Name of the Medicinal Product

Beconase Aqueous Nasal Spray

2.    Qualitative and Quantitative Composition

Beclometasone Dipropionate 50pg (as monohydrate, micronised)

Excipient with known effect:

Benzalkonium Chloride

For the full list of excipients, see section 6.1

3.    PHARMACEUTICAL FORM

Aqueous suspension for intranasal inhalation via metered dose atomising pump.

4. CLINICAL PARTICULARS

4.1. Therapeutic indications

Beconase Aqueous Nasal Spray is indicated for the prophylaxis and treatment of perennial and seasonal allergic rhinitis including hayfever, and vasomotor rhinitis. Beclometasone dipropionate has a potent anti-inflammatory effect within the respiratory tract, with a lower incidence and severity of adverse events than those observed when corticosteroids are administered systemically.

4.2. Posology and method of administration

Beconase Aqueous Nasal Spray is for administration by the intranasal route only. Adults and children over six years of age:

The recommended dosage is two sprays into each nostril twice daily (400 microgram s/day). Once control has been established it may be possible to maintain control with fewer sprays. A dosage regimen of one spray into each nostril morning and evening has been shown to be efficacious in some patients. However, should symptoms recur, patients should revert to the recommended dosage of two sprays into each nostril morning and evening. The minimum dose should be used at which effective control of symptoms is maintained. Total daily administration should not normally exceed eight sprays.

For full therapeutic benefit regular usage is essential. The co-operation of the patient should be sought to comply with the regular dosage schedule and it should be explained that maximum relief may not be obtained within the first few applications.

For children under six years old, there are insufficient clinical data to recommend use.

4.3    Contraindications

Hypersensitivity to the active substance or any of the excipients listed in section 6.1.

4.4    Special Warnings and Precautions for Use

Systemic effects of nasal corticosteroids may occur, particularly at high doses prescribed for prolonged 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).

Growth retardation has been reported in children receiving nasal corticosteroids at licensed doses. It is recommended that the height of children receiving prolonged treatment with nasal corticosteroids is regularly monitored. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of nasal corticosteroid, if possible to the lowest dose at which effective control of symptoms is maintained. In addition, consideration should be given to referring the patient to a paediatric specialist.

Treatment with higher than recommended doses may result in clinically significant adrenal suppression. If there is evidence for higher than recommended doses being used then additional systemic corticosteroid cover should be considered during periods of stress or elective surgery.

Care must be taken while transferring patients from systemic steroid treatment to Beconase Aqueous Nasal Spray if there is any reason to suppose that their adrenal function is impaired.

Infections of the nasal passages and paranasal sinuses should be appropriately treated but do not constitute a specific contra-indication to treatment with Beconase Aqueous Nasal Spray.

Although Beconase Aqueous Nasal Spray will control seasonal allergic rhinitis in most cases, an abnormally heavy challenge of summer allergens may in certain instances necessitate appropriate additional therapy particularly to control eye symptoms.

Beconase Aqueous Nasal Spray contains Benzalkonium Chloride which may cause bronchospsm.

4.5. Interactions with other medicinal products and other forms of interaction

Not applicable

4.6. Pregnancy and Lactation

Pregnancy

There is inadequate evidence of safety in human pregnancy. Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate and intra-uterine growth retardation. There may therefore be a very small risk of such effects in the human foetus. It should be noted, however, that the foetal changes in animals occur after relatively high systemic exposure. Beconase Aqueous Nasal Spray delivers beclometasone dipropionate directly to the nasal mucosa and so minimises systemic exposure.

The use of beclometasone dipropionate should be avoided during pregnancy unless thought essential by the doctor.

Breast-feeding

No specific studies examining the transference of beclometasone dipropionate into the milk of lactating animals have been performed. It is reasonable to assume that beclometasone dipropionate is secreted in milk but at the dosages used for direct intranasal administration there is low potential for significant levels in breast milk. The use of beclometasone dipropionate in mothers breast feeding their babies requires that the therapeutic benefits of the drug be weighed against the potential hazards to the mother and baby.

4.7 Effect on Ability to Drive and Use Machines

Not relevant

4.8 Undesirable Effects

Adverse reactions 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 reactions were generally determined from clinical trial data. Rare and very rare reactions were generally determined from spontaneous data. In assigning adverse reaction 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

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

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

The only harmful effect that follows inhalation of large amounts of the drug over a short time period is suppression of Hypothalamic-Pituitary-Adrenal (HPA) function. No special emergency action need be taken. Treatment with Beconase Aqueous Nasal Spray should be continued 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

Following intranasal administration of BDP in healthy males, the systemic absorption was assessed by measuring the plasma concentrations of its active metabolite 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 metabolite B-17-MP, for which the absolute bioavailability following oral 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 (< 50pg/ml) following oral or intranasal dosing. There is rapid metabolism of the majority of the swallowed portion of BDP 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 (BOH), 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 1201/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

Avicel RC 591 (Microcrystalline Cellulose And Carboxymethylcellulose Sodium) US NF

Anhydrous Dextrose BP Benzalkonium Chloride BP Phenylethyl Alcohol USP Polysorbate 80 BP Purified Water BP

6.2. Incompatibilities

Not applicable.

6.3. Shelf Life

24 months when not stored above 30°C

6.4 Special precautions for storage

Beconase Aqueous Nasal Spray should not be stored above 30°C. Keep_container in the outer carton.

Nature and Contents of Container

A 25ml amber neutral glass bottle fitted with a metering atomising pump, or a 30ml polypropylene bottle fitted with a tamper-resistant metering atomising pump. The pumps are manufactured by: Valois S.A. Le Prieure BPG, 27110 Le Neubourg, France.

Pack size: 200 Metered Spray.

6.6 Special precautions for disposal and other handling

Refer to Patient Information Leaflet.

7.    Marketing Authorisation Holder

Glaxo Wellcome UK Ltd.

Trading as GlaxoSmithKline UK Stockley Park West,

Uxbridge

Middlesex, UB11 1BT

8.    MARKETING AUTHORISATION NUMBER

PL 10949/0104

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

06 March 1995

10 DATE OF REVISION OF THE TEXT

19/02/2015