Asmaphylin M

Asmaphylin M Uses, Dosage, Side Effects, Food Interaction and all others data.

Montelukast is a selective leukotriene receptor antagonist that inhibits the effects of cysteinyl leukotrienes in the airways. Cysteinyl leukotrienes and leukotriene receptor occupation have been correlated with the pathophysiology of asthma, including airway oedema, smooth muscle contraction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma.

Montelukast is a leukotriene receptor antagonist that demonstrates a marked affinity and selectivity to the cysteinyl leukotriene receptor type-1 in preference to many other crucial airway receptors like the prostanoid, cholinergic, or beta-adrenergic receptors. As a consequence, the agent can elicit substantial blockage of LTD4 leukotriene-mediated bronchoconstriction with doses as low as 5 mg. Moreover, a placebo-controlled, crossover study (n=12) demonstrated that montelukast is capable of inhibiting early and late phase bronchoconstriction caused by antigen challenge by 75% and 57% respectively.

In particular, it has been documented that montelukast can cause bronchodilation as soon as within 2 hours of oral administration. This action can also be additive to the bronchodilation caused by the concomitant use of a beta agonist. Nevertheless, clinical investigations performed with adults 15 years of age and older revealed that no additional clinical benefit is obtained when doses of montelukast greater than 10 mg a day are used.

Additionally, in clinical trials with adults and pediatric asthmatic patients aged 6 to 14 years, it was also determined that montelukast can reduce mean peripheral blood eosinophils by about 13% to 15% from baseline in comparison to placebo during double-blind treatment periods. At the same time, in patients aged 15 years and older who were experiencing seasonal allergic rhinitis, the use of montelukast caused a median reduction of 13% in peripheral blood eosinophil counts when compared to placebo as well.

Theophylline is a bronchodilator, structurally classified as a Methylxanthine. Theophylline has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation and suppression of the response of the airways to stimuli. Theophylline also increases the force of contraction of diaphragmatic muscles. The half-life of Theophylline is influenced by a number of known variables. In adult nonsmokers with uncomplicated asthma the half-life ranges from 3 to 9 hours

Theophylline, an xanthine derivative chemically similar to caffeine and theobromine, is used to treat asthma and bronchospasm. Theophylline has two distinct actions in the airways of patients with reversible (asthmatic) obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects).

Trade Name Asmaphylin M
Generic Etofylline + Theophylline + Montelukast
Weight 231mg
Type Tablet
Therapeutic Class
Manufacturer Ici Healthcare Pvt Ltd
Available Country India
Last Updated: September 19, 2023 at 7:00 am
Asmaphylin M
Asmaphylin M

Uses

Montelukast 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.

This is used for the symptomatic treatment of reversible bronchoconstriction associated with bronchial asthma, chronic obstructive pulmonary emphysema, chronic bronchitis and related bronchospastic disorders.

Asmaphylin M is also used to associated treatment for these conditions: Asthma, Exercise-Induced Bronchospasm, Perennial Allergic Rhinitis (PAR), Seasonal Allergic RhinitisAsthma, Bronchitis, Bronchoconstriction, Bronchospasm, Chronic Obstructive Pulmonary Disease (COPD), Chronic bronchial inflammation, Airway secretion clearance therapy, Bronchodilation

How Asmaphylin M 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.

Theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. In inflammatory states, theophylline activates histone deacetylase to prevent transcription of inflammatory genes that require the acetylation of histones for transcription to begin.

Dosage

Asmaphylin M dosage

General information: Montelukast 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.

Dosages are adjusted to maintain serum theophylline concentrations that provide optimal relief of symptoms with minimal side effects. Most of the controlled release preparations may be administered every 12 hours in adults while administration every 8 hours may be necessary in some children with markedly rapid hepatic metabolism of theophylline. The recommended dosages for achieving serum theophylline concentrations within the accepted therapeutic range is as follow:

  • 1-6 months: 10mg/Kg/day
  • 6 months-1 year: 15mg/Kg/day
  • 1-9 years: 24mg/Kg/day
  • 10-16 years: 18mg/Kg/day
  • Adults: 10-15mg/Kg/day

Side Effects

Adolescents and Adults 15 years of age and older: In placebo-controlled clinical trials, Montelukast has been evaluated for safety in approximately 2600 adolescent and adult patients of 15 years and older, the following adverse experiences reported with Montelukast 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.

The following side effects have been observed:

Gastrointestinal: Nausea, vomiting, epigastric pain and diarrhoea.

Central nervous system: Headache, irritability, restlessness, insomnia, muscles twitching.

Cardiovascular: Palpitation, tachycardia, hypotension. circulatory failure.

Respiratory: Tachypnoea.Renal: Potentiation of diuresis.

Others: Alopecia, hyperglycemia, rash etc.

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.

Montelukast 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.

Symptoms of overdose include seizures, arrhythmias, and GI effects.

Precaution

Montelukast 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 Montelukast.

In rare cases, patients on therapy with Montelukast 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 Montelukast and these underlying conditions has not been established.

Careful consideration is needed for various interacting drugs and physiologic conditions that can alter Theophylline clearance. Dosage adjustment is required prior to initiation of Theophylline therapy, prior to increases in Theophylline dose, and during follow up. The dose of Theophylline selected for initiation of therapy should be low and, if tolerated, increased slowly over a period of time.

Interaction

Montelukast 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, Montelukast 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 Montelukast approximately 40% following a single 10 mg dose of Montelukast. No dosage adjustment for Montelukast 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 Montelukast.

Allopurinol, cimetidine, norfloxacin, ciprofloxacin, erythromycin, oral contraceptives and propranolol increase serum theophylline levels. Phenytoin, methotrexate and rifampicin lead to decreased serum theophylline levels

Volume of Distribution

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

  • 0.3 to 0.7 L/kg

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.

Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form.

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.

8 hours

Clearance

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

  • 0.29 mL/kg/min [Premature neonates, postnatal age 3-15 days]
  • 0.64 mL/kg/min [Premature neonates, postnatal age 25-57 days]
  • 1.7 mL/kg/min [Children 1-4 years]
  • 1.6 mL/kg/min [Children 4-12 years]
  • 0.9 mL/kg/min [Children 13-15 years]
  • 1.4 mL/kg/min [Children 16-17 years]
  • 0.65 mL/kg/min [Adults (16-60 years), otherwise healthy non-smoking asthmatics]
  • 0.41 mL/kg/min [Elderly (>60 years), non-smokers with normal cardiac, liver, and renal function]
  • 0.33 mL/kg/min [Acute pulmonary edema]
  • 0.54 mL/kg/min [COPD >60 years, stable, non-smoker >1 year]
  • 0.48 mL/kg/min [COPD with cor pulmonale]
  • 1.25 mL/kg/min [Cystic fibrosis (14-28 years)]
  • 0.31 mL/kg/min [Liver disease cirrhosis]
  • 0.35 mL/kg/min [acute hepatitis]
  • 0.65 mL/kg/min [cholestasis]
  • 0.47 mL/kg/min [Sepsis with multi-organ failure]
  • 0.38 mL/kg/min [hypothyroid]
  • 0.8 mL/kg/min [hyperthyroid]

Elimination Route

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

Theophylline does not undergo any appreciable pre-systemic elimination, distributes freely into fat-free tissues and is extensively metabolized in the liver. Renal excretion of unchanged theophylline in neonates amounts to about 50% of the dose, compared to about 10% in children older than three months and in adults.

Pregnancy & Breastfeeding use

Pregnancy: Montelukast 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, Montelukast should be used during pregnancy only if clearly needed.

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

Pregnancy: It is not known whether Theophylline can cause foetal harm when administered to pregnant woman.Xanthines should be given to a pregnant woman only if clearly needed.

Nursing mother: Theophylline is excreted into breast milk and may cause irritability or other signs of mild toxicity in nursing human infants. Serious adverse effects in the infant are unlikely unless the mother has toxic serum Theophylline concentrations.

Contraindication

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

Hypersensitivity to xanthine derivatives. It is also contraindicated in patients with active peptic ulcer disease and in individuals with underlying seizure disorders (unless receiving appropriate anti-convulsing medication).

Theophylline should not be administered concurrently with other xanthine. Use with caution in patients with hypoxemia, hypertension, or those with history of peptic ulcer. Do not attempt to maintain any dose that is not tolerated.

Special Warning

Paediatric use: Safety and efficacy of Montelukast 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 Montelukast on linear growth in paediatric patients have not been conducted.

Geriatric use: Of the total number of subjects in clinical studies of Montelukast, 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.

Symptoms may include nausea, vomiting, gastrointestinal irritation, cramps, convulsions, tachycardia & hypotension. The stomach contents should be emptied & supportive measures employed to maintain circulation, respiration & fluid & electrolyte balance. Electrocardiographic monitoring should be carried out & in severe poisoning charcoal haemoperfusion should be used.

Storage Condition

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

Store in a cool and dry place, protect from light and moisture. Keep out of the reach of children

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