Square, beige film-coated tablet, shallow convex, bevel-edged and "HD"
embossed on one face.
Each film-coated tablet contains:
Montelukast sodium equivalent to 10 mg montelukast.
Actions and Pharmacology
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, leukotriene-mediated 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
Montelukast is a potent, orally active compound that significantly improves
parameters of asthmatic inflammation. Based on biochemical and
pharmacological bioassays, it binds with high affinity and selectivity to
the CysLT1 receptor (in preference to other pharmacologically important
airway receptors such as the prostanoid, cholinergic, or β-adrenergic
receptor). Montelukast potently inhibits physiologic actions of LTC4, LTD4
and LTE4 at the CysLT1 receptor without any agonist activity.
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 10mg film-coated tablet was administered without regard to the
timing of food ingestion.
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.
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 cytochrome 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.
Plasma Protein Binding
Plasma protein binding is more than 99% (Very high).
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. It is not known whether Montelukast is removable by peritoneal
dialysis or hemodialysis. The pharmacokinetics of Montelukast is nearly
linear at doses of up to 50 mg.
For the prophylaxis and chronic treatment of asthma in adults and pediatric
patients 12 months of age and older.
• Montelukast is indicated in adults and pediatric patients 2 years of age
and older for the relief of daytime and nighttime symptoms of seasonal
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 Montelukast should not be used to
treat asthma attacks.
• 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 it they need more inhalations of short-acting
β-agonists than usual. Montelukast should not be 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.
• Treatment with Montelukast does not alter the
need for patients with aspirin-sensitive asthma to avoid taking aspirin and
other nonsteroidal anti-inflammatory drugs.
Patients with rare hereditary problems of galactose intolerance, the Lapp
lactase deficiency or glucose-galactose malabsorption should not take this