Simplaer (Tablets) Instructions for Use

Marketing Authorization Holder

Zentiva Saglik Urunleri Sanayi Ve Ticaret, A.S. (Turkey)

Manufactured By

Dr. Reddy’s Laboratories Ltd. (India)

Labeled By

ZENTIVA SAGLIK URUNLERI SANAYI VE TICARET, A.S. (Turkey)

ATC Code

R03DC03 (Montelukast)

Active Substance

Montelukast (Rec.INN registered by WHO)

Dosage Form

Simplaer

Film-coated tablets, 10 mg: 28 or 84 pcs.

Dosage Form, Packaging, and Composition

14 pcs. – blisters (2) – cardboard packs.
14 pcs. – blisters (6) – cardboard packs.

Clinical-Pharmacological Group

Leukotriene receptor antagonist. Drug for the treatment of bronchial asthma and allergic rhinitis

Pharmacotherapeutic Group

Leukotriene receptor antagonist

Pharmacological Action

Leukotriene receptor antagonist. Montelukast binds with high selectivity and affinity to CysLT₁ receptors (instead of other pharmacologically important airway receptors, such as prostanoid, cholinergic, or β-adrenergic receptors).

Montelukast inhibits the physiological actions of cysteinyl leukotrienes LTC₄, LTD₄, and LTE₄ by binding to CysLT₁ receptors without exerting any agonist activity on these receptors. Montelukast inhibits CysLT₁ receptors in the airway epithelium, thereby possessing the ability to inhibit bronchoconstriction induced by inhaled LTD₄ in patients with bronchial asthma.

A dose of 5 mg is sufficient to block LTD₄-induced bronchoconstriction.

Montelukast causes bronchodilation within 2 hours after oral administration and may add to the bronchodilation induced by beta₂-adrenergic agonists.

Pharmacokinetics

After oral administration, Montelukast is rapidly and almost completely absorbed from the gastrointestinal tract. In adults receiving doses of 5-10 mg, peak plasma concentrations (C_max) are achieved within 2-3 hours. The oral bioavailability is 64-73%.

The plasma protein binding of montelukast is more than 99%. The mean volume of distribution (V_d) is 8-11 L.

Moderate accumulation (approximately 14%) of the active substance in plasma is observed following once-daily dosing of 10 mg.

Montelukast is extensively metabolized in the liver. At therapeutic doses, the plasma concentrations of montelukast metabolites are undetectable at steady state in adults and children.

Isoenzymes CYP3A4 and CYP2C9 are involved in the metabolism of montelukast; at therapeutic concentrations, Montelukast does not inhibit CYP3A4, 2C9, 1A2, 2A6, 2C19, and 2D6 isoenzymes.

The half-life (T_1/2) of montelukast in young healthy adults ranges from 2.7 to 5.5 hours. The clearance of montelukast in healthy adults averages 45 mL/min. Following an oral dose, 86% is excreted in the feces over 5 days and less than 0.2% is excreted in the urine, confirming that Montelukast and its metabolites are excreted almost exclusively via the bile.

The pharmacokinetics of montelukast remain approximately linear following oral administration of doses greater than 50 mg.

Indications

Prophylaxis and long-term treatment of bronchial asthma, including: prevention of daytime and nighttime symptoms of the disease; treatment of asthma in patients with hypersensitivity to acetylsalicylic acid; prevention of exercise-induced bronchoconstriction.

Relief of daytime and nighttime symptoms of seasonal allergic rhinitis.

ICD codes

Dosage Regimen

Take orally, once daily at the same time each day, with or without food.

For adults and adolescents 15 years and older: take one 10 mg tablet daily.

For asthma prophylaxis and chronic treatment: administer in the evening.

For allergic rhinitis: administer at a time of day most convenient for the patient.

For exercise-induced bronchoconstriction: take at least two hours before exercise. Do not take another dose within 24 hours.

Do not use for the treatment of acute asthma attacks. Always have a short-acting inhaled beta2-agonist available for rescue.

Do not abruptly substitute montelukast for inhaled or oral corticosteroids; reduce corticosteroid dose gradually under medical supervision.

In patients with aspirin sensitivity, continue to avoid NSAIDs during treatment.

Adverse Reactions

Infections and infestations: very common – upper respiratory tract infections.

Blood and lymphatic system disorders: rare – increased tendency to bleed; frequency unknown – thrombocytopenia.

Immune system disorders: uncommon – hypersensitivity reactions, including anaphylaxis; very rare – eosinophilic hepatic infiltration.

Psychiatric disorders: uncommon – agitation, including aggressive behavior or hostility, anxiety, depression, disorientation, dream abnormalities, insomnia, psychomotor hyperactivity (including irritability, restlessness, and tremor), somnambulism, tic; rare – attention disturbance, memory impairment; very rare – hallucinations, suicidal thoughts and behavior (suicidality).

Nervous system disorders: uncommon – headache, dizziness, drowsiness, paresthesia/hypoesthesia, seizures.

Cardiac disorders: rare – palpitations.

Respiratory, thoracic and mediastinal disorders: uncommon – epistaxis; very rare – pulmonary eosinophilia.

Gastrointestinal disorders: common – diarrhea, nausea, vomiting; uncommon – dyspepsia, dry mouth; frequency unknown – abdominal pain, pancreatitis.

Hepatobiliary disorders: common – increased ALT and AST activity; very rare – hepatitis (including cholestatic, hepatocellular, and mixed-pattern liver injury).

Skin and subcutaneous tissue disorders: common – rash; uncommon – pruritus, urticaria, increased tendency to bruise; rare – angioedema; very rare – erythema nodosum, erythema multiforme.

Musculoskeletal and connective tissue disorders: uncommon – arthralgia, myalgia, including muscle cramps.

Renal and urinary disorders: frequency unknown – enuresis in children.

General disorders and administration site conditions: common – pyrexia; uncommon – asthenia (weakness)/fatigue, edema, thirst; in patients with asthma, rare – development of Churg-Strauss syndrome.

Contraindications

Hypersensitivity to montelukast; pediatric age – depending on the dosage form.

Use in Pregnancy and Lactation

During pregnancy, Montelukast should be used only if the potential benefit to the mother justifies the potential risk to the fetus, only under medical supervision, and only at the lowest effective doses.

There have been reports of congenital limb defects in newborns whose mothers took Montelukast during pregnancy. Most of these women also took other medications for asthma during pregnancy. A causal relationship between montelukast use and the occurrence of congenital limb defects has not been established.

It is not known whether Montelukast is excreted in human milk. Montelukast should not be used during lactation (breastfeeding).

Pediatric Use

Can be used in children for the indicated conditions, in age-appropriate recommended doses and dosage forms. It is necessary to strictly follow the instructions in the montelukast drug labeling regarding contraindications for the use of specific montelukast dosage forms in children of different ages.

Geriatric Use

Can be used in elderly patients for the indicated conditions in recommended doses and regimens.

Special Precautions

The efficacy of oral montelukast for the treatment of acute asthma attacks has not been established. Therefore, oral Montelukast is not recommended for the treatment of acute asthma attacks. Patients should be instructed to always have emergency medication for relief of asthma attacks (short-acting inhaled beta₂-agonists) with them.

Montelukast should not be abruptly discontinued during an asthma exacerbation or when the need for emergency medication (short-acting inhaled beta₂-agonists) arises.

Patients with known aspirin sensitivity and hypersensitivity to other NSAIDs should not take these medications during treatment with montelukast, because although Montelukast improves respiratory function in patients with allergic asthma, it cannot completely prevent NSAID-induced bronchoconstriction in these patients.

The dose of inhaled corticosteroids used concomitantly with montelukast may be reduced gradually under medical supervision; however, montelukast should not be abruptly substituted for inhaled or oral corticosteroids.

Effect on ability to drive and operate machinery

Some patients have experienced drowsiness and dizziness during treatment with montelukast. If these symptoms occur, patients should be advised not to drive vehicles or engage in other activities requiring concentration and rapid psychomotor reactions.

Drug Interactions

Concomitant administration with phenobarbital decreased the AUC of montelukast by approximately 40% (no dosage adjustment for montelukast is recommended).

In vitro studies have shown that Montelukast inhibits the CYP2C8 isoenzyme; however, in an in vivo drug interaction study of montelukast and rosiglitazone (which is metabolized by CYP2C8), no evidence of montelukast inhibiting CYP2C8 was observed. Therefore, no clinically significant effect of montelukast on CYP2C8-mediated metabolism of drugs such as paclitaxel, rosiglitazone, and repaglinide is anticipated in clinical practice.

In vitro studies indicate that Montelukast is a substrate for CYP2C8, 2C9, and 3A4 isoenzymes. Data from a clinical drug interaction study involving montelukast and gemfibrozil (an inhibitor of both CYP2C8 and 2C9 isoenzymes) demonstrate that gemfibrozil increased the systemic exposure of montelukast by 4.4-fold.

Coadministration of itraconazole, a potent CYP3A4 inhibitor, with gemfibrozil and montelukast did not further increase the systemic exposure of montelukast.

Montelukast is a rational addition to monotherapy with bronchodilators when the latter do not provide adequate control of asthma. Following achievement of a therapeutic effect with montelukast, a gradual reduction in the dose of bronchodilators can be initiated.

The use of montelukast provides additional therapeutic effect in patients receiving inhaled corticosteroids. Once clinical stability is achieved, a gradual reduction of the corticosteroid dose under medical supervision may be attempted. In some cases, complete discontinuation of inhaled corticosteroids may be possible; however, abrupt replacement of inhaled corticosteroids with Montelukast is not recommended.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.