Mastifen Lc

Uses

Ketotifen is used for the prophylactic treatment of bronchial asthma, symptomatic treatment of allergic conditions including rhinitis and conjunctivitis.

Ketotifen has antiallergic properties and has been used similarly, to Sodium Chromoglycate in the prophylactic treatment of asthma. It also has the properties of an antihistamine. Ketotifen possesses marked anti-anaphylactic properties and is effective in preventing asthmatic attack. Ketotifen exerts sustained inhibitory effect on histamine reactions, which can be clearly dissociated from its antianaphylactic properties. Experimental investigations in asthmatic subjects have shown that Ketotifen is as effective orally as administered by inhalation as a selective mast cell stabiliser. Antihistamines were ineffective in those tests. The effectiveness of Ketotifen has been studied in long term clinical trials. Asthma attacks were reduced in number, severity and duration and in some cases, the patients were completely freed from attacks. Progressive reduction of corticosteroids and/or bronchodilators was also possible. The prophylactic activity of Ketotifen may take several weeks to become fully established. Ketotifen will not abort established attacks of asthma.

Ketotifen eye drop is used for the treatment of signs & symptoms (itchy, watery, red & swollen eyes and eyelids) of allergic conjunctivitis including vernal kerato-conjunctivitis, vernal-keratitis, blepharitis, blepharo-conjunctivitis, and giant papillary conjunctivitis.

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.

Mastifen Lc is also used to associated treatment for these conditions: Allergic Rhinitis (AR), Asthma, Allergic, Eye pruritus, Seasonal Allergic ConjunctivitisAllergic Rhinitis (AR), Chronic Idiopathic Urticaria, Common Cold, Nasal Congestion, Perennial Allergic Rhinitis (PAR), Seasonal Allergic Rhinitis

How Mastifen Lc works

The precise mechanism(s) through which ketotifen exerts its therapeutic effects are unclear. Ketotifen is a potent and non-competitive antagonist of H1 histamine receptors, which is likely to be a significant contributor to its anti-allergic activity. In addition, ketotifen stabilizes mast cells and has demonstrated in vitro the ability to inhibit the release of allergic and inflammatory mediators such as histamine, leukotrienes C₄ and D₄ (i.e. SRS-A), and platelet-activating factor (PAF).

Other in vivo observations thought to contribute to ketotifen's efficacy in asthma include the inhibition of various PAF-mediated processes (e.g. airway hyperreactivity, eosinophil and platelet accumulation in the airways), prevention of leukotriene-induced bronchoconstriction, and suppression of eosinophil priming.

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.

Dosage

Mastifen Lc dosage

Adults: 1 mg twice daily with food. If necessary the dose may be increased to 2 mg twice daily in severe cases.

Children above 2 years: 1 mg twice daily with food. Patient’s known to be easily sedated should begin treatment with 0.5 to 1 mg at night for the first few days or as directed by the physician.

Use in elderly: Same as adult dose or as advised by the physician.

Adults and children 3 years and older: 1 drop in the affected eye(s) twice daily, every 8-12 hours, not more than twice per day.

Children under 3 years of age: Consult with a doctor.

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

Side Effects

Drowsiness and in isolated cases, dry mouth and slight dizziness may occur at the beginning of treatment, but usually disappear spontaneously after a few days.

Common side effects are burning, stinging, punctate corneal epithelial erosion, Blurring of vision upon drug instillation, dry eyes, eyelid disorder, conjunctivitis, eye pain, photophobia, subconjunctival haemorrhage.

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.

Toxicity

Oral ingestion of up to 60x the recommended dose has been reported, although no fatal overdoses of ketotifen have been described. Symptoms of ketotifen overdosage may include significant sedation, confusion, disorientation, tachycardia, hypotension, convulsions, hyperexcitability (particularly in children), and/or reversible coma. If ingestion is recent, consider the use of gastric lavage or activated charcoal. Other treatments should be supportive and administered as necessary based on symptoms.

Physostigmine may be useful to mitigate anticholinergic effects, and short-acting barbiturates or benzodiazepines may be used if the patient presents with excitation or convulsions.

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.

Precaution

It is important to continue the previous treatment for a minimum of two weeks after starting Ketotifen to avoid the possibility of exacerbation of asthma. This applies specially to systemic corticosteroids and ACTH because of the possible existence of adrenocortical insufficiency in steroid dependent patient. If intercurrent infection occurs, Ketotifen treatment must be supplemented by specific antimicrobial therapy. During the first day of treatment with Ketotifen, reactions may be impaired and patients should be warned not to take charge of vehicle or machinery until the effect of Ketotifen treatment on the individual is known. Patient should be advised to avoid alcoholic drinks. Ketotifen may potentiate the effects of sedatives, hypnotic, antihistamines and alcohol.

The formulation of Ketotifen 0.025% eye drops contains benzalkonium chloride as a preservative, which may be deposited in soft contact lenses; therefore this eye drops should not be instilled while the patient is wearing lenses. The lenses should be removed before application of the drops and not reinserted earlier than 15 minutes after use.

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

Interaction

A reversible fall in the platelet count has been observed in a few patients receiving Ketotifen concomitantly with oral antidiabetics and it has been suggested that this combination should therefore be avoided. Since Ketotifen has the properties of the antihistamines, it may potentiate the effects of other CNS depressant drugs such as alcohol, antihistamines, hypnotics and sedatives.

If Ketotifen eye drops is used concomitantly with other eye medications there must be an interval of at least 5 minutes between the two medications.

Volume of Distribution

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

Elimination Route

Following oral administration, absorption is relatively quick (with a T_max of ~3 hours) and nearly complete as judged by plasma concentrations and urinary excretion levels - despite this, oral bioavailability is only ~50% due to a significant first-pass effect in the liver.

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%.

Half Life

Ketotifen clearance is biphasic - the half-life of the distribution phase is approximately 3-5 hours and the half-life of the elimination phase is 22 hours.

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

Clearance

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

Elimination Route

More than 60% of an administered dose is excreted in the urine, primarily as metabolites - of this material, 5

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.

Pregnancy & Breastfeeding use

Although there is no evidence of any teratogenic effect, Ketotifen in pregnancy and lactation is not recommended.

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.

Contraindication

A reversible fall in the platelet count has been observed in a few patients receiving Ketotifen concomitantly with oral antidiabetic agent and it has been suggested that this combination should therefore be avoided.

Hypersensitivity to Ketotifen or any of the components

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

Special Warning

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

Acute Overdose

Symptoms: Drowsiness, confusion, dyspnoea, bradycardia or tachycardia, disorientation, convulsions, severe hypotension, reversible coma.

Management: Supportive and symptomatic.

No case of overdose has been reported. Oral ingestion of the contents of a 5 ml bottle would be equivalent to 1.25 mg of Ketotifen which is 60% of a recommended oral daily dose for a 3 years old child. Clinical results have shown no serious signs or symptoms after oral ingestion of up to 20 mg of Ketotifen.

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.

Storage Condition

Store at 25° C.

Store between 20-25°C.

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