Document: spc-doc_PL 40147-0010 change

• spc-doc_PL 00289-1607
• spc-doc_PL 00289-1626
• spc-doc_PL 40147-0010

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Beclometasone Dipropionate Aqueous Nasal Spray.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each metered dose contains 50 micrograms of beclometasone dipropionate.

For excipients, see 6.1.

3 PHARMACEUTICAL FORM

Nasal spray, suspension.

Aqueous suspension for intranasal inhalation via metered dose atomising pump.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Beclometasone Dipropionate Aqueous Nasal Spray is indicated for the prevention and treatment of perennial and seasonal rhinitis, including hay fever and vasomotor rhinitis.

4.2 Posology and method of administration

For nasal administration only.

It is important to use this product regularly in order to achieve maximum relief from the symptoms. It should be explained to the patient that full therapeutic benefit may not be experienced until after the first few doses of Beclometasone Dipropionate Aqueous Nasal Spray.

Adults and Children (aged 6years or over): The usual dosage is two sprays into each nostril twice a day (400 micrograms a day). Alternatively a single spray (50 micrograms) into each nostril three or four times a day may be prescribed. The dose must be titrated to the lowest level allowing effective control of symptoms. A dosage regimen of one spray into each nostril morning and evening has been shown to be efficacious in some patients. If symptoms recur, patients should revert to the recommended dosage of two sprays into each nostril morning and evening. A total of eight sprays (400 micrograms) daily should generally not be exceeded.

Children under 6 years old: Not recommended

4.3 Contraindications

Beclometasone Dipropionate Aqueous Nasal Spray is contra-indicated in patients known to have hypersensitivity to beclometasone dipropionate or to any of the other excipients present in this product.

4.4 Special warnings and precautions for use

In patients with underlying nasal infections, treatment with beclometasone dipropionate should be accompanied by appropriate anti-infective therapy.

However, these do not constitute a specific contra-indication for Beclometasone Dipropionate Aqueous Nasal Spray treatment.

If patients are transferred from long-term oral corticosteroids to Beclometasone Dipropionate Aqueous Nasal Spray, transfer must be done slowly, with gradual reduction in dose of oral corticosteroid, and at a time when the rhinitis is well controlled. This is mainly to allow for recovery of the full adrenocortical function after reduction of the dose in patients receiving prolonged oral corticosteroid treatment.

Beclometasone Dipropionate Aqueous Nasal Spray may produce systemic effects, particularly at high doses prescribed for long periods. These effects are much less likely to occur than with oral corticosteroids and may vary in individual patients and between different corticosteroid preparations. Potential systemic effects may include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).

Therefore the risk of systemic absorption should always be considered. This may induce inhibition of the hypothalamicpituitary- adrenal axis and other unwanted glucocorticoid effects. Growth retardation has been reported in children receiving nasal corticosteroids at licensed doses. Therefore prolonged administration in children should be avoided. If prolonged treatment is considered necessary, the child’s height should be regularly monitored. If growth is slowed, therapy should be reviewed and nasal corticosteroid reduced to the lowest dose at which effective control of symptoms is maintained. In addition, referral to a paediatrician should be considered.

Beclometasone Dipropionate Aqueous Nasal Spray can be highly effective against seasonal and perennial allergic rhinitis, particularly if treatment is instituted immediately prior to the allergy season and maintained regularly.

Abnormally heavy exposure to summer allergens may in certain instances necessitate appropriate additional therapy particularly to control eye symptoms.

Long-term use of topical corticosteroids should be avoided. Treatment with higher than recommended doses may result in clinically significant adrenal suppression. Use should also be avoided after nasal surgery (until healing has occurred) and in pulmonary tuberculosis.

Additional systemic corticosteroid cover should be considered during periods of stress or elective surgery or evidence of higher than recommended doses being used previously. Infections of the nasal passages and paranasal sinuses should be appropriately treated.

Beclometasone Dipropionate Aqueous Nasal Spray contains Benzalkonium Chloride which may cause bronchospasm.

4.5 Interaction with other medicinal products and other forms of interaction

There are no reports to date of interactions of Beclometasone Dipropionate Aqueous Nasal Spray with other medicinal products.

4.6 Fertility, Pregnancy and lactation

Pregnancy

The safety of Beclometasone Dipropionate Aqueous Nasal Spray in pregnancy has not been established. Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate and intrauterine growth retardation. Topical administration in pregnant animals has resulted in abnormalities in foetal development. There may therefore be a very small risk of such effects in the human foetus.

It is recommended that the use of Beclometasone Dipropionate Aqueous Nasal Spray is avoided during pregnancy unless the benefits of treatment are considered to outweigh the risks. In this case, the lowest possible dose should be prescribed over a short period.

Lactation

Oral steroids have been reported to be secreted in breast milk following oral therapy. Blood levels achieved after nasal administration of beclometasone dipropionate are not considered to be sufficiently high to reach breast milk. Should significant absorption occur, it would be reasonable to assume that beclometasone dipropionate may be secreted into breast milk.

The therapeutic benefits of the drug must be weighed against the potential risks to the mother and baby, should the use of Beclometasone Dipropionate Aqueous Nasal Spray be considered for breast-feeding mothers.

4.7 Effects on ability to drive and use machines

There are no reports of reactions to Beclometasone Dipropionate Aqueous Nasal Spray that would affect a patient’s ability to drive or use machines.

4.8 Undesirable effects

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (> 1/10), common (> 1/100 and <1/10), uncommon (>

1/1000 and <1/100), rare (> 1/10,000 and <1/1000) and very rare (<1/10,000) including isolated reports. Very common, common and uncommon events were generally determined from clinical trial data. Rare and very rare events were generally determined from spontaneous data. In assigning adverse event frequencies, the background rates in placebo groups were not taken into account, since these rates were generally comparable to those in the active treatment group.

System Organ Class	Adverse Event	Frequency
Immune system disorders	Hypersensitivity reactions including:
	Rash, urticaria, pruritis, erythema.	Common
	Angioedema	Very rare
	Dyspnoea and/or bronchospasm	Very rare
	Anaphylactoid/anaphylactic reactions	Very rare
Nervous system disorders	Unpleasant taste, unpleasant smell.	Common
Eye disorders	Glaucoma, raised intraocular pressure, cataract.	Very rare
Respiratory, Thoracic & Mediastinal disorders	Epistaxis, nasal dryness, nasal irritation, throat dryness, throat irritation.	Common
	Nasal septum perforation.	Very rare

As with other nasal sprays, dryness and irritation of the nose and throat, and epistaxis have been reported. Nasal septal perforation has also been reported following the use of intranasal corticosteroids.

Systemic effects of nasal corticosteroids may occur particularly when used at high doses for prolonged periods.

Retardation in growth is possible, following extensive use in children (please refer to section 4.4 special warnings and precautions for use).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

4.9 Overdose

There are no reported incidences of deliberate ingestion of topical Beclometasone dipropionate. The administration of large amounts of Beclometasone dipropionate over a short period of time may result in systemic absorption such that a degree of subsequent hypothalamic-pituitary-adrenal (HPA) suppression is possible. This is however reversible and emergency action is not required. Treatment should be

continued with Beclometasone Diproprionate Aqueous Nasal Spray at the recommended dose. HPA function recovers in a day or two.

Further management should be as clinically indicated or as recommended by the national poisons centre, where available.

There is no specific treatment for an overdose of beclometasone dipropionate. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Following topical administration beclometasone 17,21-dipropionate (BDP) produces potent anti-inflammatory and vasoconstrictor effects.

BDP is a pro-drug with weak corticosteroid receptor binding affinity. It is hydrolysed via esterase enzymes to the highly active metabolite beclometasone-17-monopropionate (B-17-MP), which has high topical anti-inflammatory activity.

Beclometasone dipropionate offers a preventative background treatment for hayfever when taken prior to allergen challenge. After which with regular use, BDP can continue to prevent allergy symptoms from reappearing.

5.2 Pharmacokinetic properties

Absorption

The systemic absorption of BDP in healthy males following intranasal administration was assessed by measuring plasma concentrations of its active metabolite Beclometasone-17-monopropionate (B-17-MP), for which the absolute bioavailability following intranasal administration is 44% (95%CI 28%, 70%). After intranasal administration, <1% of the dose is absorbed by the nasal mucosa. The remainder, after being cleared from the nose either by drainage or mucocilary clearance, is available for absorption from the gastrointestinal tract. Plasma B-17-MP is almost entirely due to conversion of BDP absorbed from the swallowed dose.

Following oral administration of BDP in healthy males, the systemic absorption was also assessed by measuring the plasma concentrations of its active metabolites B-17-MP for which the absolute bioavailability following administration is 41% (95%CI 27%, 62%).

Following an oral dose, B-17-MP is absorbed slowly with peak plasma levels reached 3-5 hours after dosing.

Metabolism

BDP is cleared very rapidly from the circulation and plasma concentrations are undetectable (<50 pg/ml) following oral or intranasal dosing. The majority of the swallowed portion of BDP is rapidly metabolised during its first passage through the liver. The main product of metabolism is the active metabolite (B-17-MP). Minor inactive metabolites, beclometasone-21-monopropionate (B-21-MP) and beclometasone are also formed but these contribute little to systemic exposure.

Distribution

The tissue distribution at steady-state for BDP is moderate (201) but more extensive for B-17-MP (4241). Plasma protein binding of BDP is moderately high (87%).

Elimination

The elimination of BDP and B-17-MP are characterised by high plasma clearance (150 and 120 l/h) with corresponding terminal elimination half-lives of 0.5h and 2.7h. Following oral administration of tritiated BDP, approximately 60% of the dose was excreted in the faeces within 96 hours mainly as free and conjugated polar metabolites. Approximately 12% of the dose was excreted as free and conjugated polar metabolites in the urine.

5.3 Preclinical safety data

No clinically relevant findings were observed in preclinical studies.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Anhydrous glucose, microcrystalline cellulose and sodium carboxymethylcellulose (Avicel RC-591), polysorbate 80, phenylethyl alcohol, benzalkonium chloride solution and purified water.

6.2 Incompatibilities

Not known.

6.3 Shelf life

Unopened: 2 years.

After first opening the container: 3 months

6.4 Special precautions for storage

Do not store above 30^oC. Keep container in the outer carton. Do not refrigerate.

6.5 Nature and contents of container

Beclometasone Dipropionate Aqueous Nasal Spray is supplied in either amber glass bottles or HDPE vials fitted with a metering, atomising pump and nasal applicator. Each bottle provides approximately 200 metered sprays.

6.6 Special precautions for disposal

Children should only use Beclometasone Dipropionate Aqueous Nasal Spray under the supervision of an adult. Always shake the container before use.

Instructions as shown in the leaflet:

1.    Remove the cap from the nozzle. Make sure the nozzle is clean and clear of fluff and dirt. If you have not used your spray for a few days or if your spray is new, you will have to prime it before you can use it.

2.    Priming your spray

Hold the bottle upright, with your thumb on the base and your forefinger and index finger either side of the collar. Now press the collar down with your fingers, making sure that the nozzle is pointing away from you. This will pump the spray, until a fine mist is produced. In case the mist does not appear, you may need to clean the nozzle.

Shake the spray vigorously up and down. Holding the spray well away from your nostril breathe out with your nose. Place the nozzle in one nostril, holding the bottle upright, and close your other nostril by pressing on the other side of your nose. Leaning your head slightly forward breathe in slowly and deeply through your nose. At the same time press down firmly on the collar with your fingers to squirt a spray and release the drug. Remove the nozzle from your nostril and slowly breathe out through your mouth. Repeat the procedure for the other nostril. Wipe the nozzle with a clean cloth and replace the cap after use.

3.    Cleaning the nozzle

It is very important to keep the plastic cap and the nozzle clean, to prevent any build up of powder. Washing the applicator regularly (weekly) is recommended.

To clean, remove the plastic cap and pull the white collar upwards to remove the nozzle. Soak the nozzle and cap in warm water, then rinse. Dry thoroughly, then replace the nozzle and cap. Do not put the bottle into water. You may need to prime your spray before use.