIN. Conversely, other botanicals may have coagulant properties when taken alone
capecitabine heparin propoxyphene or may decrease the effects of COUMADIN.
cefamandole ibuprofen propranolol
Some botanicals that may affect coagulation are listed below for reference; however, this list should not be
cefazolin ifosfamide propylthiouracil†
considered all-inclusive. Many botanicals have several common names and scientific names. The most widely
cefoperazone indomethacin quinidine
recognized common botanical names are listed.
cefotetan influenza virus vaccine quinine
cefoxitin itraconazole rabeprazole Botanicals that contain coumarins with potential anticoagulant effects:
ceftriaxone ketoprofen ranitidine†
celecoxib ketorolac rofecoxib Agrimony1 Celery Passion Flower
cerivastatin lansoprazole sertraline Alfalfa Chamomile Prickly Ash (Northern)
chenodiol lepirudin simvastatin Angelica (Dong Quai) (German and Roman) Quassia
chloramphenicol levamisole stanozolol Aniseed Dandelion4 Red Clover
chloral hydrate† levofloxacin streptokinase Arnica Fenugreek Sweet Clover
chlorpropamide levothyroxine sulfamethizole Asafoetida Horse Chestnut Sweet Woodruff
cholestyramine† liothyronine sulfamethoxazole Bogbean2 Horseradish Tonka Beans
cimetidine lovastatin sulfinpyrazone Boldo Licorice4 Wild Carrot
ciprofloxacin mefenamic acid sulfisoxazole Buchu Meadowsweet2 Wild Lettuce
cisapride methimazole† sulindac Capsicum3 Nettle
clarithromycin methyldopa tamoxifen Cassia4 Parsley
clofibrate methylphenidate tetracycline
COUMADIN overdose methylsalicylate ointment thyroid
cyclophosphamide† (topical) ticarcillin Miscellaneous botanicals with anticoagulant properties:
danazol metronidazole ticlopidine
dextran miconazole (intravaginal, tissue plasminogen Bladder Wrack (Fucus) Pau d’arco
dextrothyroxine oral, systemic) activator (t-PA)
diazoxide moricizine hydrochloride† tolbutamide
diclofenac nalidixic acid tramadol Botanicals that contain salicylate and/or have antiplatelet properties:
dicumarol naproxen trimethoprim/sulfamethoxazole
diflunisal neomycin urokinase Agrimony1 Dandelion4 Meadowsweet2
disulfiram norfloxacin valdecoxib Aloe Gel Feverfew Onion5
doxycycline ofloxacin valproate Garlic5 Policosanol
Aspen
erythromycin olsalazine vitamin E
esomeprazole omeprazole zafirlukast Black Cohosh German Sarsaparilla Poplar
ethacrynic acid oxandrolone zileuton Black Haw Ginger Senega
ezetimibe oxaprozin Bogbean2 Ginkgo Biloba Tamarind
fenofibrate oxymetholone Cassia4 Ginseng (Panax)5 Willow
Clove Licorice4 Wintergreen
also: other medications affecting blood elements which may modify hemostasis
dietary deficiencies
prolonged hot weather Botanicals with fibrinolytic properties:
unreliable PT/INR determinations
†Increased and decreased PT/INR responses have been reported. Bromelains Garlic5 Inositol Nicotinate
Capsicum3 Ginseng (Panax)5 Onion5
The following factors, alone or in combination, may be responsible for DECREASED PT/INR response:
ENDOGENOUS FACTORS:
Botanicals with coagulant properties:
edema hypothyroidism
hereditary coumarin resistance nephrotic syndrome Agrimony1 Mistletoe
hyperlipemia Goldenseal Yarrow
EXOGENOUS FACTORS: 1 Contains coumarins, has antiplatelet properties, and may have coagulant properties due to possible vitamin K content.
Potential drug interactions with COUMADIN are listed below by drug class and by specific drugs. 2 Contains coumarins and salicylate.
3 Contains coumarins and has fibrinolytic properties.
Classes of Drugs 4 Contains coumarins and has antiplatelet properties.
5 Has antiplatelet and fibrinolytic properties.
Adrenal Cortical Steroid Inhibitors Antipsychotic Medications Hypolipidemics†
Antacids Antithyroid Drugs† Bile Acid-Binding Resins† Effect on Other Drugs: Coumarins may also affect the action of other drugs. Hypoglycemic agents (chlorpropamide
Antianxiety Agents Barbiturates HMG-CoA Reductase Inhibitors† and tolbutamide) and anticonvulsants (phenytoin and phenobarbital) may accumulate in the body as a result of
Antiarrhythmics† Diuretics† Immunosuppressives interference with either their metabolism or excretion.
Antibiotics† Enteral Nutritional Supplements Oral Contraceptives,
Anticonvulsants† Estrogen Containing Considerations for Increased Bleeding Risk: COUMADIN is a narrow therapeutic range (index) drug, and additional
Fungal Medications, Systemic†
Antidepressants† Selective Estrogen Receptor caution should be observed when warfarin sodium is administered to certain patients. Reported risk factors for
Gastric Acidity and
Antihistamines Modulators bleeding include high intensity of anticoagulation (INR >4.0), age ≥65, highly variable INRs, history of gastroin-
Peptic Ulcer Agents†
Antineoplastics† Steroids, Adrenocortical† testinal bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, malignancy, trauma, renal
Hypnotics†
Tuberculosis Agents† insufficiency, concomitant drugs (see PRECAUTIONS), and long duration of warfarin therapy. Identification of risk
Vitamins† factors for bleeding and certain genetic variations in CYP2C9 and VKORC1 in a patient may increase the need for
more frequent INR monitoring and the use of lower warfarin doses (see CLINICAL PHARMACOLOGY:
Pharmacokinetics: Metabolism and DOSAGE AND ADMINISTRATION). Bleeding is more likely to occur during the
starting period and with a higher dose of COUMADIN (resulting in a higher INR).
Intramuscular (IM) injections of concomitant medications should be confined to the upper extremities which should be adjusted to maintain a target INR of 2.5 (INR range, 2.0-3.0) for all treatment durations. These recom-
permits easy access for manual compression, inspections for bleeding and use of pressure bandages. mendations are supported by the American College of Chest Physicians’ (7th ACCP) guidelines.15,17,21,22
Caution should be observed when COUMADIN (Warfarin Sodium) (or warfarin) is administered concomitantly with Atrial Fibrillation: Five clinical trials evaluated the effects of warfarin in patients with non-valvular atrial fibrillation
nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, to be certain that no change in anticoagulation (AF). Meta-analysis findings of these studies revealed that the effects of warfarin in reducing thromboembolic events
dosage is required. In addition to specific drug interactions that might affect PT/INR, NSAIDs, including aspirin, can including stroke were similar at either moderately high INR (2.0-4.5) or low INR (1.4-3.0). There was a significant
inhibit platelet aggregation, and can cause gastrointestinal bleeding, peptic ulceration and/or perforation. reduction in minor bleeds at the low INR. There are no adequate and well-controlled studies in populations with
atrial fibrillation and valvular heart disease. Similar data from clinical studies in valvular atrial fibrillation patients are
Information for Patients: The objective of anticoagulant therapy is to decrease the clotting ability of the blood so
not available. The trials in non-valvular atrial fibrillation support the 7th ACCP recommendation that an INR of 2.0 to
that thrombosis is prevented, while avoiding spontaneous bleeding. Effective therapeutic levels with minimal
3.0 be used for warfarin therapy in appropriate AF patients.17
complications are in part dependent upon cooperative and well-instructed patients who communicate effectively
with their physician. Patients should be advised: Strict adherence to prescribed dosage schedule is necessary. Oral anticoagulation therapy with warfarin is recommended in patients with persistent or paroxysmal AF (PAF)
Do not take or discontinue any other medication, including salicylates (eg, aspirin and topical analgesics), other (intermittent AF) at high risk of stroke (ie, having any of the following features: prior ischemic stroke, transient
over-the-counter medications, and botanical (herbal) products except on advice of the physician. Avoid alcohol ischemic attack, or systemic embolism, age >75 years, moderately or severely impaired left ventricular systolic
consumption. Do not take COUMADIN during pregnancy and do not become pregnant while taking it (see function and/or congestive heart failure, history of hypertension, or diabetes mellitus). In patients with persistent
CONTRAINDICATIONS). Avoid any activity or sport that may result in traumatic injury. Prothrombin time tests and AF or PAF, age 65 to 75 years, in the absence of other risk factors, but who are at intermediate risk of stroke,
regular visits to physician or clinic are needed to monitor therapy. Carry identification stating that COUMADIN is antithrombotic therapy with either oral warfarin or aspirin, 325 mg/day, is recommended. For patients with AF and
being taken. If the prescribed dose of COUMADIN is forgotten, notify the physician immediately. Take the dose as mitral stenosis, anticoagulation with oral warfarin is recommended (7th ACCP). For patients with AF and prosthetic
soon as possible on the same day but do not take a double dose of COUMADIN the next day to make up for missed heart valves, anticoagulation with oral warfarin should be used; the target INR may be increased and aspirin added
doses. The amount of vitamin K in food may affect therapy with COUMADIN. Eat a normal, balanced diet maintain- depending on valve type and position, and on patient factors.17
ing a consistent amount of vitamin K. Avoid drastic changes in dietary habits, such as eating large amounts of
Post-Myocardial Infarction: The results of the WARIS II study and 7th ACCP guidelines suggest that in most
green leafy vegetables. You should also avoid intake of cranberry juice or any other cranberry products. Notify your
healthcare settings, moderate- and low-risk patients with a myocardial infarction should be treated with aspirin alone
healthcare provider if any of these products are part of your normal diet. Contact physician to report any illness,
over oral vitamin-K antagonist (VKA) therapy plus aspirin. In healthcare settings in which meticulous INR monitoring
such as diarrhea, infection or fever. Notify physician immediately if any unusual bleeding or symptoms occur. Signs
is standard and routinely accessible, for both high- and low-risk patients after myocardial infarction (MI), long-term
and symptoms of bleeding include: pain, swelling or discomfort, prolonged bleeding from cuts, increased menstrual
(up to 4 years) high-intensity oral warfarin (target INR, 3.5; range, 3.0-4.0) without concomitant aspirin or moderate-
flow or vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or dark
intensity oral warfarin (target INR, 2.5; range, 2.0-3.0) with aspirin is recommended. For high-risk patients with MI,
brown urine, red or tar black stools, headache, dizziness, or weakness. If therapy with COUMADIN is discontinued,
including those with a large anterior MI, those with significant heart failure, those with intracardiac thrombus visible
patients should be cautioned that the anticoagulant effects of COUMADIN may persist for about 2 to 5 days.
on echocardiography, and those with a history of a thromboembolic event, therapy with combined moderate-intensity
Patients should be informed that all warfarin sodium, USP, products represent the same medication, and should
(INR, 2.0-3.0) oral warfarin plus low-dose aspirin (≤100 mg/day) for 3 months after the MI is suggested.23
not be taken concomitantly, as overdosage may result. A Medication Guide14 should be available to patients when
their prescriptions for warfarin sodium are issued. Mechanical and Bioprosthetic Heart Valves: For all patients with mechanical prosthetic heart valves, warfarin is
recommended. For patients with a St. Jude Medical (St. Paul, MN) bileaflet valve in the aortic position, a target INR
Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenicity and mutagenicity studies have not been per-
of 2.5 (range, 2.0-3.0) is recommended. For patients with tilting disk valves and bileaflet mechanical valves in the
formed with COUMADIN. The reproductive effects of COUMADIN have not been evaluated. The use of warfarin during
mitral position, the 7th ACCP recommends a target INR of 3.0 (range, 2.5-3.5). For patients with caged ball or caged
pregnancy has been associated with the development of fetal malformations in humans (see CONTRAINDICATIONS).
disk valves, a target INR of 3.0 (range, 2.5-3.5) in combination with aspirin, 75 to 100 mg/day is recommended. For
Use in Pregnancy patients with bioprosthetic valves, warfarin therapy with a target INR of 2.5 (range, 2.0-3.0) is recommended for
Pregnancy Category X valves in the mitral position and is suggested for valves in the aortic position for the first 3 months after valve
See CONTRAINDICATIONS. insertion.15
Pediatric Use: Safety and effectiveness in pediatric patients below the age of 18 have not been established in ran- Recurrent Systemic Embolism and Other Indications: Oral anticoagulation therapy has not been evaluated by
domized, controlled clinical trials. However, the use of COUMADIN in pediatric patients is well-documented for the properly designed clinical trials in patients with valvular disease associated with atrial fibrillation, patients with
prevention and treatment of thromboembolic events. Difficulty achieving and maintaining therapeutic PT/INR mitral stenosis, and patients with recurrent systemic embolism of unknown etiology. A moderate dose regimen
ranges in the pediatric patient has been reported. More frequent PT/INR determinations are recommended because (INR 2.0-3.0) is recommended for these patients.17
of possible changing warfarin requirements.
An INR of greater than 4.0 appears to provide no additional therapeutic benefit in most patients and is associated
Geriatric Use: Patients 60 years or older appear to exhibit greater than expected PT/INR response to the anticoag- with a higher risk of bleeding.
ulant effects of warfarin (see CLINICAL PHARMACOLOGY). COUMADIN is contraindicated in any unsupervised
patient with senility. Caution should be observed with administration of warfarin sodium to elderly patients in any Initial Dosage: The dosing of COUMADIN (Warfarin Sodium) must be individualized according to patient’s sensitivity
situation or physical condition where added risk of hemorrhage is present. Lower initiation and maintenance doses to the drug as indicated by the PT/INR. Use of a large loading dose may increase the incidence of hemorrhagic and
of COUMADIN are recommended for elderly patients (see DOSAGE AND ADMINISTRATION). other complications, does not offer more rapid protection against thrombi formation, and is not recommended. It
is recommended that COUMADIN therapy be initiated with a dose of 2 to 5 mg/day with dosage adjustments based
ADVERSE REACTIONS on the results of PT/INR determinations.17,18 The lower initiation doses should be considered for patients with
Potential adverse reactions to COUMADIN may include: certain genetic variations in CYP2C9 and VKORC1 enzymes as well as for elderly and/or debilitated patients and
• Fatal or nonfatal hemorrhage from any tissue or organ. This is a consequence of the anticoagulant effect. The patients with potential to exhibit greater than expected PT/INR responses to COUMADIN (see CLINICAL
signs, symptoms, and severity will vary according to the location and degree or extent of the bleeding. PHARMACOLOGY and PRECAUTIONS).
Hemorrhagic complications may present as paralysis; paresthesia; headache, chest, abdomen, joint, muscle or
other pain; dizziness; shortness of breath, difficult breathing or swallowing; unexplained swelling; weakness; Maintenance: Most patients are satisfactorily maintained at a dose of 2 to 10 mg daily. Flexibility of dosage is
hypotension; or unexplained shock. Therefore, the possibility of hemorrhage should be considered in evaluating provided by breaking scored tablets in half. The individual dose and interval should be gauged by the patient’s
the condition of any anticoagulated patient with complaints which do not indicate an obvious diagnosis. Bleeding prothrombin response. Acquired or inherited warfarin resistance is rare, but should be suspected if large daily
during anticoagulant therapy does not always correlate with PT/INR. (See OVERDOSAGE: Treatment.) doses of COUMADIN are required to maintain a patient’s PT/INR within a normal therapeutic range. Lower mainte-
• Bleeding which occurs when the PT/INR is within the therapeutic range warrants diagnostic investigation since nance doses are recommended for elderly and/or debilitated patients and patients with a potential to exhibit
it may unmask a previously unsuspected lesion, eg, tumor, ulcer, etc. greater than expected PT/INR response to COUMADIN (see PRECAUTIONS).
• Necrosis of skin and other tissues. (See WARNINGS.) Duration of Therapy: The duration of therapy in each patient should be individualized. In general, anticoagulant
• Adverse reactions reported infrequently include: hypersensitivity/allergic reactions, including anaphylactic reactions, therapy should be continued until the danger of thrombosis and embolism has passed.14,15,17,18,21,22
systemic cholesterol microembolization, purple toes syndrome, hepatitis, cholestatic hepatic injury, jaundice, Missed Dose: The anticoagulant effect of COUMADIN persists beyond 24 hours. If the patient forgets to take the
elevated liver enzymes, hypotension, vasculitis, edema, anemia, pallor, fever, rash, dermatitis, including bullous prescribed dose of COUMADIN at the scheduled time, the dose should be taken as soon as possible on the same
eruptions, urticaria, angina syndrome, chest pain, abdominal pain including cramping, flatulence/bloating, fatigue, day. The patient should not take the missed dose by doubling the daily dose to make up for missed doses, but
lethargy, malaise, asthenia, nausea, vomiting, diarrhea, pain, headache, dizziness, loss of consciousness, syncope, should refer back to his or her physician.
coma, taste perversion, pruritus, alopecia, cold intolerance, and paresthesia including feeling cold and chills.
Rare events of tracheal or tracheobronchial calcification have been reported in association with long-term warfarin Intravenous Route of Administration: COUMADIN for Injection provides an alternate administration route for
therapy. The clinical significance of this event is unknown. patients who cannot receive oral drugs. The IV dosages would be the same as those that would be used orally if
the patient could take the drug by the oral route. COUMADIN for Injection should be administered as a slow bolus
Priapism has been associated with anticoagulant administration; however, a causal relationship has not been established. injection over 1 to 2 minutes into a peripheral vein. It is not recommended for intramuscular administration. The
OVERDOSAGE vial should be reconstituted with 2.7 mL of sterile Water for Injection and inspected for particulate matter and
Signs and Symptoms: Suspected or overt abnormal bleeding (eg, appearance of blood in stools or urine, discoloration immediately prior to use. Do not use if either particulate matter and/or discoloration is noted. After
hematuria, excessive menstrual bleeding, melena, petechiae, excessive bruising or persistent oozing from reconstitution, COUMADIN for Injection is chemically and physically stable for 4 hours at room temperature. It does
superficial injuries) are early manifestations of anticoagulation beyond a safe and satisfactory level. not contain any antimicrobial preservative and, thus, care must be taken to assure the sterility of the prepared
solution. The vial is not recommended for multiple use and unused solution should be discarded.
Treatment: Excessive anticoagulation, with or without bleeding, may be controlled by discontinuing COUMADIN
therapy and if necessary, by administration of oral or parenteral vitamin K1. (Please see recommendations Laboratory Control: The PT reflects the depression of vitamin K dependent Factors VII, X and II. A system of
accompanying vitamin K1 preparations prior to use.) 15,16 standardizing the PT in oral anticoagulant control was introduced by the World Health Organization in 1983. It is
based upon the determination of an International Normalized Ratio (INR) which provides a common basis for
Such use of vitamin K1 reduces response to subsequent COUMADIN therapy. Patients may return to a pretreatment communication of PT results and interpretations of therapeutic ranges.24 The PT should be determined daily after
thrombotic status following the rapid reversal of a prolonged PT/INR. Resumption of COUMADIN administration the administration of the initial dose until PT/INR results stabilize in the therapeutic range. Intervals between
reverses the effect of vitamin K, and a therapeutic PT/INR can again be obtained by careful dosage adjustment. If subsequent PT/INR determinations should be based upon the physician’s judgment of the patient’s reliability
rapid anticoagulation is indicated, heparin may be preferable for initial therapy. and response to COUMADIN in order to maintain the individual within the therapeutic range. Acceptable
If minor bleeding progresses to major bleeding, give 5 to 25 mg (rarely up to 50 mg) parenteral vitamin K1. intervals for PT/INR determinations are normally within the range of 1 to 4 weeks after a stable dosage has been
In emergency situations of severe hemorrhage, clotting factors can be returned to normal by administering 200 to determined. To ensure adequate control, it is recommended that additional PT tests be done when other
500 mL of fresh whole blood or fresh frozen plasma, or by giving commercial Factor lX complex. warfarin products are interchanged with warfarin sodium tablets, USP, as well as whenever other medications
are initiated, discontinued, or taken irregularly (see PRECAUTIONS). Safety and efficacy of warfarin therapy can
A risk of hepatitis and other viral diseases is associated with the use of these blood products; Factor IX complex be improved by increasing the quality of laboratory control. Reports suggest that in usual care monitoring, patients
is also associated with an increased risk of thrombosis. Therefore, these preparations should be used only in are in therapeutic range only 33% to 64% of the time. Time in therapeutic range is significantly greater (56%-93%)
exceptional or life-threatening bleeding episodes secondary to COUMADIN overdosage. in patients managed by anticoagulation clinics, among self-testing and self-monitoring patients, and in patients
Purified Factor IX preparations should not be used because they cannot increase the levels of prothrombin, Factor managed with the help of computer programs.25 Self-testing patients had fewer bleeding events than patients in
VII and Factor X which are also depressed along with the levels of Factor IX as a result of COUMADIN treatment. usual care.25
Packed red blood cells may also be given if significant blood loss has occurred. Infusions of blood or plasma should Treatment During Dentistry and Surgery: The management of patients who undergo dental and surgical
be monitored carefully to avoid precipitating pulmonary edema in elderly patients or patients with heart disease. procedures requires close liaison between attending physicians, surgeons, and dentists.15,19 PT/INR determination
DOSAGE AND ADMINISTRATION is recommended just prior to any dental or surgical procedure. In patients undergoing minimal invasive procedures
The dosage and administration of COUMADIN must be individualized for each patient according to the particular who must be anticoagulated prior to, during, or immediately following these procedures, adjusting the dosage of
patient’s PT/INR response to the drug. The dosage should be adjusted based upon the patient's PT/INR.15,16,17,18,19 COUMADIN to maintain the PT/INR at the low end of the therapeutic range may safely allow for continued
The best available information supports the following recommendations for dosing of COUMADIN. anticoagulation. The operative site should be sufficiently limited and accessible to permit the effective use of local
procedures for hemostasis. Under these conditions, dental and minor surgical procedures may be performed
Venous Thromboembolism (including deep venous thrombosis [DVT] and pulmonary embolism [PE]): For without undue risk of hemorrhage. Some dental or surgical procedures may necessitate the interruption of
patients with a first episode of DVT or PE secondary to a transient (reversible) risk factor, treatment with warfarin COUMADIN therapy. When discontinuing COUMADIN even for a short period of time, the benefits and risks should
for 3 months is recommended. For patients with a first episode of idiopathic DVT or PE, warfarin is recommended be strongly considered.
for at least 6 to 12 months. For patients with two or more episodes of documented DVT or PE, indefinite treatment
with warfarin is suggested. For patients with a first episode of DVT or PE who have documented antiphospholipid Conversion From Heparin Therapy: Since the anticoagulant effect of COUMADIN is delayed, heparin is preferred
antibodies or who have two or more thrombophilic conditions, treatment for 12 months is recommended and initially for rapid anticoagulation. Conversion to COUMADIN may begin concomitantly with heparin therapy or may
indefinite therapy is suggested. For patients with a first episode of DVT or PE who have documented deficiency of be delayed 3 to 6 days. To ensure continuous anticoagulation, it is advisable to continue full dose heparin therapy
antithrombin, deficiency of Protein C or Protein S, or the Factor V Leiden or prothrombin 20210 gene mutation, and that COUMADIN therapy be overlapped with heparin for 4 to 5 days, until COUMADIN has produced the desired
homocystinemia, or high Factor VIII levels (>90th percentile of normal), treatment for 6 to 12 months is therapeutic response as determined by PT/INR. When COUMADIN has produced the desired PT/INR or prothrombin
recommended and indefinite therapy is suggested for idiopathic thrombosis. The risk-benefit should be activity, heparin may be discontinued.
reassessed periodically in patients who receive indefinite anticoagulant treatment.12,20 The dose of warfarin
COUMADIN (Warfarin Sodium) may increase the activated partial thromboplastin time (aPTT) test, even in the
absence of heparin. A severe elevation (>50 seconds) in activated partial thromboplastin time (aPTT) with a PT/INR
in the desired range has been identified as an indication of increased risk of postoperative hemorrhage.
During initial therapy with COUMADIN, the interference with heparin anticoagulation is of minimal clinical significance.
As heparin may affect the PT/INR, patients receiving both heparin and COUMADIN should have blood for PT/INR
determination drawn at least:
• 5 hours after the last IV bolus dose of heparin, or
• 4 hours after cessation of a continuous IV infusion of heparin, or
• 24 hours after the last subcutaneous heparin injection.
HOW SUPPLIED
Tablets: For oral use, single scored with one face imprinted numerically with 1, 2, 2-1/2, 3, 4, 5, 6, 7-1/2 or 10
superimposed and inscribed with "COUMADIN" and with the opposite face plain. COUMADIN is available in bottles
and Hospital Unit-Dose Blister Packages with potencies and colors as follows:
Hospital Unit-Dose
100’s 1000’s Blister Package of 100
1 mg pink NDC 0056-0169-70 NDC 0056-0169-90 NDC 0056-0169-75
2 mg lavender NDC 0056-0170-70 NDC 0056-0170-90 NDC 0056-0170-75
2-1/2 mg green NDC 0056-0176-70 NDC 0056-0176-90 NDC 0056-0176-75
3 mg tan NDC 0056-0188-70 NDC 0056-0188-90 NDC 0056-0188-75
4 mg blue NDC 0056-0168-70 NDC 0056-0168-90 NDC 0056-0168-75
5 mg peach NDC 0056-0172-70 NDC 0056-0172-90 NDC 0056-0172-75
6 mg teal NDC 0056-0189-70 NDC 0056-0189-90 NDC 0056-0189-75
7-1/2 mg yellow NDC 0056-0173-70 NDC 0056-0173-75
10 mg white NDC 0056-0174-70 NDC 0056-0174-75
(Dye Free)
Protect from light. Store at controlled room temperature (59°-86°F, 15°-30°C). Dispense in a tight, light-resistant
container as defined in the USP.
Hospital Unit-Dose Blister Packages are to be stored in carton until contents have been used.
Injection: Available for intravenous use only. Not recommended for intramuscular administration. Reconstitute
with 2.7 mL of sterile Water for Injection to yield 2 mg/mL. Net contents 5.4 mg lyophilized powder. Maximum
yield 2.5 mL.
5 mg vial (box of 6) NDC 0590-0324-35
Protect from light. Keep vial in box until used. Store at controlled room temperature (59°-86°F, 15°-30°C).
After reconstitution, store at controlled room temperature (59°-86°F, 15°-30°C) and use within 4 hours. Do not
refrigerate. Discard any unused solution.
REFERENCES
1. Yasar U, Eliasson E, Dahl M, Johansson I, Ingelman-Sundberg M, Sjoqvist F. Validation of methods for CYP2C9
genotyping: Frequencies of mutant alleles in Swedish population. Biochem Biophys Res Comm. 1999;254:628-631.
2. Herman D, Locatelli I, Grabnar I, et al. Influence of CYP2C9 polymorphisms, demographic factors and concomitant
drug therapy on warfarin metabolism and maintenance dose. Pharmacogenomics J. 2005;5:193-202.
3. Sanderson S, Emery J, Higgins J. CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: A
HuGEnet™ systemic review and meta-analysis. Genet Med. 2005;7:97-104.
4. Lindh JD, Lundgren S, Holm L, Alfredsson L, Rane A. Several-fold increase in risk of overanticoagulation by CYP2C9
mutations. Clin Pharmacol Ther. 2005;78:540-550.
5. Wadelius M, Chen LY, Downes K, et al. Common VKORC1 and GGCX polymorphisms associated with warfarin dose.
Pharmacogenomics J. 2005;5:262-270.
6. Veenstra DL, You JHS, Rieder MJ, et al. Association of Vitamin K epoxide reductase complex 1 (VKORC1) variants with
warfarin dose in a Hong Kong Chinese patient population. Pharmacogenet Genomics. 2005;15:687-691.
7. Takahashi H, Wilkinson GR, Nutescu EA, et al. Different contributions of polymorphisms in VKORC1 and CYP2C9 to
intra- and inter-population differences in maintenance doses of warfarin in Japanese, Caucasians and African
Americans. Pharmacogenet Genomics. 2006;16:101-110.
8. Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H. Warfarin, aspirin, or both after myocardial infarction. N Engl
J Med. 2002;347:969-974.
9. Mok CK, Boey J, Wang R, et al. Warfarin versus dipyridamole-aspirin and pentoxifylline-aspirin for prevention of
prosthetic valve thromboembolism: a prospective randomized clinical trial. Circ. 1985;72:1059-1063.
10. Saour JN, Sieck JO, Mamo LA, Gallus AS. Trial of different intensities of anticoagulation in patients with prosthetic
heart valves. N Engl J Med. 1990;322:428-432.
11. Turpie AG, Hirsh J, Gunstensen J, Nelson H, Gent M. Randomized comparison to two intensities of oral anticoagulant
therapy after tissue heart valve replacement. Lancet. 1988;331:1242-1245.
12. Büller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. Antithrombotic therapy for venous thromboembolic
disease. The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126:401S-428S.
13. Warkentin TE, Elavathil LJ, Hayward CPM, Johnston MG, Russett JI, Kelton JG. The pathogenesis of venous limb
gangrene associated with heparin-induced thrombocytopenia. Ann Intern Med. 1997;127:804-812.
14. COUMADIN Medication Guide. Princeton, NJ: Bristol-Myers Squibb Company; 2009.
15. Salem DN, Stein PD, Al-Ahmad A, et al. Antithrombotic therapy in valvular heart disease–native and prosthetic. The
Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126:457S-482S.
16. American Geriatrics Society Clinical Practice Guidelines. The use of oral anticoagulants (warfarin) in older people.
J Amer Geriatr Soc. 2000;48:224-227.
17. Singer DE, Albers GW, Dalen JE, Go AS, Halperin JL, Manning WJ. Antithrombotic therapy in atrial fibrillation. The
Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126:429S-456S.
18. Jaffer AK, Bragg L. Practical tips for warfarin dosing and monitoring. Cleveland Clinic J Med. 2003;70:361-371.
19. Jaffer AK, Brotman DJ, Chukwumerije N. When patients on warfarin need surgery. Cleveland Clinic J Med.
2003;70:973-984.
20. Kearon C, Ginsberg JS, Kovacs MJ, et al, for the Extended Low-Intensity Anticoagulation for Thrombo-Embolism
Investigators. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-
term prevention of recurrent venous thromboembolism. N Engl J Med. 2003;349:631-639.
21. Schulman S, Granqvist S, Holmström M, et al, and the Duration of Anticoagulation Trial Study Group. The duration of
oral anticoagulant therapy after a second episode of venous thromboembolism. N Engl J Med. 1997;336:393-398.
22. Ridker PM, Goldhaber SZ, Danielson E, et al, for the PREVENT Investigators. Long-term, low-intensity warfarin therapy
for the prevention of recurrent venous thromboembolism. N Engl J Med. 2003;348:1425-1434.
23. Harrington RA, Becker RC, Ezekowitz M, et al. Antithrombotic therapy for coronary artery disease. The Seventh ACCP
Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126:513S-548S.
24. Ansell J, Hirsh J, Pollen L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K
antagonists. The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126:204S-233S.
25. Heneghan C, Alonso-Coello P, Garcia-Alamino JM, Perera R, Meats E, Glasziou P. Self-monitoring of oral
anticoagulation: a systematic review and meta-analysis. Lancet. 2006;367:404-411.
Distributed by:
Princeton, New Jersey 08543 USA
COUMADIN® and the color and configuration of COUMADIN tablets are trademarks of Bristol-Myers Squibb
Pharma Company.
Copyright © Bristol-Myers Squibb Company 2009
Printed in USA
1215386A2
T1-B0001-01-09 Rev January 2009
MEDICATION GUIDE Tell your healthcare provider about all the medicines you take including prescription and non-prescription
medicines, vitamins, and herbal supplements. See “What is the most important information I should know
about COUMADIN (Warfarin Sodium)?”
COUMADIN® (COU-ma-din) Tablets How should I take COUMADIN?
(Warfarin Sodium Tablets, USP) Crystalline • Take COUMADIN exactly as prescribed. Your healthcare provider will adjust your dose from time to time depending
on your response to COUMADIN.
Read this Medication Guide before you start taking COUMADIN (Warfarin Sodium) and each time you get a refill. There
• You must have regular blood tests and visits with your healthcare provider to monitor your condition.
may be new information. This Medication Guide does not take the place of talking to your healthcare provider about
• Take COUMADIN at the same time every day. You can take COUMADIN either with food or on an empty stomach.
your medical condition or treatment. You and your healthcare provider should talk about COUMADIN when you start
• If you miss a dose of COUMADIN, call your healthcare provider. Take the dose as soon as possible on the same
taking it and at regular checkups.
day. Do not take a double dose of COUMADIN the next day to make up for a missed dose.
• Call your healthcare provider right away if you take too much COUMADIN.
What is the most important information I should know about COUMADIN?
• Call your healthcare provider if you are sick with diarrhea, an infection, or have a fever.
• Tell your healthcare provider about any planned surgeries, medical or dental procedures. Your COUMADIN may
• Take your COUMADIN exactly as prescribed to lower the chance of blood clots forming in your body. (See
have to be stopped for a short time or you may need your dose adjusted.
“What is COUMADIN?”)
• Call your healthcare provider right away if you fall or injure yourself, especially if you hit your head. Your
healthcare provider may need to check you.
• COUMADIN is very important for your health, but it can cause serious and life-threatening bleeding problems.
To benefit from COUMADIN and also lower your chance for bleeding problems, you must:
What should I avoid while taking COUMADIN?
• Get your regular blood test to check for your response to COUMADIN. This blood test is called a PT/INR
• Do not start, stop, or change any medicine without talking with your healthcare provider.
test. The PT/INR test checks to see how fast your blood clots. Your healthcare provider will decide what
• Do not make changes in your diet, such as eating large amounts of green, leafy vegetables.
PT/INR numbers are best for you. Your dose of COUMADIN will be adjusted to keep your PT/INR in a target
• Do not change your weight by dieting, without first checking with your healthcare provider.
range for you.
• Avoid drinking alcohol.
• Do not do any activity or sport that may cause a serious injury.
• Call your healthcare provider right away if you get any of the following signs or symptoms of bleeding
problems:
What are the possible side effects of COUMADIN?
• pain, swelling, or discomfort
• COUMADIN is very important for your health, but it can cause serious and life-threatening bleeding problems. See
• headaches, dizziness, or weakness
“What is the most important information I should know about COUMADIN?”
• unusual bruising (bruises that develop without known cause or grow in size)
• Serious side effects of COUMADIN also include:
• nosebleeds
• death of skin tissue (skin necrosis or gangrene). This can happen soon after starting COUMADIN. It happens
• bleeding gums
because blood clots form and block blood flow to an area of your body. Call your healthcare provider right away
• bleeding from cuts takes a long time to stop
if you have pain, color, or temperature change to any area of your body. You may need medical care right away
• menstrual bleeding or vaginal bleeding that is heavier than normal
to prevent death or loss (amputation) of your affected body part.
• pink or brown urine
• “purple toes syndrome.” Call your healthcare provider right away if you have pain in your toes and they look
• red or black stools
purple in color or dark in color.
• coughing up blood
• vomiting blood or material that looks like coffee grounds
Other side effects with COUMADIN include allergic reactions, liver problems, low blood pressure, swelling, low red
blood cells, paleness, fever, and rash. Call your healthcare provider if you have any side effect that bothers you.
• Many other medicines, including prescription and non-prescription medicines, vitamins and herbal supplements
can interact with COUMADIN and:
These are not all of the side effects of COUMADIN. For more information, ask your healthcare provider or pharmacist.
• affect the dose you need, or
• increase COUMADIN side effects.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Tell your healthcare provider about all the medicines, vitamins, and herbal supplements you take. Do not stop
How should I store COUMADIN?
medicines or take anything new unless you have talked to your healthcare provider. Keep a list of your med-
• Store COUMADIN at room temperature between 59° and 86°F. Protect from light.
icines with you at all times to show your healthcare provider and pharmacist.
• Keep COUMADIN and all medicines out of the reach of children.
• Do not take other medicines that contain warfarin. Warfarin is the active ingredient in COUMADIN.
General Information about COUMADIN
• Some foods can interact with COUMADIN and affect your treatment and dose.
Medicines are sometimes prescribed for purposes not mentioned in a Medication Guide. Do not use COUMADIN for a
• Eat a normal, balanced diet. Talk to your doctor before you make any diet changes. Do not eat large
condition for which it was not prescribed. Do not give COUMADIN to other people, even if they have the same
amounts of leafy green vegetables. Leafy green vegetables contain vitamin K. Certain vegetable oils also
condition. It may harm them.
contain large amounts of vitamin K. Too much vitamin K can lower the effect of COUMADIN.
• Avoid drinking cranberry juice or eating cranberry products.
This Medication Guide summarizes the most important information about COUMADIN. If you would like more information,
• Avoid drinking alcohol.
talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about COUMADIN
• Always tell all of your healthcare providers that you take COUMADIN.
that was written for healthcare professionals.
• Wear or carry information that you take COUMADIN.
If you would like more information, call 1-800-321-1335.
What is COUMADIN?
COUMADIN is an anticoagulant medicine. It is used to lower the chance of blood clots forming in your body. Blood clots
Rx only
can cause a stroke, heart attack, or other serious conditions such as blood clots in the legs or lungs.
COUMADIN is distributed by:
Who should not take COUMADIN?
Do not take COUMADIN if:

• your chance of having bleeding problems is higher than the possible benefit of treatment. Your healthcare
provider will decide if COUMADIN is right for you. Talk to your healthcare provider about all of your health conditions. Princeton, New Jersey 08543 USA
• you are pregnant or plan to become pregnant. COUMADIN can cause death or birth defects to an unborn baby. Use
effective birth control if you can get pregnant.
• you are allergic to warfarin or to anything else in COUMADIN. COUMADIN® is a registered trademark of Bristol-Myers Squibb Pharma Company.
What should I tell my healthcare provider before starting COUMADIN?

COUMADIN (Warfarin Sodium), the COUMADIN color logo, COLORS OF COUMADIN, and the color and configuration of
Tell your healthcare provider about all of your health conditions, including if you: COUMADIN tablets are trademarks of Bristol-Myers Squibb Pharma Company.
• have bleeding problems
• fall often **The brands listed (other than COUMADIN®) are registered trademarks of their respective owners and are not
• have liver or kidney problems trademarks of Bristol-Myers Squibb Company.
• have high blood pressure
• have a heart problem called congestive heart failure This Medication Guide has been approved by the U.S. Food and Drug Administration.
• have diabetes
• drink alcohol or have problems with alcohol abuse. Alcohol can affect your COUMADIN dose and should 1215385A2
be avoided.
• are pregnant or planning to become pregnant. See “Who should not take COUMADIN?” T1-B0001-01-09 Rev January 2009
• are breast-feeding. COUMADIN may increase bleeding in your baby. Talk to your doctor about the best way to
feed your baby. If you choose to breast-feed while taking COUMADIN, both you and your baby should be care-
fully monitored for bleeding problems.
GUÍA DEL MEDICAMENTO una lista de los medicamentos que toma para mostrársela
COUMADIN® (COU-ma-din) Comprimidos a su proveedor de atención médica y a su farmacéutico.
(Comprimidos de warfarina sódica, USP) Cristalina • No tome otros medicamentos que contengan warfarina.
Lea esta Guía del medicamento antes de comenzar a tomar La warfarina es el ingrediente activo de COUMADIN
COUMADIN (Warfarina sódica) y cada vez que reponga el (Warfarina sódica).
medicamento. Es posible que se incluya información nueva. • Algunos alimentos pueden interactuar con COUMADIN y
Esta Guía del medicamento no reemplaza la comunicación con afectar su tratamiento y dosis.
su proveedor de atención médica acerca de su afección médica • Coma una dieta normal y balanceada. Hable con su
o su tratamiento. Usted y su proveedor de atención médica médico antes de hacer cualquier cambio en su dieta. No
deberán hablar sobre COUMADIN cuando comience a tomar el coma grandes cantidades de verduras de hoja
medicamento y en los exámenes médicos periódicos. verde. Las verduras de hoja verde contienen vitamina K.
¿Qué es lo más importante que debo saber sobre Ciertos aceites vegetales también contienen grandes
COUMADIN? cantidades de vitamina K. Una cantidad excesiva de
vitamina K puede reducir el efecto del COUMADIN.
• Tome su COUMADIN exactamente como se lo recetaron,
para reducir el riesgo de que se formen coágulos de • Evite beber jugo de arándano rojo o comer
productos de arándano rojo.
sangre en su organismo. (Vea “¿Qué es COUMADIN?”)
• Evite beber alcohol.
• COUMADIN es muy importante para su salud pero
puede causar problemas hemorrágicos graves y • Siempre informe a todos sus proveedores de atención
médica que toma COUMADIN.
potencialmente mortales. Para beneficiarse con el uso de
COUMADIN y también reducir su riesgo de tener un problema • Use o lleve con usted información que identifique que
hemorrágico, usted debe: toma COUMADIN.
• Hacerse análisis de sangre periódicos para determinar ¿Qué es COUMADIN?
cómo responde a COUMADIN. Este análisis de sangre se COUMADIN es un medicamento anticoagulante. Se utiliza para
llama prueba PT/INR. La prueba PT/INR determina con qué reducir el riesgo de que se formen coágulos de sangre en el
rapidez coagula su sangre. Su proveedor de atención médica organismo. Los coágulos de sangre pueden causar un derrame
decidirá qué valores de PT/INR son más indicados para cerebral, ataque cardiaco u otras afecciones graves, tales como
usted. Su dosis de COUMADIN será ajustada para mantener coágulos de sangre en las piernas o los pulmones.
su PT/INR dentro de los valores deseados para usted. ¿Quiénes no deben tomar COUMADIN?
• Llame a su proveedor de atención médica No tome COUMADIN si:
inmediatamente si tiene alguno de los siguientes • su riesgo de tener problemas hemorrágicos es mayor
signos o síntomas de problemas hemorrágicos: que el beneficio posible del tratamiento. Su proveedor de
• dolor, hinchazón o malestar atención médica decidirá si COUMADIN es indicado para
• dolores de cabeza, mareos o debilidad usted. Hable con su proveedor de atención médica sobre
• moraduras inusual (moratones que aparecen sin una todas sus afecciones de salud.
causa conocida o que crecen de tamaño) • está embarazada o planea quedar embarazada. COUMADIN
• hemorragias nasales puede causar muerte fetal o defectos congénitos. Si tiene
• encías que sangran posibilidades de quedar embarazada, use un método
• cortes que tardan mucho tiempo en dejar de sangrar anticonceptivo eficaz.
• sangrado menstrual o vaginal que es más abundante • es alérgico a la warfarina o a algún otro ingrediente de
que lo normal COUMADIN.
• orina de color rosado o marrón ¿Qué debo decirle a mi proveedor de atención médica
• heces de color rojo o negro antes de comenzar a tomar COUMADIN?
• tose sangre Infórmele a su proveedor de atención médica todas las
• vomita sangre o materia que se parece a los posos afecciones médicas que tiene, incluso si:
del café • tiene problemas hemorrágicos
• Muchos otros medicamentos, incluso medicamentos de • se cae frecuentemente
venta con recta y de venta libre, vitaminas y suplementos • tiene problemas hepáticos o renales
de hierbas pueden interactuar con COUMADIN y: • tiene presión arterial alta
• afectar la dosis que usted necesita, o • tiene un problema cardiaco llamado insuficiencia
• incrementar los efectos secundarios de COUMADIN. cardiaca congestiva
Infórmele a su proveedor de atención médica todos los • tiene diabetes
medicamentos, vitaminas y suplementos de hierba que • bebe alcohol o tiene problemas de abuso de alcohol. El
toma. No deje de tomar sus medicamentos ni tome ningún alcohol puede afectar su dosis de COUMADIN y debe evitarlo.
medicamento nuevo a menos que haya hablado con su • está embarazada o planea quedar embarazada. Vea
proveedor de atención médica. Siempre tenga con usted “¿Quiénes no deben tomar COUMADIN?”
• está amamantando. COUMADIN puede aumentar el • Los efectos secundarios graves de COUMADIN también
sangrado en el bebé. Hable con su médico sobre la mejor incluyen:
manera de alimentar a su bebé. Si decide dar de mamar • muerte del tejido cutáneo (necrosis o gangrena
mientras está bajo tratamiento con COUMADIN, tanto usted cutánea). Esto puede ocurrir poco después de comenzar a
como su bebé deberían ser controlados cuidadosamente tomar COUMADIN. Ocurre porque se forman coágulos
por problemas hemorrágicos. sanguíneos que impiden la circulación de la sangre a un
Hable con su proveedor de atención médica sobre todos área del organismo. Si tiene dolor o un cambio de color o
los medicamentos que toma, incluso los medicamentos de temperatura en algún área del cuerpo, llame a su proveedor
venta con receta y de venta libre, las vitaminas, y los de atención médica inmediatamente. Podría necesitar
suplementos de hierbas. Vea “¿Qué es lo más importante atención médica inmediata para prevenir la muerte o
que debo saber sobre COUMADIN (Warfarina sódica)?” pérdida (amputación) de la parte afectada del cuerpo.
¿Cómo debo tomar COUMADIN? • “síndrome de dedos púrpuras”. Llame inmediatamente
• Tome COUMADIN exactamente como se lo recetaron. Su a su proveedor de atención médica si tiene dolor en los
proveedor de atención médica ajustará su dosis de vez en dedos de los pies y se ven de color púrpura u oscuro.
cuando, dependiendo de su respuesta al COUMADIN. Otros efectos secundarios de COUMADIN (Warfarina sódica)
• Usted debe hacerse análisis de sangre periódicos y incluyen reacciones alérgicas, problemas hepáticos, presión
visitar regularmente a su proveedor de atención médica arterial baja, hinchazón, bajo recuento de glóbulos rojos,
para controlar su afección. palidez, fiebre y sarpullido. Llame a su proveedor de atención
• Tome COUMADIN a la misma hora cada día. Puede tomar médica si tiene cualquier efecto secundario que le molesta.
COUMADIN con la comida o con el estómago vacío. Estos no son todos los efectos secundarios de COUMADIN. Para
• Si omite una dosis de COUMADIN, llame a su proveedor obtener más información, hable con su proveedor de atención
de atención médica. Tome la dosis lo antes posible en el médica o farmacéutico.
mismo día. No tome una dosis doble de COUMADIN al día Llame a su médico por orientación médica respecto a los
siguiente para compensar por la dosis que omitió. efectos secundarios. Puede informar efectos secundarios a la
• Si toma demasiado COUMADIN, llame de inmediato a su FDA al 1-800-FDA-1088.
proveedor de atención médica. ¿Cómo debo conservar COUMADIN?
• Llame a su proveedor de atención médica si tiene • Conserve COUMADIN a temperatura ambiente, entre 59 ºF y
diarrea, una infección o fiebre. 86 ºF. Protéjalo de la luz.
• Infórmele a su proveedor de atención médica cualquier • Mantenga COUMADIN y todos los medicamentos fuera
cirugía o procedimiento médico o dental que haya del alcance de los niños.
programado. Es posible que tenga que dejar de tomar Información general sobre COUMADIN
COUMADIN durante un tiempo corto o que necesite ajustar Los medicamentos algunas veces se recetan con fines diferentes
la dosis. de los que se mencionan en la Guía del medicamento. No utilice
• Llame inmediatamente a su proveedor de atención COUMADIN para una afección para la cual no fue recetado. No dé
médica si se cae o lesiona, especialmente si se golpea COUMADIN a otras personas, incluso si tienen la misma afección.
la cabeza. Su proveedor de atención médica podría tener Les puede hacer daño.
que examinarlo. Esta Guía del medicamento resume la información más
¿Qué debo evitar mientras tomo COUMADIN? importante sobre COUMADIN. Si desea obtener más información,
• No comience, interrumpa ni cambie ningún medicamento sin hable con su proveedor de atención médica. Puede pedirle a su
hablar con su proveedor de atención médica. proveedor de atención médica o farmacéutico la información
• No haga cambios en su dieta, tales como comer grandes sobre COUMADIN destinada a los profesionales médicos.
cantidades de verduras de hoja verde. Si desea obtener más información, llame al 1-800-321-1335.
• No haga una dieta para cambiar de peso sin primero
Solamente Rx
consultar a su proveedor de atención médica. COUMADIN es distribuido por:
• Evite beber alcohol.
• No haga ninguna actividad ni deporte que pueda causarle
Princeton, New Jersey 08543 USA
una lesión grave.
COUMADIN® es una marca registrada de Bristol-Myers Squibb Pharma Company.
¿Cuáles son los efectos secundarios posibles de COUMADIN (Warfarina sódica), el logotipo de color de COUMADIN, los COLORES
COUMADIN? DE COUMADIN, y el color y la configuración de los comprimidos de COUMADIN
• COUMADIN es muy importante para su salud pero puede son marcas comerciales de Bristol-Myers Squibb Pharma Company.
**Las marcas mencionadas (aparte de COUMADIN®) son marcas registradas de
causar problemas hemorrágicos graves y potencialmente sus dueños respectivos y no son marcas comerciales de Bristol-Myers Squibb
mortales. Vea “¿Qué es lo más importante que debo saber Company.
sobre COUMADIN?” El contenido de esta Guía del medicamento es una traducción de la sección de
Guía del medicamento de la Información de prescripción completa aprobada por
la Administración de Drogas y Alimentos (FDA) de EE.UU.
1215385A2 T1-B0001BSP-01-09 Revisado en enero de 2009

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Terapia con COUMADIN

Consulte las Indicaciones y la Información importante de seguridad en las

ESTE FOLLETO CONTIENE EN EL INTERIOR ENCONTRARÁ...

¿CUÁL ES LA INFORMACIÓN MÁS • Llame a su proveedor de atención de la

Informe a su proveedor de atención de la salud ¿QUÉ ES COUMADIN (warfarina sódica)?

¿QUÉ DEBO INFORMARLE A MI Informe a su proveedor de atención de la salud

• “síndrome de los dedos del pie morados”: ¿CÓMO DEBO ALMACENAR

Continúe leyendo este folleto para obtener más

P ¿CÓMO ACTÚA COUMADIN?

Lea las siguientes Preguntas y respuestas para

P ¿QUÉ CANTIDAD DE COUMADIN P ¿Con qué frecuencia debo realizarme análi-

Medicamentos no recetados Vitaminas

Ginkgo Biloba Ginseng

¿QUÉ SUCEDE SI...? P Qué sucede si me corto o comienzo a

¿DEBO PRESTAR ATENCIÓN A LA P ¿Cómo sé cuánta vitamina K contienen los

Consulte las Indicaciones y la Información importante de seguridad en las

INFORMACIÓN IMPORTANTE DE SEGURIDAD

CALENDARIO DE ADMINISTRACIÓN DE LA DOSIS DEL PACIENTE

CALENDARIO DE ADMINISTRACIÓN DE LA DOSIS DEL PACIENTE

CALENDARIO DE ADMINISTRACIÓN DE LA DOSIS DEL PACIENTE

COUMADIN® TABLETS CYP2C9 Genotype N S-Warfarin Clearance/Lean Body Weight

Princeton, New Jersey 08543 USA

Do not take COUMADIN if:

What should I tell my healthcare provider before starting COUMADIN?

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