Active ingredients: Montelukast
SINGULAIR 10 mg film-coated tablets
Singulair package inserts are available for pack sizes:- SINGULAIR 10 mg film-coated tablets
- SINGULAIR 5 mg chewable tablets
- SINGULAIR 4 mg chewable tablets
- SINGULAIR 4 mg granules
Indications Why is Singulair used? What is it for?
SINGULAIR is a leukotriene receptor antagonist that blocks substances called leukotrienes. Leukotrienes cause the airways in the lungs to narrow and swell and also cause allergic symptoms. Leukotriene blockade improves asthma symptoms and helps control asthma and improves symptoms of seasonal allergies (also known as hay fever and seasonal allergic rhinitis).
The doctor prescribed SINGULAIR for the treatment of asthma, to prevent asthma symptoms both during the day and at night.
- SINGULAIR is used to treat patients who are not adequately controlled on their medications and need additional medications.
- SINGULAIR also prevents exercise-induced narrowing of the airways.
- In asthma patients where SINGULAIR is indicated for asthma, SINGULAIR may provide relief from the symptoms of seasonal allergic rhinitis.
Your doctor will determine how to use SINGULAIR based on your asthma symptoms and severity.
What is asthma?
Asthma is a long-term disease.
Asthma includes:
- Difficulty breathing due to narrowing of the airways. The narrowing of the airways worsens and improves in response to various conditions.
- The airways that react to many irritating stimuli, such as cigarette smoke, pollen, cold air, or exercise.
- Swelling (inflammation) of the airways.
Symptoms of asthma include: cough, shortness of breath and chest tightness
What are seasonal allergies?
Seasonal allergies (also called hay fever or seasonal allergic rhinitis) are allergic responses often caused by airborne pollen from trees, grass and seeds. Typical symptoms of seasonal allergies can include: stuffy nose, cold, itchy nose; sneezing; red, swollen, itchy, and watery eyes.
Contraindications When Singulair should not be used
Tell your doctor about any current or past illness and any allergies.
Do not take SINGULAIR
- if you are allergic (hypersensitive) to montelukast or any of the other ingredients of SINGULAIR
Precautions for use What you need to know before taking Singulair
Take special care with SINGULAIR
- If your asthma or breathing gets worse, contact your doctor immediately.
- SINGULAIR by mouth should not be used to treat acute asthma attacks. If seizures occur, follow your doctor's instructions. Always keep emergency inhaled medications for asthma attacks with you.
- It is important that you or your child take all asthma medicines your doctor prescribes. SINGULAIR should not be used in place of other asthma medicines your doctor has prescribed for you.
- Patients taking asthma medications should be aware that if they experience a combination of symptoms such as flu-like syndrome, tingling or decreased sensation in the arms or legs, worsening lung symptoms, and / or redness of the skin, they should see their doctor.
- You should not take acetylsalicylic acid (aspirin) or anti-inflammatory drugs (also called non-steroidal anti-inflammatory drugs or NSAIDs) if they worsen asthma.
Use in children
For children 2 to 5 years, SINGULAIR 4 mg chewable tablets and 4 mg granules are available.
For children 6 to 14 years, SINGULAIR 5 mg chewable tablets are available.
Interactions What medications or foods may change the effect of Singulair
Some drugs can interfere with the way SINGULAIR works, or SINGULAIR can interfere with the way other drugs work.
Tell your doctor if you are taking or have recently taken any other medicines, even those without a prescription
Tell your doctor if you are taking the following medicines before you start taking SINGULAIR:
- phenobarbital (used to treat epilepsy)
- phenytoin (used to treat epilepsy)
- rifampicin (used to treat tuberculosis and some other infections)
- gemfibrozil (used to treat high plasma lipid levels).
Using SINGULAIR with food and drink
SINGULAIR 10 mg can be taken with or between meals.
Warnings It is important to know that:
Pregnancy and breastfeeding
Use in pregnancy
If you are pregnant or would like to become pregnant, you must consult your doctor before taking SINGULAIR. Your doctor will determine if you can or cannot take SINGULAIR under these circumstances.
Use while breastfeeding
It is not known whether SINGULAIR can appear in human milk. If you are breast-feeding or planning to breast-feed, you must consult your doctor before taking SINGULAIR.
Driving and using machines
No effects on the ability to drive and use machines are expected. Individual responses to medications, however, may vary. Some side effects (such as dizziness and somnolence) which have been reported very rarely with SINGULAIR may affect the ability to drive and use machines.
Important information about some of the ingredients of SINGULAIR
SINGULAIR 10 mg film-coated tablets contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this drug.
Dose, Method and Time of Administration How to use Singulair: Posology
- You only need to take one SINGULAIR tablet per day as prescribed by your doctor.
- The tablet should also be taken if you have no symptoms or have an acute asthma attack.
- Always take SINGULAIR exactly as your doctor has told you.
- If in doubt, you should consult your doctor or pharmacist.
- Take the tablet by mouth.
For adults aged 15 and over:
One 10 mg tablet to be taken every day in the evening. SINGULAIR 10 mg can be taken with or between meals.
If you are taking SINGULAIR, make sure you are not taking any other products that contain the same active substance, montelukast.
Overdose What to do if you have taken too much Singulair
If you take more SINGULAIR than you should
Consult your doctor immediately.
In the majority of overdose reports there were no undesirable effects. Symptoms most frequently reported with overdose in adults and children include abdominal pain, drowsiness, thirst, headache, vomiting and hyperactivity.
If you forget to take SINGULAIR
Try to take SINGULAIR as it was prescribed. However, if you forget to take a tablet, continue taking the medicine at the usual dosage.
Do not take a double dose to make up for a forgotten tablet
If you stop taking SINGULAIR
Treatment with SINGULAIR can only be effective against asthma if you continue to take it. It is important to continue taking SINGULAIR for as long as your doctor prescribes it. It will help control your asthma.
If you have any further questions on the use of SINGULAIR, ask your doctor or pharmacist.
Side Effects What are the side effects of Singulair
Like all medicines, SINGULAIR can cause side effects, although not everybody gets them.
In clinical studies with SINGULAIR 10 mg film-coated tablets, the most commonly reported undesirable effects believed to be related to SINGULAIR (occurring in at least 1 in 100 and less than 1 in 10 patients) were:
- abdominal pain
- headache
These side effects were usually mild and occurred more frequently in patients treated with SINGULAIR than in those treated with placebo (a tablet containing no drug substance).
The frequency of possible side effects listed below is defined using the following convention:
Very common (affects at least 1 user in 10)
Common (affects 1 to 10 users in 100)
Uncommon (affects 1 to 10 users in 1,000)
Rare (affects 1 to 10 users in 10,000)
Very rare (affects less than 1 user in 10,000)
In addition, the following side effects have been reported with commercial use of the medicine:
- upper respiratory tract infection (Very common)
- increased bleeding tendency (Rare)
- allergic reactions including swelling of the face, lips, tongue and / or throat which may cause difficulty in breathing or swallowing (Uncommon)
- behavior and mood changes [altered dreams, including nightmares, insomnia, sleepwalking, irritability, feeling anxious, restless, agitation including aggressive behavior or hostility, depression (Uncommon); tremor, altered attention, memory impairment (Rare); hallucinations, disorientation, suicidal thoughts and actions (Very rare)]
- dizziness, somnolence, tingling, convulsions (Uncommon)
- palpitations (Rare)
- nosebleed (Uncommon)
- diarrhea, nausea, vomiting (Common); dry mouth, digestive disturbances (Uncommon)
- hepatitis (inflammation of the liver) (Very rare)
- rash (Common); bruising, itching, hives (Uncommon); pressure-sensitive red swelling of the subcutaneous tissue most commonly located on the anterior surface of the legs (erythema nodosum), severe skin reactions (erythema multiforme) which may occur without warning (Very rare)
- joint or muscle pain, muscle cramps (Uncommon)
- fever (Common); weakness / tired feeling, malaise, swelling (Uncommon)
A complex of symptoms such as a flu-like form, tingling or numbness in the arms or legs, worsening of lung symptoms and / or skin rash has been reported in very rare cases during the treatment of asthmatic patients with montelukast. Churg-Strauss). The patient should report to the physician immediately if one or more of these symptoms occur.
Ask your doctor or pharmacist for more information on side effects. Report to your doctor or pharmacist any side effects other than those listed above or if any symptoms get worse.
Expiry and Retention
- Keep SINGULAIR out of the reach and sight of children.
- Do not use SINGULAIR after the expiry date indicated on the label with the six numbers after EXP. The first two numbers indicate the month; the last four numbers indicate the year. The expiry date refers to the last day of the month.
- Store in the original package to keep it away from light and moisture.
- Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What SINGULAIR contains
- The active ingredient is montelukast. Each tablet contains montelukast sodium which corresponds to 10 mg of montelukast.
- The other ingredients are: Microcrystalline cellulose, lactose monohydrate (89.3 mg), croscarmellose sodium, hyprolose (E463) and magnesium stearate. Coating: hypromellose, hyprolose (E463), titanium dioxide (E171), red and yellow iron oxide (E172), carnauba wax.
Description of what SINGULAIR looks like and contents of the pack
Beige in color, square shape, with rounded edges, film coated, with SINGULAIR embossed on one side, MSD 117 on the other.
Blister packs of: 7, 10, 14, 20, 28, 30, 49, 50, 56, 84, 90, 98, 100, 140, 200 tablets.
Blisters (single-dose), in packs of: 49, 50 and 56 tablets.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
SINGULAIR 10 MG TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One film-coated tablet contains: montelukast sodium, equivalent to 10 mg of montelukast.
Excipient: lactose monohydrate 89.3 mg per tablet.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablet.
Beige in color, square shape, rounded edges, film coated, 7.9mm x 7.9mm, with SINGULAIR embossed on one side and MSD 117 on the other.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
SINGULAIR is indicated for the treatment of asthma as adjunctive therapy in those patients with persistent mild / moderate asthma who are not adequately controlled with inhaled corticosteroids and in whom short-acting b-adrenergic agonists are taken at the same time. need "provide inadequate clinical control of asthma. SINGULAIR can also be used for the symptomatic treatment of seasonal allergic rhinitis in patients in whom SINGULAIR is indicated for asthma.
SINGULAIR is also indicated for asthma prophylaxis where the predominant component is exercise-induced bronchoconstriction.
04.2 Posology and method of administration
The dose for adults and adolescents aged 15 years and over with asthma, or with asthma and concomitant seasonal allergic rhinitis, is one 10 mg tablet per day, taken in the evening.
General recommendations. The therapeutic effect of SINGULAIR on asthma control parameters becomes evident within one day. SINGULAIR can be taken with or without food.Advise the patient to continue taking SINGULAIR even when 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 dose adjustments are required in the elderly or patients with renal insufficiency or mild to moderate hepatic impairment. There are no data on patients with severe hepatic impairment. The dose is the same for patients of both sexes.
SINGULAIR therapy in relation to other asthma treatments.
SINGULAIR can be added to the patient's current regimen.
Inhaled corticosteroids - SINGULAIR can be used as adjunct therapy where other agents such as inhaled corticosteroids plus fast-acting β-adrenergic agonists to be used "as needed" provide inadequate clinical control. SINGULAIR is not a replacement therapy for inhaled corticosteroids (see section 4.4).
5 mg chewable tablets are available for pediatric patients 6 to 14 years of age.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
04.4 Special warnings and appropriate precautions for use
Advise the patient not to use oral montelukast for the treatment of acute asthma attacks and to have appropriate emergency medications commonly used in such conditions on hand. In the case of an acute attack, a short-acting inhaled b-adrenergic agonist should be used. to the attending physician as soon as possible.
Montelukast should not be abruptly substituted for inhaled or oral corticosteroids.
There are no data demonstrating that the oral dose of corticosteroids can be reduced by concomitant administration of montelukast.
In rare cases, patients on anti-asthma medication including montelukast may experience systemic eosinophilia, sometimes manifesting as the clinical features of vasculitis similar to that of Churg-Strauss syndrome, a condition often treated with systemic therapy. corticosteroid. These cases have generally, but not always, been associated with the reduction or discontinuation of oral corticosteroid therapy. The possibility that leukotriene receptor antagonists may be associated with the onset of Churg-Strauss syndrome cannot be ruled out or established. Physicians should monitor patients for eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications and / or neuropathy. Patients who develop these symptoms should be evaluated and their treatment regimens should be reconsidered.
In aspirin-sensitive asthma patients, montelukast treatment does not alter the need to avoid aspirin or other non-steroidal anti-inflammatory drugs.
Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this drug.
04.5 Interactions with other medicinal products and other forms of interaction
Montelukast can be administered with other drugs commonly used in the prophylaxis and chronic treatment of asthma. In drug interaction studies, the recommended clinical dose of montelukast did not have clinically important effects on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, contraceptives oral (ethinyl estradiol / norethindrone 35/1), terfenadine, digoxin and warfarin.
The area under the plasma concentration curve (AUC) of montelukast was decreased by approximately 40% in subjects coadministered with phenobarbital. Since montelukast is metabolised by CYP 3A4, 2C8, and 2C9, caution should be used, especially in children, when montelukast is given concomitantly with inducers of CYP 3A4, 2C8, and 2C9, such as phenytoin, phenobarbital and rifampicin.
Education in vitro showed that montelukast is a potent inhibitor of CYP 2C8. However, data from a clinical drug interaction study with montelukast and rosiglitazone (a substrate used as a representative test for medicinal products metabolised primarily by CYP 2C8) have however shown that montelukast does not inhibit CYP 2C8. in vivo. Montelukast is therefore not expected to significantly alter the metabolism of medicinal products metabolised by this enzyme (e.g., paclitaxel, rosiglitazone and repaglinide).
Education in vitro showed that montelukast is a substrate of CYP 2C8, and to a lesser extent 2C9, and 3A4. In a drug-drug interaction study of montelukast and gemfibrozil (an inhibitor of both CYP 2C8 and 2C9) gemfibrozil increased the systemic exposure of montelukast by 4.4-fold. No routine dose adjustment is required. montelukast when administered concomitantly with gemfibrozil or other potent CYP 2C8 inhibitors, but the physician should be aware of the potential for increased adverse reactions.
Based on the data in vitro, clinically important drug interactions with less potent CYP 2C8 inhibitors (e.g. trimethoprim) are not expected. Co-administration of montelukast with itraconazole, a potent CYP 3A4 inhibitor, resulted in no significant increase in the systemic exposure of montelukast.
04.6 Pregnancy and lactation
Use during pregnancy
Animal studies do not indicate the presence of harmful effects on pregnancy or embryofoetal development.
The limited data available in pregnancy databases do not suggest the existence of a causal relationship between SINGULAIR and malformations (limb defects) rarely reported in post-marketing experience worldwide.
SINGULAIR can only be used in pregnancy if clearly considered essential.
Use while breastfeeding
Studies in rats have shown that montelukast is excreted in breast milk (see section 5.3). It is not known whether montelukast is excreted in the milk of lactating women.
SINGULAIR can be used during breastfeeding only if clearly considered essential.
04.7 Effects on ability to drive and use machines
Montelukast is not thought to interfere with the ability to drive or use machines. However, in very rare cases, some patients have reported drowsiness or dizziness.
04.8 Undesirable effects
Montelukast has been evaluated in clinical studies as follows:
• 10 mg film-coated tablets on approximately 4,000 adult and adolescent asthma patients ≥ 15 years of age.
• 10 mg film-coated tablets on approximately 400 adult and adolescent asthma patients with seasonal allergic rhinitis aged ≥ 15 years.
• 5 mg chewable tablets in approximately 1,750 pediatric asthma patients aged 6 to 14 years.
The following drug-related adverse reactions were reported commonly (≥1 / 100 to
With continued therapy in clinical trials for up to 2 years in a limited number of adult patients and up to 12 months in pediatric patients aged 6-14 years, the safety profile did not change.
Post-marketing experience
Adverse reactions reported from post-marketing use are listed in the table below, based on system organ class and specific adverse experience terminology. The frequency categories were estimated on the basis of relevant clinical studies.
04.9 Overdose
No specific information is available on the treatment of overdose with montelukast. In chronic asthma studies, montelukast has been administered to patients at doses up to 200 mg / day for 22 weeks and in short-term studies up to 900 mg / day for approximately one week, with no clinically important adverse events.
There have been reports of acute overdose in post-marketing experience and in clinical trials with montelukast. These include reports in adults and children with doses up to 1,000 mg (approximately 61 mg / kg in a 42 month old child). observed laboratory results were consistent with the safety profile in adults and pediatric patients. There were no adverse experiences in the majority of overdose cases. The most frequently observed 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 dialysis or hemodialysis.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Leukotriene receptor antagonists
ATC code: R03D C03
Cysteinyl-leukotrienes (LTC4, LTD4, LTE4) are potent inflammatory eicosanoids released by various cells including mast cells and eosinophils. These important asthma mediators bind to cysteinyl-leukotriene (CysLT) receptors. The CysLT type 1 receptor (CysLT1) is located in the airways in humans (including smooth myocells and airway macrophages) and on other proinflammatory cells (including eosinophils and some stem cells of the myeloid series). CysLTs have been related to the pathophysiology of asthma and allergic rhinitis. In asthma, leukotriene-mediated effects include bronchoconstriction, mucosal secretion, vascular permeability, and eosinophil recruitment. In allergic rhinitis, CysLTs are released from the nasal mucosa following exposure to allergens during both early and late reactions and are associated with the symptoms of allergic rhinitis. Intranasal stimulation with CysLTs has been shown to increase nasal airway resistance and symptoms of nasal obstruction.
Montelukast is an orally active compound which exhibits high affinity and selectivity for the CysLT1 receptor. In clinical trials montelukast at low doses, such as 5 mg, inhibits bronchoconstriction caused by inhalation of LTD4. Bronchodilation was observed within two hours of oral administration. The bronchodilator effect caused by a beta-adrenergic agonist was additive to that. produced by montelukast. Montelukast treatment inhibited both the early and late stages of bronchoconstriction caused by 'exposure to' the antigen. Montelukast, compared to placebo, decreased peripheral blood eosinophils in both adult and pediatric patients. In a separate study, montelukast treatment significantly reduced eosinophils in the respiratory tract (as a result of sputum examination) and peripheral blood, while improving clinical control of asthma.
In adult studies compared with placebo, montelukast, 10 mg once daily, was shown to improve FEV1 in the morning (changes from baseline 10.4% vs 2.7%), the antimeridian peak expiratory flow (PEFR) (changes from baseline 24.5 l / min vs 3.3 l / min), and significantly decreases the total use of b-adrenergic agonists (changes from baseline -26.1% vs -4.6%). Patient-reported improvement in day and night symptom score was significantly better than that in the placebo group.
In adult studies, montelukast has been shown to provide an additive clinical effect to that induced by inhaled corticosteroid (percentage changes from baseline for inhaled beclomethasone plus montelukast vs beclomethasone respectively of FEV1: 5.43% vs 1.04% and the use of b-adrenergic agonists: -8.70% vs -2.64%). Initial response to montelukast was shown to be more rapid than to inhaled beclomethasone (200 mg twice daily, administered via a spacer device), although beclomethasone provided over the entire twelve-week study period. a higher mean effect (percentage changes from baseline for montelukast vs beclomethasone FEV1 respectively: 7.49% vs 13.3% and the use of b-adrenergic agonists: -28.28% vs -43.89%). However, a "high percentage of patients treated with montelukast achieved a similar clinical response to that seen with beclomethasone (eg. 50% of patients treated with beclomethasone achieved an improvement in FEV1 of approximately 11% or more compared to baseline, while approximately 42% of patients treated with montelukast achieved the same response).
A clinical study was conducted to evaluate the use of montelukast in the symptomatic treatment of seasonal allergic rhinitis in adult and adolescent asthma patients aged 15 years and over with concomitant seasonal allergic rhinitis. In this study, montelukast 10 mg once daily tablets demonstrated a statistically significant improvement, compared to placebo, in the daily rhinitis symptom score. The daily rhinitis symptom score is the mean of the daytime nasal symptoms score (mean nasal congestion, rhinorrhea, sneezing and itchy nose) and the score of nocturnal symptoms (mean nasal congestion upon awakening, difficulty falling asleep, and score for nocturnal awakening). The overall ratings of allergic rhinitis by patients and physicians were also significantly improved compared to placebo. "efficacy on asthma was not an objective." or primary of this study.
In an 8-week study in patients aged 6-14 years, montelukast 5 mg once daily significantly improved respiratory function compared to placebo (percentage changes from baseline in FEV1: 8.71% vs 4.16%; percentage changes from baseline in morning PEFR 27.9 l / min vs 17.8 l / min) and reduced the "as needed" use of b-adrenergic agonists (changes from baseline -11.7% vs +8,2 %).
A significant reduction in exercise-induced bronchoconstriction (BIE) was demonstrated in a 12-week adult study (maximum reduction in FEV1 22.33% for montelukast vs 32.40% for placebo; 5% recovery time of baseline FEV1: 44.22 min vs 60.64 min). This effect was consistent throughout the 12-week duration of the study. The reduction in BIE was also demonstrated in a short-term study in pediatric patients (maximum reduction in FEV1: 18.27% vs 26.11%; 5% recovery time of baseline FEV1: 17.76 min vs 27.98 min). In both studies, the effect was demonstrated at the end of the once daily dosing interval.
In aspirin-sensitive asthma patients receiving concomitant treatment with inhaled and / or oral corticosteroids, montelukast treatment, compared to placebo, resulted in a significant improvement in asthma control (percentage changes from baseline in FEV1: 8.55% vs -1.74%; reduction in total use of b-adrenergic agonists compared to baseline: -27.78% vs 2,09%).
05.2 Pharmacokinetic properties
Absorption Montelukast is rapidly absorbed following oral administration. For the 10 mg film-coated tablets, the mean value of the maximum plasma concentration (Cmax) in adults is reached 3 hours (Tmax) after dosing in the fasted state. The mean bioavailability after oral administration is 64%. Bioavailability and Cmax. they are not affected by a standard meal Safety and efficacy have been demonstrated in clinical trials where 10 mg film-coated tablets were administered regardless of the timing of food intake.
For 5 mg chewable tablets, adult Cmax is reached after 2 hours dosing in the fasted state. Mean bioavailability after oral administration is 73% and decreases to 63% with a standard meal.
Distribution More than 99% of montelukast is bound to plasma proteins. The steady state volume of distribution of montelukast averages 8-11 liters. Rat studies with radiolabelled montelukast indicate minimal distribution across the blood brain barrier. Furthermore, 24 hours after dose administration, concentrations of radiolabelled substance were minimal in all other tissues.
Biotransformation Montelukast is extensively metabolised. In studies performed with therapeutic doses, the plasma concentration of the metabolites of montelukast was undetectable at steady state in both adults and children.
Cytochrome P450 2C8 is the major enzyme in the metabolism of montelukast. In addition, CYP 3A4 and 2C9 may have a minor contribution, although itraconazole, an inhibitor of CYP 3A4, has been shown not to modify the pharmacokinetic variables of montelukast in healthy subjects. who received 10 mg of montelukast per day. Based on results in vitro on human liver microsomes, montelukast, at therapeutic plasma concentrations, does not inhibit cytochromes P450 3A4, 2C9, 1A2, 2A6, 2C19 or 2D6. The contribution of the metabolites to the therapeutic effect of montelukast is minimal.
Elimination In the healthy adult, the plasma clearance of montelukast averages 45 ml / min. Following oral administration of a radiolabelled dose of montelukast, 86% of the radioactivity was detected on stool examination, performed for five days, and less than 0.2% was detected in the urine These data, together with those relating to the bioavailability of montelukast following oral administration, indicate that montelukast and its metabolites are excreted almost exclusively via the bile.
Characteristics of patients No dose adjustment is necessary in the elderly or patients with mild to moderate hepatic impairment. Studies in patients with renal insufficiency have not been conducted. Since montelukast and its metabolites are eliminated primarily via the biliary route, no dose adjustment is anticipated in patients with renal insufficiency. There are no pharmacokinetic data with montelukast in patients with severe hepatic impairment (Child-Pugh score> 9).
At high doses of montelukast (20 and 60 times the recommended human dose) a reduction in the plasma concentration of theophylline was observed. This effect was not observed at the recommended dose of 10 mg once daily.
05.3 Preclinical safety data
In animal toxicology studies, mild and transient changes in serum SGPT (ALT), glucose, phosphorus and triglycerides were observed. Signs of toxicity in the animal were: increased salivation, gastrointestinal symptoms, loose stools and electrolyte imbalance. These occurred at doses that provided> 17 times the systemic exposure observed with the clinical dose. In monkeys, undesirable effects appeared starting at doses of 150 mg / kg / day (> 232 times the systemic exposure observed with the clinical dose). In animal studies montelukast did not alter fertility and reproductive capacity at a systemic exposure 24 times higher than that observed with the clinical dose. In the female fertility study in rats, doses of 200 mg / kg / day (> 69 times the systemic exposure observed with the clinical dose), a slight reduction in the weight of the neonates was observed. In rabbit studies, a "higher incidence of incomplete ossification was observed than in the control group at" 24 times the systemic exposure observed at the clinical dose. No abnormalities were observed in the rat. Montelukast has been shown to cross the placental barrier and is excreted in breast milk in animals.
No deaths occurred in mice and rats after single oral doses of montelukast sodium up to 5,000 mg / kg, the maximum dose tested (15,000 mg / m2 and 30,000 mg / m2 in mice and rats, respectively). The dose is equivalent to 25,000 times the recommended human dose in adults (based on a weight of 50 kg for an adult patient).
Montelukast was found to have no UVA, UVB or visible spectrum phototoxicity at doses up to 500 mg / kg / day (approximately> 200 times the systemic exposure observed with the clinical dose) in mice.
Montelukast was neither mutagenic nor mutagenic in the rodent in vitro and in vivo nor oncogen.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Microcrystalline cellulose
Lactose monohydrate
Croscarmellose sodium
Hyprolose (E 463)
Magnesium stearate
Coating:
Hypromellose
Hyprolose (E 463)
Titanium dioxide (E 171)
Red and yellow iron oxide (E 172)
Carnauba wax
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Store in the original package to protect from light and moisture.
06.5 Nature of the immediate packaging and contents of the package
Packaged in polyamide / PVC / aluminum blisters in:
Blister packs of: 7, 10, 14, 20, 28, 30, 50, 56, 84, 90, 98, 100, 140 and 200 tablets.
Blisters (single-dose), in packs of 49, 50 and 56 tablets.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
MSD Italia S.r.l.
Via Vitorchiano, 151 - 00189 Rome
08.0 MARKETING AUTHORIZATION NUMBER
28 film-coated tablets of 10 mg No. 034001014
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
August 1998 / July 2008
10.0 DATE OF REVISION OF THE TEXT
January 2015
