®PROFILAR

 Profilar®

Ketotifen Hydrogen Fumarate

Description:

PROFILAR® (Ketotifen Hydrogen Fumarate) is a non-bronchodilator, potent anti-allergic and anti-asthmatic drug. It inhibits the effects of the inflammatory mediators, and thereby exerts its anti-allergic activity.

 It also inhibits the release of allergic mediators such as histamine and leukotrienes, suppresses the influx of eosinophils into inflammatory site and inhibits the development of airway hyperactivity associated with activation of platelets by PAF (Platelet Activating Factor) or caused by neural activation following the use of sympathomimetic drugs or the exposure to allergen, thereby exerts its anti-asthmatic activity.

Properties:

After oral administration the absorption of Ketotifen is nearly complete. Bioavailability is about 50% due to a first-pass effect of about 50% in the liver and its bioavailability is not influenced by food intake. Maximal plasma concentration reaches within 2-4 hours.

Plasma protein binding is 75%. Ketotifen is eliminated biphasically with a short half-life of 3 - 5 hours and a longer one of 21 hours.

About 60% - 70% of the administered dose is excreted as metabolites and 1% is excreted unchanged in the urine.

 The pattern of metabolism in children is the same as in adults, but the clearance is higher in children. Therefore, the children over the age of 3 years require the same daily dosage regimen as adults.

Indications:

PROFILAR® is indicated in the following cases:

- Preventative treatment of bronchial asthma: Especially when associated with atopic symptoms.

Ketotifen is not effective in aborting established attacks of asthma.

- Prevention and treatment of multisystem allergic disorders:

* Chronic urticaria.

* Atopic dermatitis.

* Allergic rhinitis and conjunctivitis.

Dosage and administration:

Adults:

One PROFILAR® tablet (1 mg) twice daily (with morning and evening meals). In patients susceptible to sedation, a slow increase in the dose is recommended during the first week of treatment, starting with ½ tablets twice daily or one PROFILAR® tablet taken in the evening, and increasing to the full therapeutic dose. If necessary, the daily dose may be increased up to 4 mg (2 PROFILAR® tablets twice daily). At the higher doses, an accelerated onset of efficacy may be expected.

Children:

Children aged 6 months to 3 years:

0.05 mg (equals to 0.25 ml) per kilogram body weight twice daily (morning and evening).

Children over 3 years of age:

5 ml (1 teaspoonful) PROFILAR® syrup or one PROFILAR® tablet twice daily with morning and evening meals.

Patient notes:

- In the prevention of bronchial asthma it may take several weeks of treatment to achieve the full therapeutic effect.  It is therefore recommended that for patients not adequately responding within a few weeks, treatment with PROFILAR® should be maintained for a minimum of 2 to 3 months.

- If it is necessary to withdraw PROFILAR®, this should be done progressively over a period of 2 to 4 weeks. Symptoms of asthma may recur.

- Concomitant bronchodilator therapy: If bronchodilators are used concomitantly with PROFILAR®, the frequency of bronchodilator dosage can be reduced.

- Use in children: Children may require a higher dose in mg/kg body weight than adults in order to obtain optimal results. This higher dose is as well tolerated as lower as lower doses.

- Use in elderly: There are no special requirements in elderly patients.

Contraindications:

Known hypersensitivity to Ketotifen or any of the excipients.

Precautions:

-Symptomatic and prophylactic anti-asthmatic drugs that are already in use should never be withdrawn abruptly when long treatment with Ketotifen is started. This applies especially to systemic corticosteroids, because of the possible existence of adrenocortical insufficiency in steroid-dependent patients; in such cases recovery of a normal pituitary-adrenal response to stress may take up to one year.

-Convulsions have been reported very rarely during Ketotifen therapy. As Ketotifen may lower the seizure threshold, it should be used with caution in patients with a history of epilepsy.

- In diabetic patients, the carbohydrate content of the syrup should be taken into consideration.

-A reversible fall in the thrombocyte count in patients receiving Ketotifen concomitantly with oral antidiabetic agents has been observed in rare cases. Thrombocyte counts should therefore be carried out in patients taking antidiabetics concomitantly.

-During the first few days of treatment with Ketotifen, the patient's reactions may be impaired; therefore caution is required when driving a vehicle or operating a machinery.

Use during pregnancy and lactation:

Pregnancy: Although Ketotifen is without effect on pregnancy and on peri- and post-natal development at dose levels which are tolerated by the mother animals, Ketotifen safety in human pregnancy has not been established. Ketotifen should therefore be given to pregnant only in compelling circumstances.

Lactation: Ketotifen is excreted in rat milk. It is assumed that Ketotifen is also excreted in human breast milk, and therefore mothers receiving Ketotifen should not breast-feed.

Drug interactions:

Ketotifen may potentiate the effect of CNS depressants, antihistamines and Alcohol.

Side effects:

Sedation, dry mouth and dizziness may occur at the beginning of the treatment, but usually disappear spontaneously with continued treatment.

Symptoms of CNS stimulation, such as excitation, irritability, insomnia and nervousness, have been observed commonly and particularly in children.

Other side effects:

- Infections and infestations: Cystitis has been occurred uncommonly.

- Immune system disorders: Erythema multiforme, Steven-Johnson syndrome and severe skin reactions have been occurred very rarely.

- Metabolism and nutrition disorders: Weight increase has been occurred rarely.

- Nervous system disorders:

• Uncommon: Dizziness.

• Rare: Sedation.

- Gastrointestinal disorders: Dry mouth has been occurred uncommonly.

- Hepatobiliary disorders: Hepatitis and increase in liver enzymes have been occurred very rarely.

Overdosage:

The main symptoms of acute overdosage include: Drowsiness to severe sedation; confusion and disorientation; tachycardia and hypotension; especially in children, hyperexcitability or convulsions; reversible coma.

Treatment should be symptomatic. If the drug has been taken very recently, emptying of the stomach may be considered. Administration of activated charcoal may by beneficial. If necessary, symptomatic treatment and monitoring of the cardiovascular system are recommended; if excitation or convulsions are present, short-acting barbiturates or benzodiazepines may be given.

Storage conditions:

PROFILAR® Syrup: Store at temperature not exceeding 25°C.

PROFILAR® Tablets: Store at temperature not exceeding 30°C.

Presentation:

PROFILAR® Syrup: Each teaspoonful (5 ml) contains Ketotifen Hydrogen Fumarate equivalent to Ketotifen 1 mg in bottles of 120 ml.

PROFILAR® Tablets: Each tablet contains Ketotifen Hydrogen Fumarate equivalent to Ketotifen 1 mg in packs of 30 tablets.

Hospital packs are also available.