Fenobat is indicated for symptomatic treatment of allergic conditions including rhinitis and conjunctivitis.

Oral administration.

Adult:

1mg twice daily with food. If necessary, the dose may be increased to 2mg twice daily. At the higher dose, an accelerated onset of efficacy may be expected.

Special populations

Pediatrics Children aged 2 to 3 years:

0.05mg (=0.25 ml Fenobat Oral Solution 1mg/5ml) per kilogram body weight twice daily (morning and evening).

Pediatrics over 3 years of age and adolescents:

1 mg twice daily with food.

Geriatrics (aged 65 years and above)

No evidence exists that elderly patients require different dosages or show different side effects from younger patients.

Patients known to be easily sedated should begin treatment with 0.5 to 1 mg at night for the first few days.

Renal impairment

No studies have been performed in renally impaired patients and hence no dosing recommendations can be provided for these patients (see section 5.2).

Hepatic impairment

No studies have been performed in hepatically impaired patients and hence no dosing recommendations can be provided for these patients (see section 5.2).

If intercurrent infection occurs Fenobat treatment must be supplemented by specific antimicrobial therapy.

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

Thrombocytopenia may occur in patients taking Fenobat at the same time as oral antidiabetic drugs (biguanides). The simultaneous administration of these drugs should therefore be avoided (see section 4.3).

In case of reduced attention, possibly due to the sedating effect of Fenobat, the dose should be reduced.

Fenobat oral solution contains maltitol liquid (hydrogenated glucose syrup). Patients with rare hereditary problems of fructose intolerance should not take this medicine.

This medicinal product contains propyl and methyl parahydroxybenzoate. They may cause allergic reactions (possibly delayed).

This medicine contains less than 1 mmol sodium (23 mg) per 5 ml dose, that is to say essentially "sodium-free".

Fenobat may potentiate the effects of CNS depressants, antihistamines, anticoagulants and alcohol.

The simultaneous administration of oral antidiabetic drugs and Fenobat should be avoided (see section 4.3 and 4.4).

Women of child-bearing potential

There is no data to support any special recommendations in women of child-bearing potential

Fertility

Treatment of male rats with a toxic oral dose of ketotifen (50 mg/kg/day) for 10 weeks prior to mating resulted in decreased fertility, but was not impaired at doses relevant for human use. The fertility of female rats as well as prenatal development, pregnancy and weaning of the offspring were not adversely affected by ketotifen treatment at oral dose levels of up to 50 mg/kg per day. There is no data available on the effect of Fenobat on fertility in humans.

Pregnancy

There are no or limited amount of data from the use of ketotifen in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

Fenobat should not be used during pregnancy unless the clinical condition of the woman requires treatment with ketotifen.

Breast-feeding

Available data in rats have shown excretion of ketotifen in milk, while there is no human data available. It is assumed that this drug is also excreted in human breast milk, and therefore mothers receiving Fenobat should not breast-feed (see section 4.3).

During the first few days of treatment with Fenobat reactions may be impaired. Patients should be warned not to take charge of vehicles or machinery until the effect of Fenobat treatment on the individual is known

Adverse drug reactions from clinical trials, spontaneous reports and literature cases are listed by MedDRA system organ class.

Adverse drug reactions are ranked under heading of Preferred Term (PT) frequency, with the most frequent first. Since reactions from spontaneous reports and literature cases are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorized as not known. The following convention is used:

very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000) very rare (< 1/10,000), not known (cannot be estimated from the available data), including isolated reports. Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness.

Infections and infestation

Uncommon: Cystitis.

Immune system disorders

Very rare: Erythema multiforme, Stevens-Johnson syndrome, Severe cutaneous adverse reaction

Metabolism and nutrition disorders

Rare: Weight increased

Psychiatric disorders**

Common: Agitation, irritability, insomnia, nervousness

Nervous system disorders Uncommon: Dizziness* Rare: Sedation*

Not known: Convulsions, somnolence, headache

Gastrointestinal disorders

Uncommon: Dry mouth*

Not known: Vomiting, nausea, diarrhea

Hepatobiliary disorders

Very rare: Hepatitis, hepatic enzymes increased

Skin and subcutaneous tissue disorders

Not known: Rash, urticaria *

*Somnolence and sedation, dry mouth and dizziness may occur at the beginning of treatment, but usually disappear spontaneously with continued medication. There have been reports of nausea, vomiting, headache, convulsion, urticaria and rash.

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

To report any side e ffect(s):

Saudia Arabia

-        The National Pharmacovigilance and Drug Safety Centre (NPC)

-        SFDA Call Center: 19999

-        E-mail: npc.drug@sfda.gov.sa

-        Website: https://ade.sfda.gov.sa/

United Arab Emirates 

-        Pharmacovigilance & Medical Device section

-     P.O.Box: 1853

-     Tel: 80011111

-        Email : pv@mohap.gov.ae

-        Drug Department Ministry of Health & Prevention Dubai, UAE

Other GCC

Please contact the relevant competent authority

The main symptoms of acute overdose include: drowsiness to severe sedation; dizziness, confusion and disorientation; tachycardia and hypotension; especially in children, hyperexcitability or convulsions; reversible coma. Bradycardia and respiratory depression should be watched for.

Treatment

Treatment should be symptomatic. If the drug has been taken very recently, emptying of the stomach may be considered. Administration of activated charcoal may be beneficial. If necessary, symptomatic treatment and monitoring of the cardiovascular system is recommended; if excitation or convulsions are present, short- acting barbiturates or benzodiazepines may be given. Fenobat cannot be eliminated by dialysis.

Pharmacotherapeutic group: Other antihistamines for systemic use, ATC code: R06AX17.

Pharmacodynamic effects

Fenobat is a non-bronchodilator, anti-asthmatic drug which inhibits the effect of certain endogenous substances known to be inflammatory mediators, and thereby exerts anti-allergic activity.

Laboratory experiments indicate that this anti-anaphylactic activity may be due to the inhibition of release of allergic mediators such as histamine and leukotrienes. The suppression of the priming of eosinophils by human recombinant cytokines and thereby suppression of the influx of eosinophils into inflammatory loci and the inhibition of 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. In addition, Fenobat exerts a non- competitive blocking effect on histamine (H1) receptors. Therefore, it can also be used in place of classical histamine (H1) receptor antagonists.

Fenobat is an established product. There are no new clinical studies.

Absorption

After oral administration, the absorption of Fenobat is almost complete. Bioavailability amounts to approximately 50% owing to a first-pass effect of about 50% in the liver. Maximal plasma concentrations are reached within 2 to 4 hours.

Distribution

Protein binding is 75%.

Biotransformation

The main metabolite is ketotifen-N-glucuronide. This is practically inactive.

Elimination

Ketotifen is eliminated biphasically, with a short half-life of 3 of 5 hours and a longer one of 21 hours. About 1% of the substance is excreted unchanged in the urine within 48 hours and 60 to 70% is excreted as metabolites.

Effect of food

The bioavailability of Fenobat is not influenced by the intake of food. Therefore, Fenobat can be taken with or without food.

However, smooth plasma concentration profile may be observed when administered with meals.

Special populations

Pediatrics

The pattern of metabolism in children is the same as in adults, but the clearance is higher in children below 3 years. Therefore, the ketotifen dose per kilogram is higher for children compared to the adults.

Children over the age of 3 years therefore require the same daily dose regimen as adults.

Hepatic impairment

No relevant pharmacokinetic studies have been performed with Fenobat in patients with hepatic impairment. Since ketotifen is metabolized in the liver and its glucuronidation may be impaired in severe hepatic impairment, the clearance of ketotifen will most likely be reduced in patients with severe hepatic impairment and the possibility of accumulation of unchanged drug cannot be excluded.

Renal impairment

No relevant pharmacokinetic studies have been performed with Fenobat in patients with renal impairment. However, considering that 60-70% of the dose is excreted in urine as metabolites, an increased risk of adverse reactions due to accumulation of metabolites cannot be excluded.

Acute toxicity

Acute toxicity studies of ketotifen in mice, rats and rabbits revealed oral LD50 values above 300mg/kg bodyweight and between 5 and 20mg/kg by the i.v route. Adverse effects induced by overdose were dyspnea and motor excitation followed by spasms and drowsiness. Toxic signs appeared rapidly and disappeared within hours; there was no evidence of cumulative or delayed effects. A total daily dose of 10- ml administered to a child of 30kg would be equivalent to 0.33ml/kg Fenobat syrup and 0.07mg/kg ketotifen base, indicating a sufficiently wide safety margin.

No evidence of skin sensitizing potential of ketotifen was obtained in guinea pigs by intracutaneous injection.

Mutagenicity

Ketotifen and/or its metabolites were devoid of genotoxic potential, when investigated in vitro for induction of gene mutation in Salmonella typhimurium, for chromosome aberrations in V79 Chinese hamster cells, or for primary DNA-damage in rat hepatocyte cultures. No clastogenic activity was observed in vivo (cytogenic analysis of bone marrow cells in the Chinese hamster, bone marrow micronucleus assay in mice). Likewise, no mutagenic effects were evident on the germ cells of male

mice in the dominant lethal test.

Carcinogenicity

In rats treated continuously in the diet for 24 months, maximum tolerated doses of 71mg/kg ketotifen per day revealed no carcinogenic potential. No evidence of tumorigenic effects was obtained in mice treated with up to 88mg/kg body weight in the diet for 74 weeks.

Reproductive Toxicity

No embryotoxic or teratogenic potential of ketotifen was revealed in rats or rabbits. In male rats treated for 10 weeks (i.e. more than a complete spermatogenic cycle) before mating, fertility was unaffected at a tolerated dose of 10mg/kg per day.

The fertility of female rats as well as prenatal development, pregnancy and weaning of the offspring were not adversely affected by ketotifen treatment at oral dose levels of up to 50mg/kg per day, although non-specific toxicity to the pregnant females was observed at and above 10mg/kg. Likewise, no adverse effect of treatment was found in the peri-natal phase. Due to the maternal toxicity, some decrease in pup survival and weight gain was recorded during the first days of postnatal development at the high dose level of 50mg/kg per day.

Maltitol syrup, Citric acid anhydrous, Disodium hydrogen phosphate, micronized Sucralose, Methylparaben, Propylparaben, Strawberry flavour liquid and Purified water.

Not applicable.

Store below 30ºC

Keep out of the sight and reach of children.

Do not use Fenobat 1 mg/5 ml oral solution after the expiry date (EXP) which is stated on the box and the label.

Fenobat oral solution is filled into an Amber glass bottle, type III of 125 ml capacity and capped with a white tamper-proof HDPE screw cap. Each bottle contains 120 mL of oral solution.

Each bottle is packed into a carton box with an insert leaflet and a graduated measuring cup.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.