Montelukast Sandoz: composition and pharmaceutical form
One chewable tablet contains 4 mg or 5 mg of montelukast as montelukast sodium, and one film-coated tablet contains 10 mg. The three strengths correspond to three age groups, and that is the main thing to know when choosing a pack.
Chewable tablets are chewed before swallowing. The 4 mg and 5 mg tablets contain aspartame, a source of phenylalanine, so they may be harmful in phenylketonuria; the 10 mg tablet contains lactose and is unsuitable in rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption syndrome.
How Montelukast Sandoz works
Cysteinyl leukotrienes — LTC4, LTD4, LTE4 — are eicosanoids with strong inflammatory activity released by various cells, including mast cells and eosinophil granulocytes. These important mediators, which promote the development of bronchial asthma, bind to cysteinyl leukotriene receptors. The type 1 receptor is found in the human airways — in airway smooth muscle cells and in macrophages — and on the surface of other pro-inflammatory cells, including eosinophil granulocytes and some bone marrow stem cells.
Cysteinyl leukotrienes are linked to the pathophysiology of asthma and of allergic inflammation of the nasal mucosa. In asthma, leukotriene-dependent effects include bronchoconstriction, mucus secretion, increased vascular permeability and the influx of eosinophil granulocytes. In allergic rhinitis they are released by the nasal mucosa after exposure to an allergen, in both the early and the late phase of the reaction; intranasal challenge with them showed increased resistance in the nasal passages with symptoms of nasal obstruction.
Indications
All three strengths are used in mild and moderate bronchial asthma as add-on treatment in patients in whom adequate symptom control cannot be achieved with inhaled corticosteroids and short-acting β-agonists as needed. Only the age differs: 4 mg from 2 to 5 years, 5 mg from 6 to 14 years, 10 mg from 15 years.
There are also two additional prescribing scenarios.
- instead of low doses of inhaled corticosteroids in mild persistent asthma, in patients who have not had severe attacks requiring oral corticosteroids in the recent period and who are unable to use inhaled corticosteroids correctly;
- for the prevention of asthma in which exercise-induced bronchoconstriction is the predominant feature — for the 4 mg strength this means patients aged 2 years and above;
- in asthma patients for whom montelukast is indicated, the 10 mg strength may additionally relieve the symptoms of seasonal allergic rhinitis.
Method of use and dosage
The medicine is taken once a day in the evening, and this rule is common to all strengths. The therapeutic effect on asthma control measures is apparent on the first day, but dosing continues both when symptoms are controlled and during exacerbations.
| Age | Dose |
| From 6 months to 5 years | 4 mg granules — a separate form for children who find the chewable tablet difficult |
| 2–5 years | one 4 mg chewable tablet a day in the evening, an hour before food or two hours after it; taken under adult supervision |
| 6–14 years | one 5 mg chewable tablet a day in the evening, an hour before food or two hours after it |
| 15 years and above | one 10 mg film-coated tablet a day in the evening, regardless of meals |
| Renal impairment, mild to moderate hepatic impairment, old age | no dose adjustment is required; there are no data on severe hepatic impairment |
| Men and women | the dose is the same |
The 4 mg strength is not used in children under 2, the 5 mg strength under 6 and the 10 mg strength under 15: safety and efficacy in those groups have not been established. Montelukast is not recommended as monotherapy in moderate persistent asthma, and replacing low doses of inhaled corticosteroids with it in mild asthma is considered only under the conditions described above. Mild persistent asthma is defined by symptoms more than once a week but less than once a day, night symptoms more than twice a month but less than once a week, and normal lung function between episodes. If by the review visit, usually within a month, symptoms cannot be satisfactorily controlled, additional or different anti-inflammatory treatment is considered. In exercise-induced asthma in children aged 2–5, the condition is assessed after 2–4 weeks. The medicine must not be taken together with other products containing montelukast.
Contraindications
Hypersensitivity to the active substance or to any excipient. A single item, which is unusual for a prescription medicine.
Far more important is the restriction on how it is used: montelukast is never taken orally to stop an acute asthma attack. In an attack an inhaled short-acting β-agonist is used, which the patient should have to hand, and if more of it than usual is needed the patient should see a doctor as soon as possible. Inhaled or oral corticosteroids must not be abruptly replaced with montelukast either.
Special warnings and precautions
There are no data showing that the dose of oral corticosteroids can be reduced when montelukast is taken alongside them. If the medicine has been added to inhaled corticosteroids, those are not swapped for it abruptly: montelukast is introduced into the existing treatment regimen.
- rarely, in patients taking anti-asthma medicines including montelukast, systemic eosinophilia may occur, sometimes with clinical signs of vasculitis consistent with a diagnosis of Churg-Strauss syndrome, which is often treated with systemic corticosteroids;
- cases of this syndrome were usually, though not always, associated with a reduction or withdrawal of the oral corticosteroid, and a link between the leukotriene receptor antagonist and the syndrome can neither be excluded nor confirmed;
- the doctor should pay particular attention if eosinophilia, a rash of vascular origin, worsening pulmonary symptoms, cardiac complications or neuropathy appear: such a patient is examined thoroughly and the treatment regimen reassessed;
- in aspirin-sensitive asthma, despite treatment with montelukast, acetylsalicylic acid and other non-steroidal anti-inflammatory drugs must still be avoided;
- safety and efficacy in patients under 2 years have not been established.
Montelukast is not expected to affect the ability to drive or operate machinery, though somnolence has very rarely been reported. The mind deserves separate attention: the list of adverse reactions includes sleep disturbances, nightmares, agitation, aggressive behaviour, depression and — very rarely — suicidal thinking and behaviour, so any change in mood or behaviour, especially in a child, should be reported to the doctor at once.
Interaction with other medicines
Montelukast can be used together with other medicines usually given for the prevention and long-term treatment of asthma. In interaction studies the recommended clinical dose of montelukast did not significantly affect the pharmacokinetics of theophylline, prednisone and prednisolone, oral contraceptives with ethinylestradiol and norethindrone in a 35:1 ratio, terfenadine, digoxin and warfarin.
- in patients taking phenobarbital at the same time, the area under the montelukast concentration-time curve fell by about 40%;
- montelukast is metabolised with the involvement of the CYP3A4 isoenzyme, so caution is needed — particularly in children — when it is given with inducers of that isoenzyme: phenytoin, phenobarbital and rifampicin;
- in vitro montelukast proved a potent inhibitor of CYP2C8, but a clinical interaction study with rosiglitazone — a representative substrate of drugs metabolised mainly by that enzyme — showed that in vivo it does not inhibit it;
- montelukast is therefore not expected to change significantly the metabolism of medicines that go through CYP2C8, such as paclitaxel, rosiglitazone and repaglinide.
The practical conclusion from this list is simple: montelukast itself interferes little with other drugs' pharmacokinetics, while its own concentration falls appreciably alongside inducers of liver enzymes. It is that combination, not the reverse, that calls for the doctor's attention.
Pregnancy and breastfeeding
Animal studies show no harmful effect on the course of pregnancy or on embryonic or fetal development. Limited data from the available databases on use during pregnancy do not point to a causal relationship between taking montelukast and the occurrence of malformations, for example limb defects, which have rarely been described worldwide after marketing.
Montelukast may be used during pregnancy only where it is judged absolutely necessary. Studies in rats show that montelukast passes into milk; whether it passes into human breast milk is not known. In breastfeeding women the medicine is used, again, only where absolutely necessary.
Adverse reactions
Montelukast was evaluated in clinical trials as follows: 10 mg tablets in about 4000 adults with asthma aged 15 and over, 10 mg tablets in about 400 adults with asthma and seasonal allergic rhinitis, and 5 mg tablets in about 1750 children with asthma aged 6–14. More often than on placebo, patients reported headache and abdominal pain. The safety profile did not change with long-term treatment — up to two years in adults and up to a year in children aged 6–14.
- very common after marketing: upper respiratory tract infection; common: diarrhoea, nausea, vomiting, raised aminotransferase activity, rash, fever;
- uncommon: hypersensitivity reactions including anaphylaxis, dizziness, somnolence, paraesthesia or hypoaesthesia, seizures, nosebleed, dry mouth, dyspepsia, bruising, urticaria, itching, joint and muscle pain including muscle cramps, asthenia and fatigue, malaise, oedema;
- psychiatric disturbances, uncommon: abnormal dreams including nightmares, insomnia, sleepwalking, irritability, anxiety, restlessness, agitation including aggressive behaviour or hostility, depression;
- rare: increased bleeding tendency, tremor, palpitations, angioedema;
- very rare: eosinophilic infiltration of the liver, hallucinations, suicidal thinking and behaviour, Churg-Strauss syndrome, hepatitis including cholestatic, hepatocellular and mixed-pattern liver injury, erythema nodosum, erythema multiforme.
The neuropsychiatric events on this list deserve a separate conversation with the doctor: they are uncommon but noticeable and reversible on withdrawal, and in children they are easier to miss, because a child does not always connect altered sleep or mood with a medicine. Raised aminotransferases, by contrast, are usually symptomless and show up in blood tests.
Overdose
There is no detailed information on the treatment of montelukast overdose. In chronic asthma studies montelukast was given to patients for 22 weeks at doses of up to 200 mg a day, and in short studies for about a week at doses of up to 900 mg a day, without clinically significant adverse effects.
There are reports of acute overdose after marketing and in clinical trials: they involved doses of up to 1000 mg 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 safety profile in adults and children, and in most overdose cases no adverse effects were recorded. The most common of those recorded were abdominal pain, somnolence, thirst, headache, vomiting and increased psychomotor activity. Whether montelukast is removed by peritoneal dialysis or haemodialysis is not known.
How to get a prescription for Montelukast Sandoz online
The medicine is prescription-only, and the first thing the doctor will establish is the patient's age and the drug's role in the regimen: an addition to inhaled corticosteroids, a replacement for their low doses in mild asthma, or prevention of exercise-induced bronchoconstriction. Both the strength and which medicines stay in the regimen follow from that.
It is worth describing what controls the asthma at present and how often the rescue inhaler is needed, whether there have been severe attacks with oral corticosteroids recently, and whether seasonal allergic rhinitis and aspirin-sensitive asthma are present. Phenylketonuria is reported separately — because of the aspartame in the chewable tablets — along with galactose intolerance because of the lactose in the 10 mg tablet, pregnancy and breastfeeding, liver disease, and the use of phenytoin, phenobarbital or rifampicin. The doctor will assess these circumstances during the online consultation and, if there are no contraindications, will issue an electronic prescription.
