Ukraine Product

Montular Tablet

Montular Tablet

Why you have been prescribed this medicine?

You have been prescribed this medicine if you have any of the following:

  • as adjunctive therapy of bronchial asthma in those patients with mild to moderate persistent asthma that are inadequately controlled on inhaled corticosteroids and in whom “as-needed” short acting beta-agonists provide inadequate clinical control of asthma. In those asthmatic patients in whom Montular® is indicated in asthma, it can also provide symptomatic relief of seasonal allergic rhinitis.
  • in the prophylaxis of asthma in which the predominant component is exercise-induced bronchoconstriction.
  • symptomatic relief of seasonal and perennial allergic rhinitis.

 

When you should consult your doctor?

You should consult your doctor if you experience any of the following:
Infections and infestations: upper respiratory infection.
Skin and subcutaneous tissue disorders: angioedema, hematoma, urticaria, pruritus, rash, erythema nodosum, erythema multiforme.
Musculoskeletal system and connective tissue disorders: arthralgia, myalgia including muscle cramps.
Nervous system disorders: headache, apathy, drowsiness, dizziness, paraesthesia/hypoesthesia, seizures.
Gastrointestinal disorders: abdominal pain, diarrhoea, dry mouth, dyspepsia, nausea, vomiting.
Hepatobiliary disorders: elevated levels of serum transaminases (ALT, AST), hepatitis (including cholestatic, hepatocellular, and mixed-pattern liver injury).
Blood and lymphatic system disorders: increased bleeding tendency.
Immune system disorder: hypersensitivity reactions including anaphylaxis, hepatic eosinophilic infiltration.
Psychiatric disorders: dream abnormalities including nightmares, insomnia, somnambulism, irritability, anxiety, agitation, restlessness, anger, impatience, excitement, including aggressive behaviour or hostility, depression, tremor, hallucinations, suicidal thinking and behaviour (suicidality), psychomotor hyperactivity, tremor, disorientation, impaired concentration, memory impairment.
Cardiac disorders: palpitations.
Respiratory, thoracic and mediastinal disorders: epistaxis, Churg-Strauss Syndrome (CSS), tropical pulmonary eosinophilia.
Kidney and urinary tract disorders: enuresis in children.
General disorders and administration site conditions: asthenia/fatigue, indisposition, discomfort, swelling, fever, thirst.

WHAT TO DO IF YOU MISS A DOSE?

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise take it as soon as you remember and then go back to taking it as you would normally.

Things you MUST NOT DO while on this medicine?

Patients should be advised to never use Montular® 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 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.

Psychoneurological events have been reported in patients treated with montelukast (see. section «Adverse effects»). Other factors may influence on these effects, therefore, it is unknown whether these effects associate with the use of montelukast. Physicians should discuss these undesirable effects with their patients and/or nurses. Patients and/or nurses should be instructed to report such changes to the doctor.
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 usually (not always) associated with the reduction or withdrawal of oral corticosteroid therapy. The probability that leukotriene receptor antagonists may be associated with the appearance of Churg-Strauss cannot be proved or disproved. 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.

Influence on velocity reactions while driving motor transport and operating other mechanisms:

Montelukast is not expected to affect a patient's ability to drive motor transport or operate other mechanisms. However, in very rare cases, individuals have reported drowsiness or dizziness.

What to do if you accidentally take too much (overdose) of the medicine?

No specific information is available on the treatment of overdose with montelukast. In chronic asthma studies, montelukast has been administered at doses up to 200 mg/day for 22 weeks and in short-term studies, up to 900 mg/day to patients for approximately one week without clinically important adverse experiences.
There have been reports of acute overdose in post-marketing experience and studies with montelukast. These include reports in adults and children with a dose as high as 1000 mg (approximately 61 mg/kg in a 42 month old child). The clinical and laboratory findings observed were consistent with the safety profile in adults and paediatric patients. There were no adverse experiences in the majority of overdose reports. The most frequently occurring adverse experiences were consistent with the safety profile of montelukast and included abdominal pain, somnolence, thirst, headache, vomiting, and psychomotor hyperactivity.
It is not known whether montelukast is dialysable by peritoneal- or haemo-dialysis. The treatment is symptomatic.

Is it safe in pregnancy and breast-feeding?

Pregnancy. Animal studies do not indicate harmful effects on pregnancy or embryonic/foetal development.
Limited data from available pregnancy databases do not suggest a causal relationship between montelukast and malformations (i.e. limb defects) that have been rarely reported in worldwide post marketing experience.
Montelukast may be used during pregnancy only if, due to doctor`s opinion, the expected benefit to the woman outweighs the potential risk to the foetus.

Lactation. Studies in rats have shown that montelukast is excreted in milk. It is not known if montelukast is excreted with human milk.
Montelukast may be used in lactation period only if, due to doctor`s opinion, the expected benefit to the mother outweighs the potential risk to the foetus.

 

Storage Conditions:

Store at temperature below 25 °C in the original package.
Keep it out of reach of children.

Drug Description

Active substance: Montelukast sodium
1 tablet contains montelukast sodium equivalent to montelukast 10 mg;

Additional ingredients: Microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulphate, magnesium stearate, Opadry 20A520035 Yellow coating: hydroxypropyl cellulose, hypromellose, titanium dioxide (E 171), carnauba wax, iron oxide yellow (E 172), iron oxide red (E 172).

Basic physic-chemical properties:beige coloured, round shape, biconvex film coated tablets plain on both sides.


Indications and dosage.

Indications:

  • as adjunctive therapy of bronchial asthma in those patients with mild to moderate persistent asthma that are inadequately controlled on inhaled corticosteroids and in whom “as-needed” short acting beta-agonists provide inadequate clinical control of asthma. In those asthmatic patients in whom Montular® is indicated in asthma, it can also provide symptomatic relief of seasonal allergic rhinitis.
  • in the prophylaxis of asthma in which the predominant component is exercise-induced bronchoconstriction.

 

  • symptomatic relief of seasonal and perennial allergic rhinitis.

 

Dosage:
The dosage for patients (aged from 15 years) with asthma or with asthma and concomitant seasonal allergic rhinitis is 10 mg (1 tablet) daily to be taken in the evening. For the relief of symptoms of allergic rhinitis dose intake time is selected individually.
General recommendations. The therapeutic effect of montelukast on parameters of asthma control occurs within one day. The medicinal product may be taken with or without food. Patients should be advised to continue taking Montular® even if their asthma is under control, as well as during periods of worsening asthma. Montular® 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 Montular® in relation to other treatments for asthma.
Montular® can be added to a patient's existing treatment regimen.
Inhaled corticosteroids. Treatment with Montular® can be used as add-on therapy in patients when inhaled corticosteroids with "as needed" short acting β-agonists provide inadequate clinical control of the disease.
It is not recommended to abruptly substitute inhaled corticosteroids with Montular®.
Children.
Use in children over 15 years of age.

Side effects and drug interactions.

Side effects:
Infections and infestations: upper respiratory infection.
Skin and subcutaneous tissue disorders: angioedema, hematoma, urticaria, pruritus, rash, erythema nodosum, erythema multiforme.
Musculoskeletal system and connective tissue disorders: arthralgia, myalgia including muscle cramps.
Nervous system disorders: headache, apathy, drowsiness, dizziness, paraesthesia/hypoesthesia, seizures.
Gastrointestinal disorders: abdominal pain, diarrhoea, dry mouth, dyspepsia, nausea, vomiting.
Hepatobiliary disorders: elevated levels of serum transaminases (ALT, AST), hepatitis (including cholestatic, hepatocellular, and mixed-pattern liver injury).
Blood and lymphatic system disorders: increased bleeding tendency.
Immune system disorder: hypersensitivity reactions including anaphylaxis, hepatic eosinophilic infiltration.
Psychiatric disorders: dream abnormalities including nightmares, insomnia, somnambulism, irritability, anxiety, agitation, restlessness, anger, impatience, excitement, including aggressive behaviour or hostility, depression, tremor, hallucinations, suicidal thinking and behaviour (suicidality), psychomotor hyperactivity, tremor, disorientation, impaired concentration, memory impairment.
Cardiac disorders: palpitations.
Respiratory, thoracic and mediastinal disorders: epistaxis, Churg-Strauss Syndrome (CSS), tropical pulmonary eosinophilia.
Kidney and urinary tract disorders: enuresis in children.
General disorders and administration site conditions: asthenia/fatigue, indisposition, discomfort, swelling, fever, thirst.

 Drug interactions
Montelukast may be administered with other preparations routinely used in the prophylaxis or chronic treatment of asthma. In drug-interactions studies, montelukast in the recommended clinical dose had no clinically important effects on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (ethinyl estradiol/norethindrone 35/1), terfenadine, digoxin and warfarin.
The area under the plasma concentration-time 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 coadministered 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 marker substrate; drug, 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 drugs metabolized by this enzyme (e.g., paclitaxel, rosiglitazone, and repaglinide).
In vitro studies have shown that montelukast is a substrate of CYP 2C8 and in a smaller extent of 2C9 and 3A4. In clinical drug-drug interaction study involving montelukast and gemfibrozil (inhibitors CYP2C8 and 2C9), gemfibrozil increased systemic exposure of montelukast 4.4 fold.
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.

 

Warnings and precautions

Patients should be advised to never use Montular® 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 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.

Psychoneurological events have been reported in patients treated with montelukast (see. section «Adverse effects»). Other factors may influence on these effects, therefore, it is unknown whether these effects associate with the use of montelukast. Physicians should discuss these undesirable effects with their patients and/or nurses. Patients and/or nurses should be instructed to report such changes to the doctor.
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 usually (not always) associated with the reduction or withdrawal of oral corticosteroid therapy. The probability that leukotriene receptor antagonists may be associated with the appearance of Churg-Strauss cannot be proved or disproved. 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.


Overdosage and Contraindications

Overdosage:
No specific information is available on the treatment of overdose with montelukast. In chronic asthma studies, montelukast has been administered at doses up to 200 mg/day for 22 weeks and in short-term studies, up to 900 mg/day to patients for approximately one week without clinically important adverse experiences.
There have been reports of acute overdose in post-marketing experience and studies with montelukast. These include reports in adults and children with a dose as high as 1000 mg (approximately 61 mg/kg in a 42 month old child). The clinical and laboratory findings observed were consistent with the safety profile in adults and paediatric patients. There were no adverse experiences in the majority of overdose reports. The most frequently occurring adverse experiences were consistent with the safety profile of montelukast and included abdominal pain, somnolence, thirst, headache, vomiting, and psychomotor hyperactivity.
It is not known whether montelukast is dialysable by peritoneal- or haemo-dialysis. The treatment is symptomatic.

 Contraindications

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

Clinical pharmacology.

Pharmacodynamic properties

Drugs for systemic use in obstructive airway diseases. Leukotriene receptor antagonists. ATC code R03D C03.

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 which are found in the human airway and provoke such reaction as bronchospasm, hypersecretion, increased vascular permeability, and increased eosinophils.

Montelukast is an orally active compound which binds with high affinity and selectivity to the CysLT1 receptors. In clinical studies, montelukast inhibits bronchospasm due to inhaled LTD4 at doses of 5 mg. Bronchodilatation was observed within 2 hours of oral administration. This effect was additive to bronchodilatation caused by a β-agonists.

Treatment with montelukast inhibited both early- and late-phases of bronchoconstriction due to antigen challenge. Clinical data have shown that treatment with montelukast significantly decreased eosinophils in peripheral blood and in airways (as measured in sputum), and improved clinical asthma control.

Pharmacokinetic properties

Absorption.
Montelukast is rapidly absorbed following oral administration. For the 10-mg film-coated tablets, the mean peak plasma concentration (Cmax) was 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 tablets were administered without regard to the timing of food ingestion.
Distribution
Montelukast is more than 99% bound to plasma proteins. The steady state volume of distribution of montelukast averages out at 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.
Metabolism
Montelukast is extensively metabolized. In studies with therapeutic doses, plasma concentrations of metabolites of montelukast are undetectable at steady state in adults and children.

Cytochrome P450 2C8 is the major enzyme in the metabolism of montelukast. Additionally CYP 3A4 and 2C9 may have a minor contribution in the metabolism of montelukast, although itraconazole (an inhibitor of CYP 3A4) was shown not to change pharmacokinetic variables of montelukast in healthy subjects that received 10 mg montelukast daily. 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.
Elimination
The plasma clearance of montelukast averages 45 ml/min in healthy adults. Following an oral dose of radiolabeled montelukast, 86% is recovered in 5 day with faeces and <0.2% is recovered in urine. Coupled with estimates of montelukast oral bioavailability, this indicates that montelukast and its metabolites are excreted almost exclusively via the bile.
Pharmacokinetics in different populations
No dosage adjustment is required for patients with mild to moderate hepatic insufficiency. Studies in patients with renal impairment have not been undertaken. Montelukast and its metabolites are eliminated by the biliary route, thus no dose adjustment is anticipated to be necessary in patients with renal impairment. There are no data on the pharmacokinetics of montelukast in patients with severe hepatic insufficiency (Child-Pugh score >9).
With high doses of montelukast (20 and 60 fold the recommended adult dose) decrease in plasma theophylline concentration was observed. This effect was not seen at the recommended dose of 10 mg once daily.

Pharmaceutical characteristics:

Shelf-life: 2 years.

Package: 10 tablets in a blister; 3 blisters in a carton pack.

Conditions of supply:
By prescription.

CERTIFICATES

KEEP IN TOUCH

Kusum Healthcare
D-158A, OKHLA,INDUSTRIAL AREA,
PHASE-I, NEW DELHI,
Pin 110020
INDIA
Tel: 011-41005147, 011-40514919
Fax: +91-11-40527575