Consumer medicine information

Singulair

Montelukast

BRAND INFORMATION

Brand name

Singulair

Active ingredient

Montelukast

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Singulair.

SUMMARY CMI

SINGULAIR®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

WARNING: Important safety information is provided in a boxed warning in the full CMI. Read before using this medicine.

1. Why am I using SINGULAIR?

SINGULAIR contains the active ingredient montelukast. SINGULAIR is used to prevent asthma symptoms, and the narrowing of airways triggered by exercise, and to treat allergic rhinitis (hayfever) symptoms.

For more information, see Section 1. Why am I using SINGULAIR? in the full CMI.

2. What should I know before I use SINGULAIR?

Do not use if you have ever had an allergic reaction to SINGULAIR or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use SINGULAIR? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with SINGULAIR and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use SINGULAIR?

  • The dose is one tablet each day.
  • Your doctor will advise you of the best time of day to take your tablet, depending on the condition being treated.

More instructions can be found in Section 4. How do I use SINGULAIR? in the full CMI.

5. What should I know while using SINGULAIR?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using SINGULAIR.
  • SINGULAIR is not for the treatment of acute asthma attacks. If an acute attack of asthma occurs, follow your doctor's instructions on what reliever medicine to use to relieve the attack. Call your doctor if your asthma gets worse while you are taking SINGULAIR.
  • Call your doctor straight away if you experience behaviour and mood-related changes including suicidal thoughts while taking SINGULAIR, or if you experience a combination of allergic symptoms including a flu-like illness, pins and needles or numbness of arms or legs, and/or rash.
Things you should not do
  • Do not stop using this medicine suddenly. Continue taking SINGULAIR every day as directed by your doctor, even if you have no asthma symptoms or if you have an asthma attack.
  • Do not take SINGULAIR to relieve an acute asthma attack.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how SINGULAIR affects you.
  • SINGULAIR may cause dizziness in some people.
Looking after your medicine
  • Keep SINGULAIR in a cool dry place, away from light, where the temperature stays below 30°C.

For more information, see Section 5. What should I know while using SINGULAIR? in the full CMI.

6. Are there any side effects?

Common side effects include headache, dizziness, unusual tiredness or weakness, insomnia, stomach pain and diarrhoea. Serious side effects include suicidal thoughts and actions, increased tendency to bleed or bruise, palpitations, swelling (inflammation) of the lungs, symptoms of liver disease such as nausea, vomiting, loss of appetite, feeling generally unwell, fever, itching, yellowing of the skin and eyes, and dark coloured urine, and allergic reactions.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

WARNING: If you experience behaviour and mood-related changes including suicidal thoughts and actions while taking SINGULAIR (see "Behavioural and mood related changes under Side Effects"), tell your doctor immediately.



FULL CMI

SINGULAIR®

Active ingredient(s): montelukast sodium

Consumer Medicine Information (CMI)

This leaflet provides important information about using SINGULAIR. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using SINGULAIR.

Where to find information in this leaflet:

1. Why am I using SINGULAIR?
2. What should I know before I use SINGULAIR?
3. What if I am taking other medicines?
4. How do I use SINGULAIR?
5. What should I know while using SINGULAIR?
6. Are there any side effects?
7. Product details

1. Why am I using SINGULAIR?

SINGULAIR contains the active ingredient montelukast sodium. SINGULAIR belongs to a group of medicines called leukotriene receptor antagonists. It works by blocking substances in your lungs called leukotrienes that cause narrowing and swelling of airways. Blocking leukotrienes improves asthma symptoms and helps prevent asthma attacks. Leukotrienes also cause allergic rhinitis symptoms. By blocking leukotrienes, SINGULAIR improves seasonal allergic rhinitis symptoms.

SINGULAIR is used to prevent asthma symptoms, including those that occur during the day and at night-time. It also prevents the narrowing of airways triggered by exercise.

If you have seasonal allergic rhinitis (hay fever), SINGULAIR also treats your allergic rhinitis symptoms.

It can be used in children 2 years of age and older, teenagers and adults.

SINGULAIR tablets are not used to treat an acute attack of asthma. If an acute attack occurs, follow your doctor's instructions for your reliever medicine, and keep taking your SINGULAIR each night or as prescribed.

As a preventive medicine for asthma, SINGULAIR can be used alone or in combination with other preventive medicines, such as inhaled corticosteroids. Your doctor may reduce your dose of inhaled corticosteroid while you are taking SINGULAIR.

Asthma is a lung disease and has the following characteristics:

  • narrowed airways causing breathing to become difficult
  • inflamed airways, which means the lining of airways become swollen
  • sensitive airways that react to many things, such as cigarette smoke, pollen, or cold air.

Symptoms of asthma include coughing, wheezing and chest tightness. Not all people with asthma wheeze. For some, coughing may be the only symptom of asthma. Symptoms often occur during the night or after exercise.

Seasonal allergic rhinitis (also known as hay fever) is an allergic response often caused by airborne pollens from trees, grasses, and weeds. The daytime and night-time symptoms of seasonal allergic rhinitis typically may include: stuffy, runny, itchy nose; sneezing; watery, swollen, red, itchy eyes.

2. What should I know before I use SINGULAIR?

Warnings

Do not use SINGULAIR if:

  • you are allergic to montelukast, or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this medicine.
  • the packaging is torn or shows signs of tampering.

Check with your doctor if:

  • you have or have had any other medical conditions
  • your child has a condition called phenylketonuria The 5 mg and 4 mg chewable tablets contain aspartame, corresponding to 0.842 mg phenylalanine in each 5 mg tablet and 0.674 mg in each 4 mg tablet.
  • you take any medicines for any other condition
  • you have any allergies to any other medicines or any other substances, such as foods, preservatives or dyes.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

SINGULAIR has not been studied in pregnant women.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

It is not known if SINGULAIR passes into breast milk.

Use in children

  • Do not give SINGULAIR to children under 2 years of age. Safety and effectiveness in children younger than 2 years of age have not been studied.
  • In studies investigating the effect of SINGULAIR on the growth rate of children, it was shown that SINGULAIR did not affect the growth rate of children when given for up to 56 weeks in one study.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with SINGULAIR and affect how it works, or SINGULAIR may affect how your other medicines work.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect SINGULAIR.

4. How do I use SINGULAIR?

How much to take

  • For patients with asthma and/or seasonal allergic rhinitis, take SINGULAIR only when prescribed by your doctor.
  • For adults and teenagers 15 years and older, the dose is one 10 mg film-coated tablet taken each day.
  • For children 6 to 14 years old, the dose is one 5 mg chewable tablet taken each day.
  • For children 2 to 5 years old, the dose is one 4 mg chewable tablet taken each day.
  • Follow the instructions provided and use SINGULAIR until your doctor tells you to stop.
  • SINGULAIR helps control your asthma. Therefore SINGULAIR must be taken every day. Continue taking SINGULAIR for as long as your doctor prescribes.

When to take SINGULAIR

  • For patients with asthma, take SINGULAIR once a day in the evening. Take your SINGULAIR at bedtime each day.
    Taking your tablet at bedtime each day is expected to have the best effect. It will also help you remember when to take the tablets.
  • For patients with seasonal allergic rhinitis, take SINGULAIR once a day as prescribed by your doctor. Your doctor will advise you on the best time of the day to take your tablet.
  • For patients with both asthma and seasonal allergic rhinitis, take your SINGULAIR at bedtime each day.
  • It does not matter if you take SINGULAIR before or after food.

How to take SINGULAIR

  • 10 mg film-coated tablets (adults and teenagers 15 years and older): Swallow the tablet with a glass of water.
  • 5 mg chewable tablets (children 6-14 years old) and 4 mg chewable tablets (children 2-5 years old): Chew the tablets thoroughly and swallow. Do not swallow whole.

If you forget to take SINGULAIR

SINGULAIR should be used regularly at the same time each day. If you miss your dose at the usual time, skip the dose you missed and take your next dose as usual.

Do not take a double dose to make up for the dose you missed.

If you have trouble remembering to take your tablets, ask your pharmacist for some hints.

If you take too much SINGULAIR

If you think that you have used too much SINGULAIR, you may need urgent medical attention.

The most common symptoms reported with overdose in adults and children include thirst, sleepiness, dilated pupils, hyperactivity, and stomach pain.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using SINGULAIR?

Things you should do

Continue taking SINGULAIR every day as directed by your doctor, even if you have no asthma symptoms or if you have an asthma attack.

SINGULAIR is not for the treatment of acute asthma attacks. If an acute attack of asthma occurs, follow your doctor's instructions on what reliever medicine to use to relieve the attack.

Call your doctor straight away if:

  • your asthma gets worse while taking SINGULAIR
  • you experience behaviour and mood-related changes including suicidal thoughts while taking SINGULAIR (see "Behaviour and mood related changes under Side Effects"). All thoughts of suicide must be taken seriously.
  • you experience a combination of allergic symptoms including a flu-like illness, pins and needles or numbness of arms or legs, and/or rash. In asthmatic patients treated with montelukast, very rare cases have been reported. Although it is unknown if montelukast can cause this condition, you must tell your doctor right away if you get one or more of these symptoms.
  • you become pregnant while taking SINGULAIR

Remind any doctor, dentist or pharmacist you visit that you are using SINGULAIR.

Things you should not do

  • If you have been prescribed the 10 mg film-coated tablets, do not take two 5 mg chewable tablets in its place. If you have been prescribed the 5 mg tablets, do not take half a 10 mg tablet in its place. The different strength tablets may not have the same effect, as they are absorbed slightly differently in the body.
  • Do not take SINGULAIR to relieve an acute asthma attack. In case of an acute asthma attack, follow your doctor's instructions on what reliever medicine to use.
  • Do not give SINGULAIR to anyone else, even if they have the same condition as you.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how SINGULAIR affects you.

SINGULAIR may cause dizziness in some people

Looking after your medicine

  • Keep your tablets in the blister pack until it is time to take them.
  • Keep SINGULAIR in a cool dry place, away from light, where the temperature stays below 30°C.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Muscle or nerve problems:
  • muscle aches or cramps, joint pain
  • decreased feeling or sensitivity, especially in the skin
  • pins and needles/numbness
Stomach or bowel problems:
  • stomach pain
  • nausea, vomiting
  • diarrhoea
Respiratory problems:
  • nose bleed
  • upper respiratory tract infection
Head and nervous system problems:
  • headache, dizziness, drowsiness
General:
  • fluid retention
  • feeling unusually weak or tired
  • bedwetting in children
Speak to your doctor if you have any of these less serious side effects and they worry you.
Behaviour and mood-related changes:
  • agitation, including aggressive behaviour or hostility
  • anxiousness, depression (sad mood)
  • disorientation, dream abnormalities, hallucinations (seeing or hearing things that are not there)
  • insomnia, irritability, restlessness, sleep walking
  • stuttering
  • tremors
  • disturbance in attention, memory impairment
  • uncontrolled muscle movements
  • obsessive-compulsive symptoms
These are usually mild side effects of SINGULAIR.		If you or your child experience these changes while taking montelukast, tell your doctor.
Behaviour and mood-related changes, including suicidal thoughts and actions, have been reported in patients taking montelukast.

Serious side effects

Serious side effectsWhat to do
  • suicidal thoughts and actions
  • skin rash or itchiness
  • increased tendency to bleed, bruising
  • fast or irregular heart beats, also called palpitations
  • swelling (inflammation) of the lungs
  • symptoms of liver disease such as nausea, vomiting, loss of appetite, feeling generally unwell, fever, itching, yellowing of the skin and eyes, and dark coloured urine
Tell your doctor immediately if you notice any of these serious side effects.
You may need urgent medical attention.
  • swelling of the face, lips, mouth, throat or tongue which may cause difficulty in breathing or swallowing
  • pinkish, itchy swellings on the skin, also called hives or nettle rash, severe skin reactions that may occur without warning
  • seizure
Stop taking SINGULAIR, call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
You may be having a serious allergic reaction to SINGULAIR. You may need urgent medical attention.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people. Some of these side effects (for example, increased bleeding tendency, low blood platelet count) can only be detected when your doctor does tests from time to time to check your progress.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What SINGULAIR contains

Active ingredient
(main ingredient)		montelukast
Other ingredients
(inactive ingredients)		10 mg film-coated tablets
microcrystalline cellulose
lactose monohydrate
croscarmellose sodium
hyprolose
magnesium stearate
hypromellose
titanium dioxide
iron oxide red
iron oxide yellow
carnauba wax
5 mg and 4 mg chewable tablets
mannitol
microcrystalline cellulose
hyprolose
croscarmellose sodium
artificial cherry flavour aromolok 181612 (proprietary ingredient: 2916)
magnesium stearate
aspartame
iron oxide red
Potential allergensLactose (10 mg tablets only)
SINGULAIR tablets do not contain gluten, sucrose, tartrazine or any other azo dyes.

Do not take this medicine if you are allergic to any of these ingredients.

What SINGULAIR looks like

SINGULAIR comes as three types of tablets:

SINGULAIR 10 mg film-coated tablet is a beige, rounded square tablet with SINGULAIR marked on one side and MSD 117 on the other (Aust R 61846).

SINGULAIR 5 mg chewable tablet is a pink, round tablet with SINGULAIR marked on one side and MSD 275 on the other (AUST R 61847)

SINGULAIR 4 mg chewable tablet is a pink, oval tablet with SINGULAIR marked on one side and MSD 711 on the other (AUST R 74890).

A box of SINGULAIR contains 14 or 28 tablets.

Who distributes SINGULAIR

Organon Pharma Pty Ltd
Level 5, 66 King St
Sydney NSW 2000
Australia

This leaflet was prepared in April 2025

S-WPPI-MK-0476-MF--052019

RCN100004592-AU

Published by MIMS June 2025

BRAND INFORMATION

Brand name

Singulair

Active ingredient

Montelukast

Schedule

S4

 

1 Name of Medicine

Montelukast sodium.

2 Qualitative and Quantitative Composition

Each 10 mg film-coated tablet contains 10.4 mg montelukast sodium, which is equivalent to 10.0 mg of montelukast, the free acid.

Excipients with known effects.

Lactose monohydrate.
Each 5 mg chewable tablet contains 5.2 mg montelukast sodium, which is equivalent to 5.0 mg of montelukast, the free acid.
Each 4 mg chewable tablet contains 4.16 mg of montelukast sodium, which is equivalent to 4.0 mg of montelukast, the free acid.

Excipients with known effects.

Aspartame.
Each packet of 4 mg oral granules contains 4.16 mg of montelukast sodium, which is equivalent to 4.0 mg of montelukast, the free acid.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

10 mg film-coated tablet.

A beige biconvex rounded square film-coated tablet engraved with SINGULAIR on one side and MSD 117 on the other.

5 mg chewable tablet.

A pink biconvex round chewable tablet engraved with SINGULAIR on one side and MSD 275 on the other.

4 mg chewable tablet.

A pink, oval, biconvex chewable tablet with SINGULAIR debossed on one side and MSD 711 on the other.

4 mg oral granules.

Coarse, white free-flowing granules sealed in a foil packet.

4 Clinical Particulars

4.1 Therapeutic Indications

Prophylaxis and treatment of chronic asthma in adults and children 2 years of age and older.
Symptomatic treatment of seasonal allergic rhinitis.

4.2 Dose and Method of Administration

Asthma and/or seasonal allergic rhinitis.

Singulair should be taken once daily.
For asthma, the dose should be taken in the evening.
For seasonal allergic rhinitis, the time of administration may be individualised to suit patient needs.
Patients with both asthma and seasonal allergic rhinitis should take only one tablet daily in the evening.

Adults 15 years of age and older.

The dosage for adults 15 years of age and older is one 10 mg tablet daily.

Paediatric patients 6 to 14 years of age.

The dosage for paediatric patients 6 to 14 years of age is one 5 mg chewable tablet daily. Chew the tablets. Do not swallow whole.

Paediatric patients 2 to 5 years of age.

The dosage for paediatric patients 2 to 5 years of age is one 4 mg chewable tablet daily or one packet of 4 mg oral granules daily. Chew the tablets. Do not swallow whole.

Administration of oral granules.

Singulair oral granules can be administered either directly in the mouth, or mixed with a spoonful of cold or room temperature soft food (e.g. applesauce). The packet should not be opened until ready to use. After opening the packet, the full dose of Singulair oral granules must be administered immediately (within 15 minutes). If mixed with food, Singulair oral granules must not be stored for future use. Singulair oral granules are not intended to be dissolved in liquid for administration. However, liquids may be taken subsequent to administration.

General recommendations.

The therapeutic effect of Singulair on parameters of asthma control occurs within one day. Singulair tablets, chewable tablets and oral granules can be taken with or without food. Patients should be advised to continue taking Singulair daily when their asthma is controlled, as well as during periods of worsening asthma.
No dosage adjustment is necessary for paediatric patients, for the elderly, for patients with renal insufficiency, or mild to moderate hepatic impairment, or for patients of either gender.

Therapy with Singulair in relation to other treatments for asthma.

Singulair can be added to a patient's existing treatment regimen.
Reduction in concomitant therapy.

Bronchodilator treatments.

Singulair can be added to the treatment regimen of patients who are not adequately controlled on bronchodilator alone. When a clinical response is evident (usually after the first dose), the patient's bronchodilator therapy can be reduced as tolerated.

Inhaled corticosteroids.

Treatment with Singulair provides additional clinical benefit to patients treated with inhaled corticosteroids. A reduction in the corticosteroid dose can be made as tolerated. The dose should be reduced gradually with medical supervision. In some patients, the dose of inhaled corticosteroids can be tapered off completely. Singulair should not be abruptly substituted for inhaled corticosteroids.

4.3 Contraindications

Hypersensitivity to any component of these products.

4.4 Special Warnings and Precautions for Use

The efficacy of oral Singulair for the treatment of acute asthma attacks has not been established. Therefore, oral tablets of Singulair should not be relied upon to treat acute asthma attacks. Patients should be advised to have appropriate rescue medication available.
While the dose of concomitant inhaled corticosteroid may be reduced gradually under medical supervision, Singulair should not be abruptly substituted for inhaled or oral corticosteroids (see Section 5.1 Pharmacodynamic Properties, Clinical trials, Clinical studies - asthma).

Neuropsychiatric events.

Neuropsychiatric events have been reported in adult, adolescent, and paediatric patients taking Singulair. Postmarketing reports with Singulair use include agitation, aggressive behaviour or hostility, anxiousness, depression, dream abnormalities, hallucinations, insomnia, irritability, restlessness, somnambulism, suicidal thinking and behaviour (including suicidality), and tremor. The clinical details of some postmarketing reports involving Singulair appear consistent with a drug induced effect.
Prescribers should discuss the benefits and risks of montelukast use with patients and caregivers when prescribing Singulair. Patients and/or caregivers should be advised to be alert for changes in behaviour or for new neuropsychiatric symptoms when taking Singulair. If changes in behaviour are observed, or if new neuropsychiatric symptoms or suicidal thoughts and/or behaviour occur, patients should be advised to discontinue Singulair and contact a healthcare provider immediately. In many cases, symptoms resolved after stopping Singulair therapy; however, in some cases symptoms persisted after discontinuation of Singulair. Therefore, patients should be monitored and provided supportive care until symptoms resolve. Prescribers should carefully evaluate the risks and benefits of continuing treatment with Singulair if such events occur.

Eosinophilic conditions.

In rare cases patients receiving antiasthma agents including leukotriene receptor antagonists, have experienced one or more of the following: eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy sometimes diagnosed as Churg-Strauss syndrome, a systemic eosinophilic vasculitis. These cases have been sometimes associated with the reduction or withdrawal of oral corticosteroid therapy. Although a causal relationship with leukotriene receptor antagonism has not been established, caution and appropriate clinical monitoring are recommended in patients receiving Singulair.
4 mg and 5 mg chewable tablets contain aspartame which is a source of phenylalanine (0.842 mg phenylalanine per 5 mg chewable tablet, and 0.674 mg phenylalanine per 4 mg chewable tablet).
Although montelukast is effective in improving airway function in asthmatics with documented aspirin sensitivity, it has not been shown to modify bronchoconstrictor response to aspirin challenge and other nonsteroidal anti-inflammatory drugs in aspirin sensitive asthmatic patients. Therefore, patients with known aspirin sensitivity should continue avoidance of aspirin or nonsteroidal anti-inflammatory agents while taking Singulair. (See Section 5.1 Pharmacodynamic Properties, Clinical studies - asthma.)

Use in hepatic impairment.

No dosage adjustment is necessary for the elderly or for patients with mild to moderate hepatic insufficiency. There are no clinical data in patients with severe hepatic insufficiency (Child-Pugh score > 9).

Use in renal impairment.

Because montelukast and its metabolites are eliminated by the biliary route, no dose adjustment is anticipated to be necessary in patients with renal impairment. Studies in patients with renal impairment have not been undertaken.

Use in the elderly.

In clinical studies, there were no age-related differences in the efficacy or safety profiles of Singulair.

Paediatric use.

In asthma.

Singulair has been studied in paediatric patients six months to 14 years of age (see Section 4.2 Dose and Method of Administration). Safety and effectiveness in paediatric patients younger than six months of age have not been studied. In studies investigating the effect of Singulair on the growth rate of paediatric patients, it has been shown in one study that Singulair does not affect the growth rate of paediatric patients when given for up to 56 weeks. The long-term clinical relevance of the growth rates studies is unknown.

In seasonal allergic rhinitis.

Singulair has been studied in paediatric patients 2 to 14 years of age (see Section 4.2 Dose and Method of Administration). Safety in paediatric patients younger than two years of age has not been studied.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Relatively high concentrations of montelukast competitively inhibit the activity of cytochromes P450 3A4 and 2C9. However, these concentrations are at least 15-fold higher than the peak plasma concentrations attained following a 10 mg oral dose of montelukast. Based on these and other in vitro results in human liver microsomes, therapeutic plasma concentrations of montelukast should not be expected to inhibit cytochromes P450 3A4, 2C9, 1A2, 2A6, 2C19 or 2D6. Theophylline plasma concentration was not affected by the recommended dose of Singulair (10 mg once daily). At 20 and 60-fold above the recommended dose, plasma concentration of concomitant theophylline was decreased. Theophylline dose adjustment or a change in the frequency of plasma theophylline monitoring is not necessary at the recommended dose of Singulair.
Singulair may be administered with other therapies routinely used in the prophylaxis and chronic treatment of asthma, and in the treatment of allergic rhinitis. 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, oral contraceptives (ethinylestradiol/ norethisterone 35/1), terfenadine, digoxin and warfarin. The effects of concomitant administration of montelukast and macrolide antimicrobials have not been studied.
The area under the plasma concentration time curve (AUC) for montelukast was decreased approximately 40% in subjects with coadministration of phenobarbital. No dosage adjustment for Singulair is recommended.
In vitro studies have shown that montelukast is an inhibitor of CYP2C8. However, data from a clinical drug-drug interaction study involving montelukast and rosiglitazone (a probe substrate representative of drugs primarily metabolized by CYP2C8) demonstrated that montelukast does not inhibit CYP2C8 in vivo. Therefore, montelukast is not anticipated to alter the metabolism of drugs metabolized by this enzyme (e.g. paclitaxel, rosiglitazone, repaglinide).
In vitro studies have shown that montelukast is a substrate of CYP 2C8, 2C9, and 3A4. Data from a clinical drug drug interaction study involving montelukast and gemfibrozil (an inhibitor of both CYP 2C8 and 2C9) demonstrated that gemfibrozil increased the systemic exposure of montelukast by 4.4-fold. Coadministration of itraconazole, a strong CYP 3A4 inhibitor, with gemfibrozil and montelukast did not further increase the systemic exposure of montelukast. Based on available clinical experience no dosage adjustment of montelukast is required upon coadministration with gemfibrozil or other potent inhibitors of CYP 2C8. Specific in vivo data are not available for other known inhibitors of CYP 2C8 (e.g. trimethoprim). Although clinically important drug interactions are not anticipated based on these findings, systemic exposure to montelukast is potentially increased and the physician should be aware of a possible increase in adverse reactions (see Section 4.9 Overdose). Coadministration of montelukast with itraconazole alone resulted in no significant increase in the systemic exposure of montelukast.
Although additional specific interaction studies were not performed, Singulair was used concomitantly with a wide range of commonly prescribed drugs in clinical studies without evidence of clinical adverse interactions. These medications included thyroid hormones, sedative hypnotics, nonsteroidal anti-inflammatory agents, benzodiazepines and decongestants.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Fertility and reproductive performance were not affected in studies with male rats given oral doses of up to 800 mg/kg/day, but fecundity was slightly reduced in female rats doses orally at 200 mg/kg/day. The no effect dose for the latter effect was 100 mg/kg/day, corresponding to systemic exposure, in terms of plasma AUC for parent drug, at least 20 times higher than that in women at recommended dose levels.
(Category B1)
In animal studies, montelukast sodium had no adverse effects on embryofoetal development at oral doses up to 400 mg/kg/day in rats or up to 100 mg/kg/day in rabbits. Retardation of foetal growth and development was observed in rabbits dosed at 200 mg/kg/day, a dose level associated with severe maternal toxicity. Foetal exposure of montelukast was demonstrated in both species.
Available data from published prospective and retrospective cohort studies with montelukast use in pregnant women evaluating major birth defects have not established a drug-associated risk. Available studies have methodologic limitations, including small sample size, in some cases retrospective data collection and inconsistent comparator groups. Singulair should be used during pregnancy only if clearly needed.
 Studies in lactating rats have shown that montelukast is excreted into milk following oral doses of 100 and 200 mg/kg/day, and growth of the pups was slightly inhibited at the higher dose level. It is not known if Singulair is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Singulair is given to a nursing mother.

4.7 Effects on Ability to Drive and Use Machines

There is no evidence that Singulair affects the ability to drive and use machines. However, adverse effects of these medicines include dizziness and drowsiness, which could affect the ability to drive or use machines (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.8 Adverse Effects (Undesirable Effects)

Singulair has been generally well tolerated. Side effects, which usually were mild, generally did not require discontinuation of therapy. The overall incidence of side effects reported with Singulair was comparable to placebo.

Adults 15 years of age and older with asthma.

Singulair has been evaluated for safety in approximately 2600 adult patients 15 years of age and older in clinical studies. In two similarly designed, 12 week placebo controlled clinical studies, the only adverse experiences reported as drug related in ≥ 1% of patients treated with Singulair and at a greater incidence than in patients treated with placebo were abdominal pain and headache. The incidences of these events were not significantly different in the two treatment groups.
In placebo controlled clinical studies, the following adverse experiences reported with Singulair occurred in ≥ 1% of patients and at an incidence greater than or equal to that in patients treated with placebo, regardless of drug relationship. See Table 1.
Cumulatively, 544 patients were treated with Singulair for at least 6 months, 253 for one year and 21 for two years in clinical studies. With prolonged treatment, the adverse experience profile did not change.

Paediatric patients 6 to 14 years of age with asthma.

Singulair has been evaluated for safety in approximately 970 paediatric patients 6 to 14 years of age. The safety profile in paediatric patients is generally similar to the adult safety profile and to placebo. Cumulatively, 263 paediatric patients 6-14 years of age were treated with Singulair for at least 3 months, 164 for 6 months or longer in clinical studies. The safety profile in paediatric patients is generally similar to the adult safety profile and to placebo. With prolonged treatment, the adverse experience profile did not change.
In a 56 week active controlled study comparing montelukast to inhaled fluticasone in paediatric patients 6-14 years of age with mild persistent asthma, the safety profile was consistent with the safety profile previously described for Singulair. In the study, the number of patients with asthma symptoms after treatment was 166 (33.5%) patients in the montelukast treatment group and 135 (27.1%) patients in the fluticasone treatment group.
In studies evaluating growth rate, the safety profile in these paediatric patients was consistent with the safety profile previously described for Singulair.

Paediatric patients 2 to 5 years of age with asthma.

Singulair has been evaluated in 573 paediatric patients 2 to 5 years of age. In a 12 week placebo controlled clinical study, the only adverse experience reported as drug related in > 1% of patients treated with Singulair and at a greater incidence than in patients treated with placebo was thirst. The incidence of thirst was not significantly different in the two treatment groups.
Cumulatively, 502 paediatric patients 2 to 5 years of age were treated with Singulair for at least 3 months, 338 for 6 months or longer, and 256 patients for 12 months or longer. With prolonged treatment, the adverse experience profile did not change.

Adults 15 years of age and older with seasonal allergic rhinitis.

Singulair has been evaluated in 2199 adult patients 15 years of age and older for the treatment of seasonal allergic rhinitis in clinical studies. Singulair administered once daily in the morning or in the evening was generally well tolerated with a safety profile similar to that of placebo. In placebo controlled clinical studies, no adverse experiences reported as drug related in ≥ 1% of patients treated with Singulair and at a greater incidence than in patients treated with placebo were observed. In a 4 week, placebo controlled clinical study, the safety profile was consistent with that observed in 2 week studies. The incidence of somnolence was similar to that of placebo in all studies.

Paediatric patients 2 to 14 years of age with seasonal allergic rhinitis.

Singulair has been evaluated in 280 paediatric patients 2 to 14 years of age for the treatment of seasonal allergic rhinitis in a 2 week, placebo controlled clinical study. Singulair administered once daily in the evening was generally well tolerated with a safety profile similar to that of placebo. In this study, no adverse experiences reported as drug related in ≥ 1% of patients with Singulair and at a greater incidence than in patients treated with placebo were observed.

Adults 15 years of age and older with asthma and seasonal allergic rhinitis.

Singulair 10 mg film coated tablets have been evaluated in approximately 400 asthmatic patients 15 years of age and older with seasonal allergic rhinitis. The safety profile in asthmatic patients with seasonal allergic rhinitis was consistent with that observed in patients with asthma.

Post-marketing experience.

The following additional side effects have been reported in postmarketing use.

Infections and infestations.

Upper respiratory tract infection.

Blood and lymphatic system disorders.

Increased bleeding tendency, thrombocytopenia.

Immune system disorders.

Hypersensitivity reactions including anaphylaxis, very rarely hepatic eosinophilic infiltration.

Psychiatric disorders.

Agitation including aggressive behaviour or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, dysphemia (stuttering), hallucinations, insomnia, memory impairment, obsessive-compulsive symptoms, psychomotor hyperactivity (including irritability, restlessness, and tremor), somnambulism (sleep walking), suicidal thinking and behaviour (suicidality), tic.

Nervous system disorders.

Dizziness, drowsiness, paraesthesia/ hypoesthesia, very rarely seizure.

Cardiac disorders.

Palpitations.

Respiratory, thoracic and mediastinal disorders.

Epistaxis, pulmonary eosinophilia.

Gastrointestinal disorders.

Diarrhoea, dyspepsia, nausea, vomiting.

Hepatobiliary disorders.

Increased ALT and AST, very rarely hepatitis (including cholestatic, hepatocellular, and mixed pattern liver injury).

Skin and subcutaneous tissue disorders.

Angioedema, bruising, erythema multiforme, erythema nodosum, pruritus, rash, urticaria.

Musculoskeletal and connective tissue disorders.

Arthralgia, myalgia including muscle cramps.

Renal and urinary disorders.

Enuresis in children.

General disorders and administration site conditions.

Oedema, pyrexia.
In rare cases, patients on therapy with Singulair may present with systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome. These events usually, but not always, have been associated with the reduction of oral corticosteroid therapy. A causal association between Singulair and these underlying conditions has not been established (see Section 4.4 Special Warnings and Precautions for Use).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

No specific information is available on the treatment of overdosage with Singulair. In chronic asthma studies, Singulair has been administered at doses up to 200 mg/day to adult 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.
There have been reports of acute overdosage in postmarketing experience and clinical studies with Singulair. These include reports in adults and children with a dose as high as 1000 mg. 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 overdosage reports.
The most frequently occurring adverse experiences were consistent with the safety profile of Singulair and included abdominal pain, somnolence, thirst, headache, vomiting, and psychomotor hyperactivity.
It is not known whether montelukast is dialyzable by peritoneal or hemodialysis.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The cysteinyl leukotrienes (LTC4, LTD4, LTE4), are potent inflammatory eicosanoids released from various cells including mast cells and eosinophils. These important proasthmatic mediators bind to cysteinyl leukotriene (CysLT) receptors. The CysLT type 1 (CysLT1) receptor is found in the human airway (including airway smooth muscle cells and airway macrophages) and on other proinflammatory cells (including eosinophils and certain myeloid stem cells). CysLTs have been correlated with the pathophysiology of asthma and allergic rhinitis. In asthma, leukotriene mediated effects include a number of airway actions, including bronchoconstriction, mucous secretion, vascular permeability, and eosinophil recruitment. In allergic rhinitis, CysLTs are released from the nasal mucosa after allergen exposure during both early and late phase reactions and are associated with symptoms of allergic rhinitis. Intranasal challenge with CysLTs has been shown to increase nasal airway resistance and symptoms of nasal obstruction. The clinical relevance of intranasal challenge studies is unknown.
Montelukast is an orally active compound which has been shown in asthmatic patients to reduce peripheral blood eosinophil counts and sputum eosinophils, which are parameters of asthmatic inflammation. The effect of montelukast on reduction of peripheral blood eosinophils was comparable to inhaled corticosteroids. Based on biochemical and pharmacological bioassays, it binds with high affinity and selectivity to the CysLT1-receptor (in preference to other pharmacologically important airway receptors such as the prostanoid, cholinergic, or β-adrenergic receptor). Montelukast potently inhibits physiologic actions of LTC4, LTD4 and LTE4 at the CysLT1-receptor without any agonist activity.
In asthmatic patients, montelukast causes potent inhibition of airway cysteinyl leukotriene receptors as demonstrated by the ability to inhibit bronchoconstriction due to inhaled LTD4. A dose of 5 mg causes substantial blockage of LTD4 induced bronchoconstriction. Montelukast causes bronchodilation within 2 hours of oral administration. β-agonists caused additive effects when added to montelukast.

Clinical trials.

Clinical studies - asthma. In clinical studies, Singulair is effective in adult and paediatric patients for the prophylaxis and chronic treatment of asthma, including protection against day- and night time symptoms, the treatment of aspirin sensitive asthmatic patients, and the prevention of exercise induced bronchoconstriction. Singulair is effective alone or in combination with other prophylactic agents used in the maintenance treatment of asthma. Singulair and inhaled corticosteroid may be used concomitantly with additive effects to control asthma or to reduce the inhaled corticosteroid dose while maintaining clinical stability. Singulair is a preventative agent which should be used in addition to other drugs for the management of asthma.

Adults 15 years of age and older.

In two similarly designed 12 week double blind placebo controlled studies in adults asthmatic patients 15 years of age and older, Singulair, 10 mg once daily in the evening, demonstrated significant improvements in parameters of asthma control measuring asthma symptoms, asthma related outcomes, respiratory function and 'as needed' β-agonist use.
Singulair significantly improved patient reported daytime symptoms and nocturnal awakenings, compared with placebo. Asthma specific outcomes, including asthma attacks, corticosteroid rescue, discontinuations due to worsening asthma, asthma exacerbations and asthma free days were also significantly better than placebo.
Physicians' and patients' global asthma evaluations and asthma specific quality of life evaluations (in all domains, including normal daily activity and asthma symptoms) were significantly better than placebo.
Singulair caused significant improvements in morning forced expiratory volume in 1 second (FEV1), am and pm peak expiratory flow rate (PEFR) and significantly decreased the use of 'as needed' β-agonist, compared with placebo.
A comparison of Singulair and inhaled beclomethasone (200 microgram twice daily with a spacer device) demonstrated that Singulair had a more rapid initial response (within the first day compared with 7-10 days for beclomethasone). While both treatments provided significantly and clinically important changes, the overall beclomethasone effect was larger over the 12 weeks duration of the study. The difference in response is, in part, a result of a small percentage of patients treated with beclomethasone (16.7%) that had a ≥ 30% increase in FEV1. However in a high proportion of patients the response was comparable, for example, 42% of patients taking montelukast compared with 50% of patients taking beclomethasone achieved an 11% or more increase in FEV1.
The treatment effect was achieved after the first dose and was maintained throughout the 24 hour dosing interval. Treatment effect also remained constant during continuous once daily administration in extension studies for up to one year. Withdrawal of Singulair after 12 weeks of use did not cause rebound worsening of asthma.

Paediatric patients 6 to 14 years of age.

In paediatric patients 6 to 14 years of age, one 5 mg chewable tablet daily in the evening significantly decreased asthma exacerbations, and improved parents' global evaluations and the paediatric asthma specific quality of life evaluations, compared with placebo. Singulair also significantly improved morning FEV1 and decreased total daily 'as needed' β-agonist use. Treatment effect was achieved after the first dose and remained constant during once daily administration for up to 6 months.

Growth rate in paediatric patients.

Two controlled clinical studies have demonstrated that montelukast did not affect the growth rate in paediatric patients with asthma. In a short-term study of children aged 6 to 11 years, growth rate as measured by lower leg length growth was similar in patients treated with montelukast 5 mg once daily for 3 weeks compared with placebo, and was significantly lower in patients treated with inhaled budesonide (200 microgram twice daily) for 3 weeks, compared with placebo. In a 56 week study in children aged 6 to 8 years, linear growth rate was similar in patients treated with montelukast 5 mg once daily and placebo (LS means for montelukast and placebo: 5.67 and 5.64 cm/year, respectively), and was significantly lower (LS mean: 4.86 cm/year) in patients treated with inhaled beclomethasone (200 microgram twice daily), compared with placebo [difference in LS means (95% CI): -0.78 (-1.06, -0.49) cm/year]. The long-term clinical relevance of these studies is unknown.

Paediatric patients 2 to 5 years of age.

In a 12 week, placebo controlled study in paediatric patients 2 to 5 years of age, Singulair 4 mg once daily consistently improved parameters of asthma control irrespective of concomitant controller therapy use compared with placebo. Sixty percent of patients were not on any other controller therapy. Singulair significantly improved daytime symptoms (including coughing, wheezing, trouble breathing and activity limitation) and night time symptoms compared with placebo (mean baseline daytime scores were Singulair 0.98 and placebo 0.95 on a 0-5 scale; mean change from baseline: Singulair -0.37 vs placebo -0.25 [p = 0.003] and mean baseline night time scores were Singulair 1.18 and placebo 1.20 on a 0-4 scale; mean change from baseline: Singulair -0.41 vs placebo -0.30 [p = 0.026]).
Singulair also significantly decreased 'as needed' β-agonist use (percentage of days used, Singulair 50.09 vs placebo 56.34 [p = 0.001]) and corticosteroid rescue (percentage of patients with corticosteroid rescue, Singulair 19.09 vs placebo 28.07 [p = 0.008]) compared with placebo. Patients receiving Singulair had significantly more days without asthma than those receiving placebo (percentage of days without, Singulair 30.50 vs placebo 23.63 [p = 0.002]). A treatment effect was achieved after the first dose. In addition, total blood eosinophil counts were significantly decreased (for total blood eosinophil counts, the between group difference in LS means was -0.04 x 103/microL, p = 0.034).

Effects in patients on concomitant inhaled corticosteroids.

Separate studies in adults demonstrated the ability of Singulair to add to the clinical effect of inhaled corticosteroid and allow steroid tapering when used concomitantly. In a placebo controlled study, stable, asthmatic patients taking initial inhaled corticosteroid doses of approximately 1600 microgram per day reduced their steroid use by approximately 37% during a placebo run-in period. Singulair allowed a further 47% reduction of the inhaled corticosteroid dose, compared with 30% for placebo. In another study, Singulair provided additional clinical benefit to a similar population of patients maintained but not adequately controlled on inhaled corticosteroid (beclomethasone 400 microgram per day). Complete abrupt removal of beclomethasone in patients receiving both Singulair and beclomethasone caused clinical deterioration in some patients, suggesting that tapering as tolerated rather than abrupt removal is preferred.

Aspirin sensitive patients.

In aspirin sensitive patients, nearly all of whom were receiving concomitant inhaled and/or oral corticosteroids, Singulair resulted in significant improvement in the parameters of asthma control.
The effect of Singulair on the bronchoconstrictor response to aspirin challenge or other nonsteroidal anti-inflammatory drugs in aspirin sensitive asthmatic patients has not been evaluated (see Section 4.4 Special Warnings and Precautions for Use).

Effects on exercise induced bronchoconstriction.

Singulair, 10 mg once daily, protected against exercise induced bronchoconstriction (EIB) in adults 15 years of age and older. In a 12 week study, Singulair significantly inhibited the extent and duration of fall in FEV1 over 60 minutes after exercise, the maximal percent fall in FEV1 after exercise, and the time to recovery to within 5% of the pre-exercise FEV1. Protection was consistent through the treatment period indicating that tolerance did not occur. In a separate crossover study, protection was observed after two once daily doses.
In paediatric patients 6 to 14 years of age, using the 5 mg chewable tablet, a similarly designed crossover study demonstrated similar protection and the protection was maintained throughout the dosing interval (24 hours).

Effects on antigen challenge and eosinophils.

In clinical studies Singulair inhibited both early and late phase bronchoconstriction due to antigen challenge. Because inflammatory cell (eosinophil) infiltration is an important feature of asthma, the effects of Singulair on eosinophils in the peripheral blood and airway were examined. In phase IIb/III clinical studies, Singulair significantly decreased peripheral blood eosinophils approximately 15% from baseline, compared with placebo. In paediatric patients 6 to 14 years of age, Singulair decreased peripheral blood eosinophils 13% over the 8 week treatment period, compared with placebo. Singulair also significantly decreased airway eosinophils in sputum, compared with placebo. In this study, peripheral blood eosinophils decreased and clinical asthma endpoints improved with treatment with Singulair.

Effects in patients with asthma and seasonal allergic rhinitis.

In a two week, placebo controlled, double blind, clinical study in adult asthmatic patients 15 years of age and older with concomitant seasonal allergic rhinitis, montelukast 10 mg tablets administered once daily demonstrated a statistically significant improvement in the primary composite variable, daily rhinitis symptoms score (average of the daytime nasal symptoms score [mean of nasal congestion, rhinorrhea, sneezing, nasal itching] and the night time symptoms score [mean of nasal congestion upon awakening, difficulty going to sleep, and night time awakenings scores]) (see Table 2). The mean difference in improvement between the two treatments was -0.12 points (95% CI: -0.18, -0.06) on a scale of 0.00 to 3.00. A change of 1.00 would correspond to an improvement of symptoms from moderate to mild, or from severe to moderate.
Clinical studies - seasonal allergic rhinitis.

Adults 15 years of age and older.

The efficacy of Singulair for the treatment of seasonal allergic rhinitis was investigated in seven similarly designed randomised, 2 week, double blind, placebo controlled trials including 4924 patients (1751 patients were treated with Singulair). Patients were 15 years of age and older with a history of seasonal allergic rhinitis, a positive skin test to at least one relevant seasonal allergen, and active symptoms of seasonal allergic rhinitis at study initiation.
Two of the three pivotal studies showed a significant reduction in daytime nasal symptoms scores with Singulair 10 mg tablets compared to placebo.
In a combined analysis of the three pivotal studies, Singulair 10 mg tablets administered to 1189 patients once daily in the evening resulted in a statistically significant improvement in the primary endpoint, daytime nasal symptoms score, and its individual components (nasal congestion, rhinorrhea, nasal itching, and sneezing); night time symptoms score, and its individual components (nasal congestion upon awakening, difficulty going to sleep, and night time awakenings); daytime eye symptoms score, and its individual components (tearing, itchy, red, and puffy eyes); global evaluation of allergic rhinitis by patients and by physicians; and composite symptoms score (composed of the daytime nasal and night time symptoms scores), compared with placebo.
The efficacy results of one trial are shown below. The mean changes from baseline in daytime nasal symptoms score in the treatment groups that received Singulair tablets, loratadine and placebo are shown in Table 3. The mean change from baseline for Singulair was 50% larger than the mean change from baseline for placebo.
The efficacy of Singulair in the treatment of seasonal allergic rhinitis was investigated in a separate 4 week study in which the primary objective of the study was to determine the treatment effect of Singulair 10 mg administered once daily in the morning, compared to placebo, in patients with seasonal allergic rhinitis over the first 2 weeks of treatment. The efficacy of Singulair over the initial 2 weeks was significantly different from placebo and consistent with the effect observed in studies using evening dosing (see Table 4). Additionally, the effect over the entire 4 weeks was consistent with the 2 week results (see Figure 1).
The study was not designed for statistical comparison between Singulair and the active control (loratadine).

Paediatric patients 2 to 14 years of age.

Efficacy studies have not been conducted in this age group.

5.2 Pharmacokinetic Properties

Absorption.

Montelukast is rapidly and nearly completely absorbed following oral administration. For the 10 mg film coated tablet, the mean peak plasma concentration (Cmax) is 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.
For the 5 mg chewable tablet, the Cmax is 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. This is unlikely to have any clinical significance with chronic administration. Efficacy was demonstrated in clinical studies in children where the montelukast 5 mg chewable tablet was administered irrespective of food.
For the 4 mg chewable tablet, Cmax is achieved 2 hours after the administration in paediatric patients 2 to 5 years of age in the fasted state.
The 4 mg oral granule formulation is bioequivalent to the 4 mg chewable tablet when administered to adults in the fasted state. The oral bioavailability is not influenced by a high fat, high calorie breakfast. This breakfast resulted in a longer tmax and a reduction in Cmax of 36%. The 4 mg oral granule formulation is bioequivalent to the 4 mg chewable tablet when administered to fasted adults either alone or with applesauce.
The 10 mg film coated tablets of montelukast are not bioequivalent to two 5 mg chewable tablets, and these two products should not be used interchangeably.

Distribution.

Montelukast is more than 99% bound to plasma proteins. The steady-state volume of distribution of montelukast averages 8-11 liters. Studies in rats with radiolabeled montelukast indicate minimal distribution across the blood brain barrier. In addition, concentrations of radiolabeled material at 24 hours postdose were minimal in all other tissues.

Metabolism.

Montelukast is extensively metabolized. In studies with therapeutic doses, plasma concentrations of metabolites of montelukast are undetectable (< 20 nanogram/mL) at steady-state in adults and children. Cytochromes P450 2C8, and to a lesser extent 3A4 and 2C9, are involved in the metabolism of montelukast.

Excretion.

The plasma clearance of montelukast averages 45 mL/min in healthy adults. Following an oral dose of radiolabeled montelukast, 86% of the radioactivity was recovered in 5 day fecal collections and < 0.2% was recovered in urine. Coupled with estimates of montelukast oral bioavailability, this indicates that montelukast and its metabolites are excreted almost exclusively via the bile.
In several studies, the mean plasma half-life of montelukast ranged from 2.7 to 5.5 hours in healthy young adults. The pharmacokinetics of montelukast are nearly linear for oral doses up to 50 mg. During once daily dosing with 10 mg montelukast, there is little accumulation of the parent drug in plasma (~ 14%).

5.3 Preclinical Safety Data

Genotoxicity.

Montelukast sodium was found not to be genotoxic. Montelukast sodium was negative in microbial and mammalian cell mutagenesis assays, with and without metabolic activation. There was no evidence of clastogenic activity in the in vitro chromosomal aberration assay in Chinese hamster ovary cells, with or without a microsomal enzyme activation system, or of DNA damage in the in vitro alkaline elution assay in rat hepatocytes. Similarly, there was no induction of chromosomal aberrations in bone marrow cells of male or female mice.

Carcinogenicity.

Montelukast sodium was not carcinogenic when administered at oral doses of up to 200 mg/kg/day in 104 week study in rats, nor at oral doses up to 100 mg/kg/day in a 91 week study in mice. Systemic exposure in these studies, in terms of the plasma AUC for parent drug, was at least 30 times higher than that in humans at recommended dose levels.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each 10 mg film-coated tablet contains the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, hyprolose, and magnesium stearate. The film-coating consists of: hypromellose, hyprolose, titanium dioxide, iron oxide red, iron oxide yellow, and carnauba wax.
Each 4 mg and 5 mg chewable tablet contains the following inactive ingredients: mannitol, microcrystalline cellulose, hyprolose, croscarmellose sodium, artificial cherry flavour aromolok 181612 (Proprietary Ingredient ID 2916), magnesium stearate, aspartame, and iron oxide red.
Each packet of 4 mg oral granules contains the following inactive ingredients: mannitol, hyprolose, and magnesium stearate.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of these medicines.

6.3 Shelf Life

The expiry date can be found on the packaging. In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG).

6.4 Special Precautions for Storage

Store below 30°C. Protect from light and moisture.

6.5 Nature and Contents of Container

10 mg film-coated tablet.

Supplied in blister packs of 4*, 14 and 28 tablets.

5 mg chewable tablet.

Supplied in blister packs of 4* and 28 tablets.

4 mg chewable tablet.

Supplied in blister packs of 4* and 28 tablets.

4 mg oral granules**.

Supplied in packs of 28 packets.
* Supplied as starter packs only.
** Not currently supplied in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Singulair (montelukast sodium) is a selective and orally active leukotriene receptor antagonist that specifically inhibits the cysteinyl leukotriene CysLT1 receptor.
Singulair (montelukast sodium) is described chemically as [R-(E)]-1-[[[1-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl] cyclopropane acetic acid, monosodium salt.
The empirical formula is C35H35ClNNaO3S, and its molecular weight is 608.18.
Montelukast sodium is a hygroscopic, optically active, white to off-white, free-flowing powder. Montelukast sodium is freely soluble in ethanol, methanol, and water and practically insoluble in acetonitrile. Montelukast is the optically active R stereoisomer.

Chemical structure.

The structural formula of montelukast sodium is:

CAS number.

151767-02-1.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).

Summary Table of Changes