LELIPEL

LELIPEL 

LELIPEL 

LELIPEL
Film coated tablets & Oral granules in sachets
Therapeutic class: LELIPEL (montelukast sodium) is a selective and orally active leukotriene receptor antagonist that specifically inhibits cysteinyl leukotriene CysLT1 receptor. Composition: Tablets: Each film coated tablet contains montelukast sodium 10.4 mg eq. to 10 mg montelukast as active ingredient. The tablet also contains inactive ingredients consists of microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, hypromellose and magnesium stearate. The film coat consists of hypromellose, polyethylene glycol, titanium dioxide, talc and iron oxide red. Oral granules sachets: Each sachet contains Montelukast sodium 4.2 mg eq. to 4 mg montelukast as active ingredient The sachet also contains inactive ingredients consists of mannitol, hydroxypropyl cellulose and magnesium stearate. Indications: LELIPEL is indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 12 months of age and older. LELIPEL is indicated for prevention of exercise-induced bronchconstriction in patients 15 years of age and older. I_ELrYEL is indicated for the relief of symptoms of allergic rhinitis (seasonal allergic rhinitis in adults and pediatric patients 2 years of age and older and perennial allergic rhinitis in adults and pediatric patients 6 months of age and older). Dosage and Administration: LELIPEL should be taken once daily. For asthma, the dose should be taken in the evening. For allergic rhinitis, the time of administration may be individualised to suit patient needs. - Patients with both asthma and allergic rhinitis should take only one tablet daily in the evening. - Adults 15 Years of Age and Older with Asthma and/or seasonal Allergic Rhinitis: The dosage for adults 15 years of age and older is one 10 mg tablet daily. - Pediatric Patients 6 to 14 Years of Age with Asthma and/or seasonal Allergic Rhinitis: The dosage for pediatric patients 6 to 14 years of age is 5 mg daily. - Pediatric Patients 2 to 5 Years of Age with Asthma and/or seasonal Allergic Rhinitis: The dosage for pediatric patients 2 to 5 years of age is one 4 mg oral granules sachet daily. - Pediatric Patients 6 months to 2 years with Asthma: The dosage for pediatric patients 6 months to 2 years of age is one packet of 4 mg oral granules daily. Administration of LELIPEL Oral Granules: LELIPEL 4 mg oral granules can be administered either directly in the mouth, dissolved in 1 teaspoonful (5 mL) of cold or room temperature baby formula or breast milk, or mixed with a spoonful of cold or room temperature soft foods; based on stability studies, only apple sauce, carrots, rice, or ice cream should be used. The packet should not be opened until ready to use. After opening the packet, the full dose (with or without mixing with baby formula, breast milk, or food) must be administered within 15 minutes. If mixed with baby formula, breast milk, or food, LELIPEL oral granules must not be stored for future use. Discard any unused portion. LELIPEL oral granules are not intended to be dissolved in any liquid other than baby formula or breast milk for administration. However, liquids may be taken subsequent to administration. General Recommendations: The therapeutic effect ofLELIPEL on parameters of asthma control occurs within one day. LELIPEL may be taken with or without food. Patients should be advised to continue taking LELIPEL while their asthma is controlled, as well as during periods of worsening asthma. - No dosage adjustment is necessary for pediatric patients, for the elderly, for patients with renal insufficiency, or mild-to-moderate hepatic impairment, or for patients of either gender. Therapy with LELIPEL in Relation to Other Treatments for Asthma: LELIPEL can be added to a patient's existing treatment regimen. Reduction in Concomitant Therapy: - Bronchodilator Treatments: LELIPEL 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 patient's bronchodilator therapy can be reduced as tolerated. - Inhaled Corticosteroids: Treatment with LELIPEL provides additional clinical benefit to patients treated with inhaled corticosteroids. A reduction in the corticosteroid dose can be made as tolerated. The dose should be reduced gradually with medical supervision. In some patients, the dose of inhaled corticosteroids can be tapered off completely. LELIPEL should not be abruptly substituted for inhaled corticosteroids. Contraindications: Hypersensitivity to any component of this product. Precautions: General' LELIPEL is not Indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus. - Patients should be advised to have appropriate rescue medication available. Therapy with LELIPEL can be continued during acute exacerbation of asthma. Patients who have exacerbations of asthma after exercise should have available for rescue a short-acting inhaled p-agonist. - While the dose of inhaled corticosteroid may be reduced gradually under medical supervision,LELIPEL should not be abruptly substituted for inhaled or oral corticosteroids. - Patients with known aspirin sensitivity should continue avoidance of aspirin or non-steroidal anti-inflamatory agents while taking LELIPEL Although LELIPEL is effective in improving airway function in asthmatics with documented aspirin sensitivity it has not been shown to truncate bronchoconstrictor response to aspirin and other non-steroidal anti-inflamatory drugs in aspirin-sensitive asthmatic patients. (see clinical pharmacology ,clinical studies)
Pregnancy: LELIPEL has not been studied in pregnant women. LELIPEL should be used during pregnancy only if clearly needed. Nursing Mothers: It is not known if LELIPEL is excreted in human milk. Because many medicines are excreted in human milk, caution should be exercised when LELIPEL is given to a nursing mother. Pediatric Use: LELIPEL has been studied in pediatric patients 2 to 14 years of age (see Dosage and Administration). Safety and effectiveness in pediatric patients younger than 2 years of age have not been studied. Studies have shown that LELIPEL does not affect the growth rate of pediatric patients. Use in the Elderly: In clinical studies, there were no age-related differences in the efficacy or safety profiles of LELIPEL. Drug Interactions: LELIPEL may be administered with other therapies routinely used in the prophylaxis and chronic treatment of asthma, and in the treatment of allergic rhinitis. In medicine-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 estradiol/norethindrone 35/1), terfenadine, 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 LELIPEL is recommended. In vitro studies have shown that montelukast is an inhibitor of CYPaCs. However. data from a clinical drug-drug interaction study involving montelukast and rosiglitazone (a probe substrate representative of drugs primarily metabolized by CYPcCu demonstrated that montelukast does not inhibit CYPCii in vivo (e.g., paclitaxel, rosiglitazone, repaglinide): however, no in vivo interaction studies have been performed. Adverse reactions: Adults and Adolescents 15 Years of Age and Older with Asthma: LELIPEL has been evaluated for safety in approximately 2950 adult and adolescent patents 15 years of age and older in clinical trials. In placebo-controlled clinical trials, the following adverse experiences reported with LELIPEL occurred in greater than or equal to 1% of patients and at an incidence greater than that in patients treated with placebo, regardless of causality assessment:
Body As A Whole LELIPEL 10 mg/day (%) (n=1955) Placebo (%) (n=1180) Asthenia/fatigue 1.8 1.2 Fever 1.5 0.9 Pain, abdominal 2.9 2.5 Trauma 1.0 0.8 Digestive System Disorders Dyspepsia 2.1 1.1 Gastroenteritis, infectious 1.5 0.5 Pain, dental 1.7 1.0 Nervous System/Psychiatric Dizziness 1.9 1_4 Headache 18.4 18.1 Respiratory System Disorders Congestion, nasal 1.6 1.3 Cough 2.7 2.4 Influenza 4-2- 3 Skin/Skin Appendages Disorder Rash 1.6 1.2 Laboratory Adverse Experiences* ALT increased 2.1 2.0 AST increased 1.6 1.2 Pyuria 1.0 0.9
• Number of patients tested (LELIPEL and placebo, respectively): ALT and AST, 1935, 1170; pyuria, 1924, 1159.
The frequency of less common adverse events was comparable between LELIPEL and placebo. The safety profile of LELIPEL when administered as a single dose for prevention of EIB in adult and adolescent patients t5 years of age and older was consistent with the safety profile previously described forLELIPEL. Cumulatively. 569 patients were treated with LELIPEL for at least 6 months, 480 for one year, and 49 for two years in clinical trials. With prolonged treatment, the adverse experience profile did not significantly change. Pediatric Patients 6 to 14 Years of Age with Asthma: LELIPEL has been evaluated for safety in 476 pediatric patients 6 to 14 years of age. Cumulatively, 289 pediatric patients were treated with LELIPEL for at least 6 months, and 241 for one year or longer in clinical trials. The safety profile ofLELIPEL in the 8-week, double-blind, pediatric efficacy trial was generally similar to the adult safety profile. In pediatric patients 6 to 14 years of age receiving LELIPEL , the following events occurred with a frequency z 2% and more frequently than in pediatric patients who received placebo, regardless of causality assessment: pharyngitis, influenza, fever, sinusitis, nausea, diarrhea, dyspepsia, otitis, viral infection, and laryngitis. The frequency of less common adverse events was comparable between LELIPEL and placebo. With prolonged treatment, the adverse experience profile did not significantly change. In studies evaluating growth rate, the safety profile in these pediatric patients was consistent with the safety profile previously described forLELIPEL . In a 56-week, double-blind study evaluating growth rate in pediatric patients 6 to 8 years of age receiving LELIPEL , the following events not previously observed with the use ofLELIPEL in this age group occurred with a frequency z 2% and more frequently than in pediatric patients who received placebo, regardless of causality assessment: headache, rhinitis (infective), varicella, gastroenteritis, atopic dermatitis, acute bronchitis, tooth infection, skin infection, and myopia. Pediatric Patients 2 to 5 Years of Age with Asthma: LELIPEL has been evaluated for safety in 573 pediatric patients 2 to 5 years of age in single-and multiple-dose studies. Cumulatively, 426 pediatric patients 2 to 5 years of age were treated with LELIPEL for at least 3 months, 230 for 6 months or longer, and 63 patients for one year or longer in clinical trials. LELIPEL 4 mg administered once daily at bedtime was generally well tolerated in clinical trials. In pediatric patients 2 to 5 years of age receiving LELIPEL , the following events occurred with a frequency a 2% and more frequently than in pediatric patients who received placebo, regardless of causality assessment: fever, cough, abdominal pain, diarrhea, headache, rhinorrhea, sinusitis, otitis, influenza, rash, ear pain, gastroenteritis, eczema, urticaria, varicella, pneumonia, dermatitis, and conjunctivitis. Pediatric Patients 6 to 23 Months of Age with Asthma: Safety and effectiveness in pediatric patients younger than 12 months of age with asthma have not been established.

LELIPEL has been evaluated for safety in 175 pediatric patients 6 to 23 months of age. The safety profile of LELIPEL in a 6-week, double-blind, placebo-controlled clinical study was generally similar to the safety profile in adults and pediatric patients 2 to 14 years of age. LELIPEL administered once daily at bedtime was generally well tolerated. In pediatric patients 6 to 23 months of age receiving LELIPEL, the following events occurred with a frequency Z 2% and more frequently than in pediatric patients who received placebo, regardless of causality assessment upper respiratory infection, wheezing; otitis media; pharyngitis, tonsillitis, cough; and rhinitis. The frequency of less common adverse events was comparable between LELIPEL and placebo. Adults and Adolescents 15 Years of Age and Older with Seasonal Allergic Rhinitis: LELIPEL has been evaluated for safety in 2199 adult and adolescent patients 15 years of age and older in clinical trials. LELIPEL administered once daily in the morning or in the evening was generally well tolerated with a safety profile similar to that of placebo. In placebo-controlled clinical trials, the following event was reported with LELIPEL with a frequency z 1% and at an incidence greater than placebo, regardless of causality assessment upper respiratory infection, 1.9% of patients receiving LELIPEL vs. 1.5% of patients receiving placebo. In a 4-week, placebo-controlled clinical study, the safety profile was consistent with that observed in 2-week studies. The incidence of somnolence was similar to that of placebo in all studies. Pediatric Patients 2 to 14 Years of Age with Seasonal Allergic Rhinitis: _ELIPEL has been evaluated in 280 pediatric patients 2 to 14 years of age in a 2-week, multicenter, double-blind, placebo-controlled, parallel-group safety study. LELIPEL administered once daily in the evening was generally well tolerated with a safety profile similar to that of placebo. In this study, the following events occurred with a frequency z 2% and at an incidence greater than placebo, regardless of causality assessment: headache. otitis media, pharyngitis, and upper respiratory infection. Adults and Adolescents 15 Years of Age and Older with Perennial Allergic Rhinitis: LELIPEL has been evaluated for safety in 3357 adult and adolescent patients 15 years of age and older with perennial allergic rhinitis of whom 1632 received LELIPEL in two, 6-week, clinical studies. LELIPEL administered once daily was generally well tolerated, with a safety profile consistent with that observed in patients with seasonal allergic rhinitis and similar to that of placebo. In these two studies, the following events were reported with LELIPEL with a frequency z 1% and at an incidence greater than placebo, regardless of causality assessment: sinusitis, upper respiratory infection, sinus headache, cough, epistaxis, and increased ALT. The incidence of somnolence was similar to that of placebo. Pediatric Patients 6 Months to 14 Years of Age with Perennial Allergic Rhinitis: The safety in patients 2 to 14 years of age with perennial allergic rhinitis is supported by the established safety in patients 2 to 14 years of age with seasonal allergic rhinitis. The safety in patients 6 to 23 months of age is supported by data from pharmacokinetic and safety and efficacy studies in asthma in this pediatric population and from adult pharmacokinetic studies. Post-Marketing Experience: The following additional adverse reactions have been reported in post-marketing use: - Blood and lymphatic system disorders: increased bleeding tendency. - Immune system disorders: hypersensitivity reactions including anaphylaxis, very rarely hepatic eosinophilic infiltration. - Psychiatric disorders: agitation including aggressive behavior or hostility, anxiousness, depression, dream abnormalities, hallucinations, insomnia, irritability, restlessness, somnambulism, suicidal thinking and behavior (including suicide), tremor (see PRECAUTIONS, Neuropsychiatric Events). - Nervous system disorders: drowsiness, paraesthesia/hypoesthesia, seizures. - Cardiac disorders: palpitations. - Respiratory, thoracic and mediastinal disorders: epistaxis. - Gastrointestinal disorders: diarrhea, dyspepsia, nausea, very rarely pancreatitis, vomiting - Hepatobiliary disorders: Rare cases of cholestatic hepatitis, hepatocellular liver-injury, and mixed-pattem liver injury have been reported in patients treated with LELIPEL. Most of these occurred in combination with other confounding factors, such as use of other medications, or when LELIPEL was administered to patients who had underlying potential for liver disease such as alcohol use or other forms of hepatitis. - Skin and subcutaneous tissue disorders: angioedema, bruising, erythema nodosum, pruritus, urticana. - Musculoskeletal and connective tissue disorders: arthralgia, myalgia including muscle cramps. - General disorders and administration site conditions: edema. In rare cases, patients with asthma on therapy with LELIPEL 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. Thde events usually, but not always, have been associated with the reduction of oral corticosteroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between LELIPEL and these underlying conditions has not been established (see PRECAUTIONS, Eosinophilic Conditions). Over dose: No specific inforrnation is available on the treatment of overdosage with montelukast. In chronic asthma studies, montelukast has been administered at doses up to 200mg daily to adult patients for 22 weeks and in short term studies up to 900 mg/day to patients for approximately one week without clinically important adverse experiences. There have been reports of acute overdosage in post-marketing experience and clinical studies with montelukast. These include reports in adults and children with a dose as high as 1000 mg . the clinical and laboratory findings observed were consistent with the safety profile in adults and pediatric patients. There were no adverse experiences in the majority of . overdosage reports . The most frequently occurring adverse experiences were consistent with the safety profile of montelukast and included abdominal pain somnolence, thirst, headache,vomiting, and psychomotor hyperactivity . - It is not known whether montelukast is dialysable by peritoneal- or haemodialysis. Availability: -LELIPEL 10 mg film coated tablets are available in a carton box contains 2 AlufTriplex consisted of 3 layers (PVC/PE/PVDC)j blisters each of 10 film coated tablets. -LELIPEL 4 mg sachets are available in a carton box containing 14 child-resistant foil packets each of 2 gram oral granules. Storage: - Store at a temperature not exceeding 30°C in a dry place. - Keep out of reach of children. 

Produced by: Egyptian Group for Pharmaceutical Industries. (EGPI) For: Globe International Pharmaceuticals. 

International Pharmaceuticals