ApoMontessan

Uses

ApoMontessan is used for-

• The prophylaxis and chronic treatment of asthma in adults and paediatric patients 12 months of age and older.
• The relief of symptoms of seasonal allergic rhinitis in adults and paediatric patients 2 years of age and older.

ApoMontessan is also used to associated treatment for these conditions: Asthma, Exercise-Induced Bronchospasm, Perennial Allergic Rhinitis (PAR), Seasonal Allergic Rhinitis

How ApoMontessan works

Cysteinyl leukotrienes (CysLT) like LTC4, LTD4, and LTE4, among others, are eicosanoids released by a variety of cells like mast cells and eosinophils. When such CysLT bind to corresponding CysLT receptors like CysLT type-1 receptors located on respiratory airway smooth muscle cells, airway macrophages, and on various pro-inflammatory cells like eosinophils and some specific myeloid stem cells activities that facilitate the pathophysiology of asthma and allergic rhinitis are stimulated.

In particular, CysLT-mediated airway bronchoconstriction, occluding mucous secretion, vascular permeability, and eosinophil recruitment are all types of effects that facilitate asthma. Alternatively, in allergic rhinitis, CysLTs are released by the nasal mucosa when exposed to allergens during both early and late phase reactions and participate in eliciting symptoms of allergic rhinitis like a congested nose and airway.

Subsequently, montelukast is a leukotriene receptor antagonist that binds with high affinity and selectivity to the CysLT type 1 receptor, which consequently assists in inhibiting any physiological actions of CysLTs like LTC4, LTD4, and LTE4 at the receptor that may facilitate asthma or allergic rhinitis.

Dosage

ApoMontessan dosage

General information: ApoMontessan should be taken once daily. For asthma, the dose should be taken in the evening. For seasonal allergic rhinitis, the time of administration may be individualised to suit patients needs. Patients with both asthma and seasonal allergic rhinitis should take only one tablet daily in the evening.

Adults and adolescents 15 years of age and older with asthma or seasonal allergic rhinitis: The dosage is one 10 mg tablet daily.

Paediatric patients 6 to 14 years of age with asthma or seasonal allergic rhinitis: The dosage is one 5 mg tablet daily. No dosage adjustment within this age group is necessary.

Paediatric patients 2 to 5 years of age with asthma or seasonal allergic rhinitis: The dosage is one 4 mg tablet daily.

Paediatric patients 12 to 23 months of age with asthma: The dosage is one 4 mg tablet daily to be taken in the evening. Safety and effectiveness in paediatric patients younger than 12 months of age have not been established.

Side Effects

Adolescents and Adults 15 years of age and older: In placebo-controlled clinical trials, ApoMontessan has been evaluated for safety in approximately 2600 adolescent and adult patients of 15 years and older, the following adverse experiences reported with ApoMontessan occurred in greater than or equal to 1% of patients.

• General: Asthenia/fatigue, Fever, Pain
• Gastrointestinal: Dyspepsia, Gastroenteritis; Nervous
• System/Psychiatric: Dizziness, Headache
• Respiratory System: Congestion, Cough, Influenza
• Skin: Rash; Laboratory adverse experiences: ALT increase, AST increase, Pyuria.

Paediatric patients 6 to 14 years of age: In paediatric patients receiving montelukast, the following events occurred with a frequency 2% are diarrhoea, laryngitis, pharyngitis, nausea, otitis, sinusitis, and viral infection. With prolonged treatment, the adverse profile did not change significantly.

Toxicity

The adverse effects associated with overdosage of montelukast include abdominal pain, somnolence, thirst, headache, vomiting, psychomotor hyperactivity, and less frequently, convulsion.

The oral LD50 value determined for mice and rats is >5000 mg/kg.

ApoMontessan has not been studied in pregnant women. Consequently, it should be used during pregnancy only if clearly needed.

Additionally, as it is unknown whether montelukast is excreted into human breast milk, there is also caution regarding the use of the medication in nursing mothers.

The plasma half-life of montelukast is somewhat prolonged in elderly patients, although no dosage adjustment is generally necessary.

Precaution

ApoMontessan is not indicated for use in the reversal of bronchospasm in acute asthma attacks (in case of status asthmaticus). Patients with known aspirin sensitivity should continue avoidance of aspirin or other NSAID, while taking ApoMontessan.

In rare cases, patients on therapy with ApoMontessan 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. Physician should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between ApoMontessan and these underlying conditions has not been established.

Interaction

ApoMontessan has been administered with other therapies routinely used in the prophylaxis and chronic treatment of asthma with no apparent increase in adverse reactions. In drug interaction studies, the recommended clinical dose of montelukast did not have clinically important effects on the pharmacokinetics of the following drugs: Theophylline, Prednisolone, oral contraceptives (Norethindrone 1 mg/Ethinyl Oestradiol 35 mg), Terfenadine, Digoxin, and Warfarin.

Although additional specific interaction studies were not performed, ApoMontessan was used concomitantly with a wide range of commonly prescribed drugs in clinical studies without clinically evident adverse interactions. These medications included thyroid hormones, sedative hypnotic, non-steroidal anti-inflammatory agents, benzodiazepines, and decongestants.

Phenobarbital, which induces hepatic metabolism, decreased the AUC of ApoMontessan approximately 40% following a single 10 mg dose of ApoMontessan. No dosage adjustment for ApoMontessan is recommended. It is reasonable to employ appropriate clinical monitoring when potent cytochrome P450 enzyme inducers, such as Phenobarbital or Rifampin, are co-administered with ApoMontessan.

Food Interaction

• Take with or without food. The absorption is unaffected by food.

ApoMontessan Drug Interaction

Unknown: fluticasone / salmeterol, aspirin, aspirin, diphenhydramine, ubiquinone, duloxetine, omega-3 polyunsaturated fatty acids, fluticasone nasal, pregabalin, metoprolol, metoprolol, albuterol, budesonide / formoterol, levothyroxine, acetaminophen, albuterol, cyanocobalamin, ascorbic acid, cholecalciferol, cetirizine

ApoMontessan Disease Interaction

Major: neuropsychiatric disordersModerate: liver disorder, PKU, pulmonary disorders

Volume of Distribution

The steady-state volume of distribution recorded for montelukast is an average between 8 to 11 litres.

Elimination Route

It has been observed that montelukast is quickly absorbed following administration by the oral route. The oral bioavailability documented for the drug is 64%. Furthermore, it seems that having a regular meal in the morning or even a high fat snack in the evening does not affect the absorption of montelukast.

Half Life

Studies have demonstrated that the mean plasma half-life of montelukast varies from 2.7 to 5.5 hours when observed in healthy young adults.

Clearance

The plasma clearance documented for montelukast is an average of 45 mL/min when observed in healthy adults.

Elimination Route

It has been reported that montelukast and its metabolites are almost exclusively excreted in the bile and into the feces.

Pregnancy & Breastfeeding use

Pregnancy: ApoMontessan crosses the placenta following oral dosing in rats and rabbits. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, ApoMontessan should be used during pregnancy only if clearly needed.

Lactation: It is not known if ApoMontessan is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ApoMontessan is given to a nursing mother.

Contraindication

ApoMontessan is contraindicated to patients with hypersensitivity to any component of this product.

Special Warning

Paediatric use: Safety and efficacy of ApoMontessan has been established in adequate and well controlled studies in paediatric patients with asthma and allergic rhinitis between age 1 to 14 years. Long term trials evaluatingthe effect of chronic administration of ApoMontessan on linear growth in paediatric patients have not been conducted.

Geriatric use: Of the total number of subjects in clinical studies of ApoMontessan, 3.5% were 65 years of age and over and 0.4% were 75 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. But greater sensitivity of some older individuals cannot be ruled out.

Acute Overdose

Symptoms: Abdominal pain, somnolence, thirst, headache, vomiting, and psychomotor hyperactivity.

Management: Supportive and symptomatic treatment. If indicated, unabsorbed material should be removed from the GI tract.

Storage Condition

Store at 25° C. Protect from moisture and light.

Innovators Monograph

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