Control of asthmatic disease development and of bronchostenotic conditions in those patients who do not obtain a satisfactory control of symptoms with the usual inhaled doses of beclometasone dipropionate.

Adults: usually, 2 inhalations twice a day. Should it be deemed as more suitable, posology can be fractioned even into 1 inhalation 4 times daily. In case of need, therapy can be increased up to 2 inhalations 3-4 times a day.Therapy with Clenil Forteshould not be abruptly interruptedChildren: Clenil Forte250mcg is not suitable for paediatric use.

Instructions for useThe successful result of treatment depends on a correct use of the inhaler.Inhaler’sworking test: before using the inhaler for the first time, or if it has not been used for three days or more, remove the mouthpiece protective closure by softly pressing it on its sides and press once in the air to release an actuation, so as to verify the correct working of the inhaler.For use, carefully follow the following instructions:1)hold the actuator between thumb and index, with the mouthpiece downwards;2)remove the protecting cap;3)place the mouthpiece firmly between the lips and make a complete expiration;4)make a long and deep inspiration with the mouth only and, at the same time press once only with the index.Once the inspiration is complete, hold breath as long as possible.When inhalations are completed, close the mouthpiece again with the protecting cap. The mouthpiece should always be kept clean. Cleaning should be made with lukewarm water, after having extracted the pressurised canister.

The patient should be instructed on how to use inhaler, in order to be sure that the medicine reaches the target area in thelungs.Clenil Forteis not efficacious in asthma attacks in progress; on the contrary, it represents a fundamental treatment of the asthmatic disease: it should be regularly taken at the prescribed doses and as long as the physician deems it as suitableeven if the patient is asymptomatic. In these cases a rapid-acting broncodilatator (administered by inhalation) is necessary for this. The patient must therefore have access to this relief medication.Severe asthma requires regular medical check-ups that include lung function tests, because there is a risk of severe attacks or even death. The patient should be instructed to seek medical help if rapid-acting, bronchodilator treatment becomes less effective (or if they need more inhalations than usual) becausethis can indicate a deterioration of asthma control. If this happens, then the patient must be assessed and the need for increased anti-inflammatory therapy considered (for example, a higher dose of inhaled corticosteroid or an oral corticosteroid). Severe worsening of asthma must be treated in the usual way (i.e. by increasing the dose of inhaled beclometasone dipropionate, by giving a systemic steroid [if necessary], and/or an appropriate antibiotic if there is an infection, along with a β-agonist therapy).

Treatment with Beclometasone dipropionate should not be stopped abruptly.Systemic reactions to inhaled corticosteroids may occur, especially when they are used for long periods and have been prescribed at high doses. These effects are much less likelyto occur than with oral corticosteroids.Possible systemic effectsinclude Cushing syndrome, Cushingoid appearance,adrenal suppression, growth retardation in children and adolescents, decrease inbone mineral density, cataract and glaucomaand more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).It is therefore important that the inhaled dose of corticosteroid is the lowest possible one allowing effective control of asthma.It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is regularly monitored. If growth is slowed, the therapy should be adjusted with the aim of reducing the doseof inhaled corticosteroids, if possible, to the lowest dose at which effective control of asthma is maintained. In addition, consideration should be given to referring the patient to a paediatric respiratory specialist.Very rare cases of acute adrenal crisis have occurred in paediatric patients exposed to higher doses than what recommended (about 1000 mcg/day) for prolonged periods (several months or years). Symptoms of adrenal insufficiency are initially aspecific and include anorexia, abdominal pain, weight loss, tiredness, nausea, vomiting; specific symptoms occurring after inhaled corticosteroid treatment include hypoglycaemia with reduced state of consciousness and/or seizures. Adrenal crisis can potentially be determined by traumas, surgery, infections and sudden reduction of posology. Patients receiving high doses should be closely followed and their dose gradually reduced. Monitoring of adrenal reserve may also be necessary.Treatment management in patients already under treatment with systemic corticosteroids requires special attention and a close monitoring, since recovery of the adrenal function, suppressed by prolonged treatment with systemic corticosteroids, is slow. In any case the disease should be relatively “stabilised” with systemic steroids. Initially, Clenil Forteshould be administered concomitantly with the systemic steroidsandafter approximately one week

this should be progressively reduced and the patient regularly monitored (in particular, adrenocortical function tests should be periodically performed), by adjusting Clenil Forteposology according to the attained results. The reductions of the dose must not be greater than 1 mg for patients receiving a maintenance dose of 10 mg per day, or less, of prednisolone (or its equivalent).Larger reductions may be appropriate with higher maintenance doses. The reduction of the oral dose should be implemented with intervals of not less than one week.Some patients feel unwell during withdrawal of systemic steroids, despite maintenance or evenimprovement of the respiratory function. They should be encouraged to persevere with inhaled beclometasone dipropionate and to continue withdrawal of systemic steroids, unless there are objective indications of adrenal insufficiency. Patients weaned off oral steroids, whose adrenocortical function is impaired may need supplementary systemic steroids in crisis situations (for example with worsening asthma attacks, chest infections, major intercurrent illness, surgery, trauma, etc.).Replacement of systemic steroids with inhaled medicines can sometimes unmask allergies (such as allergic rhinitis or eczema) that were previously suppressed by the systemic medicine. These allergies should be properly treated with antihistamines and/ortopical preparations, including topical steroids. Treatment with corticosteroids can mask some symptoms of pulmonary tuberculosis and other bacterial airway conditions, as well as fungal and viral airway infections. Pulmonary tuberculosis can also be reactivated by the (re)introduction of inhaled corticosteroids. Consideration should be given to this when treating asthma patients with airway infections, where both the asthma as well as the airway infection must be properly treated. Restraint must be exercised in the treatment of patients with lung anomalies such as bronchiectasis and pneumoconiosis, in connection with the possibility of fungal infections. Patients should be advised to thoroughly rinse their mouths with water after using the product in order to reduce the risk of Candida infection.Patients should be advisedthat the product contains small amounts of ethanoland glycerol. With normal doses, the amounts of ethanol and glycerol are negligible and do not pose a risk to the patient. However, due to the presence of alcohol, the product should be cautiously used in patients suffering from hepatic pathologies, alcoholism (see also section 4.5), epilepsy, cerebral pathologies.Keep the medicine out ofthe reach and sight of children.

CLENIL FORTEcontains a small amount of ethanol. There is the theoretical potential for interaction in particularly sensitive patients taking disulfiram or metronidazole..

In pregnant women the product should be administered in case of real need and under direct medical control. There is inadequate evidence of safety of beclometasone dipropionate or HFA 134a propellant in humans.. Product administration during pregnancy and lactation should be only taken into consideration if the envisaged benefit for the mother outweighs the potential risks for the foetus. It is reasonable to assume that, at the used inhaled doses, there are no important levels of beclometasone in the mother milk.Children born from mothers having received considerable doses of inhaled corticosteroids during pregnancy, should be carefully monitored in order to detect a possible hypoadrenalism.

Studies on the effects of the propellant HFA 134a on reproductive function and embryofoetal development in animals did not point out clinically important adverse events. Therefore, the occurrence of adverse events in humans is unlikely.

Clenil Fortehas no influence on the ability to drive and use machines

Adverse events are listed below by system class and frequency. Frequencies are defined as: very common (1/10), common (1/100 and <1/10), uncommon (1/1,000 and <1/100), rare (1/10,000 and < 1/1,000), very rare (≤1/10,000), unknown (frequency cannot be estimated from the available data).

Systemic organ ClassAdverse ReactionFrequencyInfections & Infestations Oral candidiasis (of the mouth and throat) Very Common Immune System Disorders Hypersensitivity reaction with the following manifestations: Rash, urticaria, pruritus, erythema UncommonOedema of the eyes, face, lips and throat Very RareEndocrine disorders Adrenal suppression*, growth retardation* (in children and adolescents), bone density decreased* Very RarePsychiatric disorders (see section 4.4 “Special warning and precautions for use”) Psychomotor hyperactivity, sleep disorders, anxiety, depression, aggression, behavioural disorders (predominantly in children) Unknown Eye disorders Cataract*, glaucoma* Very Rare Respiratory, Thoracic & Mediastinal Disorders Hoarseness, throat irritation Common Paradoxical bronchospasm, wheezing, dyspnoea, cough

* Systemic reactions are a possible response to inhaled corticosteroids, especially when a high dose is prescribed for a prolonged time (section 4.4 “Special Warning and precaution for use”). As with other inhalation therapies, paradoxical bronchospasm may occur, with an immediate increase in wheezing,shortness of breath and cough after intake. This should be immediately treated with a fast-acting inhaled bronchodilator and Beclometasone dipropionate should be immediately discontinued. The incidence of candidiasis of the mouth and throat increases with doses of more than 400 micrograms beclometasone dipropionate per day. Patients with high blood levels of Candida precipitins, indicating a previous infection, are most likely to develop this complication. Patients may benefit from thoroughly rinsing their mouths with water after inhalation. Symptomatic candidiasis in the mouth can be treated with a topical antifungal therapy while continuing treatment with Beclometasone dipropionate.

The hoarseness is reversible and disappears after stopping treatment and/or resting the voice. These patients must be advised to rinse their mouths with water immediately after inhalation.To report any side effect(s):The National Pharmacovigilance and Drug Safety Center (NPC)Fax +966-11-205-7662Call NPC at +966-11-2038222, Exts 2317-2356-2353-2354-2334-2340Tool Free Phone: 8002490000E-mail: npc.drug@sfda.gov.saWebsite: www.sfda.gov.sa/npc

Systemic corticosteroid effects (such as hypercorticism and adrenal suppression) can occur if beclometasone dipropionate is used at excessive dose. If these symptoms occur the treatment should be immediatelydiscontinued and the patients protected against the effects of the adrenal suppression, by a suitable systemic therapy

CLENIL FORTEcontains as its active ingredient beclometasone 17,21-dipropionate, a cortisone derivative with a marked topical antiinflammatory and antiallergic activity on the airways mucosa. In particular, beclometasone dipropionate exerts a marked anti-reactive action at bronchial level, by reducing oedema, hypersecretion and by inhibiting bronchospasm onset. Beclometasone dipropionate administered by inhalation have effects on the airways only and is therefore devoid, at the recommended dosage, of any systemic effects and inhibiting actions on the adrenocortical function. Beclometasone dipropionate (BDP) is a synthetic corticosteroid for topical use only, with potent antiinflammatory activity, reduced mineral-corticoid activity and absence of systemic effects In the cutaneous vasoconstriction test, according to McKenzie, BDP is 5000 times more active than hydrocortisone, 625 times more active than betametasone alcohol, 5 times more active than fluocinolone acetonide and 1.39 times more active than betametasone valerate. It has an intense and prolonged antiinflammatory activity towards croton oil-, carrageenan-, formaldehyde-, egg white-and dextrane-induced oedema, and towards the granulomatous reaction by foreign bodies, with effectiveness higher than that of other corticosteroids. CLENIL FORTEhas no thymolytic, splenolytic or mineralcorticoid activity, if administered at the advised doses, and does not inhibit the hypophysis-adrenal function even after repeated administrations.CLENIL FORTEis indicated particularly in patients who do not obtain a satisfactory control of symptoms with standard doses of inhaled beclometasone dipropionate. To achieve complete therapeutic success, it is necessarythat the patient carefully adheres to the prescribed instructions for inhalatory use.

Kinetic studies on labelled beclometasone dipropionate showed that after inhalation of a high dose, only 20-25% of the drug is absorbed.A part of the administered dose is swallowed and eliminated in the feaces. The fraction absorbed in circulation is metabolized by hepatic route to mono-propionate and to beclometasone alcohol, then it is excreted in the form of inactive metabolites in bile and urine.

Preclinical Safety DataAcute Toxicity: oral LD50values in rats and mice exceed 3000 mg/kg. When given by nebulisation, concentrations of 100 mcg/l for 30 minutes are well tolerated in rats and mice.Chronic Toxicity: administration by inhalation of doses far exceeding those recommended for therapy, in dogs over 27 weeks does not induce any alterations .Foetal Toxicity: studies performed in rats and rabbits caused no negative findings of reproduction toxicity.The propellant HFA 134a didnot show any toxic effects at concentrations far higher than those envisaged for human use, administered by nebulisation in different animal species exposed daily for a period of two years.

HFA 134a (norflurane), ethanol, glycerol.

Not known

The pressurised canister must not be broken, punctured or burnteven when apparentlyempty.Do not freeze, protect against frost, direct sunlightand heat. Do not store above30°C.

Primary package: pressurised aluminium canister, with metering valve, actuator and protecting cap. Outer package: overprinted cardboard box.Pressurised canister providing 200 inhalations.

No special requirements