Montelukast Sandoz (IR): composition and form
One film-coated tablet contains 10 mg of montelukast. This is the adult strength: it is prescribed from the age of 15 upwards, and for younger ages montelukast has forms of its own — 5 mg chewable tablets for children aged 6 to 14, 4 mg ones for children aged 2 to 5, and 4 mg granules for children from six months to five years.
The tablet is taken once a day in the evening, regardless of food. The evening timing is stated outright in the product information and is not a recommendation to take or leave. The composition includes lactose, so it is not used in the rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome; there is less than 1 mmol of sodium per tablet, so it counts as "sodium-free".
How Montelukast Sandoz (IR) works
Montelukast belongs to the leukotriene receptor antagonists, and to grasp the point of that action one has to know what exactly it argues with. Cysteinyl leukotrienes — LTC4, LTD4 and LTE4 — are eicosanoids with a powerful inflammatory action; they are released by various cells, mast cells and eosinophil granulocytes among them. They bind to cysteinyl leukotriene receptors, and the type 1 receptor is present precisely in the human airways. What happens next depends on where those mediators have acted.
| Where | What cysteinyl leukotrienes do |
| Bronchi | cause bronchospasm and mucus secretion |
| Airway vessels | increase the permeability of the vessel wall |
| Cellular response | bring about an influx of eosinophil granulocytes |
| Nasal mucosa | are released after allergen exposure in both the early and the late phase |
| Nasal passages | in a provocation test they raise resistance, felt as congestion |
From this it is clear why one and the same medicine works in asthma and in allergic rhinitis alike: the mediator is shared and only the site of action differs. The type 1 receptor itself has been found not only in airway smooth muscle and macrophages but also on the surface of other pro-inflammatory cells — eosinophil granulocytes and some bone marrow stem cells — and that is why cysteinyl leukotrienes are tied to the pathophysiology of both diseases at once.
Indications
There are three indications, and the first is worded as adjunctive: the medicine is used in addition in mild and moderate asthma in patients in whom adequate control of symptoms cannot be achieved with inhaled corticosteroids and as-needed short-acting beta-agonists. Montelukast is therefore added to the existing regimen rather than replacing it.
The second indication follows from the first: in asthma patients for whom montelukast is indicated, it may additionally relieve the symptoms of seasonal allergic rhinitis. The wording is worth noticing: this is not a standalone indication in rhinitis but an accompanying benefit in someone already prescribed the medicine for asthma. The third indication stands apart — prevention of asthma in which the dominant feature is exercise-induced bronchoconstriction.
Administration and dosage
Adults and adolescents from 15 years — with asthma, or with asthma and accompanying seasonal allergic rhinitis — are given one 10 mg tablet a day in the evening. The therapeutic effect on asthma control measures appears within 24 hours. The medicine has to be taken both when symptoms are under control and during periods of exacerbation; this is set down separately, because the temptation to drop the medicine "on the good days" is particularly strong here. This tablet is not taken together with other products containing montelukast.
How the medicine fits into treatment already under way is described separately. It can be added to the patient's current regimen, including as a supplement to inhaled corticosteroids if those, together with as-needed short-acting beta-agonists, do not give adequate clinical control. But abruptly replacing inhaled corticosteroids with montelukast is not allowed. Children under 15 are not given this tablet: safety and efficacy in that age group have not been established, and other forms exist for the younger ones. The dose is the same for women and men.
Contraindications
The prohibition here is exactly one: hypersensitivity to the active substance or to any excipient. For a prescription medicine that is unusual, so it is more useful to look at the list from the other side — at the states in which the dose does not have to be changed.
No dose adjustment is needed in older patients. None is needed in renal failure. None is needed in mild and moderate hepatic impairment either. The single gap in that row is severe hepatic impairment: there are simply no data on such patients, and that is not a ban but an absence of information. The age limit on this particular tablet is likewise not a contraindication but a question of form: below 15 it is not this strength that is used, but the children's ones.
Special warnings and precautions
The main warning concerns not the composition but the way the medicine is used: oral montelukast is never used to treat an acute asthma attack, and the patient is warned of this separately. For an attack an inhaled short-acting beta-agonist is used, which should always be to hand; if more inhalations of it are needed than before, medical advice must be sought as soon as possible. Abruptly replacing inhaled or oral corticosteroids with montelukast is likewise not allowed, and there are no data that the dose of oral corticosteroids can be reduced while on montelukast. And one more thing, easy to forget: treatment with montelukast does not lift, for patients with aspirin-sensitive asthma, the ban on acetylsalicylic acid and other non-steroidal anti-inflammatory drugs.
Two warnings concern possible complications. The first is the rare cases of systemic eosinophilia in people receiving anti-asthma medicines, montelukast included, sometimes with clinical signs of vasculitis matching the picture of Churg-Strauss syndrome, usually treated with systemic corticosteroids. Those cases were at times associated with a reduction or withdrawal of oral corticosteroids. A causal link with leukotriene receptor antagonists has not been established, but doctors are advised to pay particular attention to eosinophilia, to the rash typical of vasculitis, to worsening pulmonary symptoms, to cardiac complications and to neuropathy; in such patients the treatment is reviewed. The second is the reports of neuropsychiatric disturbances in adults, adolescents and children receiving montelukast. Both patients and doctors should be aware of that possibility, and patients and those caring for them are asked to report the appearance of such disturbances to the doctor: the doctor then weighs afresh the risk and the benefit of continuing.
Interactions with other medicines
It is worth starting with what there is no need to fear. Montelukast can be taken together with other medicines used as standard in preventing and in the long-term treatment of asthma, and in studies it had no clinically significant effect on the pharmacokinetics of theophylline, prednisone, prednisolone, oral contraceptives with ethinylestradiol and norethindrone, terfenadine, digoxin and warfarin. A story of its own is CYP2C8: in vitro montelukast proved a strong inhibitor of it, but in a clinical study with rosiglitazone, the test substrate for that enzyme, inhibition in vivo was not confirmed. So no appreciable changes in the conversion of paclitaxel, rosiglitazone and repaglinide are to be expected, and with weaker CYP2C8 inhibitors such as trimethoprim no clinically significant interactions are expected at all.
What matters in the section comes to two points, both expressed in figures. Phenobarbital lowered the area under the montelukast concentration curve by about 40%: montelukast is metabolised by the CYP3A4, 2C8 and 2C9 isoenzymes, so with substances that raise their activity — phenytoin, phenobarbital, rifampicin — caution is needed, especially in children. The example of the opposite sign is gemfibrozil, an inhibitor of CYP2C8 and 2C9: it increased systemic exposure to montelukast 4.4-fold. Adjusting the dose when it is given with gemfibrozil or other strong CYP2C8 inhibitors is not necessary in routine practice, but the doctor should allow for the possibility of more frequent adverse reactions. Itraconazole, a strong CYP3A4 inhibitor, did not significantly increase systemic exposure to montelukast.
Pregnancy and breastfeeding
Animal studies showed no harmful effect on the course of pregnancy or on the development of the embryo and fetus. The limited data on use of the medicine in pregnancy do not point to a causal link between taking it and the malformations — of the limbs, for instance — rarely described worldwide after the medicine came to market. The wording here is cautious: not "safe", but "no link is visible on limited data". Hence the product information's conclusion: it may be used in pregnancy only where that is judged absolutely necessary.
With breastfeeding the picture is scantier still. Studies in rats showed that montelukast passes into milk. Whether montelukast and its metabolites pass into human milk is unknown. So the same condition applies here: use during breastfeeding only where it is judged absolutely necessary — and the decision is the doctor's, not the patient's.
Adverse reactions
Of the whole list, what deserves most attention are the psychiatric disturbances, because it is exactly those that a separate paragraph in the precautions section warns about. Uncommonly described are abnormal dreams including nightmares, insomnia, sleepwalking, irritability, anxiety, restlessness and agitation, including aggressive behaviour or hostility, and also depression. Very rarely: hallucinations, suicidal thoughts and behaviour. The uncommon reactions also include neurological ones: dizziness, drowsiness, paraesthesia or reduced sensation, seizures; tremor was recorded rarely.
In the clinical trials themselves, where montelukast was assessed in about 4000 adults with asthma from the age of 15, in 400 adults with asthma and seasonal allergic rhinitis and in 1750 children aged 6 to 14, only two reactions occurred more often than on placebo: headache and abdominal pain. The safety profile did not change with long treatment — up to two years in adults and up to a year in children. The rest is known from practice after the medicine reached the market. Very commonly these are upper respiratory tract infections; commonly, diarrhoea, nausea, vomiting, raised transaminase activity, rash and fever. Uncommonly there are hypersensitivity reactions up to anaphylaxis, nosebleed, dry mouth, dyspepsia, bruising, urticaria, itching, joint and muscle pain with cramps, weakness, fatigue, malaise and oedema. Rarely: an increased tendency to bleed, palpitations, angioedema. Very rarely: eosinophilic infiltration of the liver, Churg-Strauss syndrome, cholestatic, hepatocellular or mixed hepatitis, erythema nodosum and erythema multiforme.
Overdose
More is known about the real cases than about the treatment. After the medicine reached the market, and in clinical trials, acute overdose with doses up to 1000 mg was reported in adults and children — including about 61 mg per kilogram of body weight in a 42-month-old child. Clinical and laboratory observations matched the usual safety profile, and in most cases no adverse reactions were recorded at all. Of those recorded, the most frequent were abdominal pain, drowsiness, thirst, headache, vomiting and increased psychomotor activity — that is, the same as with ordinary use.
The planned studies give the same picture from the other side. In chronic bronchial asthma montelukast was given to patients for 22 weeks at doses up to 200 mg a day, and in short studies of about a week at up to 900 mg a day, with no clinically significant adverse effects. There is no detailed information on treating an overdose, and the product information names no specific measures. Nor has it been established whether montelukast is removed by peritoneal dialysis or haemodialysis.
How to get a prescription for Montelukast Sandoz (IR) online
Montelukast plays the part of an addition: it is prescribed not instead of inhalers but alongside them, when the inhalers alone are not enough. So what decides is not the severity of symptoms in itself but what you are already treated with and how well it works. At e-zdrowie.com you fill in a medical questionnaire, the doctor examines the answers and, if the medicine is suitable, issues an electronic prescription: the code arrives by message, and with it any Polish pharmacy will dispense the tablets.
In the questionnaire give your age — this strength is prescribed from 15 — and list the inhalers you use, both the regular ones and the reliever, saying how often. Write whether you get bronchospasm on exertion and whether you have seasonal allergic rhinitis: both points belong to the indications. Be sure to report aspirin-sensitive asthma if you have it, severe liver disease, and any psychiatric disturbance — anxiety, insomnia, depression, changes in behaviour — including any that arose earlier on other medicines. List separately the medicines that act on liver enzymes: phenytoin, phenobarbital, rifampicin and gemfibrozil. And remember the main rule: montelukast does not replace the rescue inhaler, which must stay with you.
