Allair 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 β-agonists provide inadequate clinical control of asthma. In those
asthmatic patients in whom Allair is indicated in asthma, Allair can also provide symptomatic
relief of seasonal allergic rhinitis.
Allair is also indicated in the prophylaxis of asthma in which the predominant component is
exercise-induced bronchoconstriction
 

Posology
The recommended dose for adults and adolescents 15 years of age and older with asthma, or with
asthma and concomitant seasonal allergic rhinitis, is one 10 mg tablet daily to be taken in the
evening.
General recommendations
The therapeutic effect of Allair on parameters of asthma control occurs within one day. Allair
may be taken with or without food. Patients should be advised to continue taking Allair even if
their asthma is under control, as well as during periods of worsening asthma. Allair should not be
used concomitantly with other products containing the same active ingredient, montelukast.
No dosage adjustment is necessary for the elderly, or 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.
Therapy with Allair in relation to other treatments for asthma
Allair can be added to a patient's existing treatment regimen.
Inhaled corticosteroids: Treatment with Allair can be used as add-on therapy in patients when
inhaled corticosteroids plus “as needed” short acting β-agonists provide inadequate clinical
control. Allair should not be abruptly substituted for inhaled corticosteroids (see section 4.4).
Paediatric population
Do not give Allair 10 mg film-coated tablets to children less than 15 years of age. The safety and
efficacy of Allair 10 mg film-coated tablets in children less than 15 years has not been
established.
5 mg chewable tablets are available for paediatric patients 6 to 14 years of age.
4 mg chewable tablets are available for paediatric patients 2 to 5 years of age.
4 mg granules are available for paediatric patients 6 months to 5 years of age.
Other special population
N/A
Method of administration
Oral use
 

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 substituted abruptly 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.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or
glucose-galactose malabsorption should not take this medicine
 

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.
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 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 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
Allair and malformations (i.e. limb defects) that have been rarely reported in worldwide postmarketing experience.
Allair 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.
Allair may be used in breast-feeding only if it is considered to be clearly essential
 

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

Summary of the safety profile
Montelukast has been evaluated in clinical studies as follows:
• 10 mg film-coated tablets in approximately 4,000 adult and adolescent asthmatic patients 15
years of age and older.
• 10 mg film-coated tablets in approximately 400 adult and adolescent asthmatic patients with
seasonal allergic rhinitis 15 years of age and older.
• 5 mg chewable tablets in approximately 1,750 paediatric asthmatic 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 asthmatic 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.
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

Description of selected adverse events:
None
Paediatric population
Do not give Allair 10 mg film-coated tablets to children less than 15 years of age. The safety and
efficacy of Allair 10 mg film-coated tablets in children less than 15 years has not been
established.
5 mg chewable tablets are available for paediatric patients 6 to 14 years of age.
4 mg chewable tablets are available for paediatric patients 2 to 5 years of age.
4 mg granules are available for paediatric patients 6 months to 5 years of age.
Other special population
N/A

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 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.
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 haemodialysis
 

Pharmacotherapeutic group: Leukotriene receptor antagonist
ATC-code: R03D C03
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 (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, leukotrienemediated effects include bronchoconstriction, mucous secretion, vascular permeability, and
eosinophil 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.
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) and in
peripheral blood 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 patientreported 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 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).
A clinical study was conducted to evaluate montelukast for the symptomatic treatment of
seasonal allergic rhinitis in adult and adolescent asthmatic patients 15 years of age and older with
concomitant seasonal allergic rhinitis. In this study, montelukast 10 mg tablets administered once
daily demonstrated a statistically significant improvement in the Daily Rhinitis Symptoms score,
compared with placebo. The Daily Rhinitis Symptoms score is the average of the Daytime Nasal
Symptoms score (mean of nasal congestion, rhinorrhea, sneezing, nasal itching) and the
Nighttime Symptoms score (mean of nasal congestion upon awakening, difficulty going to sleep,
and nighttime awakenings scores). Global evaluations of allergic rhinitis by patients and
physicians were significantly improved, compared with placebo. The evaluation of asthma
efficacy was not a primary objective in this study.
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).
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 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.
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 radiolabeled 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), 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
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
 

Lactose monohydrate
- Microcrystalline Cellulose PH 101
- Microcrystalline Cellulose PH 102
- Hydroxypropyl Cellulose –L
- Croscarmellose Sodium
- Magnesium Stearate
- Opadry Yellow 02A22352
 

Not applicable
 

Store below 30°C
 

Allair is supplied as blister (ALU /ALU blister). Packs of 30 tablets
 

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