Montelukast Lhc 10 mg/200 mg/350 mg FC Tablets,

Montelukast LHC 10 mg film-coated tablets are indicated in adults and children 15 years of age and older for the prophylaxis and chronic treatment of atopic asthma. In those adult asthmatic patients in whom Montelukast LHC tablets are indicated in asthma, Montelukast LHC tablets may also provide some symptomatic relief of seasonal allergic rhinitis.

Posology
The recommended dose for adults and adolescents 15 years of age and older with atopic asthma, or with asthma and concomitant seasonal allergic rhinitis, is one 10 mg tablet daily to be taken in the evening with or without food. Clinical studies in adults 15 years of age and older demonstrated there is no additional clinical benefit to montelukast doses above 10 mg once daily. The therapeutic effect of Montelukast LHC on parameters of asthma control occurs within one day. Patients should be advised to continue taking Montelukast LHC even if their asthma is under control, as well as during periods of worsening asthma.
Hepatic impairment
The metabolism of montelukast may be decreased in patients with mild to moderate hepatic impairment and clinical evidence of cirrhosis. The half-life may be slightly prolonged; however, dosage adjustment is not necessary. No data are available for patients with severe hepatic impairment. The elimination of montelukast is slightly prolonged compared with that in healthy subjects (mean half-life, 7,4 hours). No dosage adjustment is required in patients with mild-to-moderate renal insufficiency (See Sec 4.4).
Renal impairment
Since montelukast and its metabolites are not excreted in the urine, the pharmacokinetics of montelukast were not evaluated in patients with renal insufficiency. No dosage adjustment is recommended in these patients (See Sec 5.2).
Elderly
The pharmacokinetic profile and the oral bioavailability of a single 10 mg oral dose of montelukast are similar in elderly and younger adults. The plasma half-life of montelukast is slightly longer in the elderly. No dosage adjustment in the elderly is required (See Sec 5.2).
Children
Montelukast LHC 10 is not recommended to children under the age of 15 years, as safety and efficacy have not been demonstrated (See Sec 4.3).
Therapy with Montelukast LHC in relation to other treatments for asthma
Montelukast LHC can be added to a patient's existing treatment regimen.
Reduction in Concomitant Therapy

• Bronchodilator Treatments: Montelukast LHC can be added to the treatment regimen of patients who are not adequately controlled on bronchodilator alone. When a clinical response is evident (usually after the first dose), the patientu2019s bronchodilator therapy may be reduced as tolerated.
• Inhaled Corticosteroids: A reduction in the corticosteroid dose can be made as tolerated. The dose should be reduced gradually with medical supervision. Montelukast LHC should not be abruptly substituted for inhaled corticosteroids.

• Hypersensitivity to montelukast or any component of Montelukast LHC tablets.
• Children under the age of 15 years, as safety and efficacy of Montelukast LHC 10 have not been demonstrated.

Montelukast LHC is not indicated in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus as the efficacy of Montelukast LHC has not been established for the treatment of acute asthma attacks. Patients should be advised to have appropriate rescue medication available. During acute exacerbations of asthma, therapy with Montelukast LHC can be continued.
Eosinophilic Conditions: Patients on therapy with Montelukast LHC tablets 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 events usually, but not always, have been associated with the reduction of oral corticosteroid therapy. Medical practitioners should be on the alert to eosinophillia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. In such patients Montelukast LHC tablets should be withdrawn.
Neuropsychiatric events: Neuropsychiatric events have been reported in adults, adolescents, and children taking Montelukast LHC. Post-marketing reports with Montelukast LHC use include agitation, aggressive behaviour or hostility, anxiousness, depression, disorientation, disturbance in attention, abnormal dreams, hallucinations, insomnia, irritability, memory impairment, restlessness, somnambulism, suicidal ideation and behaviour (including suicide), tic and tremor. Patients and medical practitioners should be alert for neuropsychiatric events. Patients should be instructed to notify their medical practitioners if these changes occur. Medical practitioners should carefully evaluate the risks and benefits of continuing treatment with Montelukast LHC if such events occur.
Hypersensitivity to aspirin: Patients with a known aspirin sensitivity should be advised to avoid taking aspirin or non-steroidal anti-inflammatory agents while taking Montelukast LHC tablets. Although Montelukast LHC is effective in improving airway function in asthmatics, it has not been demonstrated to reduce the bronco-constrictor response to aspirin or other NSAIDs in aspirin-sensitive asthmatic patients.
Hepatic impairment: The metabolism of montelukast may be decreased in patients with mild to moderate hepatic impairment and clinical evidence of cirrhosis. The half-life may be slightly prolonged; however, dosage adjustment is not necessary. No data are available for patients with severe hepatic impairment.

Montelukast LHC tablets may be administered with other therapies routinely used in the prophylaxis and chronic treatment of atopic asthma and seasonal allergic rhinitis. In interactions studies, the recommended clinical dose of montelukast did not have clinically important effects on the pharmacokinetics of the following medicines: theophylline, prednisone, prednisolone, oral contraceptives (ethinyl oestradiol/ norethindrone 35/1), digoxin and warfarin. The area under the plasma concentration time curve (AUC) for montelukast was decreased approximately 40 % in subjects with co-administration of phenobarbital. No dosage adjustment for Montelukast LHC tablets is recommended. Clinical monitoring is recommended when potent hepatic enzyme inducers (such as ritonavir, phenytoin, phenobarbitone, rifampicin, or St Johnu2019s wort are given concurrently with Montelukast LHC. In vitro studies have shown that montelukast is an inhibitor of CYP2C8. However, data from a clinical interaction study involving montelukast and rosiglitazone (a probe substrate representative of medicines primarily metabolised by CYP2C8) demonstrated that montelukast does not inhibit CYP2C8 in vivo. Therefore is not anticipated to alter the metabolism of medicines metabolised by this enzyme (e.g. paclitaxel, rosiglitazone and repaglinide). In vitro studies have shown that montelukast is a substrate of CYP2C8, CYP2C9, and CYP3A4. Data from an interaction study involving montelukast and gemfibrozil (an inhibitor of both CYP2C8 and CYP2C9) demonstrated that gemfibrozil increased the systemic exposure of montelukast by 4,4-fold. Co-administration of itraconazole, a strong CYP3A4 inhibitor, with gemfibrozil and montelukast did not further increase the systemic exposure of montelukast. The effect of gemfibrozil on systemic exposure of montelukast is not considered to be clinically meaningful based on clinical safety data with doses greater than the 10 mg approved dose in adults (e.g., 200 mg/day to adult patients for 22 weeks, and up to 900 mg/day to patients for approximately one week) where clinically important adverse experiences were not observed. Therefore, no dosage adjustment of Montelukast LHC is required upon co-administration with gemfibrozil. Based on in vitro data, important interactions with other known inhibitors of CYP2C8 (e.g., trimethoprim) are not anticipated. In addition, co-administration of montelukast with itraconazole alone resulted in no significant increase in the systemic exposure of montelukast.

The safety of Montelukast LHC tablets in pregnant and breastfeeding women has not been established. Available data from published prospective and retrospective cohort studies with montelukast use in pregnant women evaluating major birth defects have not established a drug-associated risk. Available studies have methodologic limitations, including small sample size, in some cases retrospective data collection, and inconsistent comparator groups. It is not known if Montelukast LHC is excreted in human milk. Women using Montelukast LHC should not breastfeed their infants. The effect of Montelukast LHC on fertility has not been established.

Montelukast LHC tablets may cause adverse effects such as dizziness and drowsiness which may affect ability to drive and operate machines safely. Patients should therefore be advised not to drive or operate machinery until their individual susceptibility is known.

Body System Class
Frequency
Frequent
Less Frequent
Unknown
Blood and lymphatic system disorders
Churg-Strauss Syndrome (see sec 4.4). Increased bleeding tendency and thrombocytopenia.
Immune system disorders
Hypersensitivity reactions including allergy, anaphylaxis, angiodema, hepatic eosinophilic, rashes and urticaria.
Endocrine disorders
Pancreatitis
Psychiatric disorders
Abnormal dreams, hallucinations, agitation including aggressive behavior/hostility, restlessness, anxiousness, depression, irritability, suicidality, tic, obsessive-compulsive symptoms, dysphemia and tremor.
Nervous system disorders
Dizziness, Headache and Insomnia. Drowsiness, paraesthesia, hypoaesthesia and seizure.
Cardiac disorders
Palpitations
Respiratory, thoracic and mediastinal disorders:
Nasal congestion, epistaxis cough, influenza, asthma, pulmonary eosinophilia, Churg-Strauss syndrome, and increased incident of respiratory tract infections.
Gastrointestinal disorders
Abdominal pains Dyspepsia and gastroenteritis. Nausea, vomiting and diarrhoea.
Hepato-biliary disorders
Elevated hepatic enzymes (AST, ALT), symptomatic hepatitis or hyperbilirubinaemia. Cholestatic hepatitis.
Skin and subcutaneous tissue disorders
Skin rash and acne. Angioedema, erythema multiforme, erythema nodosum, bruising, pruritus, and urticaria.
Musculoskeletal and connective tissue disorders
Arthralgia and myalgia including muscle cramps.
Renal and urinary disorders
Pyuria and enuresis in children.
General disorders and administration site disorders
Asthenia, fatigue, dental pain, and fever. Oedema, generalised pain, and fatalities.

Treatment is symptomatic and supportive. No specific information is available on the treatment of overdosage with Montelukast LHC tablets. The most frequent adverse experience observed were abdominal pain, somnolence, thirst, headache, vomiting and psychomotor hyperactivity. It is not known whether montelukast is dialysable by peritoneal or haemodialysis.