Singular, 4 mg 28 pcs

Bronchospasm, Bronchial Asthma

• Prevention and long-term treatment of bronchial asthma in children aged 2 years and older: To control daytime and nighttime symptoms of the disease;

• Relieving symptoms of allergic rhinitis in children 2 years of age and older.

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Active ingredient

Composition

How to take, the dosage

One time per day regardless of meals.

In the treatment of bronchial asthma, Singular® should be taken in the evening.

In the treatment of allergic rhinitis, the drug can be taken at any time of the day if the patient wishes.

Patients with bronchial asthma and allergic rhinitis should take 1 tablet of Singular® once daily in the evening.

Children 2 to 5 years of age

In bronchial asthma and/or allergic rhinitis, 1 chewable tablet 4 mg daily.

General recommendations

The therapeutic effect of Singulair® on bronchial asthma indices develops within the first day. The patient should continue to take Singular® both during the period of achieving control of bronchial asthma symptoms and during periods of exacerbation of bronchial asthma.

In elderly patients, patients with renal insufficiency, and patients with mild to moderate impairment of liver function, as well as depending on gender, no special dose adjustment is required.

Prescribing Singular® concomitantly with other bronchial asthma treatment

The drug Singular® may be added to patient treatment with bronchodilators and inhaled GCS.

Interaction

The drug Singulair® may be administered together with other drugs that are usually used for the prevention and long-term treatment of bronchial asthma and/or treatment of allergic rhinitis. The recommended therapeutic dose of montelukast had no clinically significant effect on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (ethinylestradiol/norethisterone 35/1), terfenadine, digoxin and warfarin.

The AUC of montelukast is decreased by about 40% when concomitant administration of phenobarbital, and this does not require changes in the dosing regimen of Singulair®.

In in vitro studies, montelukast was found to inhibit the CYP 2C8 isoenzyme of the cytochrome P450 system, but an in vivo drug interaction study of montelukast and rosiglitazone (metabolized involving the CYP 2C8 isoenzyme of the cytochrome P450 system) showed that montelukast did not inhibit the CYP 2C8 isoenzyme. Thus, no effect of montelukast on CYP 2C8-mediated metabolism of drugs (e.g., paclitaxel, rosiglitazone, repaglinide) is expected.

In vitro studies have shown that montelukast is a substrate of the CYP2C8 isoenzymes. 2C9 and 3A4. Data from a clinical drug interaction study of montelukast and gemfibrozil (an inhibitor of both CYP2C8 and 2C9) demonstrate that gemfibrozil increases the systemic effect of montelukast 4.4-fold.

The co-administration of itraconazole, a potent CYP3A4 inhibitor, together with gemfibrozil and montelukast did not result in an additional increase in the systemic effect of montelukast. The effect of gemfibrozil on the systemic effects of montelukast cannot be considered clinically significant based on safety data when used at doses greater than the approved dose of 10 mg for adult patients (for example, no clinically significant adverse effects were observed when used at a dose of 200 mg/day for adult patients for 22 weeks and up to 900 mg/day for approximately one week).

Hence, no dose adjustment of montelukast is required when coadministered with gemfibrozil. In vitro studies do not suggest clinically significant drug interactions with other known CYP2C8 inhibitors (e.g., trimethoprim). In addition, co-administration of montelukast with itraconazole alone did not significantly increase the systemic effect of montelukast.

Combined treatment with bronchodilators

The drug Singulair® is a reasonable adjunct to monotherapy with bronchodilators if the latter do not adequately control bronchial asthma. When therapeutic effect of treatment with Singulair® has been achieved, a gradual reduction in the dose of bronchodilators may be initiated.

Combined treatment with inhaled glucocorticosteroids

The treatment with Singular® provides additional therapeutic benefit to patients who use inhaled glucocorticosteroids. Once the condition has stabilized, a gradual reduction in the dose of the glucocorticosteroid under medical supervision may begin. In some cases, complete withdrawal of inhaled glucocorticosteroids is acceptable; however, abrupt substitution of inhaled glucocorticosteroids for Singular® is not recommended.

Special Instructions

The efficacy of Singular® for oral administration with respect to the treatment of acute attacks of bronchial asthma has not been established, therefore, Singular® tablets are not recommended for the treatment of acute attacks of bronchial asthma. Patients should be instructed to always carry emergency medications for bronchial asthma attacks (short-acting inhaled beta-2-agonists).

The use of the drug Singular® should not be discontinued during an asthma exacerbation and the need to use emergency medicines for relieving attacks (short-acting inhaled beta-2-agonists).

Patients with confirmed allergies to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs (NSAIDs) should not take these drugs during treatment with Singular® , since Singular®, while improving respiratory function in patients with allergic bronchial asthma, cannot completely prevent bronchoconstriction caused by NSAIDs.

The dose of inhaled glucocorticosteroids used concomitantly with Singular® may be decreased gradually under medical supervision; however, abrupt replacement of inhaled or oral glucocorticosteroids with Singular® should not be performed.

Psychoneurological disorders have been described in patients who have taken Singulair® (see section “Side effects”). Given that these symptoms may have been caused by other factors, it is unknown whether they are related to the administration of Singulair®. The physician should discuss these NIHs with the patients and/or their parents/guardians. Patients and/or their parents/guardians should be advised that if such symptoms occur, it is important to inform the treating physician.

In rare cases, patients receiving anti-asthmatic medications, including leukotriene receptor antagonists, have experienced one or more of the following: eosinophilia, rash, worsening of pulmonary symptoms, cardiac complications and/or neuropathy, sometimes diagnosed as Churg-Strauss syndrome, systemic eosinophilic vasculitis.

These cases have sometimes been associated with dose reductions or withdrawal of oral glucocorticosteroid therapy. Although a causal relationship between these AFs and therapy with leukotriene receptor antagonists has not been established, caution should be exercised in patients treated with Singulair®: appropriate clinical monitoring should be performed in these patients.

The drug Singular® 10 mg film-coated tablets contain lactose monohydrate. Patients with a rare form of hereditary galactose intolerance, congenital lactase deficiency or glucose-galactose malabsorption should not take the preparation Singular® 10 mg film-coated tablets.

The use in elderly patients

There are no differences in the age-related efficacy and safety profiles of Singulair®.

Impact on driving ability :

The administration of Singular® is not expected to affect the ability to drive vehicles and operate machinery. However, individual reactions to the drug may vary. Some side effects (such as dizziness and somnolence), which have been reported to occur very rarely with Singular® , may affect the ability of some patients to drive vehicles and operate machinery.

Contraindications

Side effects

Children 2 to 5 years of age with bronchial asthma

The clinical trials of Singulair® enrolled 573 patients aged 2 to 5 years. In a 12-week placebo-controlled clinical trial, the only adverse event (AE) evaluated as drug-related was thirst, observed in >1% of patients taking Singulair® and more frequently than in the placebo group. Differences in the frequency of this NIH between the two treatment groups were statistically insignificant.

A total of 426 patients aged 2 to 5 years were treated with Singulair® for at least 3 months. 230 were treated for 6 months or longer, and 63 patients were treated for 12 months or longer. There was no change in the NOI profile with longer treatment.

Children aged 2 to 14 years with seasonal allergic rhinitis

A 280 patients aged 2 to 14 years participated in a 2-week placebo-controlled clinical trial using Singular® for the treatment of seasonal allergic rhinitis. The drug Singular® was taken by patients once a day in the evening and was generally well tolerated; the safety profile of the drug was similar to that of placebo.

In this clinical trial, there were no reported NTs that were considered to be related to taking the drug, observed in ?1% of patients taking Singulair® and more frequently than in the group of patients taking placebo.

Children aged 6 to 14 years with bronchial asthma

The safety profile of the drug in children was generally similar to that in adults and comparable to that of placebo.

In an 8-paediatric placebo-controlled clinical trial, the only NIH assessed as related to drug ingestion observed in >1% of patients taking Singulair® and more frequently than in the placebo-treated group was headache.

The difference in frequency between the two treatment groups was statistically insignificant. In the pacing studies, the safety profile in patients in this age group was consistent with the previously described safety profile of Singulair®. There was no change in the NS profile with longer treatment (more than 6 months).

Adults and children 15 years of age and older with bronchial asthma

In two 12-week placebo-controlled clinical trials with a similar design, the only NTs assessed as related to drug administration observed in ?1% of patients taking Singulair® and more frequently than in the placebo group were abdominal pain and headache.

The differences in the frequency of these NIHs between the two treatment groups were statistically insignificant. The NJ profile did not change with longer treatment (for 2 years).

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

Singulair® was taken by patients once daily in the morning or evening and was generally well tolerated; the safety profile of the drug was similar to that of placebo. In placebo-controlled clinical trials there were no reported NTs that were considered to be related to taking the drug, observed in ?1% of patients taking Singulair® and more frequently than in the group of patients taking placebo.

In a 4-week placebo-controlled clinical trial, the safety profile of the drug was similar to that in 2-week studies. The incidence of somnolence when taking the drug was similar to that of placebo in all studies.

Adults and children 15 years of age and older with year-round allergic rhinitis

Singulair® was taken by patients once daily and was generally well tolerated. The safety profile of the drug was similar to the safety profile observed in patients with seasonal allergic rhinitis and when taking placebo.

In these clinical trials, there were no reported NTs that were considered to be related to taking the drug, observed in 21% of patients taking Singulair® and more frequently than in the group of patients taking placebo. The incidence of drowsiness was the same with the drug as with placebo.

A generalized analysis of clinical trial results

A generalized analysis of 41 placebo-controlled clinical trials (35 studies involving patients aged 15 years or older; 6 studies involving patients aged 6 to 14 years) using validated suicide assessment methods was performed. Among the 9,929 patients who took Singulair® and the 7,780 patients who took placebo in these studies, one patient with suicidal tendencies was identified in the patient group who took Singulair®. There were no suicides, suicide attempts, or other preparations indicating suicidal behavior in either treatment group.

Separately, a pooled analysis of 46 placebo-controlled clinical trials (35 studies involving patients aged 15 years or older; 11 studies involving patients aged 3 months to 14 years) was conducted to assess adverse behavioral effects (ABEs). Among I 1,673 patients taking Singulair® and 8,827 patients taking placebo in these studies, the percentage of patients with at least one NPE was 2.73% among those taking Singulair® and 2.27% among those taking placebo: the odds ratio was 1.12(95% confidence interval [0.93; 1.361).

During post-registration use of the drug, the following identified adverse events were reported:

infectious and parasitic diseases: upper respiratory tract infections;

Blood and lymphatic system disorders: increased susceptibility to bleeding, thrombocytopenia;

immune system disorders: hypersensitivity reactions, including anaphylaxis, very rare (< 1 /10000) eosinophilic liver infiltration;

mental disorders: agitation, including aggressive behavior or hostility, anxiety, depression, disorientation, attention disorders, abnormal dreams, hallucinations, insomnia, memory disturbances, psychomotor activity (including irritability, restlessness and tremor), somnambulism, suicidal thoughts and behavior (suicidality);

Nervous system disorders: dizziness, somnolence, paresthesia/hypoesthesia, very rare (< 1/10000) seizures;

cardiac disorders: palpitations;

respiratory, thoracic and mediastinal disorders: nasal bleeding, pulmonary eosinophilia;

gastrointestinal tract disorders: diarrhea, dyspepsia, nausea, vomiting, pancreatitis;

liver and biliary tract disorders: Increased alanine aminotransferase (ALT) and aspartate aminotransferase (ACT) activity in blood, very rare (< 1 /10000) hepatitis (including cholestatic, hepatocellular and mixed liver lesions);

Heat and subcutaneous tissue disorders: angioneurotic edema, tendency to form hematomas, erythema nodosa, erythema multiforme, itching, rashes, urticaria;

Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, including muscle cramps:

Renal and urinary tract disorders: enuresis in children;

General disorders and disorders at the site of administration: asthenia (weakness)/fatigue, edema, pyrexia.

Overdose

There is no specific information on the treatment of overdose with Singulair®. Overdose symptoms were not observed in clinical studies of long-term (22 weeks) treatment of adult patients with bronchial asthma with daily doses of Singular® up to 200 mg, or in short (about 1 week) clinical studies with daily doses up to 900 mg.

There have been cases of acute overdose (administration of at least 1000 mg of the drug per day) with Singular® during the post-registration period and during clinical trials in adults and children. Clinical and laboratory data demonstrated comparable safety profiles of Singulair® in children, adults and elderly patients.

The most common side effects were thirst, drowsiness, vomiting, psychomotor agitation, headache and abdominal pain. These side effects are consistent with the safety profile of Singulair®.

The treatment in case of acute overdose is symptomatic.

There are no data on the effectiveness of peritoneal dialysis or hemodialysis of montelukast.

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