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Y
PROCESO INFLAMATORIO
DOLOROSO
Reaccin inflamatoria
La inflamacin es normal,
protectivo, de defensa ante
trauma fsico, qumico o x
microrganismos.
organisms, remove irritants, and set the stage for tissue repair. Pero el exceso
produce enfermedad Ejm Artritis Reumatoidea.
El proceso
inflamatorio
AGENTE AGRESOR
chuch.. Ayayayyy!!!
(mediadores de la inflam)
Dolor
Rubor
Bradicinina
Histamina
Il-1
Dilatacin
pqos vasos
Calor
Ardor
Activ nociceptores
x autacoides: H,bradic
Serot,Pg, Sust P.
Edema
Escape de plasma
por vasodilatacin
PROCESO INFLAMATORIO
Mediadores qumicos
Mediador qumico
Accin local
Histamina
Vasodilatacin
Aumenta la permeabilidad vascular
Serotonina
Vasodilatacin
Bradicinina
Prostaglandinas
Leucotrienos
Quimiotaxis (LTB4)
Sustancia de reaccin lenta de la anafilaxia (LTC4 + LTD4)
Factor de Necrosis
Tumoral alfa
rectivas.
Prostanoides e inflamacin
x Tx A2
-PgE2. tejidos inflamados (quemad solar, edema, AR). vasodilatador eritema y edema;
dolor. Agente piretgeno.
-Otros en t. inflamado x COX-2:
PgF2a (uteroconst y broncocont, en dismenorrea),
PgI2 (vasodilat y fibrinolisis).
PgD2 (vasodil, *agreg plaquet, uterorelaj, GI-relajante. TX A2 (vasocontrac y agreg plaq)
COX-2
1.
1.
Mantiene la homeostasis de la
mucosa gstrica (PgE2).
2.
3.
Participa en la funcin de
2.
plaquetas.
4.
Induce la produccion de
3.
Tromboxano A2 (agregante
plaq y vasoconstrictor) (ASA
inhibe su produc = corazn).
4.
A.I.N.E.S
ANTI-INFLAMATORIOS NO ESTEROIDALES
3. Alcalonas
2.
Pirazolonas
4. Inhibidores prefe
renciales COX-2 y
oxicamos
Celecoxib, Rofecoxib
Metamizol
Fenilbutazona
Etoricoxib
(Retirado x hepatotoxicidad)
Lumiracoxib
t > 10 horas
Naproxeno
Piroxicam
Meloxicam
Celecoxib
Rofecoxib
MECANISMO de
ACCIN
INHIBICIN de la ENZIMA
CICLOOXIGENASA (COX)
por tanto en la inhibicin de la
produccion de PGS y
TROMBOXANOS que CAUSAN
INFLAMACIN, DOLOR y FIEBRE.
Fosfolipasa A2
Glucocorticoides
inducible
y constitutiva en
rion, cerebro y
endotelio (PgI).
Pg=vasodilatac
Asma
Rinitis
x * leucotrienes
Tromboxano A2
Agregacin plaquetaria y
vasoconstrictor
Prostaciclina
(PGI2). Inh
Aspirina a dosis baja inh COX-1 y x ende inh a Tromboxano A2= inh agregacion agregac plaquet y
vasodilatador
plaquetaria, pero a dosis terapeutica se hace mas selectiva a COX-2 o
los COX-2 selectivos no inh a Tx-A2
-Desarrollo folicular y ruptura, *x meloxicam (CO?)
AINES tradicionales o
no selectivos
INHIBEN la COX-1 y COX-2
del cido araquidnico.
PRINCIPALES EFECTOS
FARMACOLOGICOS
Anti-inflamatorios
Antipireticos
Analgesicos
bloquear too R NMDA
OTROS
- la agregacin plaquetaria
- la contraccin uterina (tocoliticos y dismenorrea)
-Cierre del conducto arterioso en infantes
-Px de Ca de colon y poliposis intestinal (ASA)
GENERALIDADES
Absorben pcipalmente en 2da porcin del duodeno.
Vida media : 2 12 h.
Eliminacin renal.
INDICACIONES
Aprobado por la
1. Enfermedades musculo-esqueleticas
2. Enfermedades respiratorias agudas
3. Enfermedades de la cavidad bucal
4. Enfermedades ginecolgicas
1. ENFERMEDADES MUSCULOESQUELETICAS
Mialgias y artralgias
Artrosis
Contusin muscular
Artritis
Distensin muscular
Gota
Espasmo muscular
Post operatorio
Bursitis
Tenosinovitis
Tendinitis
Luxaciones
Esguinces
2. ENFERMEDADES
RESPIRATORIAS AGUDAS
Controla la inflamacin y el exudado por lesin de tejidos blandos
til junto con el antibitico en procesos infecciosos con inflamacin
Otitis
Sinusitis
Amigdalitis
Amigdalectoma/tonsilectoma
Faringitis
Bronquitis
3. ENFERMEDADES DE LA
CAVIDAD BUCAL
Periodontitis
Pulpitis
Gingivitis
Odontalgias
4. ENFERMEDADES
GINECOLGICAS
Dismenorrea
Anexitis
Postinsercin de DIU
+ antibiticos en IVU
AINES
EFECTOS
INDESEABLES
Many adverse reactions are associated with the use of the
NSAIDs. However, many patients take these drugs and
experience few, if any, side effects.
Some of the adverse reactions associated with the use of
these drugs are listed here:.
ADVERSE REACTIONS
Gastrointestinal tract: nausea, vomiting, diarrhea, constipation, epigastric pain, indigestion,
abdominal distress or discomfort, intestinal ulceration, stomatitis, jaundice, bloating, anorexia,
and dry mouth
CNS dizziness, anxiety, lightheadedness, vertigo, headache, drowsiness, insomnia, confusion,
depression, and psychic disturbances
Cardiovascularcongestive heart failure, decrease or increase in blood pressure, and cardiac
arrhythmias, IAM.
Renalhematuria, cystitis, elevated blood urea nitrogen, polyuria, dysuria, oliguria, and acute
renal failure in those with impaired renal function
Special senses: visual disturbances, blurred or diminished vision, diplopia, swollen or irritated
eyes, photophobia, reversible loss of color vision, tinnitus, taste change, and rhinitis
Hematologic: neutropenia, eosinophilia, leukopenia, pancytopenia, thrombocytopenia,
agranulocytosis, and aplastic anemia
Skin: rash, erythema, irritation, skin eruptions, exfoliative dermatitis, Stevens-Johnson
syndrome, ecchymosis, and purpura
Metabolic/endocrinologic: decreased appetite, weight increase or decrease, hyperglycemia,
hypoglycemia, flushing, sweating, menstrual disorders, and vaginal bleeding
Other: thirst, fever, chills, and vaginitis
GASTROINTESTINALES:
N-v, pirosis, gastralgias, hematemesis,
melenas y perforaciones GI.
The NSAIDs prolong bleeding time and increase the effects of anticoagulants, lithium,
cyclosporine, and the hydantoins. These drugs may decrease the effects of diuretics or
antihypertensive drugs.
Long-term use of the NSAIDs with acetaminophen may increase the risk of renal impairment.
AINES
CONTRAINDICACIONES
Hipersensibilidad:
Urticaria, edema facial, Sibilancias, disnea.
rinitis alrgica.
PRECAUCIONES
Pctes con antecedentes digestivos de:
Gastritis
lceras
Sangrado
Perforacin
Disfuncin renal
1.
DERIVADOS DEL
ACIDO SALICILICO
(Ac acetil salicilico o ASA, Acetil salicilato de Lisina, salicilato de Na,
Trisalicilato de colina magnesica, Sulfazalacina, Olsalazina, salsalato,
berorilato y diflunisal)
2.
3.
5. Efectos Metablicos
+ sobredosificacin: hiperglicemia y glucosuria.
Balance nitrogenado negativo y reduccin de la
lipognesis. Acidosis metabolica.
6. Efectos locales.
Aplicado tpicamente tienen efecto queratolitico
(callicida y verrugas).
2.
3.
November 4, 2012. NEJM
In 1977, aspirin (at a dose of 600 mg twice daily) was shown to reduce the risk of venous thrombosis when it was given to patients after they had undergone hip
arthoplasty.2 Thirty-five years later, guidelines include aspirin as one option for preventing venous thromboembolism after orthopedic surgery.3 However, many experts
regard aspirin as inferior therapy for this indication, preferring treatment with conventional anticoagulants (heparin, fondaparinux, or warfarin) or the new oral agents
(dabigatran or rivaroxaban). In part, this approach reflects scientific considerations: anticoagulants are especially active in the low-flow, low-shear venous vasculature
where fibrin-rich clots form in contrast to the high-flow, high-shear arterial circulation where platelet adhesion and aggregation are more important. But it also reflects
the superior efficacy albeit shown through indirect comparisons of anticoagulants over aspirin in postoperative patients.3
Is there a clinical setting in which a moderate venous thromboembolismpreventing activity of aspirin can be exploited? For patients who have had unprovoked venous
thromboembolism, the risk of a recurrence of venous thromboembolism after initial active treatment with warfarin, dabigatran, or rivaroxaban for 3 to 12 months (or
even longer) rises transiently to as high as 20 events per 100 patient-years (and even higher if the active treatment period is <3 months) before settling at a long-term rate
of about 5 events per 100 patient-years. Effect of Aspirin on Risk of Recurrence of Venous Thromboembolism (VTE) and Major Vascular Events.).7 Could aspirin
represent a reasonable intermediate option between the extremes of indefinite anticoagulation and no ongoing anticoagulation, particularly from the additional
perspective of concomitant prevention of arterial thrombosis? Indeed, a dual benefit of aspirin in both arterial and venous circulations might be expected: atherosclerosis
is a risk factor for unprovoked venous thromboembolism,8 and patients with idiopathic venous thromboembolism are at increased risk for subsequent arterial
cardiovascular events.9
Two recent clinical trials, the Warfarin and Aspirin (WARFASA) study4 and the Aspirin to Prevent Recurrent Venous Thromboembolism (ASPIRE) study,5 evaluated
aspirin as compared with placebo in patients with unprovoked venous thromboembolism who had completed initial treatment with heparin followed by warfarin for a
minimum of 6 weeks (most received therapy for at least 3 months). Both studies used identical low-dose aspirin regimens (100 mg per day) and had similar enrollment
criteria and outcome measures, making them amenable to meta-analysis. Together, these two studies indicate that aspirin reduces by one third the rate of recurrence of
venous thromboembolism as well as the rate of major vascular events, a composite outcome of venous thromboembolism, stroke, myocardial infarction, or
cardiovascular death. Moreover, these benefits were achieved with a low risk of bleeding.
The WARFASA study,4 in which 402 patients were included in the analyses, showed a 42% reduction in the rate of recurrence of venous thromboembolism with aspirin
as compared with placebo (rate of recurrence, 6.6% vs. 11.2% per year; hazard ratio with aspirin, 0.58; 95% confidence interval [CI], 0.36 to 0.93; P=0.02); however, a
few more patients in the aspirin group than in the placebo group had arterial events (8 patients vs. 5 patients), and the rate of the secondary end point of major vascular
events (i.e., venous thromboembolism, myocardial infarction, stroke, or cardiovascular death) was nonsignificantly reduced with aspirin (hazard ratio, 0.67; 95% CI, 0.43
to 1.03; P=0.06).
In contrast, as now reported in the Journal, 5 the ASPIRE trial, which involved 822 patients, showed a nonsignificant decrease in the rate of recurrent venous
thromboembolism with aspirin as compared with. However, since arterial thrombotic events occurred only about half as often in the aspirin-treated group as in the
placebo group (10 events vs. 19 events), aspirin was associated with a significant reduction in the rate of major vascular events.
When data from these two trials were pooled, there was a 32% reduction in the rate of recurrence of venous thromboembolism (hazard ratio, 0.68; 95% CI, 0.51 to 0.90;
P=0.007) and a 34% reduction in the rate of major vascular events (hazard ratio, 0.66; 95% CI, 0.51 to 0.86; P=0.002).
How should these studies influence practice? Before physicians consider prescribing aspirin for patients who have had acute unprovoked venous thromboembolism, it is
important that they treat the patients with effective anticoagulation for at least 3 months, to avoid the high risk of early recurrence. For patients who then wish to stop
anticoagulation, a switch to aspirin at a dose of 100 mg daily will reduce by one third the risk of recurrent venous thromboembolism, as well as of arterial cardiovascular
events, and may also attenuate the early burst of thrombosis recurrence after cessation of oral anticoagulation. Aspirin is inexpensive, does not require monitoring (in
contrast to warfarin), and does not accumulate in patients with renal insufficiency (in contrast to dabigatran and rivaroxaban); in addition, if major bleeding occurs or the
patient requires urgent surgery, the antiplatelet effects of aspirin can be reversed with transfusion of platelets. Among patients with unprovoked venous
thromboembolism who have completed initial anticoagulation, aspirin would seem to be a reasonable option for long-term dual prevention of recurrent venous
thromboembolism and arterial cardiovascular events.
Reyes syndrome
CONTRAINDICACIONES:
Ulcera peptica. Nios < de 12 aos con viruela,
varicela, o gripe no deben usar esta medicina sin
antes haber consultado al medico.
Symptoms of Salicylism
Dizziness
Tinnitus (a ringing sound in the ear)
Impaired hearing
Nausea
Vomiting
Flushing
Sweating
Rapid deep breathing
Tachycardia
Diarrhea
Mental confusion
Lassitude
Drowsiness
Respiratory depression and coma (large doses)
This study included more than 100,000 men and women without a history of
cancer, some of whom were taking aspirin daily. Of the study participants, 5 138
eventually died from cancer.
Aspirin use was associated with an up to 16 percent lower risk of dying from
cancer, which, however, was less than that seen in another recent stud. Aspirin
use reduced cancer deaths by 37 percent during five years of follow-up and 15
percent during 10 years of follow-up.
"Although recent evidence about aspirin use and cancer is encouraging, it is still
premature to recommend people start taking aspirin specifically to prevent
cancer. Even low-dose aspirin can substantially increase the risk of serious
gastrointestinal bleeding. Decisions about aspirin use should be made by
balancing the risks against the benefits in the context of each individual's medical
history
2. DERIVADOS DEL
ACIDO ACETICO
Derivados indol e indenos
indometacina, sulindaco y bencidamina.
a. Indometacina
1.
Es inhibidor irreversible no
selectivo de la COX-1.
1.
2.
3.
Indometacina-Farmacocintica
1.
2.
3.
4.
5.
Indometacina-Farmacocintica
6.
7.
8.
9.
Indometacina-Efectos Adversos
1. Todos los efectos adversos que aparecen con este
frmaco estn en estrecha relacin con la dosis.
2. Un 35-50% de los pctes que reciben dosis
teraputicas presentan sntomas indeseables. Un
20% abandona.
3. Trastornos GI. (anorexia, nuseas, dolor
abdominal, lceras que pueden evolucionar a la
perforacin y hemorragia con trastornos anmicos
posteriores); pancreatitis aguda, diarreas (como
consecuencia de lesiones ulcerosas en el intestino) y
algunos casos letales de hepatitis e ictericia.
Indometacina-Contraindicaciones
1.
2.
3.
Enfermedad de Parkinson
4.
Epilepsia
5.
Nefropatas
6.
Enfermedades clorhidroppticas
7.
Embarazadas y lactancia
Indometacina-Aplicaciones
teraputicas
1.
2.
3.
Indometacina-Dosis
1. Debe comenzar el Tx con no ms de 25 mg (2
veces/d), subiendo la dosis (25-50 mg/d) cada
semana hasta alcanzar el efecto deseado o la
aparicin de reacciones adversas o una dosis de
150 mg/d.
2. No se requiere modificar la dosis en pctes con
insuficiencia renal.
3. En los ancianos deben tomarse las mismas
precauciones que con aspirina.
b. SULINDACO
Prodroga que se metaboliza en un
metabolito sulfido activo con una potencia
500 v > de inhibir a COX.
Usado como:
antirreumtico, tocoltico, actualmente
usado para plipos intestinales.
c. BENCIDAMINA
Efectos antiiflamatorios, anestsicos locales y ligero
efecto anticolinrgico.
Uso tpico como antiinflamatorio:
En odontologa se lo usa para lavados bucales
En ginecologa se lo usa para lavados vaginales en
concentraciones del 0.5%: cervicitis, vaginitis y
colpitis.
3. DERIVADOS
HETROARIL ACETICOS
Diclofenaco, aceclofenaco y
ketorolaco.
a. DICLOFENACO
SDICO y POTSICO
Inhibidor no selectivo de la COX, de muy
alta eficacia clnica que comparte la
mayora de las acciones farmacolgicas y
efectos adversos del resto de los AINEs.
D Na
Biodisponibilidad: 80%
1h
Sustancia
Diclofenaco
1,6%
Ibuprofeno
2,5%
0
2,5%
5%
Evolucin de la enfermedad
ANTIBITICO
DICLOFENACO + ANTIBITICO
5,5 das
3 das
INDICACIONES
1.
Osteoartritis
2.
Espondilitis anquilosante
3.
Artritis reumatoidea
4.
Tendinitis bicipital
5.
Bursitis subdeltoidea
6.
Dismenorrea
7.
Dolor postoperatorio
8.
DOSIS
Diclofenac sdico
Diclofenac potsico
b. KETOROLACO
Derivado del cido actico
con una importante
actividad antipirtica,
analgsica; esta ltima
de mayor nivel que la
antiinflamatoria.
En dolores severos
KETOROLACO
FARMACOCINTICA
1. Por VO e IM, alcanza concentraciones
plasmticas mx en 30-50 min.
2. Su biodisponibilidad oral es del orden del 80%.
3. El 90% de la droga se elimina por orina, la
mayor parte sin modificarse (60%) y el resto en
forma de metabolitos conjugados con
glucurnido.
4. La t de eliminacin es de 5-6 hs.
KETOROLACO
EFECTOS ADVERSOS
1.
2.
3.
4.
KETOROLACO
INDICACIONES
Hasta el presente se ha utilizado como
analgsico en los postoperatorios y en
patologas con dolor agudo y severo (por
ejemplo clico renal).
Tambin en forma de colirio para el Tx de
la conjuntivitis alrgica estacional.
4. DERIVADOS DEL
ACIDO PROPIONICO
Ibuprofeno, Naproxeno, Fenoprofeno,
Ketoprofeno y Flurbiprofeno.
1.
2.
3.
sintomtico
de
la
osteoartritis,
aguda.
a. IBUPROFENO
El ibuprofeno es un compuesto
quiral constituido por S(+)
ibuprofeno y R(-) ibuprofeno.
El S(+) ibuprofeno es el
enantimero responsable de la
inhibicin de la COX y,
R(-) ibuprofeno contribuira a la
accin farmacolgica del
ibuprofeno por su accin
antineutrofila y porque se
biotransforma
unidireccionalmente a S(+)
ibuprofeno a nivel heptico.
Ibuprofeno-Farmacocintica
1.
2.
3.
4.
Su t de eliminacin es de 2 h.
5.
Ibuprofeno-Efectos adversos
-Se encuentra en teraputica desde hace ms de 20 aos y es
considerado uno de los AINEs ms seguros.
b. Naproxeno
1. La velocidad de absorcin
est influenciada por los alimentos.
1.
2.
3.
4.
Naproxeno-Efectos adversos
6.
7.
+++ Gastrointestinales,
+SNC (iguales a los de la indometacina) aunque de <
intensidad. Too puede producir somnolencia, sudacin,
fatiga, ototoxicidad y depresin.
5. DERIVADOS FENAMICO Y
ANTRANILICOS
Acido mefenamico o fenamatos
-En desuso x
diarrea y potencial hemoltico
-No ventaja sobre otros AINES
6. OXICAMOS
Piroxicam, tenoxicam y meloxicam
PIROXICAM
(artronil, feldene)
Restringido en Europa !! x hemorragia GI y
reacciones dermatolgicas graves.
a. Piroxicam-Efectos Adversos
Son GI (que ocasionan el
tratamiento en el 5 % de pctes).
abandono
del
b. MELOXICAM
Este AINEs, a diferencia de los anteriores es
inhibidor preferencial de la COX-2.
De esta manera mantienen sus propiedades
analgsicas, antipirticas y antiinflamatorias con
mejor tolerabilidad gastrointestinal y un mejor
perfil de seguridad a nivel renal (?).
Su farmacocintica es similar a piroxicam con la
excepcin de la t de eliminacin que es 15-20 hs.
La DOSIS recomendada es de 7,5 mg QD en
osteoartritis y de 15 mg/da en casos graves o en
artritis reumatoidea. CO??
7. ALCANONAS
a. Nabumetona
Es un dbil inhibidor de la COX que tiene propiedades
antiinflamatoria, analgsica y antipirtica.
Farmacocintica
Luego de su administracin por v.o., se transforma en hgado
en metabolitos activos, dentro de los cuales se ubica el cido
6-metoxi-2-naftilactico, que es potente inhibidor de la
COX-2. Este metabolito se inactiva por O-desmetilacin en
hgado para luego conjugarse y excretarse por va renal.
Su t de eliminacin es de 24 hs.
Nabumetona
Efectos adversos
Baja toxicidad GI y renal.
Igualmente, se han descrito alteraciones a nivel intestinal,
heptico, prurito y cefaleas.
Aplicaciones teraputicas y dosificacin
La dosis estudiada en pacientes con osteoartritis y artritis
reumatoidea fue de 1.000 mg/da en una sola toma.
Con la misma dosis, la nabumetona ha demostrado ser
eficaz en tratamiento cortos de procesos inflamatorios de
tejidos blandos.
MISCELANEO
Nimesulida
Retirado !!
Es sulfonanilida.
Inhibicin preferencial de la sntesis de Pg va inhibicin
de COX-2.
Too bloquea la funcin leucocitaria tanto in vitro como in
vivo. Este efecto es mucho ms notable en la repuesta
oxidativa de PMN y la liberacin de mediadores de la
inflamacin. Tambin bloquean la actividad de la metaloproteinasa de los condrocitos articulares y su metabolito
(4-hidroxinimesulida).
Nimesulida-Farmacocintica
La nimesulida, administrada VO se absorbe rpida y
completamente alcanzando la Cmax entre 3 y 4 h.
La biodisponibilidad por va rectal es 70 - 90%.
La unin a protenas plasmticas es >95 %.
Su t de eliminacin es de 5-6 h. Su metabolismo genera 4
hidroxi derivados que son eliminados en su mayor parte
por orina.
Nimesulida-Efectos AdversosDosificacin
La incidencia de efectos adversos es del 5% siendo los
principales los que afectan al Hgado, SNC, piel y GI.
Dosificacin
Adultos : 100 a 200 mg/d. NO + de 5 d
Nios : 5 mg/kg/d en 2 tomas. EVITAR en .
inhibidores selectivos-COX-2
1996
Meloxicam
1997
Nimesulida
1999
Celecoxib (Celebrex)
Rofecoxib (Vioxx-MSD, retirado)
2001
2002
5.
inhibidores selectivos-CoX-2
1996
Meloxicam
1997
Nimesulida
1999
2001
2002
Celecoxib
Rofecoxib
Valdecoxib
Parecoxib
Etoricoxib
Fosfolipasa A2
Glucocorticoides
inducible
y constitutiva en
rion, cerebro y
endotelio (PgI).
Troboxano A2
Agregacin plaquetaria y
vasoconstrictor
Prostaciclina
(PGI2). Inh
Aspirina a dosis baja inh COX-1 y x ende inh a Tromboxano A2= inh agregacion agregac plaquet y
vasodilatador
plaquetariapero a dosis terapeutica se hace mas selectiva a COX-2 o
los COX-2 selectivos ya no inh a Tx-A2
-Desarrollo folicular y ruptura, *x meloxicam CO?)
BENEFICIOS
infarto ,
angina,
HTA,
hiperlipidemia,
meses).
3. El riesgo de dao renal es = a los AINES
convencionales (viejos, post-cirugia, dao
renal) (Funcion renal es mantenida x Pg via
de COX-2).
4. No son modificadores de la enfermedad (ejm.
Metrotexate) en AR.
5. Caros (USD)
6. Usar con precaucion en pctes con falla renal y
cardiaca e HTA (monitoreo).
7. Interacciones medicamentosas (too otros
AINES): AnticoagO, prednisona, diureticos,
B- bloq, inh ACE I otros anti-HTA.
8. NO a pctes con historia o riesgo de
coronariopatias, HTA, etc
la recurrencia
colonicos.
de
polipos
FDA-Bextra
Bextra (valdecoxib tablets): FDA has concluded that the overall risk versus
benefit profile is unfavorable at this time and has requested the manufacturer
of Bextra, Pfizer, Inc., to voluntarily withdraw Bextra from the market. This
request is based on:
the lack of adequate data on the cardiovascular safety of long-term use of
Bextra, along with the increased risk of adverse CV events in short-term
coronary artery bypass surgery (CABG) trials that FDA believes may be
relevant to chronic use,
reports of serious and potentially life-threatening skin reactions, including
deaths, in patients using Bextra. The risk of these serious skin reactions in
individual patients is unpredictable, occurring in patients with and without a
prior history of sulfa allergy, and after both short- and long-term use, and
the lack of any demonstrated advantages for Bextra compared with other
NSAIDs.
Pfizer has agreed to suspend sales and marketing of Bextra in the U.S. pending
further discussions with the agency.
FDA-Celecoxib
Celebrex (celecoxib tablets): We have concluded that the benefits of Celebrex outweigh
the potential risks in properly selected and informed patients. FDA has decided to allow
Celebrex to remain and has asked Pfizer to take the actions listed below:
Revise the Celebrex label to include a boxed warning containing the class NSAID
warnings and contraindication about CV and GI risk, plus specific information on the
controlled clinical trial data that demonstrate an increased risk of adverse CV events for
celecoxib.
Encourage practitioners to use the lowest effective dose for the shortest duration
consistent with individual patient treatment goals.
Include a Medication Guide as part of the labeling. It will be required to be given at the
time the drug is dispensed to inform patients of the potential for CV and GI risk
associated with NSAIDS, in general, and Celebrex specifically. The Medication Guide
will inform patients of the need to discuss with their doctor the risks and benefits of
using NSAIDs and the importance of using the lowest effective dose for the shortest
duration possible.
Commit to conduct a long-term study of the safety of Celebrex compared to naproxen
and
other
appropriate
drugs.
FDA-Vioxx
Vioxx (rofecoxib tablets and suspension): Vioxx
was voluntarily removed from the market by
Merck in September 2004. FDA will carefully
review any proposal from Merck for resumption
of marketing of Vioxx, and would likely discuss
the review with the new FDA Drug Safety
Oversight Board and an Advisory Committee
before making a final decision.
FISIOLGICAMENTE la COX-2
Gran riesgo de
trombosis
Inclusion criteria were active or placebo (inert carrier)controlled trials in adults with strains, sprains, or
sports or overuse-type injuries causing acute pain, with 10 or more participants in each treatment group,
and treatment application at least once daily.
Two reviewers independently examined trial quality and validity and extracted data from 47 included
studies enrolling a total of 3455 participants for overall efficacy analysis. Most of the identified studies
compared topical NSAID gel, spray, or cream vs a similar placebo, Relative risk and numbers needed to
treat or number needed to harm for topical NSAIDs vs placebo or other active treatment were determined
from numbers of participants achieving each outcome.
The number needed to treat for clinical success, defined as 50% pain relief, for all topical NSAIDs
combined vs placebo was 4.5 (95% confidence interval [CI], 3.9 - 5.3) for treatment periods of 6 to 14
days. Although topical diclofenac, ibuprofen, ketoprofen, and piroxicam were similarly effective,
indomethacin and benzydamine were not significantly more effective than placebo.