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Montelukast GH 4mg, 5mg and 10mg
NAME OF MEDICINE
Montelukast sodium, the active ingredient in Montelukast GH, is a selective and orally active
leukotriene receptor antagonist that inhibits the cysteinylleukotriene
structural formula is:
CAS Number: 151767-02-1
Montelukast sodium is a hygroscopic, optically active, white to off-white, free-flowing
powder. Montelukast sodium is freely soluble in ethanol, methanol, and water and practically
insoluble in acetonitrile. Montelukast is the optically active R stereoisomer.
Each 10-mg tablet contains 10.4 mg montelukast sodium, which is equivalent to 10.0 mg of
montelukast, the free acid. Each 5-mg chewable tablet contains 5.2 mg montelukast sodium,
which is equivalent to 5.0 mg of montelukast, the free acid. Each 4-mg chewable tablet
contains 4.16 mg montelukast sodium, which is equivalent to 4.0 mg of montelukast, the free
Each 10-mg tablet contains the following inactive ingredients: mannitol, microcrystalline
aspartame and magnesium stearate. Each 4-mg and 5-mg chewable tablet contains the
croscarmellose sodium, cherry flavour, aspartame, and magnesium stearate.
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released from various cells including mast cells and eosinophils. These important pro-
asthmatic mediators bind to cysteinyl leukotriene (CysLT) receptors. The CysLT type-1
(CysLT1) receptor is found in the human airway (including airway smooth muscle cells and
airway macrophages) and on other pro-inflammatory cells (including eosinophils and certain
myeloid stem cells). CysLTs have been correlated with the pathophysiology of asthma and
allergic rhinitis. In asthma, leukotriene-mediated effects include a number of airway actions,
recruitment. In allergic rhinitis, CysLTs are released from the nasal mucosa after allergen
exposure during both early- and late-phase reactions and are associated with symptoms of
allergic rhinitis. Intranasal challenge with CysLTs has been shown to increase nasal airway
resistance and symptoms of nasal obstruction. The clinical relevance of intranasal challenge
studies is unknown.
Montelukast is an orally active compound which has been shown in asthmatic patients to
reduce peripheral blood eosinophil counts and sputum eosinophils
which are parameters of
pharmacological bioassays, it binds with high affinity and selectivity to the CysLT
(in preference to other pharmacologically important airway receptors such as the prostanoid,
cholinergic, or β-adrenergic receptor). Montelukast potently inhibits physiologic actions of
, and LTE
at the CysLT
receptor without any agonist activity.
In asthmatic patients, montelukast causes potent inhibition of airway cysteinyl leukotriene
receptors as demonstrated by the ability to inhibit bronchoconstriction due to inhaled LTD
Montelukast causes bronchodilation within 2 hours of oral administration. β-agonists caused
additive effects when added to montelukast.
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Montelukast is rapidly and nearly completely absorbed following oral administration. For the
10-mg film-coated tablet, the mean peak plasma concentration (C
) is achieved 3 hours
) after administration in adults in the fasted state. The mean oral bioavailability is 64%.
The oral bioavailability and C
are not influenced by a standard meal.
For the 5-mg chewable tablet, the C
is achieved in 2 hours after administration in adults in
the fasted state. The mean oral bioavailability is 73% and is decreased to 63% by a standard
meal. This is unlikely to have any clinical significance with chronic administration. Efficacy
was demonstrated in clinical studies in children where the montelukast 5-mg chewable tablet
was administered irrespective of food.
For the 4-mg chewable tablet, C
is achieved 2 hours after the administration in paediatric
patients 2 to 5 years of age in the fasted state.
Safety and efficacy were demonstrated in clinical studies where the 4-mg chewable tablet , 5-
mg chewable tablet, and 10-mg film-coated tablet were administered without regard to the
timing of food ingestion.
The 10-mg film coated tablets of montelukast are not bioequivalent to two 5-mg chewable
tablets, and these two products should not be used interchangeably.
Montelukast is more than 99% bound to plasma proteins. The steady-state volume of
distribution of montelukast averages 8-11 liters. Studies in rats with radiolabeled montelukast
indicate minimal distribution across the blood-brain barrier. In addition, concentrations of
radiolabeled material at 24 hours postdose were minimal in all other tissues.
Montelukast is extensively metabolized. In studies with therapeutic doses, plasma
concentrations of metabolites of montelukast are undetectable (<20 ng/mL) at steady state in
adults and children. Further studies showed that relatively high concentrations of montelukast
competitively inhibit the activity of cytochromes P450 3A4 and 2C9. However, these
concentrations are at least 15 fold higher than the peak plasma concentrations attained
following a 10-mg oral dose of montelukast. Based on these and other in vitro results in
human liver microsomes, therapeutic plasma concentrations of montelukast should not be
expected to inhibit cytochromes P450, 3A4, 2C9, 1A2, 2A6, 2C19 or 2D6
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The plasma clearance of montelukast averages 45 mL/min in healthy adults. Following an
oral dose of radiolabeled montelukast, 86% of the radioactivity was recovered in 5-day fecal
collections and <0.2% was recovered in urine. Coupled with estimates of montelukast oral
bioavailability, this indicates that montelukast and its metabolites are excreted almost
In several studies, the mean plasma half-life of montelukast ranged from 2.7 to 5.5 hours in
healthy young adults. The pharmacokinetics of montelukast are nearly linear for oral doses up
to 50 mg. During once-daily dosing with 10-mg montelukast, there is little accumulation of
the parent drug in plasma (
Characteristics in patients
No dosage adjustment is necessary for the elderly or for patients with mild to moderate hepatic
insufficiency. There are no clinical data in patients with severe hepatic insufficiency (Child-Pugh
score > 9). Because montelukast and its metabolites are eliminated by the biliary route, no dose
adjustment is anticipated to be necessary in patients with renal impairment. Studies in patients with
renal impairment have not been undertaken.
In clinical studies, montelukast is effective in adult and paediatric patients for the prophylaxis
and chronic treatment of asthma, including protection against day- and nighttime symptoms,
the treatment of aspirin-sensitive asthmatic patients, and the prevention of exercise-induced
bronchoconstriction. Montelukast is effective alone or in combination with other prophylactic
agents used in the maintenance treatment of asthma. Montelukast and inhaled corticosteroid
may be used concomitantly with additive effects to control asthma or to reduce the inhaled
corticosteroid dose while maintaining clinical stability. Montelukast is a preventative agent
which should be used in addition to other drugs for the management of asthma.
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Adults 15 years of age and older
asthmatic patients 15 years of age and older, montelukast, 10-mg once daily in the evening,
demonstrated significant improvements in parameters of asthma control measuring asthma
symptoms, asthma-related outcomes, respiratory function and “as-needed” β-agonist use.
awakenings, compared with placebo. Asthma-specific outcomes, including asthma attacks,
corticosteroid rescue, discontinuations due to worsening asthma, asthma exacerbations and
asthma-free days were also significantly better than placebo.
evaluations (in all domains, including normal daily activity and asthma symptoms) were
significantly better than placebo.
Montelukast caused significant improvements in morning forced expiratory volume in 1
), AM and PM peak expiratory flow rate (PEFR) and significantly decreased
the use of “as-needed” β-agonist, compared with placebo.
A comparison of montelukast and inhaled beclomethasone (200 mcg twice daily with a
spacer device) demonstrated that montelukast had a more rapid initial response (within the
first day compared with 7-10 days for beclomethasone). While both treatments provided
significantly and clinically important changes, the overall beclomethasone effect was larger
over the 12 weeks duration of the study. The difference in response is, in part, a result of a
small percentage of patients treated with beclomethasone (16.7%) that had a ≥30% increase
). However in a high proportion of patients the response was comparable, for
beclomethasone achieved an 11% or more increase in FEV
The treatment effect was achieved after the first dose and was maintained throughout the 24
hour dosing interval. Treatment effect also remained constant during continuous once-daily
administration in extension studies for up to one year. Withdrawal of montelukast after 12
weeks of use did not cause rebound worsening of asthma.
Paediatric patients 6 to 14 years of age
In paediatric patients 6 to 14 years of age, one 5-mg chewable tablet daily in the evening,
significantly decreased asthma exacerbations, and improved parents’ global evaluations and
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Montelukast also significantly improved morning FEV
and decreased total daily “as-needed”
β-agonist use. Treatment effect was achieved after the first dose and remained constant
during once-daily administration for up to 6 months.
Growth Rate in Paediatric Patients
Two controlled clinical studies have demonstrated that montelukast did not affect the growth
rate in paediatric patients with asthma. In a short term study of children aged 6 to 11 years,
growth rate as measured by lower leg length growth was similar in patients treated with
montelukast 5 mg once daily for 3 weeks compared with placebo, and was significantly lower
in patients treated with inhaled budesonide (200 μg twice daily) for 3 weeks, compared with
placebo. In a 56-week study in children aged 6 to 8 years, linear growth rate was similar in
patients treated with montelukast 5 mg once daily and placebo (LS means for montelukast
and placebo: 5.67 and 5.64 cm/year, respectively), and was significantly lower (LS mean:
compared with placebo [difference in LS means (95% CI): -0.78 (-1.06, -0.49) cm/year]. The
long term clinical relevance of these studies is unknown.
Paediatric patients 2 to 5 years of age
In a 12-week, placebo-controlled study in paediatric patients 2 to 5 years of age, montelukast
concomitant controller therapy use compared with placebo. Sixty percent of patients were not
on any other controller therapy. Montelukast significantly improved daytime symptoms
(including coughing, wheezing, trouble breathing and activity limitation) and nighttime
symptoms compared with placebo (mean baseline daytime scores were montelukast 0.98 and
placebo 0.95 on a 0-5 scale; mean change from baseline: Montelukast –0.37 vs placebo –0.25
[p=0.003] and mean baseline nighttime scores were montelukast 1.18 and placebo 1.20 on a
0-4 scale; mean change from baseline: Montelukast –0.41 vs placebo –0.30 [p=0.026]).
Montelukast also significantly decreased "as-needed" β-agonist use (percentage of days used,
montelukast 50.09 vs placebo 56.34 [p=0.001]) and corticosteroid rescue (percentage of
patients with corticosteroid rescue, montelukast 19.09 vs placebo 28.07 [p=0.008]) compared
with placebo. Patients receiving montelukast had significantly more days without asthma than
those receiving placebo (percentage of days without, montelukast 30.50 vs placebo 23.63
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[p=0.002]). A treatment effect was achieved after the first dose. In addition, total blood
eosinophil counts were significantly decreased (for total blood eosinophil counts, the between
group difference in LS means was –0.04 10
/ μL, p=0.034).
Effects in patients on concomitant inhaled corticosteroids
Separate studies in adults demonstrated the ability of montelukast to add to the clinical effect
of inhaled corticosteroid and allow steroid tapering when used concomitantly. In a placebo-
controlled study, stable, asthmatic patients taking initial inhaled corticosteroid doses of
approximately 1600 μg per day reduced their steroid use by approximately 37% during a
corticosteroid dose, compared with 30% for placebo. In another study, montelukast provided
additional clinical benefit to a similar population of patients maintained but not adequately
controlled on inhaled corticosteroid (beclomethasone 400 μg per day). Complete abrupt
removal of beclomethasone in patients receiving both montelukast and beclomethasone
caused clinical deterioration in some patients, suggesting that tapering as tolerated rather than
abrupt removal is preferred.
In aspirin-sensitive patients, nearly all of whom were receiving concomitant inhaled and/or
oral corticosteroids, montelukast resulted in significant improvement in the parameters of
The effect of montelukast on the bronchoconstrictor response to aspirin challenge or other
non-steroidal anti- inflammatory drugs in aspirin-sensitive asthmatic patients has not been
evaluated (see PRECAUTIONS)
Effects on exercise-induced bronchoconstriction
Montelukast, 10-mg once daily, protected against exercise-induced bronchoconstriction (EIB)
in adults 15 years of age and older. In a 12-week study, montelukast significantly inhibited
the extent and duration of fall in FEV
over 60 minutes after exercise, the maximal percent
fall in FEV
after exercise, and the time to recovery to within 5% of the pre-exercise FEV
Protection was consistent through the treatment period indicating that tolerance did not occur.
In a separate cross-over study, protection was observed after two once-daily doses.
In paediatric patients 6 to 14 years of age, using the 5-mg chewable tablet, a similarly
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designed cross-over study demonstrated similar protection and the protection was maintained
throughout the dosing interval (24 hours).
Effects on antigen challenge and eosinophils
In clinical studies montelukast inhibited both early- and late-phase bronchoconstriction due to
antigen challenge. Because inflammatory cell (eosinophil) infiltration is an important feature
of asthma, the effects of montelukast on eosinophils in the peripheral blood and airway were
examined. In Phase IIb/III clinical studies, montelukast significantly decreased peripheral
blood eosinophils approximately 15% from baseline, compared with placebo. In paediatric
patients 6 to 14 years of age, montelukast decreased peripheral blood eosinophils 13% over
decreased airway eosinophils in sputum, compared with placebo. In this study, peripheral
blood eosinophils decreased and clinical asthma endpoints improved with treatment with
Effects in Patients with Asthma and Seasonal Allergic Rhinitis
In a two week, placebo controlled, double blind, clinical study in adult asthmatic patients 15
years of age and older with concomitant seasonal allergic rhinitis, montelukast 10-mg tablets
administered once daily demonstrated a statistically significant improvement in the primary
composite variable, Daily Rhinitis Symptoms score (average of the Daytime Nasal Symptoms
score [mean of nasal congestion, rhinorrhoea, sneezing, nasal itching] and the Nighttime
Symptoms score [mean of nasal congestion upon awakening, difficulty going to sleep, and
nighttime awakenings scores]) (see TABLE 1). The mean difference in improvement between
the two treatments was 0.12 points (95% CI: -0.18, -0.06) on a scale of 0.00 to 3.00. A
change of 1.00 would correspond to an improvement of symptoms from moderate to mild, or
from severe to moderate.
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Daily Rhinitis Symptom Score
Montelukast Minus Placebo
LS Mean Difference
Clinical Studies - Seasonal Allergic Rhinitis
Adults 15 years of age and older
The efficacy of montelukast for the treatment of seasonal allergic rhinitis was investigated in
including 4924 patients (1751 patients were treated with montelukast). Patients were 15 years
of age and older with a history of seasonal allergic rhinitis, a positive skin test to at least one
Two of the three pivotal studies showed a significant reduction in daytime nasal symptoms
scores with montelukast 10-mg tablets compared to placebo.
In a combined analysis of the three pivotal studies, montelukast 10-mg tablets administered to
1189 patients once daily in the evening resulted in a statistically significant improvement in
the primary endpoint, daytime nasal symptoms score, and its individual components (nasal
congestion, rhinorrhoea, nasal itching, and sneezing); nighttime symptoms score, and its
individual components (nasal congestion upon awakening, difficulty going to sleep, and
nighttime awakenings); daytime eye symptoms score, and its individual components (tearing,
physicians; and composite symptoms score (composed of the daytime nasal and nighttime
symptoms scores), compared with placebo.
The efficacy results of one trial are shown below. The mean changes from baseline in
daytime nasal symptoms score in the treatment groups that received montelukast tablets,
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montelukast was 50% larger than the mean change from baseline for placebo.
Effects of Montelukast on Daytime Nasal Symptoms Score* in a Placebo- and Active-
controlled Trial in Patients with Seasonal Allergic Rhinitis
Treatment Group (N)
Placebo (95% CI)
Montelukast 10 mg (344)
(Loratadine 10 mg) (599)
*Average of individual scores of nasal congestion, rhinorrhoea, nasal itching, sneezing as assessed by patients on a 0-3 categorical scale.
The study was not designed for statistical comparison between montelukast sodium and the active control (loratadine).
Statistically different from placebo (p≤0.001).
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The efficacy of montelukast in the treatment of seasonal allergic rhinitis was investigated in a
separate 4-week study in which the primary objective of the study was to determine the
treatment effect of montelukast 10 mg administered once daily in the morning, compared to
placebo, in patients with seasonal allergic rhinitis over the first 2 weeks of treatment. The
efficacy of montelukast over the initial 2 weeks was significantly different from placebo and
Additionally, the effect over the entire 4 weeks was consistent with the 2-week results (see
Effects of Montelukast on Daytime Nasal Symptoms Score* in a Placebo- and Active-
controlled Trial in Patients with Seasonal Allergic Rhinitis
Treatment Group (N)
Placebo (95% CI)
Montelukast 10 mg (445)
(Loratadine 10 mg) (180)
* Average of individual scores of nasal congestion, rhinorrhoea, nasal itching, sneezing as assessed by patients on a 0-3
† The study was not designed for statistical comparison between SINGULAIR and the active control (loratadine).
†† Statistically different from placebo (p=0.003); ‡ Statistically different from placebo (p≤0.001).
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The study was not designed for statistical comparison between montelukast and the active
Paediatric patients 2 to 14 years of age
Efficacy studies have not been conducted in this age group.
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Prophylaxis and treatment of chronic asthma in adults and children 2 years of age and older.
Symptomatic treatment of seasonal allergic rhinitis.
Hypersensitivity to the active substance or to any of the excipients.
The efficacy of oral montelukast for the treatment of acute asthma attacks has not been
established. Therefore, oral tablets of montelukast should not be relied upon to treat acute
asthma attacks. Patients should be advised to have appropriate rescue medication available.
While the dose of concomitant inhaled corticosteroid may be reduced gradually under
medical supervision, montelukast should not be abruptly substituted for inhaled or oral
Clinical Studies - Asthma
Neuropsychiatric events have been reported in adult, adolescent, and paediatric patients
behaviour (including suicidality), and tremor. The clinical details of some post-marketing
reports involving montelukast appear consistent with a drug-induced effect.
Patients and prescribers should be alert for neuropsychiatric events. Patients should be
instructed to notify their prescriber if these changes occur. Prescribers should carefully
evaluate the risks and benefits of continuing treatment with montelukast if such events occur.
including leukotriene receptor antagonists has been followed in rare cases by the occurrence
symptoms, cardiac complications, and/or neuropathy sometimes diagnosed as Churg-Strauss
syndrome, a systemic eosinophilic vasculitis. Although a causal relationship with leukotriene
receptor antagonism has not been established, caution and appropriate clinical monitoring are
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recommended when systemic corticosteroid reduction is considered in patients receiving
4-mg and 5-mg chewable tablets contain aspartame which is a source of phenylalanine (0.842
mg phenylalanine per 5-mg chewable tablet, and 0.674 mg phenylalanine per 4-mg chewable
documented aspirin sensitivity, it has not been shown to modify bronchoconstrictor response
to aspirin challenge and other non-steroidal anti-inflammatory drugs in aspirin-sensitive
avoidance of aspirin or non-steroidal anti-inflammatory agents while taking montelukast. (see
PHARMACOLOGY, Clinical Studies - Asthma).
Effects on fertility
Fertility and reproductive performance were not affected in studies with male rats given oral
doses of up to 800 mg/kg/day, but fecundity was slightly reduced in female rats doses orally
at 200 mg/kg/day. The no-effect dose for the latter effect was 100 mg/kg/day, corresponding
to systemic exposure, in terms of plasma AUC for parent drug, at least 20 times higher than
that in women at recommened dose levels.
Use in Pregnancy (Category B1)
(Australian Categorisation B1): Drugs which have been taken by only a limited number of
pregnant women and women of childbearing age, without an increase in the frequency of
malformation or other direct or indirect harmful effects on the human fetus having been
observed. Studies in animals have not shown evidence of an increased occurrence of fetal
In animal studies, montelukast sodium had no adverse effects on embryofoetal development
at oral doses up to 400 mg/kg/day in rats or up to 100 mg/kg/day in rabbits. Retardation of
foetal growth and development was observed in rabbits dosed at 200 mg/kg/day, a dose level
associated with severe maternal toxicity. Foetal exposure of montelukast was demonstrated in
both species. Montelukast has not been studied in pregnant women. Montelukast should be
used during pregnancy only if clearly needed.
During worldwide marketing experience, congenital limb defects have been rarely reported in
the offspring of women being treated with montelukast during pregnancy. Most of these
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relationship between these events and montelukast has not been established.
Use in Lactation
Studies in lactating rats have shown that montelukast is excreted into milk following oral
doses of 100 and 200 mg/kg/day, and growth of the pups was slightly inhibited at the higher
dose level. It is not known if montelukast is excreted in human milk. Because many drugs are
excreted in human milk, caution should be exercised when montelukast is given to a nursing
In asthma: Montelukast has been studied in paediatric patients six months to 14 years of age
(see Dosage and Administration). Safety and effectiveness in paediatric patients younger that
six months of age have not been studied. In studies investigating the effect of montelukast on
the growth rate of paediatric patients, it has been shown in one study that montelukast does
not affect the growth rate of paediatric patients when given for up to 56 weeks. The long term
clinical relevance of the growth rates studies is unknown.
In seasonal allergic rhinitis : montelukast has been studied in paediatric patients 2 to 14 years
of age (see Dosage and Administration). Safety in paediatric patients younger than two years
of age has not been studied.
Use in the Elderly
In clinical studies, there were no age-related differences in the efficacy or safety profiles of
Montelukast sodium was not carcinogenic when administered at oral doses of up to 200
mg/kg/day in 104 week study in rats, nor at oral doses up to 100 mg/kg/day in a 91 week
study in mice. Systemic exposure in these studies, in terms of the plasma AUC for parent
drug, was at least 30 times higher than that in humans at recommended dose levels.
Montelukast sodium was found not to be genotoxic. Montelukast sodium was negative in
microbial and mammalian cell mutagenesis assays, with and without metabolic activation.
There was no evidence of clastogenic activity in the
chromosomal aberration assay in
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Chinese Hamster Ovary cells, with or without a microsomal enzyme activation system, or of
DNA damage in the
alkaline elution assay in rat hepatocytes. Similarly, there was no
induction of chromosomal aberrations in bone marrow cells of male or female mice.
INTERACTIONS WITH OTHER MEDICINES
cytochromes P450 3A4 and 2C9. However, these concentrations are at least 15 fold higher
than the peak plasma concentrations attained following a 10-mg oral dose of montelukast.
montelukast (10-mg once daily). At 20 and 60 fold above the recommended dose, plasma
concentration of concomitant theophylline was decreased. Theophylline dose adjustment or a
recommended dose of montelukast.
Montelukast may be administered with other therapies routinely used in the prophylaxis and
chronic treatment of asthma, and in the treatment of allergic rhinitis. In drug-interactions
studies, the recommended clinical dose of montelukast did not have clinically important
prednisolone, oral contraceptives (ethinyl estradiol/ norethisterone 35/1), terfenadine, digoxin
and warfarin. The effects of concomitant administration of montelukast and macrolide
antimicrobials have not been studied.
The area under the plasma concentration-time curve (AUC) for montelukast was decreased
adjustment for Montelukast GH is recommended.
studies have shown that montelukast is an inhibitor of CYP 2C8. However, data from
a clinical drug-drug interaction study involving montelukast and rosiglitazone (a probe
substrate representative of drugs primarily metabolized by CYP2C8) demonstrated that
montelukast does not inhibit CYP2C8
. Therefore, montelukast is not anticipated to
alter the metabolism of drugs metabolized by this enzyme (e.g., paclitaxel, rosiglitazone,
Page 17 of 23
Although additional specific interaction studies were not performed, montelukast was used
concomitantly with a wide range of commonly prescribed drugs in clinical studies without
evidence of clinical adverse interactions. These medications included thyroid hormones,
Montelukast has been generally well tolerated. Side effects, which usually were mild,
generally did not require discontinuation of therapy. The overall incidence of side effects
reported with montelukast was comparable to placebo.
Adults 15 years of Age and Older with Asthma
Montelukast has been evaluated for safety in approximately 2600 adult patients 15 years of
age and older in clinical studies. In two similarly designed, 12 week placebo-controlled
clinical studies, the only adverse experiences reported as drug-related in ≥ 1% of patients
treated with montelukast and at a greater incidence than in patients treated with placebo were
abdominal pain and headache. The incidences of these events were not significantly different
in the two treatment groups.
montelukast occurred in ≥1% of patients and at an incidence greater than or equal to that in
patients treated with placebo, regardless of drug relationship:
Page 18 of 23
ADVERSE EXPERIENCES OCCURRING IN ≥1% OF PATIENTS WITH AN INCIDENCE GREATER THAN OR
EQUAL TO THAT IN PATIENTS TREATED WITH PLACEBO, REGARDLESS OF DRUG RELATIONSHIP
(n = 1955)
(n = 1180)
Body As A Whole
Digestive System Disorders
Respiratory System Disorders
Skin/Skin Appendages Disorder
Laboratory Adverse Experiences*
Number of patients tested (Montelukast and placebo, respectively): ALT and AST, 1935, 1170; pyuria, 1924,
Cumulatively, 544 patients were treated with montelukast for at least 6 months, 253 for one year and
21 for two years in clinical studies. With prolonged treatment, the adverse experience profile did not
Paediatric Patients 6 to 14 Years of Age with Asthma
Montelukast has been evaluated for safety in approximately 970 paediatric patients 6 to 14
years of age. The safety profile in paediatric patients is generally similar to the adult safety
profile and to placebo. Cumulatively, 263 paediatric patients 6-14 years of age were treated
with montelukast for at least 3 months, 164 for 6 months or longer in clinical studies. The
safety profile in paediatric patients is generally similar to the adult safety profile and to
placebo. With prolonged treatment, the adverse experience profile did not change.
Page 19 of 23
In a 56 week active-controlled study
comparing montelukast to inhaled fluticasone in
paediatric patients 6-14 years of age with mild persistent asthma, the safety profile was
consistent with the safety profile previously described for montelukast. In the study, the
number of patients with asthma symptoms after treatment was 166 (33.5%) patients in the
montelukast treatment group and 135 (27.1%) patients in the fluticasone treatment group.
In studies evaluating growth rate, the safety profile in these paediatric patients was consistent
with the safety profile previously described for montelukast.
Paediatric Patients 2 to 5 Years of Age with Asthma
Montelukast has been evaluated in 573 paediatric patients 2 to 5 years of age. In a 12-week
placebo-controlled clinical study, the only adverse experience reported as drug related in >
1% of patients treated with montelukast and at a greater incidence than in patients treated
with placebo was thirst. The incidence of thirst was not significantly different in the two
Cumulatively, 502 paediatric patients 2 to 5 years of age were treated with montelukast for at
least 3 months, 338 for 6 months or longer, and 256 patients for 12 months or longer. With
prolonged treatment, the adverse experience profile did not change.
Adults 15 years of Age and Older with Seasonal Allergic Rhinitis
Montelukast has been evaluated in 2199 adult patients 15 years of age and older for the
treatment of seasonal allergic rhinitis in clinical studies. Montelukast administered once daily
in the morning or in the evening was generally well tolerated with a safety profile similar to
that of placebo. In placebo-controlled clinical studies, no adverse experiences reported as
drug related in ≥1% of patients treated with montelukast and at a greater incidence than in
patients treated with placebo were observed. In a 4-week, placebo-controlled clinical study,
the safety profile was consistent with that observed in 2-week studies. The incidence of
somnolence was similar to that of placebo in all studies.
Paediatric Patients 2 to 14 Years of Age with Seasonal Allergic Rhinitis
Montelukast has been evaluated in 280 paediatric patients 2 to 14 years of age for the
Montelukast administered once daily in the evening was generally well tolerated with a safety
profile similar to that of placebo. In this study, no adverse experiences reported as drug
Page 20 of 23
related in ≥1% of patients with montelukast and at a greater incidence than in patients treated
with placebo were observed.
Adults 15 Years of Age and Older with Asthma and Seasonal Allergic Rhinitis
Montelukast 10-mg film-coated tablets have been evaluated in approximately 400 asthmatic
patients 15 years of age and older with seasonal allergic rhinitis. The safety profile in
asthmatic patients with seasonal allergic rhinitis was consistent with that observed in patients
The following additional side effects have been reported in post-marketing use:
Infections and infestations: upper respiratory tract infection
Blood and lymphatic system disorders: increased bleeding tendency
Immune system disorders: hypersensitivity reactions including anaphylaxis, very rarely
hepatic eosinophilic infiltration
Psychiatric disorders: agitation including aggressive behaviour or hostility, anxiousness,
restlessness, somnambulism (sleep walking), suicidal thinking and behaviour (suicidality),
Cardiac disorders: palpitations
Respiratory, thoracic and mediastinal disorders: epistaxis
Gastrointestinal disorders: diarrhoea, dyspepsia, nausea, vomiting
Hepatobiliary disorders: increased ALT and AST, very rarely hepatitis (including cholestatic,
hepatocellular, and mixed-pattern liver injury)
erythema nodosum, pruritus, rash, urticaria
General disorders and administration site conditions: oedema, pyrexia
In rare cases, patients on therapy with montelukast may present with systemic eosinophilia,
syndrome. These events usually, but not always, have been associated with the reduction of
Page 21 of 23
oral corticosteroid therapy. A causal association between montelukast and these underlying
conditions has not been established (see PRECAUTIONS).
DOSAGE AND ADMINISTRATION
Asthma and/or Seasonal Allergic Rhinitis
Montelukast GH should be taken once daily.
For asthma, the dose should be taken in the evening.
For seasonal allergic rhinitis, the time of administration may be individualised to suit patient
Patients with both asthma and seasonal allergic rhinitis should take only one tablet daily in
Adults 15 Years of Age and Older
The dosage for adults 15 years of age and older is one 10-mg tablet daily.
Paediatric Patients 6 to 14 Years of Age
The dosage for paediatric patients 6 to 14 years of age is one 5-mg chewable tablet daily.
Paediatric Patients 2 to 5 Years of Age
The dosage for paediatric patients 2 to 5 years of age is one 4-mg chewable tablet daily.
Montelukast GH may be taken with or without food. Tablets are not to be broken prior to
The therapeutic effect of montelukast on parameters of asthma control occurs within one day.
Patients should be advised to continue taking Montelukast GH daily when their asthma is
controlled, as well as during periods of worsening asthma.
No dosage adjustment is necessary for paediatric patients, for the elderly, for patients with
renal insufficiency, or mild to moderate hepatic impairment, or for patients of either gender.
Therapy with montelukast in Relation to Other Treatments for Asthma
Montelukast can be added to a patient’s existing treatment regimen.
Reduction in Concomitant Therapy:
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: montelukast can be added to the treatment regimen of
patients who are not adequately controlled on bronchodilator alone. When a clinical
response is evident (usually after the first dose), the patient’s bronchodilator therapy
can be reduced as tolerated.
: Treatment with montelukast provides additional clinical benefit to
patients treated with inhaled corticosteroids. A reduction in the corticosteroid dose can be
made as tolerated. The dose should be reduced gradually with medical supervision. In some
patients, the dose of inhaled corticosteroids can be tapered off completely. Montelukast
should not be abruptly substituted for inhaled corticosteroids.
No specific information is available on the treatment of overdosage with montelukast. In
chronic asthma studies, montelukast has been administered at doses up to 200 mg/day to
adult patients for 22 weeks and in short-term studies, up to 900 mg/day to patients for
approximately one week without clinically important adverse experiences.
There have been reports of acute overdosage in postmarketing experience and clinical studies
with montelukast. These include reports in adults and children with a dose as high as 1000
mg. The clinical and laboratory findings observed were consistent with the safety profile in
The most frequently occurring adverse experiences were consistent with the safety profile of
montelukast and included abdominal pain, somnolence, thirst, headache, vomiting, and
psychomotor hyperactivity. It is not known whether montelukast is dialyzable by peritoneal-
PRESENTATION AND STORAGE
Montelukast GH is supplied in three tablet presentations as follows:
10-mg tablet - Light brown colored, round biconvex shaped, uncoated tablets, with a
score line on both sides. Supplied in blister packs of 4 x 7 tablets.
5-mg chewable tablet -
pink colored, round shaped, uncoated, chewable tablets, with a
score line on both sides
. Supplied in blister packs of 4 x 7 tablets.
4-mg chewable tablet - pink colored, oval biconvex shaped, uncoated, chewable
tablets, with a score line on both sides. Supplied in blister packs of 4 x 7 tablets.
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Store below 30°C. Store in the original package in order to protect from light and moisture.
NAME AND ADDRESS OF THE SPONSOR
Torrent Australasia Pty Ltd
Level 9, 100 George Street,
Parramatta NSW 2150
Prescription Only Medicine (Schedule 4)
Date of first inclusion in the Australian Register of Therapeutic Goods (ARTG)