What is Singulair??
1. Name of the medicinal product
SINGULAIR® Paediatric 4 mg Granules
2. Qualitative and quantitative composition
One sachet of granules contains montelukast sodium, which is equivalent to 4 mg montelukast.
For a full list of excipients, see section 6.1.
3. Pharmaceutical form
Granules.
White granules
4. Clinical particulars
4.1 Therapeutic indications
SINGULAIR is indicated in the treatment of asthma as add-on therapy in those 6 months to 5 year old 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.
SINGULAIR may also be an alternative treatment option to low-dose inhaled corticosteroids for 2 to 5 year old 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 (see section 4.2).
SINGULAIR is also indicated in the prophylaxis of asthma from 2 years of age and older in which the predominant component is exercise-induced bronchoconstriction.
4.2 Posology and method of administration
This medicinal product is to be given to a child under adult supervision. The dosage for paediatric patients 6 months to 5 years of age is one sachet of 4 mg granules daily to be taken in the evening. No dosage adjustment within this age group is necessary. Efficacy data from clinical trials in paediatric patients 6 months to 2 years of age with persistent asthma are limited. Patients should be evaluated after 2 to 4 weeks for response to montelukast treatment. Treatment should be discontinued if a lack of response is observed. The SINGULAIR Paediatric 4 mg granules formulation is not recommended below 6 months of age.
Administration of SINGULAIR granules:
SINGULAIR granules can be administered either directly in the mouth, or mixed with a spoonful of cold or room temperature soft food (e.g., applesauce, ice cream, carrots and rice). The sachet should not be opened until ready to use. After opening the sachet, the full dose of SINGULAIR granules must be administered immediately (within 15 minutes). If mixed with food, SINGULAIR granules must not be stored for future use. SINGULAIR granules are not intended to be dissolved in liquid for administration. However, liquids may be taken subsequent to administration. SINGULAIR granules can be administered without regard to the timing of food ingestion.
General recommendations. The therapeutic effect of SINGULAIR on parameters of asthma control occurs within one day. Patients should be advised to continue taking SINGULAIR 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.
SINGULAIR 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 2 to 5 years old 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 (see section 4.1). 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.
SINGULAIR as prophylaxis of asthma for 2 to 5 year old patients in whom the predominant component is exercise-induced bronchoconstriction:
In 2 to 5 year old patients, exercise-induced bronchoconstriction may be the predominant manifestation of persistent asthma that requires treatment with inhaled corticosteroids. Patients should be evaluated after 2 to 4 weeks of treatment with montelukast. If satisfactory response is not achieved, an additional or different therapy should be considered.
Therapy with SINGULAIR in relation to other treatments for asthma.
When treatment with SINGULAIR is used as add-on therapy to inhaled corticosteroids, SINGULAIR should not be abruptly substituted for inhaled corticosteroids (see section 4.4).
10 mg film-coated tablets are available for adults 15 years of age and older.
5 mg chewable tablets are available for paediatric patients 6 to 14 years of age.
4 mg chewable tablets are available as an alternative formulation for paediatric patients 2 to 5 years of age.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
4.4 Special warnings and precautions for use
The diagnosis of persistent asthma in very young children (6 months – 2 years) should be established by a paediatrician or pulmonologist.
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 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.
4.5 Interaction with other medicinal products and other forms of interaction
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 metabolised 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.
4.6 Pregnancy and lactation
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 SINGULAIR and malformations (i.e. limb defects) that have been rarely reported in worldwide post marketing experience.
SINGULAIR 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 (see section 5.3). It is not known if montelukast is excreted in human milk.
SINGULAIR may be used in breast-feeding mothers only if it is considered to be clearly essential.
4.7 Effects on ability to drive and use machines
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.
4.8 Undesirable effects
Montelukast has been evaluated in clinical studies in patients with persistent asthma as follows:
• 10 mg film-coated tablets in approximately 4000 adult patients 15 years of age and older
• 5 mg chewable tablets in approximately 1750 paediatric patients 6 to 14 years of age
• 4 mg chewable tablets in 851 paediatric patients 2 to 5 years of age, and
• 4 mg granules in 175 paediatric patients 6 months to 2 years of age.
Montelukast has been evaluated in a clinical study in patients with intermittent asthma as follows:
• 4 mg granules and chewable tablets in 1038 paediatric patients 6 months to 5 years of age
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