Monocast®

Tablet

Description

The active ingredient of Monocast tablet is Montelukast Sodium INN.

Montelukast is a selective and orally active leukotriene receptor antagonist

that inhibits the cysteinyl leukotriene CysLT1 receptor. The cysteinyl

leukotrienes (LTC4, LTD4, LTE4) are products of Arachidonic acid

metabolism and are released from various cells, including mast cells and

oeosinophils. These eicosanoids 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 oeosinophils and certain

myeloid stem cells). CysLTs have been correlated with the

pathophysiology of asthma and allergic rhinitis. In asthma, leukotrienemediated effects include airway oedema, smooth muscle contraction, and

altered cellular activity associated with the inflammatory process. 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.

Montelukast is an orally active compound that binds with high affinity

and selectivity to the CysLT1 receptor (in preference to other

pharmacologically important airway receptors, such as the prostanoid,

cholinergic, or b adrenergic receptors). Montelukast inhibits physiologic

actions of LTD4 at the CysLT1 receptor without any agonist activity.

Indications

Monocast is indicated for the prophylaxis and chronic treatment of

asthma in adults and paediatric patients 12 months of age and older.

Monocast is indicated for the relief of symptoms of seasonal allergic

rhinitis in adults and paediatric patients 2 years of age and older.

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THERAPEUTIC INDEX

257

Dosage and Administration

General information : Monocast should be taken once daily. For asthma,

the dose should be taken in the evening. For seasonal allergic rhinitis, the

time of administration may be individualised to suit patients’ needs.

Patients with both asthma and seasonal allergic rhinitis should take only

one tablet daily in the evening.

Adults and adolescents 15 years of age and older with asthma or seasonal

allergic rhinitis : The dosage is one 10 mg tablet daily.

Paediatric patients 6 to 14 years of age with asthma or seasonal allergic

rhinitis : The dosage is one 5 mg chewable tablet daily. No dosage

adjustment within this age group is necessary.

Paediatric patients 2 to 5 years of age with asthma or seasonal allergic

rhinitis : The dosage is one 4 mg chewable tablet daily.

Paediatric patients 12 to 23 months of age with asthma : The dosage is

one 4 mg chewable tablet daily to be taken in the evening. Safety and

effectiveness in paediatric patients younger than 12 months of age have

not been established.

Contraindication

Hypersensitivity to any component of this product.

Precautions

General : Montelukast is not indicated for use in the reversal of

bronchospasm in acute asthma attacks, including status asthmaticus.

Patients should be advised to have appropriate rescue medication

available. Therapy with Montelukast can be continued during acute

exacerbation of asthma. While the dose of inhaled corticosteroid may be

reduced gradually under medical supervision, montelukast should not be

abruptly substituted for inhaled or oral corticosteroids. Montelukast

should not be used as monotherapy for the treatment and management

of exercise induced bronchospasm. Patients who have exacerbation of

asthma after exercise should continue to use their usual regimen of

inhaled b agonist as prophylaxis and have available for rescue a short

acting inhaled b agonist. Patients with known Aspirin sensitivity should

continue avoidance of aspirin or non-steroidal anti-inflammatory

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THERAPEUTIC INDEX

258

agents while taking Montelukast. Although montelukast is effective in

improving airway function in asthmatics with documented aspirin

sensitivity, it has not been shown to truncate bronchoconstrictor

response to aspirin and other non-steroidal anti-inflammatory drugs in

aspirin-sensitive asthmatic patients.

Eosinophilic Conditions : In rare cases, patients on therapy with

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 events usually, but not always, have been

associated with the reduction of oral corticosteroid therapy. Physicians

should be alert to eosinophilia, vasculitic rash, worsening pulmonary

symptoms, cardiac complications, and/or neuropathy presenting in their

patients. A causal association between montelukast and these underlying

conditions has not been established.

Drug Interactions

Montelukast has been administered with other therapies routinely used in

the prophylaxis and chronic treatment of asthma with no apparent

increase in adverse reactions. In drug interaction studies, the

recommended clinical dose of montelukast did not have clinically

important effects on the pharmacokinetics of the following drugs :

Theophylline, Prednisolone, oral contraceptives (Norethindrone 1

mg/Ethinyl Oestradiol 35 mg), Terfenadine, Digoxin, and Warfarin.

Although additional specific interaction studies were not performed,

Montelukast was used concomitantly with a wide range of commonly

prescribed drugs in clinical studies without clinically evident adverse

interactions. These medications included thyroid hormones, sedative

hypnotic, non-steroidal anti-inflammatory agents, benzodiazepines, and

decongestants.

Phenobarbital, which induces hepatic metabolism, decreased the AUC of

Montelukast approximately 40% following a single 10 mg dose of

Montelukast. No dosage adjustment for Montelukast is recommended. It

is reasonable to employ appropriate clinical monitoring when potent

cytochrome P450 enzyme inducers, such as Phenobarbital or Rifampin,

are co-administered with Montelukast.

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THERAPEUTIC INDEX

259

Side Effects

Adolescents and Adults 15 years of age and older : In placebo-controlled

clinical trials, Montelukast has been evaluated for safety in approximately

2600 adolescent and adult patients of 15 years and older, the following

adverse experiences reported with Montelukast occurred in greater than

or equal to 1% of patients. General : Asthenia/fatigue, Fever, Pain;

Gastrointestinal : Dyspepsia, Gastroenteritis; Nervous System/Psychiatric :

Dizziness, Headache; Respiratory System : Congestion, Cough, Influenza;

Skin : Rash; Laboratory adverse experiences : ALT increase, AST increase,

Pyuria.

Paediatric patients 6 to 14 years of age : In paediatric patients receiving

montelukast, the following events occurred with a frequency ³ 2% are

diarrhoea, laryngitis, pharyngitis, nausea, otitis, sinusitis, and viral

infection. With prolonged treatment, the adverse profile did not change

significantly.

Use in Special Populations

Pregnancy : Montelukast crosses the placenta following oral dosing in rats

and rabbits. There are, however, no adequate and well controlled studies

in pregnant women. Because animal reproduction studies are not always

predictive of human response, Montelukast should be used during

pregnancy only if clearly needed.

Lactation : It is not known if Montelukast is excreted in human milk.

Because many drugs are excreted in human milk, caution should be

exercised when Montelukast is given to a nursing mother.

Paediatric use : Safety and efficacy of Montelukast has been established in

adequate and well controlled studies in paediatric patients with asthma

and allergic rhinitis between age 1 to 14 years. Long term trials evaluating

the effect of chronic administration of Montelukast on linear growth in

paediatric patients have not been conducted.

Geriatric use : Of the total number of subjects in clinical studies of

Montelukast, 3.5% were 65 years of age and over and 0.4% were 75 years

of age and over. No overall differences in safety or effectiveness were

observed between these subjects and younger subjects. But greater

sensitivity of some older individuals cannot be ruled out.