Leukotriene receptor antagonists - ATC-code: R03D C03

montelukast sodium

One film-coated tablet contains montelukast sodium, which is equivalent to 10 mg montelukast. Excipient: Lactose monohydrate 89.3 mg per tablet

Film-coated tablet. Beige, rounded square, film-coated, size 7.9 mm x 7.9 mm with 'SINGULAIR' engraved on one side and 'MSD 117' on the other.

SINGULAIR 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 SINGULAIR is indicated in asthma, SINGULAIR can also provide symptomatic relief of seasonal allergic rhinitis.

SINGULAIR is also indicated in the prophylaxis of asthma in which the predominant component is exercise-induced bronchoconstriction.

The dosage for adults 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 SINGULAIR on parameters of asthma control occurs within one day. SINGULAIR may be taken with or without food. Patients should be advised to continue taking SINGULAIR even if their asthma is under control, as well as during periods of worsening asthma. SINGULAIR 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 SINGULAIR in relation to other treatments for asthma.

SINGULAIR can be added to a patient's existing treatment regimen.

Inhaled corticosteroids: Treatment with SINGULAIR can be used as add-on therapy in patients when inhaled corticosteroids plus "as needed" short acting β-agonists provide inadequate clinical control. SINGULAIR should not be abruptly substituted for inhaled corticosteroids.

5-mg chewable tablets are available for paediatric patients 6 to 14 years of age.

Singulair Paediatric: Under six years, not recommended; six to 14 years, 5 mg at bedtime. If with food, take one hour before or two hours after.

Hypersensitivity to the active substance or to any of the excipients.

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 doctor's 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 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 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, caution should be exercised, particularly in children, when montelukast is co-administered with inducers of CYP 3A4, 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.)

Montelukast has been evaluated in clinical studies as follows:

• 10 mg film-coated tablets in approximately 4000 adult asthmatic patients 15 years of age and older.

• 10 mg film-coated tablets in approximately 400 adult asthmatic patients with seasonal allergic rhinitis 15 years of age and older.

• 5 mg chewable tablets in approximately 1750 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.

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.

Merck Sharp & Dohme Limited

(POM)

22 March 2012