Topraz 4mg, 5mg, 10mg Chewable tablet, FC tablet

TOPRAZ 4 chewable tablets are indicated for paediatric patients 2 to 5 years of age for the prophylaxis and chronic treatment of atopic asthma. TOPRAZ 5 chewable tablets are indicated for paediatric patients over 6 years of age for the prophylaxis and chronic treatment of atopic asthma. TOPRAZ 10 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 TOPRAZ is indicated in asthma, TOPRAZ may also provide some symptomatic relief of seasonal allergic rhinitis.

TOPRAZ 4 chewable tablets

Paediatric patients 2 to 5 years of age with atopic asthma: One 4 mg chewable tablet daily.

TOPRAZ 5 chewable tablets

Paediatric patients 6 to 14 years of age with atopic asthma: One 5 mg chewable tablet daily.

TOPRAZ 4 mg and 5 mg tablets have not been studied in seasonal allergic rhinitis in children with asthma.

TOPRAZ 10 film-coated tablets

Adults and children 15 years of age and older with atopic asthma with or without seasonal allergic rhinitis: One 10 mg film-coated tablet daily. Clinical studies in adults and children 15 years of age and older did not demonstrate additional clinical benefit to montelukast, as in TOPRAZ at doses above 10 mg daily. A therapeutic effect of TOPRAZ on parameters of asthma control occurs within one day. Patients are advised to continue taking TOPRAZ while their asthma is controlled, as well as during periods of worsening asthma.

No dosage adjustment is necessary for the elderly, paediatric patients, for patients with renal insufficiency or mild-to-moderate hepatic impairment.

Therapy with TOPRAZ in relation to other treatments for asthma

TOPRAZ can be added to a patientu2019s existing treatment regimen. Reduction in Concomitant Therapy

Bronchodilator Treatments: TOPRAZ 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. TOPRAZ should not be abruptly substituted for inhaled corticosteroids.

Method of administration

TOPRAZ should be taken once daily in the evening. TOPRAZ can be taken with or without food.

• Hypersensitivity to montelukast or to any other components of TOPRAZ.
• TOPRAZ 4 should not be used in children under the age of 2 years as safety and efficacy have not been demonstrated.
• TOPRAZ 5 should not be used in children under the age of 6 years as safety and efficacy have not been demonstrated.
• TOPRAZ 10 should not be used in children under the age of 15 years.

TOPRAZ is not indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus as the efficacy of TOPRAZ has not been established for the treatment of acute asthma attacks. Patients should be advised to have appropriate rescue medicine available. Therapy with TOPRAZ can be continued during acute exacerbations of asthma. Patients should be advised to take TOPRAZ daily as prescribed, even when they are asymptomatic, as well as during periods of worsening asthma, and to contact their medical practitioners if their asthma is not well controlled. Medical attention should be sought if more than the prescribed maximum number of inhalations of short-acting bronchodilator treatment for a 24-hour period, are needed.

TOPRAZ should not be used as monotherapy for the prophylactic treatment of exercise-induced bronchospasm. Patients who have exacerbations of asthma after exercise should continue to use their usual regimen of inhaled beta-agonists as prophylaxis and have available for rescue a short-acting inhaled beta-agonist.

While the dose of inhaled corticosteroid may be reduced gradually under medical supervision TOPRAZ should not be abruptly substituted for inhaled or oral corticosteroids.

Eosinophilic Conditions

Patients on therapy with TOPRAZ 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 doctors should be on the alert for patients presenting with eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between TOPRAZ and these underlying conditions has not been established.

Hypersensitivity to aspirin

Patients with known aspirin sensitivity should continue avoidance of aspirin or non-steroidal anti-inflammatory (NSAID) medicines while taking TOPRAZ. Although TOPRAZ is effective in improving airway function in asthmatics with documented aspirin sensitivity, it has not been shown to truncate broncho-constrictor response to aspirin and other non-steroidal anti-inflammatory medicines in aspirin-sensitive asthmatic patients.

Neuropsychiatric events

Neuropsychiatric events have been reported in adult, adolescent and paediatric patients taking TOPRAZ. Post-marketing reports with TOPRAZ 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 TOPRAZ if such events occur.

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.

Renal Insufficiency (See section 5.2).

Use in Elderly

There are no age-related differences in the efficacy or safety profiles of TOPRAZ.

Intolerance to excipients

TOPRAZ 4 & 5 chewable tablets contain mannitol which may have a laxative effect. TOPRAZ 10 film-coated tablets contain lactose. Patients with the rare hereditary conditions of galactose intolerance e.g. galactosaemia, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. Lactose may have an effect on the glycaemic control of patients with diabetes mellitus.

TOPRAZ 4 & 5 Phenylalanine

Pheynylketonurics: Phenylketonuric patients should be informed that TOPRAZ 4 & 5 contains phenylalanine (a component of aspartame) 1,2 mg per 4 mg chewable tablet and 1,5 mg per 5 mg chewable tablet. It may be harmful for patients with phenylketonuria.

TOPRAZ may be administered together with other therapies used in the prophylactic treatment of atopic asthma and seasonal allergic rhinitis. In interaction studies, the recommended clinical dose of montelukast as in TOPRAZ did not have clinically important effects on the pharmacokinetics of the following medicines: Theophylline, prednisone, prednisolone, oral contraceptives (ethinyl oestradiol-norethindrone 35 mcg/1 mg), digoxin and warfarin. The area under the plasma concentration-time curve (AUC) for montelukast was decreased approximately 40 % in subjects with co-administration of phenobarbitone. If co-administration with phenobarbitone, dosage adjustments of TOPRAZ may be necessary. Clinical monitoring is recommended when potent hepatic enzyme inducers such as phenytoin, phenobarbitone or rifampicin, St. Johnu2019s Wort, or potent hepatic enzyme inhibitors (such as ketoconazole, itraconazole or voriconazole) are given with TOPRAZ.

In vitro studies have shown that montelukast is an inhibitor of CYP 2C8. However, data from an interaction study involving montelukast and rosiglitazone (a probe substrate representative of medicine primarily metabolised by CYP 2C8) demonstrated that montelukast doesnu2019t not inhibit CYP 2C8 in vivo. Therefore, TOPRAZ is not anticipated to markedly alter the metabolism of medicines metabolised by this enzyme (e.g. paclitaxel, rosiglitazone and repaglinide, but the doctor should be aware of the potential for an increase in adverse reactions.

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 TOPRAZ 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.

Pregnancy

The safety of TOPRAZ in pregnant and lactating 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.

Breastfeeding

It is not known if TOPRAZ is excreted in human milk. Women taking TOPRAZ should not breastfeed their babies.

As this medicine may cause drowsiness patients are advised not to drive or operate machinery while on this treatment.

Infections and infestations

Frequent: Upper respiratory tract infections.

Blood and the lymphatic system disorders

Less frequent: Increased bleeding tendency, thrombocytopenia.

Immune system disorders

Less frequent: Hypersensitivity reactions including anaphylaxis, angioedema, hepatic eosinophilic infiltration, systemic eosinophilia (see section 4.5), decreased immune responsiveness.

Psychiatric disorders

Less frequent: Abnormal dreams, dysphemia (stuttering), [and] hallucinations, agitation including aggressive behaviour or hostility, anxiousness, depression, disorientation, disturbance in attention, insomnia, memory impairment, obsessive-compulsive symptoms, psychomotor hyperactivity (including irritability, restlessness, and tremor), somnambulism, suicidal thinking and behaviour (suicidality), tic.

Nervous system disorders

Frequent: Headache.

Less frequent: Drowsiness, dizziness, paraesthesia/ hypoaesthesia, seizure.

Eye disorders

Less frequent: Blepharospasm, mydriasis.

Ear and labyrinth disorders

Less frequent: vertigo.

Cardiac disorders

Less frequent: Palpitations, chest pain.

Respiratory, thoracic and mediastinal disorders

Frequent: Congestion (nasal), cough, influenza.

Less frequent: Epistaxis, pulmonary eosinophilia, and Churg-Strauss syndrome.

Gastrointestinal disorders

Less frequent: Nausea, diarrhoea, vomiting, abdominal pain, bowel movement irregularity, dry mouth, dyspepsia, flatulence, salivary hypersecretion.

Hepato-biliary disorders

Less frequent: Hepatitis (including cholestatic, hepatocellular and mixed-pattern liver injury).

Skin and subcutaneous tissue disorders

Frequent: Rash.

Less frequent: Pruritus, urticaria, erythema nodosum, erythema multiforme, angioedema, bruising.

Musculoskeletal, connective tissue and bone disorders

Less frequent: Arthralgia, myalgia including muscle cramps.

Renal and urinary disorders

Less frequent: Enuresis in children.

General disorders and administrative site conditions

Frequent: Asthenia, fatigue, fever, increased sweating, abdominal pain, trauma, thirst.

Less frequent: Oedema, pyrexia, anaphylaxis.

Investigations

Frequent: ALT increased, AST increased.

Less frequent: Eosinophil count increased, haematocrit decreased, haemoglobin decreased, white blood cell count decreased.

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