Cetriluc

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT CETRILUK (CETRILUK)

Composition:

Active substances: montelukast, levocetirizine;

1 tablet contains montelukast sodium equivalent to montelukast 10 mg, levocetirizine dihydrochloride 5 mg;

Excipients: lactose monohydrate; microcrystalline cellulose; sodium croscarmellose; hypromellose; low-substituted hydroxypropylcellulose; magnesium stearate; film coating Opadry white OY 58900 (film coating composition: hypromellose, titanium dioxide (E 171), polyethylene glycol).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: biconvex, round-shaped, smooth on both sides, film-coated tablets, white to almost white in color. Cross-section from almost white to greenish-yellow in color.

Pharmacotherapeutic group.

Agents acting on the respiratory system. Medicinal products for the treatment of obstructive airway diseases. Leukotriene receptor antagonists. Montelukast in combination with other medicinal agents. ATC code R03DC53.

Pharmacological Properties

Pharmacodynamics

Levocetirizine

Levocetirizine is the active, stable R-enantiomer of cetirizine and belongs to the class of competitive histamine antagonists. Its pharmacological action is mediated through blockade of H1-histamine receptors.

Binding studies have demonstrated that levocetirizine has high affinity for human H1 receptors (Ki = 3.2 nmol/L). The affinity of levocetirizine is twice that of cetirizine (Ki = 6.3 nmol/L). Levocetirizine dissociates from H1 receptors with a half-life of 115±38 minutes. After single-dose administration, receptor binding of levocetirizine was 90% at 4 hours and 57% at 24 hours.

Pharmacodynamic studies in healthy volunteers showed that half the dose of levocetirizine has comparable activity to cetirizine in terms of both skin and nasal responses.

Montelukast

Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are potent inflammatory eicosanoids released by various cells, including mast cells and eosinophils. These key mediators of asthmatic reactions bind to cysteinyl leukotriene receptors (CysLT). The CysLT type 1 receptor (CysLT1) is located in the human airways (including airway smooth muscle cells and airway macrophages) and on other proinflammatory cells (including eosinophils and certain myeloid lineage bone marrow stem cells). CysLTs are implicated in the pathophysiology of both asthma and allergic rhinitis. In asthma, leukotriene-mediated effects include bronchoconstriction, mucus secretion, vascular permeability, and eosinophil influx. In allergic rhinitis, CysLT protein is released from nasal mucosa following allergen exposure during both early and late-phase reactions, contributing to the development of allergic rhinitis symptoms. Studies have shown that intranasal administration of CysLT increases nasal airway resistance and exacerbates nasal congestion symptoms.

Montelukast, administered orally, is an active compound that binds selectively and with high affinity to CysLT1 receptors.

Clinical studies have demonstrated that montelukast at a dose of 5 mg inhibits bronchoconstriction induced by inhaled LTD4. Bronchodilation was observed for up to 2 hours after oral administration, and this effect was additive to bronchodilation caused by β-agonists. Montelukast treatment suppressed both early and late phases of bronchoconstriction induced by antigen stimulation. Compared to placebo, montelukast reduced peripheral blood eosinophil counts in both adult and pediatric patients. In a separate study, montelukast significantly reduced eosinophil counts in the airways (measured in sputum) and in peripheral blood, and improved clinical control of asthma.

Pharmacokinetics

Levocetirizine

The pharmacokinetics of levocetirizine are linear, dose- and time-independent, and exhibit low interpatient variability. The pharmacokinetic profile following administration of a single enantiomer is identical to that observed with cetirizine. No chiral inversion occurs during absorption or elimination.

Absorption. Levocetirizine is rapidly and extensively absorbed after oral administration. Peak plasma concentration is reached within 0.9 hours after intake. Steady state is achieved within 2 days. Peak concentrations typically reach 270 ng/mL and 308 ng/mL after single and multiple doses of 5 mg once daily, respectively. The extent of absorption is dose-independent. Food does not affect the overall extent of absorption, but it reduces the maximum concentration (Cmax) and delays its attainment.

Distribution. There are no data available on the distribution of the drug in human tissues or on its ability to cross the blood-brain barrier. In animal studies, the highest concentrations were observed in the liver and kidneys, while the lowest were found in central nervous system tissues. Distribution of levocetirizine is limited, with a volume of distribution of 0.4 L/kg. Plasma protein binding in humans is 90%.

Metabolism. In humans, metabolism accounts for less than 14% of the administered dose, suggesting that differences due to genetic polymorphism or concomitant use of hepatic enzyme inhibitors are likely to be minimal. Metabolic pathways include aromatic oxidation, N- and O-dealkylation, and conjugation with taurine. Dealkylation is primarily mediated by cytochrome CYP3A4, while aromatic oxidation involves multiple and/or undefined CYP isoenzymes. Levocetirizine does not affect the activity of cytochrome isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 at concentrations significantly exceeding those achieved after a 5 mg oral dose. Due to its low metabolic rate and lack of inhibitory potential, drug interactions between levocetirizine and other substances (and vice versa) are unlikely.

Excretion. The drug is eliminated via two pathways: glomerular filtration and active tubular secretion. The elimination half-life (T1/2) in plasma in adults is 7.9+1.9 hours. The elimination half-life is shorter in younger children. The mean apparent total clearance in adults is 0.63 mL/min/kg. Levocetirizine and its metabolites are primarily excreted in urine (on average, 85.4% of the administered dose). Only 12.9% of the administered dose is excreted in feces.

Patients with renal impairment. Apparent total clearance of levocetirizine correlates with creatinine clearance. Therefore, dosing intervals should be adjusted in patients with moderate to severe renal impairment based on creatinine clearance. In patients with end-stage renal disease and anuria, total clearance is reduced by approximately 80% compared to individuals without renal impairment. The amount of levocetirizine removed during a standard 4-hour hemodialysis session is less than 10%.

Montelukast

Absorption. Montelukast is rapidly absorbed after oral administration. In adults, following administration of 10 mg film-coated tablets on an empty stomach, the mean peak plasma concentration (Cmax) is reached within 3 hours (Tmax). Mean oral bioavailability is 64%. Food does not affect bioavailability or Cmax when administered orally. Safety and efficacy have been confirmed in clinical trials where 10 mg film-coated tablets were administered regardless of food intake.

For chewable tablets (5 mg), the Cmax in adults was achieved within 2 hours after administration on an empty stomach. Mean oral bioavailability was 73% and decreased to 63% with a standard meal.

Distribution. Over 99% of montelukast is bound to plasma proteins. The steady-state volume of distribution averages between 8 and 11 liters. In rat studies using radiolabeled montelukast, penetration across the blood-brain barrier was minimal. Additionally, concentrations of radiolabeled drug in all other tissues 24 hours after dosing were also minimal.

Metabolism. Montelukast is extensively metabolized. In studies using therapeutic doses, metabolite concentrations in plasma at steady state in adults and pediatric patients were not detectable.

Cytochrome P450 2C8 is the primary enzyme involved in montelukast metabolism. Cytochromes CYP3A4 and 2C9 play a minor role. However, itraconazole (a CYP3A4 inhibitor) did not alter the pharmacokinetic parameters of montelukast in healthy volunteers receiving 10 mg daily. In vitro studies using human liver microsomes showed that therapeutic plasma concentrations of montelukast do not inhibit cytochrome P450 enzymes: 3A4, 2C9, 1A2, 2A6, 2C19, or 2D6. The contribution of metabolites to the therapeutic effect of montelukast is negligible.

Excretion. Plasma clearance of montelukast in healthy adult volunteers averages 45 mL/min. After oral administration of radiolabeled montelukast, 86% is excreted in feces within 5 days and less than 0.2% in urine. Combined with the oral bioavailability of montelukast, this indicates that montelukast and its metabolites are almost entirely eliminated via bile.

Pharmacokinetics in specific patient populations.

Dose adjustment is not required in patients with mild to moderate hepatic impairment. Studies in patients with renal impairment have not been conducted. Since montelukast and its metabolites are primarily excreted via bile, dose adjustment in patients with renal impairment is not considered necessary. There are no data on the pharmacokinetics of montelukast in patients with severe hepatic impairment (Child-Pugh score >9).

Administration of high doses of montelukast (20 and 60 times the recommended adult dose) was associated with decreased plasma theophylline concentrations. This effect was not observed at the recommended dose of 10 mg once daily.

Clinical characteristics.

Indications.

For symptomatic treatment of seasonal (intermittent) and perennial (persistent) allergic rhinitis.

Contraindications.

Hypersensitivity to montelukast, levocetirizine, cetirizine, hydroxyzine, to any other piperazine derivatives, or to any of the excipients of the medicinal product.

Severe form of chronic renal insufficiency (creatinine clearance < 10 mL/min).

Rare hereditary disorders of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.

Children under 15 years of age.

Pregnancy and breastfeeding.

Interaction with other medicinal products and other forms of interaction.

Interaction studies for the fixed-dose combination of montelukast and levocetirizine have not been conducted. Information on interactions with other medicinal products and other types of interactions is provided below for each active ingredient separately.

Levocetirizine

Interaction studies with levocetirizine have not been performed (including studies with CYP3A4 inducers); studies with the racemic form of cetirizine showed no clinically significant adverse interactions (with pseudoephedrine, cimetidine, ketoconazole, erythromycin, antipyrine, azithromycin, glipizide, and diazepam). A slight decrease in cetirizine clearance (16%) was observed in a multiple-dose study with concomitant administration of theophylline (400 mg once daily); theophylline distribution was not altered when co-administered with cetirizine.

The extent of levocetirizine absorption is not reduced when taken with food, although the rate of absorption is decreased.

When ritonavir (600 mg twice daily) and cetirizine (10 mg daily) were administered concomitantly, cetirizine exposure increased by 40%, while ritonavir exposure changed only slightly (-11%).

When cetirizine or levocetirizine is used concomitantly with alcohol or other CNS depressants, effects on the central nervous system may occur. However, it has been shown that racemic cetirizine does not potentiate the effects of alcohol. The medicinal product may cause drowsiness or impair performance.

Montelukast

Montelukast may be used concomitantly with other medicinal products commonly used for long-term management of bronchial asthma. In drug interaction studies, the recommended clinical dose of montelukast had no significant clinical effect on the pharmacokinetics of the following medicinal products: theophylline, prednisone, prednisolone, oral contraceptives (ethinylestradiol/norethindrone, 35/1), terfenadine, digoxin, and warfarin.

The area under the plasma concentration–time curve (AUC) for montelukast decreased by approximately 40% in patients receiving concomitant phenobarbital. Since montelukast is metabolized via CYP 3A4, 2C8, and 2C9, montelukast should be used with caution in combination with inducers of CYP 3A4, 2C8, and 2C9 (e.g., phenytoin, phenobarbital, rifampicin), especially in children.

In vitro studies have shown that montelukast is a potent inhibitor of CYP 2C8. However, clinical drug interaction data using montelukast and rosiglitazone (a probe substrate primarily metabolized by CYP 2C8) demonstrated that montelukast does not inhibit CYP 2C8 in vivo. Therefore, montelukast is unlikely to significantly affect the metabolism of medicinal products metabolized by this enzyme (such as paclitaxel, rosiglitazone, and repaglinide).

In vitro studies indicate that montelukast is a substrate of CYP 2C8 and, to a lesser extent, of CYP 2C9 and 3A4. In a clinical drug interaction study using montelukast and gemfibrozil (an inhibitor of both CYP 2C8 and 2C9), gemfibrozil increased systemic exposure to montelukast by 4.4-fold. Although dose adjustment is not required when montelukast is co-administered with gemfibrozil or other potent CYP 2C8 inhibitors, physicians should carefully monitor patients for possible increased adverse reactions.

Based on in vitro data, clinically significant drug interactions with weaker inhibitors of CYP 2C8 (e.g., trimethoprim) are not expected. Administration of montelukast with itraconazole, a potent CYP 3A4 inhibitor, does not lead to a significant increase in systemic exposure to montelukast.

Special precautions for use.

Levocetirizine

Use with caution in patients with chronic renal insufficiency (dose adjustment required) and in elderly patients with renal impairment (possible reduction in glomerular filtration rate).

When prescribing the medicinal product to patients with factors predisposing to urinary retention (e.g., spinal cord injury, benign prostatic hyperplasia), it should be noted that levocetirizine may increase the risk of urinary retention. Dosing intervals should be individually adjusted depending on the degree of renal function impairment.

Caution is advised when prescribing the medicinal product to patients with epilepsy or those at risk of seizures, as levocetirizine may provoke seizure exacerbation.

Antihistamine medicinal products suppress the response to skin allergy tests; therefore, administration of the medicinal product should be discontinued at least 3 days prior to testing (elimination period).

Pruritus may occur after discontinuation of levocetirizine, even if these symptoms were not present before treatment initiation. These symptoms may resolve spontaneously. In some cases, symptom severity may be significant, requiring resumption of the medicinal product. Symptoms should resolve after resuming treatment.

During clinical studies, cases of somnolence, increased fatigue, and general weakness were reported in some patients receiving levocetirizine.

Patients should be advised to avoid activities requiring high mental alertness and precise motor coordination, including operating machinery or driving vehicles, during therapy. Alcohol consumption and concomitant use of central nervous system (CNS) depressants should be avoided during levocetirizine therapy, as this may result in additional CNS depression and enhanced impairment of mental and physical performance.

Montelukast

Patients must be informed that montelukast oral medicinal products are not intended for relief of bronchospasm during acute asthma attacks, including status asthmaticus. In such cases, patients must always have immediate access to appropriate rescue medication. If an asthma attack occurs, short-acting β-agonist inhalation should be used. Patients should consult their physician as soon as possible if they require more frequent use of short-acting β-agonists than usual.

Medicinal products containing montelukast should not be used as a rapid substitute for inhaled or oral corticosteroids.

There are no data confirming that the dose of oral corticosteroids can be reduced when montelukast is used concomitantly. The doses of inhaled glucocorticoids may be gradually reduced under physician supervision during concomitant montelukast therapy; however, inhaled or oral glucocorticoids should not be abruptly replaced with montelukast. In isolated cases, patients with bronchial asthma receiving montelukast-containing medicinal products may develop systemic eosinophilia, sometimes accompanied by clinical features of vasculitis, known as Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis, EGPA), which is treated with systemic corticosteroid therapy. Such cases have usually (but not always) been associated with dose reduction or discontinuation of oral corticosteroids. A possible link between leukotriene receptor antagonists and the development of Churg-Strauss syndrome cannot be definitively ruled out or confirmed. Physicians should be aware of the potential for eosinophilia, vasculitic skin rash, worsening pulmonary symptoms, or cardiac and/or neuropathic complications in patients. Additional evaluation and treatment adjustment are required if these symptoms occur.

Montelukast therapy does not allow patients with aspirin-induced asthma to use acetylsalicylic acid (aspirin) or other nonsteroidal anti-inflammatory drugs (NSAIDs).

Medicinal products containing montelukast should not be used in patients with confirmed allergy to acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs), as montelukast, although improving lung function in patients with allergic bronchial asthma, cannot fully prevent NSAID-induced bronchoconstriction.

Psychoneurological reactions have been reported in patients taking montelukast-containing medicinal products (see section "Adverse reactions"). As other factors may influence the occurrence of these reactions, it is unknown whether they are directly related to montelukast use. Physicians should inform patients and/or their caregivers about the possibility of neuropsychiatric disorders. Patients and/or caregivers should be instructed to seek medical advice if such reactions occur. If such events occur, the physician must carefully weigh the risks and benefits of continuing montelukast therapy.

The medicinal product contains lactose; therefore, patients with rare hereditary conditions associated with galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

The medicinal product contains less than 1 mmol (23 mg) of sodium per tablet, i.e., it is practically sodium-free.

Use in elderly patients.

Montelukast

No differences in safety and efficacy profiles have been observed between elderly and younger patients during clinical use, and no evidence has been reported suggesting different responses to the drug in these two populations. However, increased sensitivity to the drug in some elderly patients cannot be excluded.

Levocetirizine

The number of patients aged 65 years and older included in clinical trials of levocetirizine for each approved indication was insufficient to determine whether their response differs from that of younger patients. In clinical practice, no evidence of differential response between elderly and younger patients has been reported. In general, dose selection for elderly patients should be cautious; therapy should usually begin at the lower end of the recommended dose range, considering the higher prevalence of impaired hepatic, renal, or cardiac function, comorbidities, and concomitant medication use in this population.

Use during pregnancy or breastfeeding.

No well-controlled and adequately designed clinical studies on the use of the medicinal product in pregnant women have been conducted. Use during pregnancy is contraindicated. Animal studies do not indicate direct or indirect harmful effects on pregnancy, embryonic/fetal development, parturition, or postnatal development.

Based on published data from prospective and retrospective cohort studies evaluating major congenital malformations in children exposed to montelukast during pregnancy, no drug-related risk has been established. However, these studies have methodological limitations, including small sample size, retrospective data collection in some cases, and non-comparable control groups.

Adverse reactions associated with levocetirizine may occur in breastfed infants. Since levocetirizine is excreted in breast milk, use of this combination during breastfeeding is not recommended.

Ability to affect reaction speed when driving vehicles or operating machinery.

No studies have been conducted on the effect of the fixed-dose combination of montelukast and levocetirizine on the ability to drive vehicles or operate machinery. Some patients may experience somnolence, dizziness, increased fatigue, and weakness during levocetirizine therapy. Patients should refrain from driving vehicles and operating potentially hazardous machinery during treatment with this medicinal product.

Method of administration and dosage.

The recommended dose for adults and children aged 15 years and older is 1 tablet per day, regardless of food intake. Tablets should be swallowed whole, without chewing, with water.

Elderly patients

Dosage adjustment is recommended for elderly patients with moderate to severe renal impairment.

Patients with renal impairment

Dosing intervals should be individually adjusted depending on the degree of renal function impairment. For dosage adjustment, see Table 1 below. To use this table for dosage adjustment, the creatinine clearance (CrCl) in ml/min must be measured. CrCl (ml/min) can be calculated from serum creatinine level (mg/dl) using the following formula:

Table 1

Dosage adjustment for patients with renal impairment

Renal function status	Creatinine clearance (mL/min)	Dosage and frequency of administration
Normal	≥ 80	1 tablet daily
Mild impairment	50 – 79	1 tablet daily
Moderate impairment	30 – 49	1 tablet every 2 days
Severe impairment	< 30	1 tablet every 3 days
End-stage renal disease – dialysis patients	< 10	Contraindicated

For children with impaired renal function, the dose should be individually adjusted based on renal clearance and patient body weight. Specific data in children with impaired renal function are lacking.

Patients with hepatic impairment

Dose adjustment is not required in patients with hepatic impairment.

Children

The medicinal product is contraindicated in children under 15 years of age.

Overdose

There are no data on overdose with this combined medicinal product. However, cases of overdose with individual components have been reported.

Levocetirizine

Symptoms of overdose in adults may include somnolence. In children, initial symptoms may include agitation and increased irritability, followed by somnolence.

There is no specific antidote for levocetirizine overdose. In case of overdose, symptomatic or supportive treatment is recommended. Gastric lavage may be considered shortly after drug administration. Hemodialysis is not effective for removing levocetirizine from the body.

Montelukast

There is no specific information available on the treatment of overdose with medicinal products containing montelukast.

In clinical studies of chronic bronchial asthma, montelukast was administered to adult patients at doses up to 200 mg/day for 22 weeks and, in short-term studies, up to 900 mg/day for approximately one week, without clinically significant adverse reactions.

During post-marketing use and clinical trials, acute montelukast overdose has been reported, including ingestion by adults and children at doses exceeding 1000 mg (approximately 61 mg/kg for a 42-month-old child). The observed clinical and laboratory findings were consistent with the safety profile in adult and pediatric patients.

In most cases, no adverse reactions were reported.

The most commonly observed adverse reactions were consistent with the safety profile of medicinal products containing montelukast and included: abdominal pain, somnolence, thirst, headache, vomiting, and psychomotor hyperactivity.

It is unknown whether montelukast is eliminated by peritoneal dialysis or hemodialysis.

Treatment is symptomatic.

Adverse Reactions

There are no data on adverse events for the fixed-dose combination of montelukast and levocetirizine. Data on adverse reactions for each active substance individually are presented below.

Levocetirizine

The use of levocetirizine in patients aged 12 years and older has been associated with the following adverse effects: headache, somnolence, fatigue, weakness, rhinopharyngitis, dry mouth, and pharyngitis. Uncommon adverse effects included asthenia and abdominal pain. Post-marketing surveillance has reported isolated cases of adverse reactions, namely:

Immune system disorders: hypersensitivity, including anaphylaxis.

Metabolism and nutrition disorders: increased appetite.

Psychiatric disorders: aggression, sleep disturbances, excitation, depression, hallucinations, insomnia, suicidal thoughts, nightmares.

Nervous system disorders: seizures, cerebral venous sinus thrombosis, paresthesia, dizziness, loss of consciousness, tremor, dysgeusia.

Eye disorders: vision disturbances, blurred vision, inflammatory manifestations.

Ear and labyrinth disorders: vertigo.

Cardiac disorders: palpitations, angina pectoris, tachycardia, jugular vein thrombosis.

Respiratory, thoracic and mediastinal disorders: dyspnea.

Gastrointestinal disorders: diarrhea, vomiting, constipation, dry mouth, nausea, abdominal pain.

Hepatobiliary disorders: hepatitis, changes in liver function test parameters.

Renal and urinary disorders: dysuria, urinary retention.

Skin and subcutaneous tissue disorders: angioedema, fixed drug eruption, pruritus, rash, urticaria, hypotrichosis, fissures, photosensitivity.

Musculoskeletal and connective tissue disorders: myalgia, arthralgia.

General disorders: peripheral edema, weight gain.

Other: cross-reactivity.

Investigations: weight gain, abnormal liver function test results.

Description of selected adverse reactions: pruritus has been reported after discontinuation of levocetirizine.

The drug should be discontinued if any of the above adverse effects occur and when the cause of their development cannot be clearly established.

Montelukast

Montelukast was evaluated in clinical studies in the following forms:

• 10 mg film-coated tablets – in approximately 4000 asthma patients aged 15 years and older.
• 10 mg film-coated tablets – in approximately 400 asthma patients with seasonal allergic rhinitis.
• 5 mg chewable tablets – in approximately 1750 asthma patients aged 6 to 14 years.

Table 2 presents data on adverse reactions observed during clinical trials in patients with asthma (frequency ≥ 1/100 to < 1/10) treated with montelukast, which occurred more frequently than in patients receiving placebo.

Table 2

Organ system class	Adult patients and children aged 15 years and older (two 12-week studies; n = 795)	Patients aged 6 to 14 years (one 8-week study; n = 201) (two 56-week studies; n = 615)
Nervous system	Headache	Headache
Gastrointestinal	Abdominal pain	-

During clinical studies with prolonged treatment of a small number of adult patients over 2 years and children aged 6 to 14 years over 12 months, the safety profile did not change.

Post-marketing period

The table 3 below presents data on adverse reactions reported during the post-marketing period, grouped by system organ classes and individual adverse reactions. The frequency classification is based on relevant clinical studies.

Table 3

Organ system class	Adverse reaction	Frequency category*
Infections and infestations	Upper respiratory tract infections$	Very common
Blood and lymphatic system disorders	Increased tendency to bleed	Uncommon
	Thrombocytopenia	Very rare
Immune system disorders	Hypersensitivity reactions, including anaphylaxis	Uncommon
	Hepatic eosinophilic infiltration	Very rare
Psychiatric disorders	Sleep disorders, including nightmares, insomnia, sleepwalking, anxiety, dysphemia, agitation (including aggressive behavior or hostility), depression, psychomotor hyperactivity (including irritability, restlessness, tremor§)	Uncommon
	Attention disorders, memory impairment, tic	Uncommon
	Hallucinations, disorientation, suicidal thoughts and behavior (suicidality), obsessive-compulsive disorders, dysphemia	Very rare
Nervous system disorders	Dizziness, lethargy, paresthesia/hypoesthesia, seizures	Uncommon
Cardiac disorders	Palpitations	Uncommon
Respiratory, thoracic and mediastinal disorders	Nosebleeds, upper respiratory tract infections	Uncommon
	Churg-Strauss syndrome (see section "Special warnings and precautions for use"), pulmonary eosinophilia	Very rare
Gastrointestinal disorders	Diarrhea**, nausea**, pancreatitis**, vomiting**	Common
	Dry mouth, dyspepsia	Uncommon
Hepatobiliary disorders	Increased serum levels of transaminases (ALT, AST)	Common
	Hepatitis (including cholestatic, hepatocellular and mixed types of liver injury)	Very rare
Skin and subcutaneous tissue disorders	Rash**	Common
	Ecchymosis, urticaria, pruritus	Uncommon
	Angioedema	Uncommon
	Nodular erythema, multiform erythema	Very rare
Musculoskeletal and connective tissue disorders	Arthralgia, myalgia, including muscle cramps	Uncommon
Renal and urinary disorders	Nocturnal enuresis in children	Uncommon
General disorders and administration site conditions	Hyperthermia, pyrexia**	Common
	Asthenia/fatigue, malaise, swelling	Uncommon
* - Frequency is defined according to the frequency of reports in the clinical trial database: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1000 to <1/100), rare (≥ 1/10000 to <1/1000), very rare (<1/10000). $ - This adverse reaction was reported with "very common" frequency in patients receiving montelukast as well as in patients receiving placebo during clinical trials. ** - This adverse reaction was reported with "common" frequency in patients receiving montelukast as well as in patients receiving placebo during clinical trials. § - Frequency of occurrence: uncommon.

Shelf life.

2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging.

10 tablets per blister pack, 3 blisters per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Dr. Reddy’s Laboratories Limited.

Manufacturer’s address and place of business.

Manufacturing site: VІ c. Khola, Nalagarh Road, Baddi, Solan District, Himachal Pradesh, 173205, India.

To report adverse reactions or lack of efficacy during the use of the medicinal product, please call (24/7):
+380 44 207 51 97 or +380 50 414 39 39;
or e-mail: [email protected]