Introduction
Montelukast drug is sold under the brand name of Singulair. Montelukast was first approved by the US FDA in 1998 for clinical use to treat asthma. Montelukast is a leukotriene receptor antagonist (LTRA).it works by inhibiting the binding of leukotrienes to the receptor site, therefore, minimizing the leukotrienes associated symptoms of inflammation and allergy.
When any allergen is entered into the body it causes the release of various inflammatory mediators such as leukotrienes (LTRA) that will lead to the inflammation and tightening of airway muscles. As a result, there is difficulty in breathing as in the case of asthma.
Montelukast acts by minimizing the activity of these Leukotrienes (LTRA) and relieves the symptoms of asthma and allergy such as bronchoconstriction and difficulty in breathing by relaxing the smooth muscles of the airway.
Pharmacokinetics
Absorption
Montelukast is well absorbed after oral administration.
Bioavailability
The oral bioavailability of montelukast is 64%. The bioavailability of the drug is not affected by meals.
Distribution
The volume of distribution of montelukast ranges between 8-10 liters. Peak plasma concentration is achieved within 3-4 hours in the case of a 10mg tablet and 2-2.5 hours in the case of a 5mg tablet.
Protein binding
Montelukast is a highly plasma protein-binding drug. After oral administration, about 99% of, the drug is bound to blood plasma proteins. At therapeutic dose average plasma half-life of montelukast is 2.2 to 5.5 hours.
Solubility
Montelukast is freely soluble in methanol, ethanol, and water and the drug is practically insoluble in acetonitrile.
Metabolism
Cytochrome P450 enzymes particularly cytochrome 2C9,3A4 and 2C8 isoenzymes are responsible for the metabolism of montelukast. but CYP 2C8 plays a vital role in the metabolism of drugs.
Elimination
Montelukast and its metabolites are mainly excreted through bile and feces (about 86% ) and only a small amount is excreted through urine(0.2%). In young healthy adults, the average clearance of montelukast is 45ml/min. The duration of action of montelukast is 24 hours after a single dose.
Pharmacodynamics
Cysteinyl Leukotrienes are the inflammatory mediators that are produced by mast cells and eosinophils as a result of Arachidonic acid metabolism. when these Cysteinyl Leukotrienes (LTC4, LTD4, LTE4) bind to their specific receptor site such as CysLT type-1 receptors present on the lungs produce various types of symptoms such as bronchoconstriction, increase vascular permeability, occluding of mucous secretion that ultimately results in a severe attack of asthma and allergy.
Montelukast is a leukotriene receptor antagonist. The drug has high affinity and selectivity for leukotriene receptors particularly leukotriene receptor type-1(CysLT type-1) as compared to other types of receptors present on airway paths such as Beta-adrenergic receptors, cholinergic receptors, and prostanoids. It inhibits the binding of leukotrienes to their receptor site, as a result, inhibits the pathophysiological effects of these mediators (LTC4, LTD4, LTE4) that may facilitate the symptoms of asthma and allergy.
Therapeutic indications
Montelukast is indicated for the treatment and prevention of
- Asthma (both prophylactic and chronic treatment of asthma) in adults and children as young as 12 months or older.
- Exercise-induced bronchoconstriction (EIB) in adults and children more than 6 years of age. Regional health authorities specifically indicate the montelukast for Exercise-induced bronchoconstriction in adults who are 15 years of age or older.
- Seasonal allergic rhinitis in children who are 2 years of age or older and perennial allergic rhinitis in children who are 6 months of age or older. Regional health authorities specifically indicate the montelukast for Exercise-induced bronchoconstriction in adults who are 15 years of age or older.
Montelukast doesn’t provide a quick relief to treat sudden attacks of asthma. In this case, fast-acting inhalational corticosteroids should be used to overcome the symptoms. It takes several weeks to resolve the symptoms of asthma and other allergic conditions. contact your physician if you don’t feel any improvement in the symptoms after several weeks of drug use.
Montelukast Dosage
Montelukast is available in the form of
- Tablets 10mg (film-coated tablets)
- Chewable tablets (4mg,5mg)
- Granules (4mg/packet)
Chewable tablets are recommended for use in children aged between 6-15 years and tablets are recommended for use in children of 15 years of age and adults.
The dose of the drug for the prevention and treatment of asthma
In adults
10mg tablet once daily in the evening
Pediatric dose
12-23 months of children
One sachet of oral granules (4mg) once daily.
2-5 years of children
One chewable tablet of 4mg or one sachet of granules once daily.
6-14 years
5mg chewable tablet once a day.
15 years and older
One tablet of 10mg daily
Preferably the drug should be taken in the evening without regard to the meal for its high efficacy.
The dose of the drug for the treatment of Seasonal allergic rhinitis
In Adults
10mg tablet once daily in the evening
Less than 2 years of age
For the treatment of seasonal allergic rhinitis, montelukast is not recommended for children of less than 2 years.
2-5 years of children
A single chewable tablet of 4mg or a sachet of mg once daily.
6-14 years of children
A single 5mg chewable tablet once a day.
15 years or older
A single oral dose of 10 mg tablet preferably in the evening.
The dose of the drug for the treatment of perennial allergic Rhinitis:-
Less than 6 months
Montelukast is not recommended for use in children under the age of 6 months.
6-23 months of age
A single 4mg sachet of oral granules once daily
2-5 years of children
Chewable tablet of 4mg daily once.
6-14 years of age
Chewable tablet of 5mg once daily.
15 years or older
A single 10mg tablet once a day.
Patients suffering from both medical conditions such as asthma and allergic rhinitis should take a single oral dose in the evening. Don’t take a double dose or extra dose of the drug for both conditions separately.
The dose of montelukast for the treatment of exercise-induced asthma:-
In adults
A single oral dose of montelukast 10mg tablet is recommended 2 hours before the exercise. care must be taken not to take a second dose of the drug within 24 hours of your regular dose.
6-14 years of children
A single oral dose of montelukast 5mg tablet is recommended 2 hours before the exercise. care must be taken not to take a second dose of the drug within 24 hours of your regular dose.
If the patient is taking the montelukast drug for another indication such as asthma or allergic rhinitis then the drug should not be used for the prevention of exercise-induced bronchoconstriction. Otherwise, it may lead to toxic reactions.in this case, short-acting beta agonistic drugs should be used.
How to take the drug
The maximum therapeutic efficacy of montelukast is achieved when the drug is taken inappropriate manner. Always follow the instructions of your physician to achieve maximum benefit and to resolve the symptoms. Following instructions should be kept in mind while taking the drug because a sub-therapeutic dose and overdose of the drug will not produce the desired effects.
- Swallow the tablet as a whole with a full glass of water. Don’t break the tablet into several pieces as its effectiveness is decreased.
- In the case of chewable tablets, the drug should be chewed completely before swallowing.
- While taking montelukast oral granules, the granules should be placed directly in the mouth cavity and then swallow. These granules can also be used after mixing with mashed carrot, ice cream, and rice. These granules are also dissolved in one teaspoon of breast milk and any baby formula. but Don’t use any other liquid to dissolve the granules.
- Montelukast oral granules should be used within 15minutes after the opening of the sachet.
- It can be taken with or without food.
- Continue the drug even when symptoms of asthma and other allergic reactions are resolved. The drug should not be discontinued abruptly without consulting your physician. The drug dose should be taper off before discontinuation or as the doctor recommended.
Missed dose
In the case of the missed dose, take the drug as soon as possible. if it is too late to nearly reach your next dose then skip the missed dose and take your regular dose of the drug. Don’t take a double dose of the drug.
Montelukast Side effects
Most common side effects are
- Headache.
- Abdominal pain, heartburn and upset in the stomach
- Nausea
- Diarrhea.
- Tooth pain.
- Tired feeling.
- Dizziness.
- Fever, stuffy nose, sore throat, cough, hoarseness.
- Mild rash.
- Upper respiratory tract infection.
- Life-threatening angioedema that may lead to the discontinuation of therapy.
Toxicity
Rarely Montelukast causes severe toxic reactions within the body when ingested at high doses or when used for a prolonged period of time.in a clinical trial study, the safety of montelukast was determined in adults by giving the drug at a dose of up to 200mg /day for 22 weeks and up-to 900mg/day for about one week. No significant toxic or adverse effect was seen in the patients. It produces toxic symptoms in adults and children only when giving at a dose of 1000mg.
However if you may experience some of these toxic symptoms, call your doctor on an urgent basis for medical care. these toxic symptoms include
- Systemic vasculitis
- Pulmonary infiltration
- Leukocytosis
- Skin rashes
- Dry cough
- Shortness of breath
- Eosinophilic hepatitis (with a serum bilirubin level of more than 3mg/dl)
- Generalized malaise
- Psychomotor hyperactivity
- Convulsion (less frequently).
Supportive therapy for Montelukast Toxicity
In the case of toxicity following supportive measures must be taken to cure the patient.
- Gastric lavage
- Adsorption with activated charcoal
- Clinical monitoring
- No antidote is available for montelukast overdose. Hemodialysis and peritoneal dialysis may be done to remove the drug from the body but no data is available to show the efficiency of dialysis in montelukast overdose.
Patient monitoring while taking Montelukast
Patients should be monitored regularly while taking the drug. Observe any symptoms of behavioral and mood changes such as suicidal thoughts or any other neuropsychic signs that may occur due to montelukast.
Precautions
Care must be taken before using the montelukast. Tell your doctor or pharmacist if you are
- Allergic to aspirin
- Allergic to Non-steroidal anti-inflammatory drugs such as ibuprofen, naproxen, etc. Discontinue these medications while using montelukast.
- suffering from Phenylketonuria (PKU). Phenylalanine is present in chewable tablets of montelukast if the patients with Phenylketonuria are using the drug may lead to severe toxic symptoms.
- Suffering from liver disease.
- Pregnant or trying to get pregnant.
- If you feel the numbness of arms and legs, skin rashes, pain and swelling of sinuses because Montelukast drug may increase the level of eosinophils in the blood that leads to systemic vasculitis. tell your physician right away if you experience any of these symptoms.
Interaction of Montelukast with other drugs (Drug-drug interaction)
The therapeutic efficacy of montelukast is affected when used in combination with other drugs. Therefore tell your physician if you are already using other medications such as warfarin, abatacept, acetohexamide, acetaminophen, etc for various medical conditions.
1. Concomitant use of Montelukast and warfarin
Metabolism of warfarin is decreased when used in combination with montelukast.
2: Use of Montelukast with Abatacept
Metabolism of montelukast is increased when used in combination with abatacept.
3.Concomitant use of Montelukast and Acetaminophen
Metabolism of montelukast is decreased when used in combination with acetaminophen.
4. Concomitant use of Montelukast and Acetyl sulfisoxazole
Metabolism of montelukast is decreased when used in combination with acetyl sulfisoxazole.
5. Drug interaction with Acetylsalicylic acid
When montelukast is used in combination with acetylsalicylic acid, the metabolism of acetylsalicylic acid is increased.
6: Concomitant use of Montelukast and Acetohexamide
Metabolism of montelukast is decreased when using in combination with Acetohexamide
7: Concomitant use of Montelukast and Acipimox
When montelukast is used in combination with acipimox, severe toxic reactions will produce within the body such as rhabdomyolysis, myopathy, and myoglobinuria.
Storage of Montelukast
- The drug should be stored at room temperature
- Keep out of reach of children
- The drug should be protected for heat, moisture, and sunlight
- Tablets, oral granules, and chewable tablets should be stored in their original containers and sachet.
- Open the sachet of granules when you are ready to use the drug otherwise, moisture will contaminate the drug leading to decrease therapeutic efficacy.
Contraindications of Montelukast
Montelukast should be contraindicated in patients with a known history of hypersensitivity to the drug or any of its components. caution is also taken in patients suffering from phenylketonuria before using the phenylalanine containing formulation.
Sources:
- Montelukast Sodium
https://www.webmd.com/drugs/2/drug-6478-8277/montelukast-oral/montelukast-oral/details - Montelukast
https://medlineplus.gov/druginfo/meds/a600014.html - Montelukast
https://www.drugs.com/mtm/montelukast.html
