MONTELUKAST

Actualización de sus indicaciones terapéuticas

Dr. Gonzalo Castillo Barreda

Pediatra
 LEUCOTRIENOS
 Eicosanoides que actúan como potentes mediadores pro-inflamatorios.

 Originados en las membranas celulares gracias a la acción de las fosfolipasas-

A2.

 Derivados del Acido Araquidónico, que se sintetizan gracias a la acción

catalítica secuencial de la 5-lipooxigenasa.

 Síntesis ocurre en diferentes células incluyendo: eosinófilos, neutrófilos,

basófilos, linfocitos, macrófagos y mastocitos.
 Fosfolípidos de membrana
Lesión
Fosfolipasa A2 Tisular

Ácido Araquidónico

COX-1
5-Lipooxigenasa
Ciclooxigenasa

COX-2
5-HETE
12-Lipooxigenasa 15-Lipooxigenasa

TXB2
Tromboxano
LT A4 Sintetasa
PROSTANOIDES

12-HETE LIPOXINAS A -B Peroxidasas Prostaciclina

TXA2
Sintetasa

LT C4 LT B4
SNC
LT D4 PGI2 Endotelio
Riñón
LT E4 Plaquetas

Bronquios
Piel
Macrófagos
PGD2 PGF2
Bronquios Neutrófilos
Eosinófilos
 Fosfolípidos de membrana
AG /
AC
Fosfolipasa A2

Ácido Araquidónico
O2

5-Lipooxigenasa

5-HETE

H2O

LTA4 -Hidrolasa
LT A4

Glutation

LT B4 LT C4 Bronquios
Ac. Glutámico Glutamil transpeptidasa Piel
Macrófagos
LT D4
Bronquios Neutrófilos
Glicina Cisteinil-glicina dipeptidasa
Eosinófilos
LT E4
LEUCOTRIENOS

El paso final en la síntesis de los leucotrienos ocurre

subsecuentemente a través de dos pasos separados
que producen:

Leucotrieno B4 (LTB4) y
Cisteinil leucotrienos (LTC4, LTD4 y LTE4).
 LEUCOTRIENOS
Cisteinil - Leucotrienos ( CysLT )

Mediadores clave de la respuesta alérgica e inflamatoria.

Responsables de los síntomas del asma, las reacciones

atópicas y anafilácticas.
LEUCOTRIENOS

Receptores CISTEINIL- LEUCOTRIENOS

Los cisteinil-leucotrienos ejercen sus acciones biológicas al

unirse y activar a los receptores específicos: CysLT1r y
CysLT2r .

Estos subtipos de receptores de leucotrienos han sido

identificados farmacológicamente, pero sus estructuras
moleculares no son del todo conocidas.
LEUCOTRIENOS
ANTILEUCOTRIENOS
 ANTILEUCOTRIENOS

INHIBIDORES Y ANTAGONISTAS DE LOS LEUCOTRIENOS

 Farmacológicamente, existen dos mecanismos para inhibir la acción de los

leucotrienos:

 inhibiendo su producción bloqueando la 5-LOX (inhibidor)

 por bloqueo de sus receptores (antagonistas)
 ANTILEUCOTRIENOS

INHIBIDORES Y ANTAGONISTAS DE LOS LEUCOTRIENOS

 Todos los antagonistas disponibles al momento, ejercen su acción en el

único receptor que se ha demostrado que juega un papel importante en el
asma y otros procesos atópicos: CysLT1

 Actúan de forma competitiva.

ANTILEUCOTRIENOS

INHIBIDORES Y ANTAGONISTAS DE LOS LEUCOTRIENOS

 Múltiples estudios han demostrado que estos agentes

farmacológicos mejoran los síntomas de la rinitis alérgica, en el
asma, la función pulmonar y que mejoran la calidad de vida de los
pacientes.

 Se asocian con una baja incidencia de efectos adversos y tienen

una muy buena tolerabilidad.
ANTILEUCOTRIENOS

MONTELUKAST

 El montelukast es el más reciente de los antagonistas de los receptores de los leucotrienos

que ha sido aprobado.

 Es el único antileucotrieno cuyo uso es aprobado en niños desde los seis años de edad. Se
administra una vez al día, vía oral, con la ventaja que su biodisponibilidad no es afectada por
los alimentos en los adultos y mínimamente afectado en los niños.

 No inhibe las isoenzimas CYP2C9 y CYP3A4 del citocromo P450 con lo que presenta muchas
menos interacciones con otros fármacos.
ANTILEUCOTRIENOS

Farmacocinética:
 Concentraciones plasmáticas máximas entre las 2.5- 4 horas.

 La biodisponibilidad global oscila, entre el 65 y el 75% y puede disminuir

con la comida, si bien la eficacia clínica no se ve afectada.

 Unión a las proteínas del plasma (>99%)

 Volumen de distribución pequeño.

 No atraviesa la barrera hematoencefálica,

 ANTILEUCOTRIENOS

 Actúa solamente sobre los receptores CysLT1, no antagonizando las contracciones del músculo
liso producidas por la acetilcolina, la histamina, la serotonina o las prostaglandinas.

 No interacciona con warfarina, terfenadina, teofilina, prednisona, digoxina ni anticonceptivos

orales.

 El fenobarbital reduce la concentración plasmática del montelukast.

 La semivida de eliminación: 2.7 a 5.5 horas,

 Eliminado, conjuntamente con sus metabolitos, casi exclusivamente por vía biliar.
ANTILEUCOTRIENOS

MONTELUKAST

 La dosis recomendada:

Adultos: 10 mg / día
Niños 6-12 años: 5 mg/ día
Menores de 6 años: 4 mg/ día
INDICACIONES DEL MONTELUKAST
MONTELUKAST

 Su eficacia clínica ha sido demostrada en diversos estudios aleatorios,

controlados.

 VENTILAR provee un discreto efecto broncodilatador en pacientes con asma

leve a moderada, pocas horas posterior a la primera administración.

 Tratamientos más largos (1 a 6 meses), han inducido un incremento progresivo

y dosis dependiente del FEV1, junto con una significativa eficacia sobre
síntomas, consumo de broncodilatadores de acción corta y sobre el uso de
corticoides sistémicos.
MONTELUKAST
MONTELUKAST
 NUEVOS USOS TERAPEUTICOS
Basados en la evidencia científica.
DERMATITIS ATOPICA
Montelukast treatment in children with moderately severe
atopic dermatitis
M.-S. Ehlayel, MD, FAAP, FACAAI ; A. Bener, PhD, FFPH, FRSS, A. Sabbah, MD

Eur. Annals of Allergy and Clinical Immunology • October 2007

Method:
Randomized, double blind, placebo-controlled crossover trial with washout period,
conducted from May 2002 to February 2006. The study involved 25 patients, 2-16 years old
with dermatitis, receiving montelukast.

Conclusion:
This study showed that montelukast reduces itching, sleep disturbance, disease extent and
severity, blood eosinophil count and serum IgE.
 OTRAS EVIDENCIAS CLINICAS:
MONTELUKAST en DERMATITIS ATOPICA
Author(s), Method Duration Subjects Intervention Outcomes Results
Date Measured
Pei, A.Y. Randomized 12 weeks 15 subjects Montelukast 5mg OD Impact of eczema on Statistically significant
(2001)52 double-blind age 6-16 yr vs. placebo daily living (subjective) improvement in severity
placebo-controlled mod-severe AD Disease extent, severity of AD in patients on
crossover study (objective) active treatment
compared with placebo
(p<0.05)

Yanase,D and Randomized 8 weeks 8 subjects Montelukast 10mg OD Clinical severity scores Improvement in:
David-Bajar, K. double-blind, adult (male and vs. placebo (6 signs of AD) • Scaling/dryness
(2001)53 placebocontrolled, female) Continuous adjunctive (p=0.003)
crossover study with AD treatment: emollients, • Lichenification
antihistamines, weak (p=0.009)
topical corticosteroids • Induration (p=0.016)
• Erythema (p=0.024)
• Erosions (p=0.027)

Capella, GL. Randomized 6 weeks 20 males Montelukast 10 mg OD SCORAD index Significant reduction in
(2001)31 double-blind Age range: 18-28 n=10) vs. placebo (n=10) (objective and disease activity
study yr. Severe AD No other treatment for subjective criteria). (measured by SCORAD
(SCORAD index) AD index) in the montelukast
allowed. group compared with
placebo group. (p<0.02)
HIPERTROFIA de ADENOIDES
Montelukast in Adenoid Hypertrophy: Its Effect
on Size and Symptoms
Farshid Shokouhi, Ahmad Meymaneh Jahromi, Mohamad Reza Majidi, Maryam Salehi

Iranian Journal of Otorhinolaryngology, Vol.27(6), No.83, Nov 2015

Methods: 60 children between the ages of 4–12 years with >75% choanal
obstruction on primary nasal endoscopy were recruited in this randomized, placebo-
controlled trial divided into two groups. The study group was treated with
montelukast 5 mg daily for 12 weeks while the control group received matching
placebo for the same period of time.
Results: Adenoid size decreased in 76% of the study group compared with 3% of
the placebo group after 12 weeks.
Conclusion: Montelukast chewable tablets achieved a significant reduction in
adenoid size and improved the related clinical symptoms of AH and can therefore be
considered an effective alternative to surgical treatment in children with adenoid
hypertrophy.
APNEA OBSTRUCTIVA DEL SUEÑO (OSA)
Montelukast for Children With Obstructive Sleep
Apnea: A Double-blind, Placebo-Controlled Study
Aviv D. Goldbart, MD, MSc; Sari Greenberg-Dotan, PhD,
Asher Tal, MD

PEDIATRICS Volume 130, Number 3, September 2012

Conclusion:
There is increasing evidence that even mild OSA may be associated with significant cognitive,
behavioral, and vascular morbidity. This sequel may have a major impact on quality of life and
health care costs. The results of this study supported the introduction of a leukotriene modifier as a
novel, safe, therapeutic alternative for the treatment of children with a non-severe form of OSA.
Montelukast potentially efficacious in children with non-
severe obstructive sleep apnea in the short term
Joanna E MacLean

Evid Based Med October 2013 . volume 18 , number 5 ; 173 -174

Method: This study was conducted in a single tertiary care centre in a metropolitan
area. This is a double-blind randomised placebo-controlled trial of montelukast for
the treatment of non-severe OSA in children. The population for recruitment was
children referred for evaluation of snoring. Subjects were 2–10 years of age,
had habitual snoring, non-severe OSA (defined as an apnoea/hypopnoea index <10
events/h) and were naive to montelukast therapy as well as adenotonsillectomy.
Conclusion: The current study does support the use of montelukast as safe and
potentially efficacious in children with non-severe OSA, at least as short-term
therapy.
OTITIS MEDIA CON EFUSION
 The effect of montelukast sodium on the duration of effusion of
otitis media.
Combs JT. Clin Pediatr (Phila). 2004 Jul-Aug;43(6):529-33.
Objective:
This study tests the hypothesis that montelukast sodium, will decrease the duration of the effusion of otitis media.

Method: Tympanometry and spectral gradient acoustic reflectometry were used to confirm the effusion of otitis media in
patients between 2 and 12 years of age. Patients were treated with amoxicillin for 10 days and montelukast sodium or placebo
for 30 days in a random, double-blind manner. Sixty patients completed the study: 31 received placebo and 29 received
montelukast sodium. At a 4-week follow-up visit, 5 ears (16%) were free of effusion in the placebo group and 17 (58%) in the
montelukast sodium group.

Conclusions:
The difference was significant. The efficacy of montelukast sodium in clearing the effusion was 58%.

PMID: 15248005
 Improvement of otitis media with effusion after treatment of asthma with leukotriene
antagonists in children with co-existing disease.

Balatsouras DG , Eliopoulos P , Rallis E , Sterpi P , Korres S , Ferekidis E Department of Otolaryngology, Tzanion General
Hospital, Piraeus, Greece. Drugs Under Experimental and Clinical Research [2005, 31 Suppl:7-10]

 Objective:
 The aim of this study was to evaluate the impact of leukotriene inhibitor therapy for asthma on the clinical course of OME in children with co-existing
disease.

 Method: Comparative study. Fifty children with bilateral OME and asthma, divided equally into two groups, were studied. The children in the first group
were treated with budesonide and terbutaline inhalers together with the leukotriene inhibitor montelukast, whereas the children in the second group were
treated with the inhalers alone. Duration of treatment was 30 days. Pneumatic otoscopy, tympanometry and pure-tone audiometry were performed at the
beginning and at the end of treatment.

 Results: Fifteen (60%) of the children receiving inhalers and montelukast and nine (36%) of those receiving only inhalers were found free of OME after 30
days of therapy.

 Conclusion: Thus, it may be concluded that a statistically significant beneficial effect on the clinical course of OME resulted from the addition of
montelukast to the treatment of children with co-existing asthma and OME.
 VENTILAR®

COMPOSICION : Montelukast Sódico

Cada Comprimido recubierto de VENTILAR® 10 contiene10mg de Montelukast sódico

Cada Comprimido masticable de VENTILAR® 5 contiene 5mg de Montelukast sódico
Cada Comprimido masticable de VENTILAR® 4 contiene 4mg de Montelukast sódico

PRESENTACIONES

VENTILAR® 10: Comprimidos recubiertos de 10mg x 10.

VENTILAR® 5: Comprimidos masticables sabor a tutti-chicle de 5mg x 10
VENTILAR® 4: Comprimidos masticables sabor a naranja de 4mg x 10
MUCHAS GRACIAS…