Broncast 5mg Chewable Tablet is indicated in the treatment of asthma as add-on therapy in those
patients with mild to moderate persistent asthma who are inadequately controlled on inhaled
corticosteroids and in whom "as-needed" short-acting Beta-agonists provide inadequate clinical
control of asthma.
Broncast 5 mg Chewable Tablet may also be an alternative treatment option to low-dose inhaled
corticosteroids for 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.

Broncast 5mg Chewable Tablet is also indicated in the prophylaxis of asthma in which the
predominant component is exercise-induced bronchoconstriction.

Dose and method of administration:
The dosage for paediatric patients 6-14 years of age is one 5 mg chewable tablet daily to be taken
in the evening. If taken in connection with food, Broncast 5mg chewable Tablet 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 5mg chewable tablet on parameters of asthma control occurs
within one day. Patients should be advised to continue taking Broncast 5mg Chewable tablet
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 5mg chewable tablet 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. 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.
Therapy with Broncast 5mg chewable tablet in relation to other treatments for asthma.
When treatment with Broncast 5mg chewable tablet is used as add-on therapy to inhaled
corticosteroids, Broncast 5mg chewable tablet should not be abruptly substituted for inhaled
corticosteroids.
10 mg tablets are available for adults 15 years of age and older.

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 beta-agonist should be used. Patients should seek their doctor's advice
as soon as possible if they need more inhalations of short-acting beta-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 usually, but not always, have been associated with the reduction or
withdrawal of oral corticosteroid therapy. The possibility that leukotriene receptor antagonists
may be associated with emergence of Churg-Strauss syndrome can neither be excluded nor
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.
Broncast 5mg chewable tablet contains aspartame, a source of phenylalanine. Patients with
phenylketonuria should take into account that each 5mg chewable tablet contains phenylalanine
in an amount equivalent to 0.842 mg phenylalanine per dose.

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
metabolized 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 metabolized 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 metabolized by this enzyme (eg.,
paclitaxel, rosiglitazone, and repaginate).
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.

Use during 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 5mg Chewable Tablet and malformations (i.e. limb defects) that have been rarely
reported in worldwide post marketing experience.
Broncast 5mg Chewable Tablet may be used during pregnancy only if it is considered to be
clearly essential.
Use during lactation:
Studies in rats have shown that montelukast is excreted in milk. It is not known if montelukast is
excreted in human milk.
Broncast 5mg chewable tablet may 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.

Montelukast has been evaluated in clinical studies as follows:
. 10 mg film-coated tablets in approximately 4,000 adult patients 15 years of age and older, and
. 5 mg chewable tablets in approximately 1,750 paediatric patients 6 to 14 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:

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.
Post-marketing Experience
Adverse reactions reported in post-marketing use are listed, by System Organ Class and specific
Adverse Experience Term, in the table below. Frequency Categories were estimated based on
relevant clinical trials.

the clinical trials data base: Very Common (≥1/10), Common (≥1/100 to <1/10), Uncommon
(≥1/1000 to <1/100), Rare (≥1/10,000 to <1/1000), Very Rare (<1/10,000).
†This adverse experience, reported as Very Common in the patients who received montelukast,
was also reported as Very Common in the patients who received placebo in clinical trials.
‡This adverse experience, reported as Common in the patients who received montelukast, was
also reported as Common in the patients who received placebo in clinical trials.

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 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 antagonist
The cysteinylleukotrienes (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 beta-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) and in
peripheral blood 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 beta-agonist use (-26.1% vs -4.6% change from baseline). Improvement in patientreported
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 beclometasone plus montelukast vs
beclometasone, respectively for FEV1: 5.43% vs 1.04%; beta-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%; beta-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 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' beta-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 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 beta-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 beta-agonist use was 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 (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 filmcoated
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.
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.

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, gastro-intestinal 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.

Mannitol 
Microcrystalline cellulose 
hydroxypropylcellulose 
Crosscarmellose sodium 
Red Iron Oxide 
Bubble Gum Flavor
Aspartame
Colloidal Silicon Dioxide
Magnesium Stearate

None.

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

Packaged in polyamide/PVC/aluminium blister package in:
Blisters in packages of: 28 Tablets
Blisters (unit doses), in packages of: 28 tablets.

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