with mild to moderate persistent asthma who are inadequately controlled on inhaled corticosteroids and in whom “asneeded”
short-acting β-agonists provide inadequate clinical control of asthma.
Broncast Paediatric 4 mg may also be an alternative treatment option to low-dose inhaled corticosteroids for 2 to 5
years 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).
Broncast Paediatric 4 mg is also indicated in the prophylaxis of asthma from 2 years of age and older in which the
predominant component is exercise-induced bronchoconstriction.

Posology
This medicinal product is to be given to a child under adult supervision. The recommended dose 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, Broncast
Paediatric 4 mg should be taken 1 hour before or 2 hours after food. No dosage adjustment within this age group is
necessary.
General recommendations
The therapeutic effect of Broncast Paediatric 4 mg on parameters of asthma control occurs within one day. Patients
should be advised to continue taking Broncast Paediatric 4 mg even 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.

Broncast Paediatric 4 mg as 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 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 antiinflammatory
therapy based on the step system for asthma therapy should be evaluated. Patients should be periodically
evaluated for their asthma control.
Broncast Paediatric 4 mg as prophylaxis of asthma for 2 to 5 years old patients in whom the predominant component
is exercise-induced bronchoconstriction
In 2 to 5 years 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 Broncast Paediatric 4 mg in relation to other treatments for asthma
When treatment with Broncast Paediatric 4 mg is used as add-on therapy to inhaled corticosteroids, Broncast Paediatric
4 mg should not be abruptly substituted for inhaled corticosteroids (see section 4.4).
10 mg film-coated tablets are available for adults and adolescents 15 years of age and older.

Paediatric population
Do not give Broncast Paediatric 4 mg chewable tablets to children less than 2 years of age. The safety and efficacy of
Broncast Paediatric 4 mg chewable tablets in children less than 2 years of age has not been established.
5 mg chewable tablets are available for paediatric patients 6 to 14 years of age.
Method of administration
Oral use.
The tablets are to be chewed before swallowing.

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 doctors' 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.
Treatment with montelukast does not alter the need for patients with aspirin-sensitive asthma to avoid taking aspirin
and other non-steroidal anti-inflammatory drugs.
Broncast Paediatric 4 mg contains aspartame, a source of phenylalanine. Patients with phenylketonuria should take
into account that each 4 mg chewable tablet contains phenylalanine in an amount equivalent to 0.0449 mg
phenylalanine per dose.
Neuropsychiatric events have been reported in adults, adolescents, and children taking Broncast Paediatric 4 mg (see
section 4.8). Patients and physicians should be alert for neuropsychiatric events. Patients and/or caregivers should be
instructed to notify their physician if these changes occur. Prescribers should carefully evaluate the risks and benefits
of continuing treatment with Broncast Paediatric 4 mg if such events occur.

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 oestradiol/norethindrone 35/1), terfenadine, digoxin and warfarin.
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 co-administered with inducers of CYP 3A4, 2C8, and 2C9,
such as phenytoin, phenobarbital and rifampicin.
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
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 Broncast Paediatric 4
mg and malformations (i.e. limb defects) that have been rarely reported in worldwide post-marketing experience.
Broncast Paediatric 4 mg may be used during pregnancy only if it is considered to be clearly essential.

Breast-feeding
Studies in rats have shown that montelukast is excreted in milk (see section 5.3). It is unknown whether
montelukast/metabolites are excreted in human milk.
Broncast Paediatric 4 mg may be used in breast-feeding mothers only if it is considered to be clearly essential.

Broncast Paediatric 4 mg has no or negligible influence on the ability to drive and use machines. However, individuals
have reported drowsiness or dizziness.

Montelukast has been evaluated in clinical studies in patients with persistent asthma as follows:
• 10 mg film-coated tablets in approximately 4,000 adult and adolescent patients 15 years of age and older
• 5 mg chewable tablets in approximately 1,750 paediatric patients 6 to 14 years of age, and
• 4 mg chewable tablets in 851 paediatric patients 2 to 5 years of age.
Montelukast has been evaluated in a clinical study in patients with intermittent asthma as follows:
• 4 mg granules and chewable tablets in 1,038 paediatric patients 6 months to 5 years of age.

With prolonged treatment in clinical trials with a limited number of patients for up to 2 years for adults, and up to 12
months for paediatric patients 6 to 14 years of age, the safety profile did not change.
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 534 patients for 12 months or longer. With prolonged treatment, the safety profile did not change
in these patients either.
Tabulated list of Adverse Reactions
Adverse reactions reported in post-marketing use are listed, by System Organ Class and specific Adverse Reactions,
in the table below. Frequency Categories were estimated based on relevant clinical trials.

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 1,000 mg (approximately 61 mg/kg in 42 months 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.
Symptoms of overdose
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.
Management of overdose
No specific information is available on the treatment of overdose with montelukast. It is not known whether montelukast
is dialysable by peritoneal- or haemo-dialysis.

Pharmacotherapeutic group: Leukotriene receptor antagonist.
Mechanism of action
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.
Pharmacodynamic effects
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 2 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.
Clinical efficacy and safety
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 night-time 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 beclomethasone plus montelukast vs beclomethasone, respectively for FEV1: 5.43% vs 1.04%;
β-agonist use: -8.70% vs 2.64%). Compared with inhaled beclomethasone (200 μg twice daily with a spacer device),
montelukast demonstrated a more rapid initial response, although over the 12-week study, beclomethasone provided
a greater average treatment effect (% change from baseline for montelukast vs beclomethasone, respectively for
FEV1: 7.49% vs 13.3%; β-agonist use: -28.28% vs -43.89%). However, compared with beclomethasone, a high
percentage of patients treated with montelukast achieved similar clinical responses (e.g., 50% of patients treated with
beclomethasone 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 night-time symptoms compared with placebo. Montelukast also decreased “as needed” 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 a placebo-controlled study in paediatric patients 6 months to 5 years of age who had intermittent asthma but did not
have persistent asthma, treatment with montelukast was administered over a 12-month period, either as a once-daily
4 mg regimen or as a series of 12-day courses that each were started when an episode of intermittent symptoms began.

No significant difference was observed between patients treated with montelukast 4 mg or placebo in the number of
asthma episodes culminating in an asthma attack, defined as an asthma episode requiring utilization of health-care
resources such as an unscheduled visit to a doctor's office, emergency room, or hospital; or treatment with oral,
intravenous, or intramuscular corticosteroid.
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 pre-defined to be clinically not inferior. Both
montelukast and fluticasone also improved asthma control on secondary variables assessed over the 12 months
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 significant: -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 3 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 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.
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 steady-state volume of distribution of montelukast
averages 8-11 litres. 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.
Cytochrome P450 2C8 is the major enzyme in the metabolism of montelukast. Additionally, CYP 3A4 and 2C9 may
have a minor contribution, although itraconazole, an inhibitor of CYP 3A4, was shown not to change pharmacokinetic
variables of montelukast in healthy subjects that received 10 mg montelukast daily. Based on 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 thepharmacokinetics 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 decreasein 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 5,000 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.

‐ Mannitol
‐ Microcrystalline cellulose
‐ Hydroxypropyl cellulose
‐ Croscarmellose sodium
‐ Red iron oxide
‐ Bubble gum flavor
‐ Aspartame
‐ Colloidal anhydrous silica
‐ Magnesium stearate

Not applicable.

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

Packaged in Aluminum/Aluminum blister pack.
Pack of 28 tablets.
 

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