Repnea

Uses

• • Acute and chronic diseases of respiratory tracts associated with viscid mucus including acute and chronic bronchitis
• • Productive cough
• • Inflammatory diseases of Rhinopharyngeal tract (e.g. Laryngitis, Pharyngitis, Sinusitis and Rhinitis) associated with viscid mucus
• • Asthmatic bronchitis, Bronchial asthma with difficult departure of mucus
• • Bronchiectasis
• • Chronic pneumonia.

Levocetirizine Dihydrochloride is used for the treatment of symptoms associated with allergic conditions such as seasonal allergic rhinitis, perennial allergic rhinitis and chronic idiopathic urticaria.

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.

Repnea is also used to associated treatment for these conditions: Airway secretion clearance therapyAllergic Rhinitis (AR), Chronic Idiopathic Urticaria, Common Cold, Nasal Congestion, Perennial Allergic Rhinitis (PAR), Seasonal Allergic RhinitisAsthma, Exercise-Induced Bronchospasm, Perennial Allergic Rhinitis (PAR), Seasonal Allergic Rhinitis

How Repnea works

Ambroxol is a mucolytic agent. Excessive Nitric oxide (NO) is associated with inflammatory and some other disturbances of airways function. NO enhances the activation of soluble guanylate cyclase and cGMP accumulation. Ambroxol has been shown to inhibit the NO-dependent activation of soluble guanylate cyclase. It is also possible that the inhibition of NO-dependent activation of soluble guanylate cyclase can suppress the excessive mucus secretion, therefore it lowers the phlegm viscosity and improves the mucociliary transport of bronchial secretions.

Levocetirizine selectively inhibits histamine H₁ receptors. This action prevents histamine from activating this receptor and causing effects like smooth muscle contraction, increased permeability of vascular endothelium, histidine uptake in basophils, stimulation of cough receptors, and stimulation of flare responses in the nervous system.

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

Repnea dosage

Average daily dose (preferably after meal):Pediatric Drops:

• 0-6 months: 0.5 ml 2 times a day
• 6-12 months: 1 ml 2 times a day
• 1-2 years: 1.25 ml 2 times a day

Syrup:

• 2-5 years: 2.5 ml (1/2 teaspoonful) 2-3 times a day
• 5-10 years: 5 ml (1 teaspoonful) 2-3 times a day
• 10 years and adults: 10 ml (2 teaspoonful) 3 times a day.

Sustained release capsule:

• Adult and children over 12 years old: 1 capsule once daily

Specific application features: Ambroxol may be prescribed to patients suffering from diabetes mellitus.

Adults and children 12 years of age and older: 5 mg once daily in the evening

Children 6 to 11 years of age: 2.5 mg once daily in the evening

Children 6 months to 5 years of age: 1.25 mg (1/2 teaspoon oral solution) once daily in the evening

Renal Impairment: Adjust the dose in patients 12 years of age and older with decreased renal function

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.

Side Effects

Gastrointestinal side-effects like epigastric pain, gastric fullness may occur occasionally. Rarely allergic responses such as eruption, urticaria or angioneurotic edema may occur.

The most common adverse reactions (rate ≥2% and > placebo) were somnolence, nasopharyngitis, fatigue, dry mouth, and pharyngitis in subjects 12 years of age and older, and pyrexia, somnolence, cough, and epistaxis in children 6 to 12 years of age. In subjects 1 to 5 years of age, the most common adverse reactions (rate ≥2% and > placebo) were pyrexia, diarrhea, vomiting, and otitis media. In subjects 6 to 11 months of age, the most common adverse reactions (rate ≥3% and > placebo) were diarrhea and constipation.

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.

Toxicity

Patients experiencing an overdose may present with drowsiness. Children may become agitated and restless before drowsiness. Patients should be treated with supportive measures. Dialysis will not assist in removing the drug from the body.

The maximal nonlethal dose in mice and rats is 240mg/kg.

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.

Precaution

Ambroxol should be given cautiously to patients with gastric and duodenal ulceration or convulsive disorders. Patients with hepatic and renal insufficiency should take it with caution.

Epileptic patients and patients at risk of convulsions. Renal impairment. Pregnancy and lactation.

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.

Interaction

Ambroxol has no interaction with cardioactive glycosides, corticosteroids, bronchodilators, diuretics and antibiotics (normally used in the treatment of bronchopulmonary affections). But Ambroxol should not be taken simultaneously with antitussives (e.g. Codeine) because mucus, which has been liquefied by Ambroxol, might not be expectorated.

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.

Volume of Distribution

The volume of distribution of levocetirizine is 0.33±0.02L/kg.

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

Elimination Route

Rapid and almost complete.

Following a 5mg oral dose of levocetirizine, a C_max of 0.27±0.04µg/mL with a T_max of 0.75±0.50h. The AUC of levocetirizine is 2.31±0.50µg*h/mL. Taking levocetirizine with food does not affect the AUC but delays T_max by 1.25 hours and lowers C_max by 36%.

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

7-12 hours

The average half life of levocetirizine is 7.05±1.54 hours.

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 average clearance of levocetirizine is 0.57±0.18mL/min/kg.

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

Elimination Route

168 hours post dose an average of 85.4% of a radiolabeled dose was recovered with an average of 80.8% in the urine and 9.5% in the feces. In the urine, 77% of the dose was recovered as unchanged drug, 0.5% as the M8 and M9 metabolites, 0.4% as the M10a metabolite, 0.4% as the M10b metabolite, 0.3% as the M3 metabolite, 0.3% as the M4 and M5 metabolite, 0.2% as the M2 metabolite, and 0.1% as the M1 metabolite. In the feces, 9.0% of the dose was recovered as unchanged drug, 1.0% as the M4 and M5 metabolite, and 0.1% as the M1 metabolite.

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

Pregnancy & Breastfeeding use

Pregnancy: Teratogenic and fetal toxicity studies have shown no harmful effect of Ambroxol. However, it is advised not to use during pregnancy, especially in the 1st trimester.

Lactation: Safety during lactation has not been established.

Pregnancy: The safety of Levocetirizine in pregnancy has not been established. Therefore, it should be used with caution during pregnancy and only if the potential benefits to the mother outweigh any risks to the foetus.

Lactation: Levocetirizine passes into breast milk. So, it should be used with caution in nursing mothers and only if the expected benefit to the mother is greater than the risk to the nursing infant.

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.

Contraindication

Contraindicated in known hypersensitivity to Ambroxol or Bromhexine.

It is contraindicated in patients who are hypersensitive to this medication or to any of its ingredients.

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

Special Warning

Paediatric use: Not recommended for use in children less than 6 years of age.

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: Drowsiness, agitation, restlessness, confusion, diarrhoea, dizziness, fatigue, headache, malaise, mydriasis, pruritus, sedation, somnolence, stupor, tachycardia, tremor and urinary retention.

Management: Symptomatic and supportive treatment. Gastric lavage must be considered shortly following ingestion.

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 between 20-25°C.

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

Innovators Monograph

You find simplified version here Repnea