SINTRINE Oral granules Ref.[115333] Active ingredients: Montelukast

Patients should be advised never to use oral montelukast to treat acute asthma attacks, including status asthmaticus and to keep their usual appropriate rescue medication for this purpose readily available. SINTRINE ORAL GRANULES is not indicated for use in the reversal of bronchospasm in acute asthma attacks. If an acute attack occurs, a short-acting inhaled β-agonist should be used. Patients should seek their doctors' advice as soon as possible if they need more inhalations of short-acting β-agonists than usual.

SINTRINE ORAL GRANULES should not be used as monotherapy for the treatment and management of exercise-induced bronchospasm. Patients who have exacerbations of asthma after exercise should continue to use their usual regimen of inhaled beta-agonists as prophylaxis and have available for rescue a short-acting inhaled beta-agonist.

Montelukast should not be abruptly substituted for inhaled or oral corticosteroids. There are no data demonstrating that oral corticosteroids can be reduced when SINTRINE ORAL GRANULES is given concomitantly.

Renal Insufficiency

Since SINTRINE ORAL GRANULES and its metabolites are not excreted in the urine, the pharmacokinetics of SINTRINE ORAL GRANULES were not evaluated in patients with renal insufficiency. No dosage adjustment is recommended in these patients.

Patients on therapy with anti-asthma medicines including SINTRINE ORAL GRANULES may present with systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition which is often treated with systemic corticosteroid therapy. 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, medical practitioners should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. Patients who develop these symptoms should be reassessed and their treatment regimens evaluated.

Treatment with montelukast does not alter the need for patients with aspirin-sensitive asthma to avoid taking aspirin and other non-steroidal anti-inflammatory medicines.

Neuropsychiatric events such as behavioural changes, depression and suicidality have been reported in all age groups taking montelukast (see section 4.8). The symptoms may be serious and continue if the treatment is not withdrawn. Therefore the treatment with montelukast should be discontinued if neuropsychiatric symptoms occur during treatment.

Advise patients and/or caregivers to be alert for neuropsychiatric events and instruct them to notify their physician if these changes in behaviour occur.

SINTRINE ORAL GRANULES as an alternative treatment option to low-dose inhaled corticosteroids for mild, persistent asthma

Montelukast is not recommended as monotherapy in patients with moderate persistent asthma. The use of montelukast as an alternative treatment option to low-dose inhaled corticosteroids for children 2 to 5 years old with mild persistent asthma should only be considered for patients who do not have a recent history of serious asthma attacks that required oral corticosteroid use and who have demonstrated that they are not capable of using inhaled corticosteroids (see section 4.1). Mild persistent asthma is defined as asthma symptoms more than once a week but less than once a day, nocturnal symptoms more than twice a month but less than once a week, normal lung function between episodes. If satisfactory control of asthma is not achieved at follow-up (usually within one month), the need for an additional or different anti-inflammatory therapy based on the step system for asthma therapy should be evaluated. Patients should be periodically evaluated for their asthma control.

Information for Patients:

• Patients should be advised to take SINTRINE ORAL GRANULES daily as prescribed, even when they area symptomatic, as well as during periods of worsening asthma, and to contact their physicians if their asthma is not well controlled.
• Patients should be advised that SINTRINE ORAL GRANULES are not for the treatment of acute asthma attacks. They should have appropriate short-acting inhaled beta-agonist medication available to treat asthma exacerbations.
• Patients should be advised that, while using SINTRINE ORAL GRANULES, medical attention should be sought if short-acting inhaled bronchodilators are needed more often than usual, or if more than the maximum number of inhalations of short-acting bronchodilator treatment prescribed for a 24-hourperiod are needed.
• Patients receiving SINTRINE ORAL GRANULES should be instructed not to decrease the dose or stop taking any other anti-asthma medications unless instructed by a physician.
• Patients who have exacerbations of asthma after exercise should be instructed to continue to use their usual regimen of inhaled beta-agonists as prophylaxis unless otherwise instructed by their medical practitioner. All patients should have available for rescue a short-acting inhaled beta-agonist.
• Patients with known aspirin sensitivity should be advised to continue avoidance of aspirin or non-steroidal anti-inflammatory agents while taking SINTRINE ORAL GRANULES.

Montelukast may be administered with other therapies routinely used in the prophylaxis and chronic treatment of asthma. In medicine-interactions studies, the recommended clinical dose of montelukast did not have clinically important effects on the pharmacokinetics of the following medicinal products: theophylline, prednisone, prednisolone, oral contraceptives (ethinyl estradiol/norethindrone 35/1), terfenadine, digoxin and warfarin.

The area under the plasma concentration curve (AUC) for montelukast was decreased approximately 40% in subjects with co-administration of phenobarbital. Since montelukast is metabolised by CYP 3A4, 2C8, and 2C9, caution should be exercised, particularly in children, when montelukast is co-administered with inducers of CYP 3A4, 2C8, and 2C9, such as phenytoin, phenobarbital and rifampicin.

In vitro studies have shown that montelukast is a potent inhibitor of CYP 2C8. However, data from a clinical medicine interaction study involving montelukast and rosiglitazone (a probe substrate representative of medicinal products primarily metabolised by CYP 2C8) demonstrated that montelukast does not inhibit CYP 2C8 in vivo. Therefore, montelukast is not anticipated to markedly alter the metabolism of medicinal products metabolised by this enzyme (e.g., paclitaxel, rosiglitazone, and repaglinide).

In vitro studies have shown that montelukast is a substrate of CYP 2C8, and to a less significant extent, of 2C9, and 3A4. In a clinical drug-drug interaction study involving montelukast and gemfibrozil (an inhibitor of both CYP 2C8 and 2C9) gemfibrozil increased the systemic exposure of montelukast by 4.4-fold. No routine dosage adjustment of montelukast is required upon co-administration with gemfibrozil or other potent inhibitors of CYP 2C8, but the medical practitioner should be aware of the potential for an increase in adverse reactions.

Based on in vitro data, clinically important medicine interactions with less potent inhibitors of CYP 2C8 (e.g., trimethoprim) are not anticipated. Co-administration of montelukast with itraconazole, a strong inhibitor of CYP 3A4, resulted in no significant increase in the systemic exposure of montelukast.

Pregnancy

The safety of montelukast in pregnant and lactating women has not been established. SINTRINE ORAL GRANULES should not be used during pregnancy.

During worldwide marketing experience, congenital limb defects have been reported in offspring of women treated with SINTRINE ORAL GRANULES during pregnancy. A causal relationship between these events and SINTRINE ORAL GRANULES has not been established.

Lactation

Studies in rats have shown that montelukast is excreted in milk (see section 5.3). It is unknown whether montelukast/metabolites are excreted in human milk. SINTRINE ORAL GRANULES should not be used in breastfeeding mothers.

SINTRINE ORAL GRANULES has no or negligible influence on the ability to drive and use machines. However, individuals have reported drowsiness or dizziness.

Tabulated list of Adverse Reactions:

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website.

Suspected adverse reactions can also be reported directly to the HCR via the website: https://pvi1j.solutions.iqvia.com or the e-mail address, adverse.event.sac@sandoz.com.

Not applicable.