Allair 4 mg chewable tabletis indicated in the treatment of asthma as add-on therapy
in those 2 to 5 year old patients with mild to moderate persistent asthma who are
inadequately controlled on inhaled corticosteroids and in whom “as-needed” short
acting β-agonists provide inadequate clinical control of asthma.
Allair 4 mg chewable tabletmay also be an alternative treatment option to low-dose
inhaled corticosteroids for 2 to 5 year old patients with mild persistent asthma who
do not have a recent history of serious asthma attacks that required oral
corticosteroid use, and who have demonstrated that they are not capable of using
inhaled corticosteroids (see section 4.2).
Allair 4 mg chewable tabletis also indicated in the prophylaxis of asthma from 2
years of age and older in which the predominant component is exercise-induced
bronchoconstriction.
 

Method of administration:
For oral use. The tablet should be chewed.
This medicinal product is to be given to a child under adult supervision. The dosage
for paediatric patients 2-5 years of age is one 4 mg chewable tablet daily to be taken
in the evening. If taken in connection with food, Allair 4 mg chewable tabletshould
be taken 1 hour before or 2 hours after food. No dosage adjustment within this age
group is necessary. The Allair 4 mg chewable tablet formulation is not recommended
below 2 years of age.
For children who have problems consuming a chewable tablet, a granule formulation
is available.
General recommendations:
The therapeutic effect of Allair 4 mg chewable tableton parameters of asthma
control occurs within one day. Patients should be advised to continue taking Allair 4
mg chewable tableteven if their asthma is under control, as well as during periods of
worsening asthma.
No dosage adjustment is necessary for patients with renal insufficiency, or mild to
moderate hepatic impairment. There are no data on patients with severe hepatic
impairment. The dosage is the same for both male and female patients.
Allair 4 mg chewable tabletas an alternative treatment option to low-dose inhaled
corticosteroids for mild, persistent asthma:
Montelukast is not recommended as monotherapy in patients with moderate
persistent asthma. The use of montelukast as an alternative treatment option to
low-dose inhaled corticosteroids for children 2 to 5 years old with mild persistent
asthma should only be considered for patients who do not have a recent history of
serious asthma attacks that required oral corticosteroid use and who have
demonstrated that they are not capable of using inhaled corticosteroids (see section
4.1). Mild persistent asthma is defined as asthma symptoms more than once a week
but less than once a day, nocturnal symptoms more than twice a month but less
than once a week, normal lung function between episodes. If satisfactory control of
asthma is not achieved at follow-up (usually within one month), the need for an
additional or different anti-inflammatory therapy based on the step system for
asthma therapy should be evaluated. Patients should be periodically evaluated for
their asthma control.
Allair 4 mg chewable tabletas prophylaxis of asthma for 2 to 5 years old patients in
whom the predominant component is exercise-induced bronchoconstriction:
In 2 to 5 year old patients, exercise-induced bronchoconstriction may be the
predominant manifestation of persistent asthma that requires treatment with
inhaled corticosteroids. Patients should be evaluated after 2 to 4 weeks of treatment
with montelukast. If satisfactory response is not achieved, an additional or different
therapy should be considered.
Therapy with Allair 4 mg chewable tabletin relation to other treatments for asthma:
When treatment with Allair 4 mg chewable tabletis used as add-on therapy to
inhaled corticosteroids, Allair 4 mg chewable tabletshould not be abruptly
substituted for inhaled corticosteroids (see section 4.4).
For other age groups, other strengths and pharmaceutical forms of montelukast are
available.
10mg film-coated tablets are available for adults 15 years of age and older.
5mg chewable tablets are available for paediatric patients 6 to 14 years of age.
4mg granules are available for paediatric patients 6 months to 5 years of age.
 

The diagnosis of persistent asthma in very young children (6 months – 2 years)
should be established by a pediatrician or pulmonologist.
Patients should be advised never to use oral montelukast to treat acute asthma
attacks and to keep their usual appropriate rescue medication for this purpose
readily available. If an acute attack occurs, a short-acting inhaled β-agonist should be
used. Patients should seek their doctor's advice as soon as possible if they need
more inhalations of short-acting β-agonists than usual.
Montelukast should not be abruptly substituted for inhaled or oral corticosteroids.
There are no data demonstrating that oral corticosteroids can be reduced when
montelukast is given concomitantly.
In rare cases, patients on therapy with anti-asthma agents including montelukast
may present with systemic eosinophilia, sometimes presenting with clinical features
of vasculitis consistent with Churg-Strauss syndrome, a condition which is often
treated with systemic corticosteroid therapy. These cases have been sometimes
associated with the reduction or withdrawal of oral corticosteroid therapy. Although
a causal relationship with leukotriene receptor antagonism has not been established,
physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary
symptoms, cardiac complications, and/or neuropathy presenting in their patients.
Patients who develop these symptoms should be reassessed and their treatment
regimens evaluated.
Allair 4 mg chewable tabletcontains aspartame, a source of phenylalanine. May be
harmful for people with phenylketonuria
Allair 4 mg chewable tabletcontains lactose. Patients with rare hereditary problems
of galactose intolerance, the Lapp lactase deficiency or glucose-galactose
malabsorption should not take this medicine.
 

The area under the plasma concentration curve (AUC) for montelukast was
decreased approximately 40% in subjects with co-administration of phenobarbital.
Since montelukast is metabolised by CYP 3A4, 2C8 and 2C9, caution should be
exercised, particularly in children, when montelukast is coadministered with
inducers of CYP 3A4, 2C8 and 2C9, such as phenytoin, phenobarbital and rifampicin.
Montelukast may be administered with other therapies routinely used in the
prophylaxis and chronic treatment of asthma. In drug-interactions studies, the
recommended clinical dose of montelukast did not have clinically important effects
on the pharmacokinetics of the following medicinal products:theophylline,
prednisone, prednisolone, oral contraceptives (ethinyl estradiol/norethindrone
35/1), terfenadine, digoxin and warfarin.
In vitro studies have shown that montelukast is a potent inhibitor of CYP 2C8.
However, data from a clinical drug-drug interaction study involving montelukast and
rosiglitazone (a probe substrate representative of medicinal products primarily
metabolised by CYP 2C8) demonstrated that montelukast does not inhibit CYP 2C8 in
vivo. Therefore, montelukast is not anticipated to markedly alter the metabolism of
medicinal products metabolised by this enzyme (e.g., paclitaxel, rosiglitazone, and
repaglinide.)
In vitro studies have shown that montelukast is a substrate of CYP 2C8, and to a less
significant extent, of 2C9, and 3A4. In a clinical drug-drug interaction study involving
montelukast and gemfibrozil (an inhibitor of both CYP 2C8 and 2C9) gemfibrozil
increased the systemic exposure of montelukast by 4.4-fold. No routine dosage
adjustment of montelukast is required upon co-administration with gemfibrozil or
other potent inhibitors of CYP 2C8, but the physician should be aware of the
potential for an increase in adverse reactions.
Based on in vitro data, clinically important drug interactions with less potent
inhibitors of CYP 2C8 (e.g., trimethoprim) are not anticipated. Co-administration of
montelukast with itraconazole, a strong inhibitor of CYP 3A4, resulted in no
significant increase in the systemic exposure of montelukast.
 

Pregnancy
Pregnancy category: B
Animal studies do not indicate harmful effects with respect to effects on pregnancy
or embryonal/foetal development.
Limited data from available pregnancy databases do not suggest a causal
relationship between montelukast and malformations (i.e. limb defects) that have
been rarely reported in worldwide post marketing experience.
Allair 4 mg chewable tabletmay be used during pregnancy only if it is considered to
be clearly essential.
Breastfeeding
Studies in rats have shown that montelukast is excreted in milk (see section 5.3). It is
not known if montelukast is excreted in human milk.
Allair 4 mg chewable tabletmay be used in breast-feeding mothers only if it is
considered to be clearly essential.
 

Montelukast is not expected to affect a patient's ability to drive a car or operate
machinery. However, in very rare cases, individuals have reported drowsiness or
dizziness.
 

a. Summary of the safety profile
the most commonly reported side effects thought to be related to Montelukast 5mg
were:
• headache
Adverse reactions in clinical trials, post-authorisation safety studies and spontaneous
reporting are summarised in the below table based on the known safety profile of
this substance.
b. Tabulated list of Adverse reaction:
Montelukast has been evaluated in clinical studies in patients with persistent asthma
as follows:
• 10 mg film-coated tablets in approximately 4000 adult patients 15 years of age and
older
• 5 mg chewable tablets in approximately 1750 paediatric patients 6 to 14 years of
age, and
• 4 mg chewable tablets in 851 paediatric patients 2 to 5 years of age, and
• 4mg granules in 175 paediatruc patients 6 months to 2 years of age.
Montelukast has been evaluated in a clinical study in patients with intermittent
asthma as follows:
• 4mg granules and chewable tablets in 1038 paediatric patients 6 months to 5 years
of age.
The following drug-related adverse reactions in clinical studies were reported
commonly (≥1/100 to <1/10) in patients treated with montelukast and at a greater
incidence than in patients treated with placebo:

No specific information is available on the treatment of overdose 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 overdose in post-marketing experience and clinical
studies with montelukast. These include reports in adults and children with a dose as
high as 1000 mg (approximately 61 mg/kg in a 42 month old child). The clinical and
laboratory findings observed were consistent with the safety profile in adults and
paediatric patients. There were no adverse experiences in the majority of overdose
reports. 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 dialysable by peritoneal- or haemo-dialysis.
 

Pharmacotherapeutic group: Leukotriene receptor antagonists
ATC-code: R03DC03
The cysteinyl leukotrienes (LTC4, LTD4, LTE4) are potent inflammatory eicosanoids
released from various cells including mast cells and eosinophils. These important
pro-asthmatic mediators bind to cysteinyl leukotriene receptors (CysLT) found in the
human airway and cause airway actions, including bronchoconstriction, mucous
secretion, vascular permeability, and eosinophil recruitment.
Montelukast is an orally active compound which binds with high affinity and
selectivity to the CysLT1 receptor. In clinical studies, montelukast inhibits
bronchoconstriction due to inhaled LTD4 at doses as low as 5 mg. Bronchodilation
was observed within two hours of oral administration. The bronchodilation effect
caused by a β-agonist was additive to that caused by montelukast. Treatment with
montelukast inhibited both early- and late-phase bronchoconstriction due to antigen
challenge. Montelukast, compared with placebo, decreased peripheral blood
eosinophils in adult and paediatric patients. In a separate study, treatment with
montelukast significantly decreased eosinophils in the airways (as measured in
sputum). In adult and paediatric patients 2 to 14 years of age, montelukast,
compared with placebo, decreased peripheral blood eosinophils while improving
clinical asthma control.
In studies in adults, montelukast, 10 mg once daily, compared with placebo,
demonstrated significant improvements in morning FEV1 (10.4% vs 2.7% change
from baseline), AM peak expiratory flow rate (PEFR) (24.5 L/min vs 3.3 L/min change
from baseline), and significant decrease in total β-agonist use (-26.1% vs -4.6%
change from baseline). Improvement in patient-reported daytime and nighttime
asthma symptoms scores was significantly better than placebo.
Studies in adults demonstrated the ability of montelukast to add to the clinical effect
of inhaled corticosteroid (% change from baseline for inhaled beclometasone plus
montelukast vs beclometasone, respectively for FEV1: 5.43% vs 1.04%; β-agonist use:
-8.70% vs 2.64%). Compared with inhaled beclometasone (200 μg twice daily with a
spacer device), montelukast demonstrated a more rapid initial response, although
over the 12-week study, beclometasone provided a greater average treatment effect
(% change from baseline for montelukast vs beclometasone, respectively for FEV1:
7.49% vs 13.3%; β-agonist use: -28.28% vs -43.89%). However, compared with
beclometasone, a high percentage of patients treated with montelukast achieved
similar clinical responses (e.g., 50% of patients treated with beclometasone achieved
an improvement in FEV1 of approximately 11% or more over baseline while
approximately 42% of patients treated with montelukast achieved the same
response).
In a 12-week, placebo-controlled study in paediatric patients 2 to 5 years of age,
montelukast 4 mg once daily improved parameters of asthma control compared with
placebo irrespective of concomitant controller therapy (inhaled/nebulised
corticosteroids or inhaled/nebulised sodium cromoglycate). Sixty percent of patients
were not on any other controller therapy. Montelukast improved daytime symptoms
(including coughing, wheezing, trouble breathing and activity limitation) and
nighttime symptoms compared with placebo. Montelukast also decreased "asneeded" β-agonist use and corticosteroid rescue for worsening asthma compared
with placebo. Patients receiving montelukast had more days without asthma than
those receiving placebo. A treatment effect was achieved after the first dose.
In a 12-month, placebo-controlled study in paediatric patients 2 to 5 years of age
with mild asthma and episodic exacerbations, montelukast 4 mg once daily
significantly (p≤0.001) reduced the yearly rate of asthma exacerbation episodes (EE)
compared with placebo (1.60 EE vs. 2.34 EE, respectively), [EE defined as ≥3
consecutive days with daytime symptoms requiring β-agonist use, or corticosteroids
(oral or inhaled), or hospitalisation for asthma]. The percentage reduction in yearly
EE rate was 31.9%, with a 95% CI of 16.9, 44.1.
In an 8-week study in paediatric patients 6 to 14 years of age, montelukast 5 mg
once daily, compared with placebo, significantly improved respiratory function (FEV1
8.71% vs 4.16% change from baseline; AM PEFR 27.9 L/min vs 17.8 L/min change
from baseline) and decreased "as-needed" β-agonist use (-11.7% vs +8.2% change
from baseline).
In a 12-month study comparing the efficacy of montelukast to inhaled fluticasone on
asthma control in paediatric patients 6 to 14 years of age with mild persistent
asthma, montelukast was non-inferior to fluticasone in increasing the percentage of
asthma rescue-free days (RFDs), the primary endpoint. Averaged over the 12-month
treatment period, the percentage of asthma RFDs increased from 61.6 to 84.0 in the
montelukast group and from 60.9 to 86.7 in the fluticasone group. The between
group difference in LS mean increase in the percentage of asthma RFDs was
statistically significant (- 2.8 with a 95% CI of -4.7, -0.9), but within the limit predefined to be clinically not inferior. Both montelukast and fluticasone also improved
asthma control on secondary variables assessed over the 12 month treatment
period:
FEV1 increased from 1.83 L to 2.09 L in the montelukast group and from 1.85 L to
2.14 L in the fluticasone group. The between-group difference in LS mean increase in
FEV1 was -0.02 L with a 95% CI of -0.06, 0.02. The mean increase from baseline in %
predicted FEV1 was 0.6% in the montelukast treatment group, and 2.7% in the
fluticasone treatment group. The difference in LS means for the change from
baseline in the % predicted FEV1 was -2.2% with a 95% CI of -3.6, -0.7.
The percentage of days with β-agonist use decreased from 38.0 to 15.4 in the
montelukast group, and from 38.5 to 12.8 in the fluticasone group. The between
group difference in LS means for the percentage of days with β-agonist use was
significant: 2.7 with a 95% CI of 0.9, 4.5.
The percentage of patients with an asthma attack (an asthma attack being defined as
a period of worsening asthma that required treatment with oral steroids, an
unscheduled visit to the doctor's office, an emergency room visit, or hospitalisation)
was 32.2 in the montelukast group and 25.6 in the fluticasone group; the odds ratio
(95% CI) being significant: equal to 1.38 (1.04, 1.84).
The percentage of patients with systemic (mainly oral) corticosteroid use during the
study period was 17.8% in the montelukast group and 10.5% in the fluticasone
group. The between group difference in LS means was significant 7.3% with a 95%CI
of 2.9; 11.7.
Significant reduction of exercise-induced bronchoconstriction (EIB) was
demonstrated in a 12-week study in adults (maximal fall in FEV1 22.33% for
montelukast vs 32.40% for placebo; time to recovery to within 5% of baseline FEV1
44.22 min vs 60.64 min). This effect was consistent throughout the 12- week study
period. Reduction in EIB was also demonstrated in a short term study in paediatric
patients 6 to 14 years of age (maximal fall in FEV1 18.27% vs 26.11%; time to
recovery to within 5% of baseline FEV1 17.76 min vs 27.98 min). The effect in both
studies was demonstrated at the end of the once-daily dosing interval.
In aspirin-sensitive asthmatic patients receiving concomitant inhaled and/or oral
corticosteroids, treatment with montelukast, compared with placebo, resulted in
significant improvement in asthma control (FEV1 8.55% vs -1.74% change from
baseline and decrease in total β-agonist use -27.78% vs 2.09% change from
baseline).
 

Absorption. Montelukast is rapidly absorbed following oral administration. For the 10
mg film-coated tablet, the mean peak plasma concentration (Cmax) is achieved three
hours (Tmax) after administration in adults in the fasted state. The mean oral
bioavailability is 64%. The oral bioavailability and Cmax are not influenced by a
standard meal. Safety and efficacy were demonstrated in clinical trials where the 10
mg film-coated tablet was administered without regard to the timing of food
ingestion.
For the 5 mg chewable tablet, the Cmax is achieved in two hours after administration
in adults in the fasted state. The mean oral bioavailability is 73% and is decreased to
63% by a standard meal.
After administration of the 4 mg chewable tablet to paediatric patients 2 to 5 years
of age in the fasted state, Cmax is achieved 2 hours after administration. The mean
Cmax is 66% higher while mean Cmin is lower than in adults receiving a 10 mg tablet.
Distribution. Montelukast is more than 99% bound to plasma proteins. The steadystate volume of distribution of montelukast averages 8-11 liters. Studies in rats with
radiolabelled montelukast indicate minimal distribution across the blood-brain
barrier. In addition, concentrations of radiolabelled material at 24 hours post-dose
were minimal in all other tissues.
Biotransformation . Montelukast is extensively metabolised. In studies with
therapeutic doses, plasma concentrations of metabolites of montelukast are
undetectable at steady state in adults and children.
In vitro studies using human liver microsomes indicate that cytochromes P450 3A4,
2A6 and 2C9 are involved in the metabolism of montelukast. Based on further in
vitro results in human liver microsomes, therapeutic plasma concentrations of
montelukast do not inhibit cytochromes P450 3A4, 2C9, 1A2, 2A6, 2C19, or 2D6. The
contribution of metabolites to the therapeutic effect of montelukast is minimal.
Elimination. The plasma clearance of montelukast averages 45 ml/min in healthy
adults. Following an oral dose of radiolabelled montelukast, 86% of the radioactivity
was recovered in 5-day faecal 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 exclusively via the bile.
Characteristics in patients. No dosage adjustment is necessary for the elderly or mild
to moderate hepatic insufficiency. Studies in patients with renal impairment have
not been undertaken. Because montelukast and its metabolites are eliminated by
the biliary route, no dose adjustment is anticipated to be necessary in patients with
renal impairment. There are no data on the pharmacokinetics of montelukast in
patients with severe hepatic insufficiency (Child-Pugh score >9).
With high doses of montelukast (20- and 60-fold the recommended adult dose), a
decrease in plasma theophylline concentration was observed. This effect was not
seen at the recommended dose of 10 mg once daily.
 

In animal toxicity studies, minor serum biochemical alterations in ALT, glucose,
phosphorus and triglycerides were observed which were transient in nature. The
signs of toxicity in animals were increased excretion of saliva, gastrointestinal
symptoms, loose stools and ion imbalance. These occurred at dosages which
provided >17-fold the systemic exposure seen at the clinical dosage. In monkeys, the
adverse effects appeared at doses from 150 mg/kg/day (>232-fold the systemic
exposure seen at the clinical dose). In animal studies, montelukast did not affect
fertility or reproductive performance at systemic exposure exceeding the clinical
systemic exposure by greater than 24-fold. A slight decrease in pup body weight was
noted in the female fertility study in rats at 200 mg/kg/day (>69-fold the clinical
systemic exposure). In studies in rabbits, a higher incidence of incomplete
ossification, compared with concurrent control animals, was seen at systemic
exposure >24-fold the clinical systemic exposure seen at the clinical dose. No
abnormalities were seen in rats. Montelukast has been shown to cross the placental
barrier and is excreted in breast milk of animals.
No deaths occurred following a single oral administration of montelukast sodium at
doses up to 5000 mg/kg in mice and rats (15,000 mg/m2 and 30,000 mg/m2 in mice
and rats, respectively), the maximum dose tested. This dose is equivalent to 25,000
times the recommended daily adult human dose (based on an adult patient weight
of 50 kg).
Montelukast was determined not to be phototoxic in mice for UVA, UVB or visible
light spectra at doses up to 500 mg/kg/day (approximately >200-fold based on
systemic exposure).
Montelukast was neither mutagenic in in vitro and in vivo tests nor tumorigenic in
rodent species.
 

Cellulose, Microcrystalline
Hydroxypropylcellulose
Croscarmellose Sodium
Mannitol
Aspartame
Peach flavor
Sodium stearyl fumarate
 

Not applicable.
 

Store in the original package in order to protect from light and moisture.
Store below 30°C.
 

Al/Al blister packs:
30 chewable tablets
 

Any unused product or waste material should be disposed of in accordance with
local requirements.