Montelukast Mylan 10 mg film-coated tablets

4.2 Posology and method of administration

Posology
The recommended dosage for adult patients and adolescents 15 years of age and older with asthma, or with asthma and concomitant seasonal allergic rhinitis, is one 10 -mg tablet daily to be taken in the evening.

Paediatric population
Do not give Montelukast Mylan 10 mg film-coated tablets are not appropriate for  to children less than and adolescents under the age of 15 years of age. The safety and efficacy of montelukast tablets in children less than 15 years has not been established.
 Further pharmaceutical forms/strengths of the active substance montelukast are available. 4 mg & 5 mg chewable tablets can be used to treat paediatric patients from 2 to 14 5 years of age and 6 to 14 years of age respectively. 4 mg granules may be available for paediatric patients 6 months to 5 years of age.

4.6 Fertility, pregnancy and lactation

Breast-feeding
Studies in rats have shown that montelukast is excreted in milk (see section 5.3). It is not known if montelukast/metabolites isare excreted in human milk.

 

4.7 Effects on ability to drive and use machines

Montelukast has no or negligible influence on theis not expected to affect a patient's ability to drive and use  a car or operate machinersy. However, in very rare cases, individuals have reported drowsiness or dizziness.

4.8 Undesirable effects

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 1,750 paediatric asthmatic patients 6 to 14 years of age.
 

Body System Class	Adult Patients 15 years and older (two 12-week studies; n=795)	Paediatric Patients 6 to 14 years old (one 8-week study; n=201) (two 56-week studies; n=615)
Nervous system disorders	headache	headache
Gastrointestinal disorders	abdominal pain

With prolonged treatment in clinical trials with a limited number of adult 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.

Post-marketing ExperienceTabulated list of Adverse Reactions
Adverse reactions reported in post-marketing use are listed, by System Organ Class and specific Adverse Experience TermReactions, in the table below. Frequency Categories were estimated based on relevant clinical trials.

System Organ Class

Adverse Experience TermReactions

Frequency Category*

* Frequency Category: Defined for each Adverse Experience TermReaction by the incidence reported in the clinical trials data base: Very Common  (≥ 1/10), Common (≥
1/100 to <1/10), Uncommon (≥ 1/1,000 to <1/100), Rare (≥ 1/10,000 to <1/1,000), Very Rare (<1/10,000).

4.9 Overdose
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 to patients for 22 weeks and in short term studies, up to 900 mg/day to patients for approximately one week without clinically important adverse experiences.

Management of overdose
No specific information is available on the treatment of overdose with montelukast.
It is not known whether montelukast is dialysable by peritoneal- or hemo-dialysis.

5.1  Pharmacodynamic properties 

Clinical efficacy and safety

A clinical study was conducted to evaluate montelukast for the symptomatic treatment of seasonal allergic rhinitis in adult asthmatic patients 15 years of age and older with concomitant seasonal allergic rhinitis. In this study, montelukast 10 mg tablets administered once daily demonstrated a statistically significant improvement in the Daily Rhinitis Symptoms score, compared with placebo. The Daily Rhinitis Symptoms score is the average of the Daytime Nasal Symptoms score (mean of nasal congestion, rhinorrhea, sneezing, nasal itching) and the Nighttime Symptoms score (mean of nasal congestion upon awakening, difficulty going to sleep, and nighttime awakenings scores). Global evaluations of allergic rhinitis by patients and physicians were significantly improved, compared with placebo. The evaluation of asthma efficacy was not a primary objective in this study.

In an 8­week study in paediatric patients 6 to 14 years of age, montelukast 5 mg once daily, compared with placebo, significantly improved respiratory function (FEV1 8.71% vs 4.16% change from baseline; AM PEFR 27.9 L/min vs 17.8 L/min change from baseline) and decreased “as­needed” β­agonist use (­11.7% vs +8.2% change from baseline).

Significant reduction of exercise-induced bronchoconstriction (EIB) was demonstrated in a 12-week study in adults (maximal fall in FEV1 22.33% for montelukast vs. 32.40% for placebo; time to recovery to within 5% of baseline FEV1 44.22 min vs. 60.64 min). This effect was consistent throughout the 12-week study period. Reduction in EIB was also demonstrated in a short term study in paediatric patients (maximal fall in FEV1 18.27% vs. 26.11%; time to recovery to within 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.

5.2 Pharmacokinetic properties

Biotransformation
Montelukast is extensively metaboliszed. In studies with therapeutic doses, plasma concentrations of metabolites of montelukast are undetectable at steady state in adults and children.
 

 

section 4.1
Montelukast is indicated in the treatment of asthma as add-on therapy in those patients with mild to moderate persistent asthma who are inadequately controlled on inhaled corticosteroids and in whom “as-needed” short acting beta-agonists provide inadequate clinical control of asthma.

Montelukast Mylan 10mg film-coated tablets are indicated in adults and adolescents 15 years of age and older.

section 4.2

Posology

The dosage for adult patients and adolescents 15 years of age and older with asthma, or with asthma and concomitant seasonal allergic rhinitis, is one 10-mg tablet daily to be taken in the evening.

No dosage adjustment is necessary for the elderly, or for patients with renal insufficiency, or mild to moderate hepatic impairment.

Method of administration

For oral use.

 

Montelukast may be taken with or without food.

section 4.4

If an acute attack occurs, a short-acting inhaled beta-agonist should be used. Patients should seek their doctors' advice as soon as possible if they need more inhalations of short-acting beta-agonists than usual.

The film-coated tablets also contain sunset yellow (E110), which may cause allergic reactions.

section 4.6

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.

section 4.8

• 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.

 

section 4.8 : Table

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517; Website: www.hpra.ie; E-mail: medsafety@hpra.ie

section 5.2

For the 5 mg chewable tablet, the C_maxis achieved in 2 hours after administration in adults in the fasted state. The mean oral bioavailability is 73% and is decreased to 63% by a standard meal.

 

Metabolism changed to Biotransformation

section 6.1

Sodium laurilsulfate

Silica, colloidal anhydrous

Titanium dioxide

Indigo carmineAluminium Lake (E132)

Sunset yellowAluminium Lake (E110)

July 2015

section 4.6section 4.8section 4.8 : Tablesection 5.2Metabolism changed to section 6.1

section 4.4section 4.6section 4.8section 4.8 : Tablesection 5.2Metabolism changed to section 6.1

Section 4.2
Dosage changed to Posology
Montleukast may be taken with or without food-removed
Montelukast Mylan should not be used concomitanlty with other products containing the same active ingredient, montelukst-removed
 for the elderly-removed
Montelukast Mylan can be added to a patients exisiting treatment regimen-removed
Inhaled corticosteroids paragraph updated.

Section 4.4
Warnings header added
paragraph 'In rare cases...etc' updated

Section 4.5
Paragraph 'In drug-interactions studies etc...' moved up to first paragraph.


Section 4.6
Fertility added to header
Use During Pregnancy amended to Pregnancy
Use During Lactation amended to Breast-feeding

Section 4.7
'in very rare cases' added

Section 4.8
'10 mg film coated tablets in approximately 400 adult asthmatic patients with seasonal allergic rhinitis 15 years of age and older' -removed
Frequencies very common, common, uncommon, rare, very rare, not known-removed
System Organ Class table amended for Frequency Category
Reporting of suspected adverse reactions added


Section 5.2
Biotransformation amended to 'Metabolism'

Section 6.6
medicinal added

Section 10
February 2014

$04.2 Posology and method of administration$0$0$0$0$0Added under General recommendations -$0$0Montelukast may be taken with or without food. $0$0$0$0$0Added information for paediatric -$0$04 mg & 5 mg chewable tablets can be used to treat paediatric patients from 2 to 14 years of age.$0$0$0$0$0$0$0$04.5 Interaction with other medicinal products and other forms of interaction$0$0$0$0$0Added - $0$0In 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.$0$0$0$0$0Based 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.$0$0$0$0$0$0$0$04.6 Pregnancy and lactation$0$0$0$0$0Changed the term "nursing mothers" to "breast-feeding"$0$0$0$0$0$0$0$04.7 Effects on ability to drive and use machines$0$0$0$0$0Removed -$0$0No studies on the effects on the ability to drive and use machines have been reported.$0$0$0$0$0$0$0$04.8 Undesirable effects$0$0$0$0$0Added - $0$0Post-marketing Experience$0$0Adverse 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.$0$0$0$0$0Side effects put into table with frequency.$0$0$0$0$0$0$0$05.2 Pharmacokinetic properties$0$0$0$0$0Added - $0$0Cytochrome P450 2C8 is the major enzyme in the metabolism of montelukast. Additionally CYP 3A4 and 2C9 may have a minor contribution, 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. Based on 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. $0$0$0$0$0Removed - $0$0In 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. $0$0$0$0$0$0$0$06.5 Nature and contents of container$0$0$0$0$0Added -$0$0Aluminium/Aluminium perforated unit dose blisters within a cardboard carton containing pack sizes of 28 x 1 film-coated tablets.$0$0$0$0$0$0$0$0$0$0$0(Internal Ref: CRN 2122601 Renewal R1) $0

None provided