MONTELUKAST Film-coated tablet Ref.[7322] Active ingredients: Montelukast

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 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.

This medicinal product contains lactose monohydrate.

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

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 Montelukast 10 mg film-coated tablets and malformations (i.e. limb defects) that have been rarely reported in worldwide post marketing experience.

Montelukast 10 mg film-coated tablets may be used during pregnancy only if it is considered to be clearly essential.

Breastfeeding

It is unknown whether montelukast is excreted in human milk. Studies in rats have shown that montelukast is excreted in milk (see section 5.3).

Montelukast 10 mg film-coated tablets may be used in breast-feeding only if it is considered to be clearly essential.

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

Montelukast has been evaluated in clinical studies as follows:

• 10 mg film-coated tablets in approximately 4000 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 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.

Tabulated list of Adverse Reactions

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.

Infections and infestations

Very Common: upper respiratory infection†

Blood and lymphatic system disorders

Rare: increased bleeding tendency

Very Rare: thrombocytopenia

Immune system disorder

Uncommon: hypersensitivity reactions including anaphylaxis

Very Rare: hepatic eosinophilic infiltration

Psychiatric disorders

Uncommon: dream abnormalities including nightmares, insomnia, somnambulism, anxiety, agitation including aggressive behaviour or hostility, depression, psychomotor hyperactivity (including irritability, restlessness, tremor§)

Rare: disturbance in attention, memory impairment, tic

Very Rare: hallucinations, disorientation, suicidal thinking and behaviour (suicidality)

Nervous system disorder

Uncommon: dizziness, drowsiness paraesthesia/hypoesthesia, seizure

Cardiac disorders

Rare: palpitations

Respiratory, thoracic and mediastinal disorders

Uncommon: epistaxis

Very Rare: Churg-Strauss Syndrome (CSS) (see section 4.4), pulmonary eosinophilia

Gastrointestinal disorders

Common: diarrhoea‡, nausea‡, vomiting‡

Uncommon: dry mouth, dyspepsia

Hepatobiliary disorders

Common: elevated levels of serum transaminases (ALT, AST)

Very Rare: hepatitis (including cholestatic, hepatocellular, and mixed-pattern liver injury)

Skin and subcutaneous tissue disorders

Common: rash‡

Uncommon: bruising, urticaria, pruritus

Rare: angiooedema

Very Rare: erythema nodosum, erythema multiforme

Musculoskeletal, connective tissue and bone disorders

Uncommon: arthralgia, myalgia including muscle cramps

Renal and urinary disorders

Uncommon: enuresis in children

General disorders and administration site conditions

Common: pyrexia‡

Uncommon: asthenia/fatigue, malaise, oedema,

* Frequency Category: Defined for each Adverse Experience Term by the incidence reported in the clinical trials data base: Very Common (≥1/10), Common (≥1/100 to </10), Uncommon (≥1/1000 to </100), Rare (≥1/10,000 to </1000), Very Rare (</10,000).
^† This adverse experience, reported as Very Common in the patients who received montelukast, was also reported as Very Common in the patients who received placebo in clinical trials.
^‡ This adverse experience, reported as Common in the patients who received montelukast, was also reported as Common in the patients who received placebo in clinical trials.
^§ Frequency Category: Rare

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Not applicable.