Active ingredients: Montelukast
SASLONG 4 mg chewable tablets For children 2 to 5 years
Saslong package inserts are available for pack sizes:- SASLONG 4 mg chewable tablets For children 2 to 5 years
- SASLONG 5 mg chewable tablets For children from 6 to 14 years
- SASLONG 10 mg film-coated tablets For adolescents and adults from 15 years of age
Why is Saslong used? What is it for?
SASLONG is a leukotriene receptor antagonist that blocks substances called leukotrienes. Leukotrienes cause the airways in the lungs to narrow and swell. By blocking leukotrienes, SASLONG improves asthma symptoms and helps control asthma.
Her doctor prescribed SASLONG to treat her son's asthma by preventing asthma symptoms during the day and night.
- SASLONG is used to treat children between the ages of 2 and 5 who are not adequately supervised in their care and need further therapy.
- SASLONG can also be used as an alternative treatment to inhaled corticosteroids for children 2 to 5 years of age who have not recently taken oral corticosteroids for asthma and have been shown to be unable to take inhaled corticosteroids.
- SASLONG also helps prevent narrowing of exercise-stressed airways in children 2 years and older.
Your doctor will decide how to take SASLONG based on the symptoms and severity of your child's asthma.
What is asthma?
Asthma is a long-term disease.
Asthma includes:
- difficulty in breathing due to narrowing of the airways. This shrinkage worsens and improves in response to various conditions;
- sensitive airways that react to many things, such as cigarette smoke, pollen, cold area, or exercise;
- swelling (inflammation) within the airways. Asthma symptoms include: coughing, wheezing and a stiff chest.
Contraindications When Saslong should not be used
Do not give SASLONG to your child if she / he
You are allergic (hypersensitive) to montelukast or to any of the other ingredients of SASLONG
Precautions for use What you need to know before taking Saslong
Tell your doctor about any medical problems or allergies your child has or has had.
Take special care with SASLONG
- If your child's asthma or breathing gets worse, tell your doctor right away.
- Oral SASLONG is not indicated for the treatment of acute asthma attacks. If an attack occurs, follow the instructions your doctor has given you for your child. Always carry emergency inhaled medicine for attacks with you. asthma.
- It is important that your child takes all asthma medicines prescribed by the doctor. SASLONG should not be substituted for the other asthma treatments that the doctor has prescribed for your child.
- If your child is on anti-asthma medication, be aware that if he / she develops a combination of symptoms, such as flu-like fever syndromes, tingling or numbness in the arms or legs, worsening of lung symptoms, and / or rash, should consult your doctor.
- Your child should not take acetyl-salicylic acid (aspirin) or other anti-inflammatory drugs (also known as non-steroidal anti-inflammatory drugs or NSAIDs) if they make your child's asthma worse.
Interactions Which drugs or foods can change the effect of Saslong
Some medicines can affect the way SASLONG works, or SASLONG can affect the way some other medicines work in your child.
Tell your doctor or pharmacist if your child is taking or has recently taken any other medicines, including those not prescribed.
Tell your doctor if your child is taking the following medications before starting SASLONG:
- phenobarbital (used to treat epilepsy)
- phenytoin (used to treat epilepsy)
- rifampicin (used to treat turbocolosis and some other infections).
Taking SASLONG with food and drink
SASLONG should not be taken immediately after eating; it should be taken at least one hour before or two hours after food.
Warnings It is important to know that:
Pregnancy and breastfeeding
This subsection is not applicable to SASLONG 4 mg chewable tablets as it is intended for use in children 2 to 5 years of age, however the following information relates to the active ingredient, montelukast.
Use in pregnancy
Women who are pregnant or planning to become pregnant should consult their doctor before taking SASLONG. Your doctor will assess whether you can take SASLONG during this period.
Use in lactation
It is not known if SASLONG occurs in breast milk. You must consult your doctor before taking SASLONG if you are breast-feeding or planning to breast-feed.
Driving and using machines
This subsection is not applicable to SASLONG 4 mg chewable tablets as it is intended for use in children 2 to 5 years of age, however the following information relates to the active ingredient, montelukast.
SASLONG is not believed to affect the ability to drive or use machines.
However, individual responses to treatment may vary.Some side effects (such as dizziness and somnolence) which have been reported very rarely with SASLONG may affect some patients' ability to drive or use machines.
Important information about some of the ingredients of SASLONG
SASLONG chewable tablets contains aspartame, a source of phenylalanine. It could be dangerous for people with phenylketonuria.
If your child has phenylketonuria (a rare inherited disorder of metabolism) you should be aware that each 4 mg chewable tablet contains phenylalanine in quantities of 0.898 mg phenylalanine per dose.
Dose, Method and Time of Administration How to use Saslong: Posology
- This drug should be given to a child under the supervision of an adult.
- Your child should only take one SASLONG tablet per day as prescribed by the doctor.
- Always have your child take SASLONG according to the doctor's instructions. If in doubt, consult your child's doctor or pharmacist.
- Take by mouth.
For children from 2 to 5 years:
One 4 mg chewable tablet per day to be taken in the evening. SASLONG 4 mg chewable tablets should not be taken immediately after eating; should be taken at least one hour or two hours after food intake.
If your child is taking SASLONG, make sure he / she does not take any other medicines that contain the same active ingredient, montelukast.
For children 2 to 5 years, SASLONG 4 mg chewable tablets are available.
For children 6 to 14 years, SASLONG 5 mg chewable tablets are available.
The SASLONG 4 mg chewable tablet formulation is not recommended for children under 2 years of age.
Overdose What to do if you have taken too much Saslong
If your child takes more SASLONG than he / she owes
Contact your child's doctor immediately for a consultation.
No side effects were reported in most overdose reports. More frequent symptoms associated with overdose in adults and children include abdominal pain, insomnia, thirst, headache, vomiting and hyperactivity.
If you forget to give SASLONG to your child
Try to give SASLONG as prescribed. However, if your child misses a dose, go back to the usual schedule of one tablet once a day.
Do not use a double dose to make up for a forgotten dose.
If your child stops using SASLONG
SASLONG can only cure your child's asthma if he / she takes it continuously.
It is important that your child takes SASLONG continuously for as long as the doctor prescribes. It will help control your child's asthma.
If you have any further questions on the use of this medicine, ask your child's doctor or pharmacist.
Side Effects What are the side effects of Saslong
Like all medicines, SASLONG can cause side effects, although not everybody gets them.
In clinical trials with SASLONG 4 mg chewable tablets, the most commonly reported side effects (occurring in at least 1 in 100 patients and less than 1 in 10 pediatric patients treated) thought to be attributable to SASLONG were:
- abdominal pain;
- thirst.
In addition, the following side effect was reported in clinical studies with SASLONG 10 mg film-coated tablets and 5 mg chewable tablets:
- headache.
Usually, these were mild and occurred more frequently in patients treated with SASLONG than with placebo (a pill that contains no medicine).
The frequency of possible side effects listed below is defined using the following convention:
Very common: may affect more than 1 in 10 people
Common: may affect up to 1 in 10 people
Uncommon: may affect up to 1 in 100 people
Rare: may affect up to 1 in 1000 people
Very rare: may affect up to 1 in 10,000 people
In addition, during the time the medicine has been on the market, the following have been reported:
- upper respiratory tract infections (very common);
- increased bleeding tendency (rare);
- allergic reactions, including rash, swelling of the face, lips, tongue and / or throat, which may cause difficulty in breathing and swallowing (uncommon);
- behavior and mood changes [strange dreams, such as nightmares, sleep disturbances, sleepwalking, irritability, feelings of anxiety, restlessness, agitation including aggressive behavior or hostility, depression (uncommon), tremor (rare), hallucinations, disorientation, suicidal thoughts and actions (very rare)];
- dizziness, sleepiness, tingling / numbness, convulsions (uncommon);
- palpitations (rare);
- diarrhea, nausea, vomiting (common), dry mouth, indigestion (uncommon);
- elevated blood levels of transaminases (ALT, AST) (common), hepatitis (inflammation of the liver) (very rare)
- rash (common), bruises, itching, hives (uncommon), painful, red lumps under the skin usually on the shins (erythema nodosum), severe skin reactions (erythema multiforme) (very rare)
- joint or muscle pain, muscle cramps (uncommon);
- fever (common), feeling sick / tired, feeling sick, swelling (uncommon);
Very rare cases of combination of symptoms such as flu-like fever, tingling or numbness in the arms and legs, worsening of lung symptoms and / or rash (Churg-Strauss syndrome) have been reported in asthmatic patients treated with montelukast.
Tell your doctor right away if your child has one or more of these symptoms.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information about safety of this medicine
Expiry and Retention
- Keep out of the reach and sight of children.
- Do not use this medicine after the expiry date indicated by the 6 digits after EXP on the blister. 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 protect 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 SASLONG contains
The active ingredient is montelukast.
Each tablet contains montelukast sodium which corresponds to 4 mg of montelukast.
The other ingredients are: mannitol, microcrystalline cellulose, low substituted hydroxypropylcellulose (E 463), red iron oxide (E 172), croscarmellose sodium, cherry flavor (E1518- glyceryltriacetate; E1450- sodium octylsuccinate), aspartame (E 951) and magnesium stearate .
Description of SASLONG's appearance and contents of the package
SASLONG 4 mg chewable tablets are pink oval and biconvex tablets with MOK4 scored on one side and PHD471 on the other.
Packaged in oPA / Al / PVC blisters contained in cardboard boxes.
Packs of 14, 20, 28, 30, 50, 98 and 100 chewable 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
SASLONG 4 MG CHEWABLE TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One chewable tablet contains montelukast sodium, which corresponds to 4 mg of montelukast.
Excipients: aspartame (E 951) 1.6 mg per tablet.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Chewable tablet
Pink, oval, biconvex shaped tablets with MOK4 debossed on one side and PHD471 on the other.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
SASLONG 4 mg is indicated in the treatment of asthma as adjunct therapy in those children 2 to 5 years of age with mild to moderate persistent asthma who are not adequately controlled with inhaled corticosteroids and in whom any beta-agonists short-acting provide inadequate clinical control of asthma.
SASLONG 4 mg may also be an alternative treatment to low-dose inhaled corticosteroids for children 2 to 5 years of age with mild persistent asthma who have no recent history of severe asthma attacks that required the use of a corticosteroid to orally and who have been shown to be unable to use inhaled corticosteroids (see section 4.2).
SASLONG 4 mg is also indicated in the prophylaxis of asthma for children aged 2 years and over in cases where the predominant component is exercise-induced bronchoconstriction.
04.2 Posology and method of administration
This medicine should be given to the child under the supervision of an adult. The posology for pediatric patients 2 to 5 years of age is one 4 mg chewable tablet to be taken once daily in the evening. When taken concomitantly with food, SASLONG 4 mg should be taken 1 hour before or 2 hours after food. No dosage adjustments are required in this age group. The SASLONG 4 mg chewable tablet formulation is not recommended below. 2 years of age.
General recommendations:
The therapeutic effect of SASLONG on asthma control parameters occurs within one day. Patients should be advised to continue taking SASLONG even if their asthma is under control, as well as during periods when their asthma gets worse.
No dosage adjustment is necessary for patients with renal insufficiency, or mild or moderate hepatic dysfunction. There are no data for patients with severe hepatic dysfunction. The dosage is the same for male and female patients.
SASLONG 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 corticosteroids in children with persistent mild asthma should only be considered for patients who have no recent history of severe asthma attacks requiring the use of a corticosteroid for orally and who have been shown to be unable to use inhaled corticosteroids (see section 4.1). Persistent mild asthma is defined as asthma symptoms that occur more than once per week but less than once per day, nocturnal symptoms more than twice per month but less than once per week, normal lung function between episodes. If satisfactory asthma control is not achieved with the follow up (usually within one month), the need for additional or different anti-inflammatory therapy based on the step system for asthma therapy should be considered. Patients should be seen periodically for asthma control.
SASLONG as a prophylaxis of asthma in patients from 2 to 5 years in which the preodimant component is exercise-induced bronchoconstriction:
In patients 2 to 5 years, exercise-induced bronchoconstriction may be the predominant manifestation of persistent asthma requiring treatment with inhaled corticosteroids. Patient status should be assessed after 2 to 4 weeks of montelukast treatment. If a satisfactory response is not obtained, additional or different therapy should be considered.
SASLONG therapy in relation to other asthma treatments:
When SASLONG treatment is used as add-on therapy to inhaled corticosteroids, SASLONG should not be abruptly substituted for inhaled corticosteroids (see section 4.4).
10 mg film-coated tablets are available for adolescents over 15 years of age and for adults.
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
Patients should be advised never to use oral montelukast to treat acute asthma attacks and to always have their usual emergency medications on hand. If an acute attack occurs, a beta agonist should be used short-acting by inhalation. Patients should see their doctor as soon as possible if they require multiple inhalations of beta agonists short-acting than usual.
Montelukast should not be abruptly substituted for oral or inhaled corticosteroids.
There is no evidence that oral corticosteroids can be reduced when montelukast is taken concomitantly.
In rare cases, patients receiving therapy with anti-asthma agents including montelukast may present with systemic eosinophilia, sometimes accompanied by clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition usually treated with systemic corticosteroid therapy. Usually, but not always, these cases have been associated with the reduction or cessation of oral corticosteroid therapy. The possibility that leukotriene receptor antagonists may be associated with the development of Churg-Strauss syndrome can neither be excluded nor established. The general practitioner should be informed in case of eosinophilia, vasculitic rash, worsening of pulmonary symptoms, cardiac complications and / or neuropathy occurring in patients. The status of patients experiencing these symptoms should be reassessed and their treatment regimens reviewed.
SASLONG 4 mg contains aspartame, a source of phenylalanine. It can be dangerous for people (in this case children) with phenylketonuria. Patients with phenylketonuria should be aware that each 4 mg chewable tablet contains phenylalanine equivalent to 0.898 phenylalanine per dose.
04.5 Interactions with other medicinal products and other forms of interaction
SASLONG can be administered with other therapies usually used in the prophylaxis and chronic treatment of asthma. In drug interaction studies, the recommended clinical dose of montelukast had no clinically important effect 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 reduced by approximately 40% in subjects co-administered with phenorbitol. Since montelukast is metabolised by CYP 3A4, caution is required, especially in children. , when montelukast is co-administered with CYP 3A4 inducers, such as phenytoin, phenorbitol and rifampicin.
Education in vitro showed that montelukast is a potent inhibitor of CYP 2C8. However, data from a drug-drug interaction study involving montelukast and rosiglitazone (a substrate probe representing drugs primarily metabolised by CYP 2C8) have shown that montelukast does not inhibit CYP 2C8 in vivo. Therefore, montelukast is not expected to markedly alter the metabolism of medicinal products metabolised by this enzyme (e.g. paclitaxel, rosiglitazone and repaglinide).
04.6 Pregnancy and lactation
Use in pregnancy
Animal studies do not indicate harmful effects with respect to pregnancy or embryonal / fetal development.
The limited data available from pregnancy databases do not indicate a causal relationship between montelukast and malformations (i.e. limb defects) which have rarely been reported post-marketing worldwide.
SASLONG can only be used during pregnancy if it is strictly necessary.
Use while breastfeeding
Studies in rats have shown that montelukast is secreted in milk (see section 5.3). It is not known whether montelukast is secreted in human milk.
SASLONG can be used in nursing mothers only if strictly necessary.
04.7 Effects on ability to drive and use machines
Montelukast is not expected to affect the patient's ability to drive or use machines. However, in very rare cases, individuals have reported drowsiness and dizziness.
04.8 Undesirable effects
Montelukast was evaluated in clinical studies as follows:
• 10 mg film-coated tablets in approximately 4000 adult patients aged 15 years and above
• 5 mg chewable tablets in approximately 1750 pediatric patients 6 to 4 years of age, e
• 4 mg chewable tablets in 851 pediatric patients 2 to 5 years of age.
The following drug-related undesirable effects in clinical trials were reported commonly (> 1/100 to
With prolonged treatment in clinical trials with a limited number of patients lasting up to 2 years for adults, and up to 12 months for pediatric patients 6 to 14 years, the safety profile did not change.
In total, 502 pediatric patients 2 to 5 years of age were treated with montelukast for at least 3 months, 338 for 6 months or more, and 534 patients for 12 months or more. With prolonged treatment, the safety profile did not change in these patients either.
The following adverse reactions have been reported in post-marketing use:
Infections and infestations: upper respiratory tract infection.
Disorders of the blood and lymphatic system: increased tendency to bleed.
Disorders of the immune system: hypersensitivity reactions including anaphylaxis, hepatic eosinophilic infiltration.
Psychiatric disorders: strange dreams including nightmares, hallucinations, insomnia, sleepwalking, irritability, feelings of anxiety, restlessness, agitation including aggressive behavior and hostility, tremor, depression, suicidal thoughts and actions (suicidality) in very rare cases.
Nervous system disorders: dizziness, somnolence, paraesthesia / hypoesthesia, convulsions.
Cardiac pathologies: palpitations.
Respiratory, thoracic and mediastinal disorders: epistaxis.
Gastrointestinal disorders: diarrhea, dry mouth, dyspepsia, nausea, vomiting.
Hepatobiliary disorders: elevated serum transaminase levels (ALT, AST), hepatitis (including cholestatic, hepatocellular and mixed lesion).
Skin and subcutaneous tissue disorders: angioedema, bruises, urticaria, pruritus, rash, erythema nodosum.
Musculoskeletal and connective tissue disorders: arthralgia, myalgia including muscle cramps.
General disorders and administration site conditions: asthenia / fatigue, malaise, edema, pyrexia.
Very rare cases of Churg-Struss syndrome (CSS) have been reported during treatment with montelukast in patients with asthma (see section 4.4).
04.9 Overdose
No specific information is available regarding the treatment of overdose with montelukast. In chronic asthma studies, montelukast was administered at doses up to 200 mg / day in adult patients for 22 weeks and in short-term studies, up to 900 mg / day in patients for approximately one week, without major adverse events. from a clinical point of view.
There have been reports of acute overdose with montelukast in the post-marketing setting and in clinical trials. These include reports from adults and children with a dose of 1000 mg (approximately 61 mg / kg in a 42 month old baby). Observed clinical and laboratory data were consistent with the safety profile in adults and pediatric patients. There were no adverse events in most overdose reports. The most frequently occurring adverse events 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 in peritoneal dialysis or in hemodialysis.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: other anti-asthmatics for systemic use, leukotriene receptor antagonists.
ATC code: R03D C03.
Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are potent anti-inflammatory eicosanoids released by several cells, including mast cells and eosinophils. These important pro-asthmatic mediators bind to cysteinyl leukotriene (CysLT) receptors in human airways and cause airway actions, including bronchoconstriction, mucosal secretion, vascular permeability, and eosinophil recruitment.
Montelukast is an orally active compound which binds to the CysLT1 receptor with high affinity and selectivity. In clinical studies, montelukast inhibits bronchoconstriction due to inhalation of LTD4 at low doses of 5 mg. Bronchodilation was observed within 2 hours of oral administration. The bronchodilation effect caused by a beta agonist was added to that. caused by montelukast. Montelukast treatment inhibited both early and late stages of bronchoconstriction due to antigen treatment. Montelukast, compared to placebo, decreased peripheral blood eosinophils in adult and pediatric patients. In a separate study, montelukast treatment significantly decreased eosinophils in the airways (as measured in sputum). In adult and pediatric patients aged 2 to 14 years, montelukast, compared to placebo, decreased peripheral blood eosinophils and improved control of clinical asthma.
In adult studies, montelukast 10 mg, taken once daily, compared to placebo demonstrated significant improvements in morning FEV1 (10.4% change versus 2.7% from baseline), peak expiratory flow morning (AM PEFR) (change of 24.5 l / min vs 3.3 l / min from baseline), and a significant decrease in total beta-agonist use (change of -26.1% vs - 4.6% from baseline.) The improvement in patient-reported asthma symptom scores during day and night was significantly greater than placebo.
Studies in adults have shown the ability of montelukast to enhance the clinical effect of inhaled corticosteroids (% change from baseline for inhaled beclomethasone plus montelukast versus beclomethasone, respectively for FEV1: 5.43% versus 1.04 %; beta-agonist use: -8.70% vs + 2.64%) Compared to inhaled beclomethasone (200 mcg twice daily with a spacer device - spacer), montelukast demonstrated a faster initial response, although in a 12-week study, beclomethasone treatment resulted in an average greater effect (% change from baseline for montelukast compared to beclomethasone, for FEV1: 7 , 9% versus 13.3%; beta-agonist use: -28.8% versus -43.89%). However, compared to beclomethasone, a "high percentage of patients treated with montelukast achieved similar clinical responses (eg. 50% of patients treated with beclomethasone achieved an improvement in FEV1 of approximately 11% or more over baseline. while approximately 42% of patients treated with montelukast achieved the same response).
In a 12-week placebo-controlled study in pediatric patients aged 2 to 5 years, montelukast 4 mg taken once daily improved asthma control parameters compared to placebo, regardless of concomitant control therapy ( inhaled / nebulized corticosteroids or inhaled / nebulized sodium cromoglycate). 60% of patients received no control therapy. Compared to placebo, montelukast improved daytime symptoms (including cough, dyspnoea, breathing problems and limited activity) and nocturnal symptoms. Compared to placebo, montelukast also decreased the necessary use of the beta-agonist and corticosteroid in emergency cases due to worsening of asthma. Patients given montelukast had more days without asthma symptoms compared to those given placebo. The treatment effect was achieved after the first dose.
In a 12-month placebo-controlled study in pediatric patients aged 2 to 5 years with mild asthma and episodic exacerbations, montelukast 4 mg taken once daily significantly reduced (p ≤ 0.001) the annual rate of exacerbation episodes (EE ) from asthma, compared to placebo (1.60 EE and 2.34 EE, respectively), [EE defined as ≥ 3 consecutive days with daytime symptoms requiring beta-agonists, or corticosteroids (orally or inhaled ), or "hospitalization for asthma]. The rate of reduction in annual EEs was 31.9%, with a 95% CI of 16.9, 44.1.
In an 8-week study in pediatric patients aged 6 to 14 years, montelukast 5 mg administered once daily significantly improved respiratory function compared to placebo (FEV1: change from baseline of 8.71% compared to 4.16%; AM PEFR: change from baseline of 27.9 L / min compared to 17.8 L / min) and decreased the necessary use of the beta-agonist (change of -11.7% compared to + 8.2% of the base value).
In a 12-month study comparing the efficacy of montelukast versus inhaled fluticasone in controlling asthma in pediatric patients aged 6 to 14 years with persistent mild asthma, montelukast was not inferior to fluticasone in increasing the rate of asthma-free days (RFD - Rescue-free days), the primary endpoint. Mediated over a 12-month treatment period, the percentage of asthma RFD increased from 61.6% to 84.0% in the montelukast group and from 60.9% to 86.7% in the fluticasone group. The increase, in percentage of asthma RFD, in the difference between groups on least squares mean (least square, LS) was statistically significant (2.8% with a 95% CI of - 4.7, - 0.9), but within the predefined limit that it should not be clinically lower. Both montelukast and fluticasone also improved asthma control with respect to secondary variables determined during the 12-month treatment period:
• FEV1 increased from 1.83 L to 2.09 L in the montelukast group and from 1.85 L to 2.14 L in the fluticasone group. The LS mean increase in difference between groups was -0.02 L with a 95% CI of -0.06, 0.02. The mean increase from baseline in% predicted FEV1 was 0 , 6% in the montelukast treatment group, and 2.7% in the fluticasone treatment group. The LS mean difference for the change from baseline in% predicted FEV1 was -2.2% with a 95% CI of -3.6, -0.7.
• The percentage of days using beta agonists decreased from 38.0 to 15.4 in the montelukast group and from 38.5 to 12.8 in the fluticasone group. The difference between the groups in LS mean for the percentage of days with beta-agonist use was significant: 2.7% with 95% CI of 0.9, 4.5.
• The percentage of patients with an asthma attack (asthma attack defined as a period of worsening of asthma that required oral steroids, an unscheduled visit to the doctor, an emergency room visit, or " hospitalization) was 32.2% in the montelukast group and 25.6% in the fluticasone group, with odds ratio (95% CI) significant: equal to 1.38.
• The percentage of patients using systemic corticosteroids (predominantly oral) during the study period was 17.8% in the montelukast group and 10.5% in the fluticasone group. The difference between the groups in LS mean was significant: 7.3 with a 95% CI of 2.9; 11.7.
A significant reduction in exercise-induced bronchoconstriction was shown in a 12-week study in adults (exercise-induced bronchoconstriction, EIB) (maximum loss in FEV1: 22.33% for montelukast versus 32.40% for placebo; time to healing at 5% of baseline FEV1: 44.22 min vs 60.64 min). This effect occurred regularly throughout the 12-week study period. The decrease in EIB was also demonstrated in a short-term study in pediatric patients aged 6 to 14 years (maximum loss in FEV1: 18.27% vs.26.11%, time to healing at 5% of baseline FEV1 : 17.76 min vs 27.98 min). The effect in both studies was demonstrated at the end of the once daily dosing interval.
In aspirin-sensitive asthma patients who were given concomitantly inhaled and / or oral corticosteroids, treatment with montelukast compared to placebo showed a significant improvement in asthma control (FEV1: change from base 8.55% vs -1.74% and decrease in total beta-agonist use: change from baseline - 27.78% vs 2.09%).
05.2 Pharmacokinetic properties
Absorption:
Montelukast is rapidly absorbed following oral administration. For the 10 mg film-coated tablet, the mean peak plasma concentration (Cmax) is reached after 3 hours (Tmax) after dosing in fasted adults. The mean oral bioavailability is 64%. Oral bioavailability and Cmax are not affected by a standard meal. Safety and efficacy have not been demonstrated and clinical studies in which the 10 mg film-coated tablet was administered without particular attention to the time of food intake.
For 5 mg chewable tablets, Cmax is reached within 2 hours after dosing in fasted adults. The mean oral bioavailability is 73% and decreases to 63% with a standard meal.
After administration of a 4 mg chewable tablet to pediatric patients 2 to 5 years of age in the fasted state, Cmax is reached 2 hours after dosing. The mean Cmax value is 66% and is higher as well as the mean Cmin value is lower than in adults receiving a 10 mg film-coated tablet.
Distribution:
More than 99% of montelukast is bound to plasma proteins. In conditions of steady-state the volume of distribution of montelukast hovers around 8 - 11 liters. Studies in rats administered radiolabeled montelukast indicate minimal distribution around the blood brain barrier. Furthermore, concentrations of radio-labeled substance 24 hours after administration were minimal in all other tissues.
Biotransformation:
Montelukast is extensively metabolised. In studies with therapeutic doses, concentrations of montelukast metabolites in plasma are not detectable under conditions of steady-state in both adults and children.
Education in vitro on human liver microsomes, indicate that cytochromes P450 3A4, 2A6 and 2C9 take part in the metabolism of montelukast. Based on further findings in vitro on human liver microsomes, montelukast therapeutic plasma concentrations do 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:
There clearance plasma concentration of montelukast is around 45 ml / min in healthy adults. Following oral administration of a radiolabelled montelukast dose, 86% of the radioactive component was achieved in the 5-day stool and urine collections. Together with estimates of the oral bioavailability of montelukast, this indicates that montelukast and its metabolites are secreted almost exclusively through the bile.
Characteristics in patients:
No dose adjustment is necessary for elderly patients or mild to moderate renal insufficiency. Studies in patients with renal dysfunction have not been conducted. Since montelukast and its metabolites are eliminated via the biliary route, no dose adjustment is expected to be required in patients with renal dysfunction. There are no data available on the pharmacokinetics of montelukast in patients with severe hepatic impairment (Child-Pugh score> 9).
With high doses of montelukast (20 and 60 times the recommended adult dose), a decrease in plasma theophylline concentration was observed. This effect was not observed at the recommended dose of 10 mg once daily.
05.3 Preclinical safety data
In animal toxicity studies, minor biochemical changes in serum, of a transient nature, were observed in ALT, glucose, phosphorus and triglycerides. Manifestations of toxicity in animals were increased saliva secretion, gastrointestinal symptoms, loose stools and ion imbalance. These effects occurred at doses that induced systemic exposure> 17 times that of clinical doses. In monkeys, side effects occurred at doses of 150 mg / kg / day (> 232 times the systemic exposure at corresponding clinical dose). In animal studies, montelukast did not affect fertility or reproductive performance at systemic exposures exceeding the clinical systemic exposure by more than 24 times. A slight decrease in pup body weight of 200 mg / kg / day was observed. in the female fertility study in rats (> 69 times the systemic clinical exposure).In the rabbit studies, a higher incidence of incomplete ossification compared with control animals was noted at a systemic exposure> 24 times the clinical systemic exposure observed at the clinical dose. No abnormalities were noted in rats. Montelukast has been observed to cross the placental barrier and is secreted in the milk of animals.
There was no death following a single oral administration of montelukast sodium at doses up to 5,000 mg / kg in mice and rats (15,000 mg / m2 and 30,000 mg / m2 in mice and rats, respectively), the highest dose tested. . This dose is equivalent to 25,000 times the recommended dose per day for an adult man (considered an adult patient weighing 50 kg).
Montelukast was determined not to be phototoxic in mice by UVA, UVB or visible light spectra at doses up to 500 mg / kg / day (> approximately 200 times the systemic exposure).
Montelukast was neither mutagenic in tests in vitro And in vivo nor carcinogenic in rodent species.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Mannitol (E421),
microcrystalline cellulose,
croscarmellose sodium,
low substituted hydroxypropylcellulose (E 463),
aspartame (E 951),
red iron oxide (E 172),
cherry flavoring (E1518 - glyceryl triacetate; E1450 - sodium octylsucinate)
magnesium stearate.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
2 years
06.4 Special precautions for storage
Store in the original package to keep the medicine away from light and moisture.
06.5 Nature of the immediate packaging and contents of the package
Packaged in oPA / Al / PVC blisters contained in cardboard boxes.
Packs of 14, 20, 28, 30, 50, 98 and 100 chewable tablets.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
Unused medicine and waste from this medicine should be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
So.Se.PHARM S.r.l.
Via dei Castelli Romani, 22
00040 Pomezia (RM)
Italy
08.0 MARKETING AUTHORIZATION NUMBER
SASLONG 4 mg chewable tablets - AIC n. 040649030 / M
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
08/2012
10.0 DATE OF REVISION OF THE TEXT
AIFA Determination of 23/07/2012
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