Budesonide 64 micrograms/actuation, Aqueous Nasal Spray

The delivered (metered) dose of 0.05 ml nasal spray, suspension contains 64 micrograms of budesonide.

Excipients:

0.06 mg of potassium sorbate / 0.05 ml nasal spray, suspension

For a full list of excipients, see section 6.1.

Nasal spray, suspension.

White homogeneous suspension

Treatment and prevention of signs and symptoms of seasonal and perennial allergic rhinitis.

Treatment of signs and symptoms of nasal polyps.

For nasal use only.

The dosage should be determined individually. The dose should be titrated to the lowest dose at which effective control of symptoms is maintained.

The duration of the therapy with Budesonide nasal spray should be restricted to the period of allergen exposure and depends on the nature and the characteristics of the allergen. For a full therapeutic benefit regular use is essential.

Allergic rhinitis

Initial dose

Adults, adolescents and children from 6 years of age:

The recommended initial dose of 256 micrograms may be administered once daily in the morning or divided into two administrations, in the morning and in the evening.

2 actuations into each nostril once daily in the morning or 1 actuation into each nostril in the morning and in the evening

Children should be treated under guidance of an adult.

Treatment of seasonal allergic rhinitis should be initiated, if possible, before the patient is exposed to allergens.

Concomitant therapy may sometimes be necessary to treat the symptoms affecting the eye caused by the allergy.

Maintenance dose

The desired clinical effect appears within about 1-2 weeks.

Afterwards, the lowest dose should be chosen that keeps the patient just without symptoms. No better efficacy is to be expected with a dose greater than 256 micrograms.

Nasal polyps

Adults, adolescents and children from 6 years of age:

The recommended dose for the treatment of nasal polyps is 256 micrograms. The dose may be administered once daily in the morning or divided into two administrations, in the morning and in the evening.

2 actuations into each nostril once daily in the morning or

1 actuation into each nostril in the morning and in the evening

Children should be treated under guidance of an adult.

After the desired clinical effect has appeared, the lowest dose should be chosen that keeps the patient without symptoms.

Method of administration

1. Gently blow your nose to clean the nostrils, if necessary.

2. Shake the bottle (figure 1). Remove the protective cap.

Figure 1.

3. Hold the bottle as shown in figure 2. Before using Budesonide nasal spray suspension for the first time you must prime the nozzle (i.e. fill it with medicine). Pump the nozzle up and down several times (5-10 times), spraying into the air until an even mist is seen. The priming effect remains for approximately 24 hours. If a longer period of time passes before the next dose is taken, the nozzle must be primed (filled with medicine) again. If Budesonide nasal spray suspension is used at shorter intervals it is sufficient to spray just once into the air.

Figure 2.

4. Insert the tip of the nozzle into your nostril as shown in figure 3 and spray once (or more if your doctor has told you to). Use the pray into the other nostril in the same way. Note, it is not necessary to breathe in at the same time as you spray.

Figure 3.

5. Wipe the nozzle with a clean tissue and replace the protective cap.

6. Store the bottle in an upright position.

Cleaning your Budesonide nasal spray suspension

You should clean the plastic nozzle of Budesonide nasal spray suspension regularly, and at any time the spray of medicine is not coming out as it should. If this happens, first check if the nozzle is primed with medicine (see earlier). If after priming the nozzle again the pump is still not working, clean the nozzle by using the following instructions:

− Remove the plastic nozzle with a clean tissue and wash in warm – not hot – water.

− Rinse the nozzle thoroughly, dry it and then replace onto the top of the bottle.

− Never try to unblock the nozzle by using a pin or other sharp object.

After cleaning the nozzle must be primed (filled with medicine) again before use.

Hypersensitivity to the active substance or to any of the excipients.

Systemic effects of inhaled 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 the paediatric specialist.

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

In case of infections of the nose caused by bacteria or fungi, Budesonide nasal spray suspension should be used only if concomitant antibacterial or antifungal treatment is carried out.

In continuous long-term treatment, the nasal mucosa should be inspected regularly e.g. every 6 months.

Impaired liver function influences the pharmacokinetics of corticosteroids. Severe impairment of hepatic function influences the pharmacokinetics of orally administered budesonide resulting in increased systemic availability and reduced elimination capacity. However, the intravenous pharmacokinetic of budesonide in healthy volunteers and patients with liver cirrhosis is approximately the same. Consideration of potential systemic effects may be needed in severe impairment of hepatic function.

Budesonide nasal spray is not recommended in patients with epistaxis and in patients, with herpetic infection of oral, nasal or ophthalmic region.

Budesonide nasal spray is not recommended in patients with nasal ulcerations, in cases of recent surgery or nasal trauma until it is fully recovered.

Special care is needed in patients with tuberculosis.

The use of budesonide nasal spray is not recommended in patients with infections of the airways.

The patient should be informed that the full effect is not achieved until after a few days of treatment. Treatment of seasonal rhinitis should, if possible, start before exposure to the allergens.

This medicinal product contains potassium sorbate and may cause skin reactions (e.g. contact dermatitis).

Concomitant administration of oral ketoconazol 200 mg once daily and oral budesonide (3 mg single dose) increased the plasma concentrations of budesonide on average 6-fold. When ketoconazol was administered orally 12 hours after the budesonide dose, the concentrations of budesonide increased on average 3-fold. There is no information about this interaction following nasal administration of budesonide, but increased plasma concentrations are expected. The combination should be avoided as there are no dose recommendations for the combination, but if not possible the time interval between the administrations of the two drugs should be as long as possible. A reduction of the dose may also be considered. Concomitant administration of other potent inhibitors of CYP3A4 (e.g.: ketoconazol, ciclosporin, ethinylestradiol und troleandomycin) is likely to result in a marked increase of budesonide plasma concentrations.

Data on a limited number (over 2000) of exposed pregnancies indicate no adverse effects of budesonide on pregnancy or on the health of the foetus/new-born child. To date, no other relevant epidemiological data are available. Animal studies have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Budenoside nasal spray should be used during pregnancy only if clearly needed.

As it is not known to which extent budesonide is excreted into breast milk, use in lactation requires that the therapeutic benefit to the mother be weighed against any potential risk to the neonate.

Budesonide nasal spray suspension has no influence on the ability to drive or use machines.

When patients are transferred from systemic corticosteroid (oral or parenteral) to Budesonide nasal spray suspension, undesirable effects outside the nasal area which were previously under control by systemic therapy e.g. allergic conjunctivitis or dermatitis, may become unmasked. They should be treated additionally if needed.

Systemic effects of nasal corticosteroids may occur, particularly when prescribed at high doses.

Undesirable effects frequencies were defined as follows:

- 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)

An acute overdose with Budesonide nasal spray suspension is unlikely even if all the sprays contained in the bottle are administered all at once. Administration of doses higher than recommended (see section 4.2) for a longer period (over months) may result in suppression of hypothalamic-pituitary-adrenal axis.

Pharmacotherapeutic group: Decongestants and other nasal preparations for topical use, Corticosteroids

ATC Code: R01AD05

Budesonide is a glucocorticosteroid with a strong topical anti-inflammatory effect on the nasal mucosa and weak systemic effects after topical administration.

Following intranasal application budesonide is absorbed through nasal and to some extent through gastrointestinal mucosa. The systemic availability of budesonide is 33% of the delivered intranasal amount of budesonide.

In adults the maximal plasma concentration after administration of 256 micrograms of budesonide is 0,64 nmol/L and is reached within 0,7 hours.

The area under the curve (AUC) after administration of 256 micrograms of Budesonide nasal spray suspension is 2.7 nmol*h/L in adults and 5.5 nmol*h/L in children, indicating a higher systemic exposure in children.

At clinically relevant doses the kinetics of budesonide are dose proportional.

The volume of distribution of budesonide is approximately 3 L/kg. Protein binding is 85-90%.

Budesonide is eliminated through metabolism, mainly by the enzyme CYP3A4. Budesonide has a high systemic clearance (appr. 1.2 L/min) and the half-life in plasma following an intravenous dose is on average appr. 4 hours. The metabolites are eliminated in the urine in unchanged or conjugated form. The main metabolites 6-beta-hydroxybudesonide and 16-alpha-hydroxyprednisolon are almost ineffective.

Orally ingested budesonide is in the first passage rapidly and extensively biotransformed by the liver (90%) to metabolites with lower glucocorticosteroid activity. Budesonide in not metabolised locally in the nasal mucosa.

Non-clinical data reveal no special hazard for humans at therapeutic doses based on studies of chronic toxicity, genotoxicity and carcinogenicity.

Glucocorticosteroids including budesonide have produced teratogenic effects in animals, including cleft palate and skeletal abnormalities. Similar effects are considered unlikely to occur in humans at therapeutic doses.

Dispersible cellulose (Microcrystalline cellulose and carboxymethylcellulose sodium, (89:11, w/w))

Polysorbate 80

Potassium sorbate E 202

Glucose, anhydrous

Disodium edetate

Hydrochloric acid, concentrated

Ascorbic acid E300

Purified water

Not applicable.

2 years

After first opening: 3 months

Do not store above 30C

Do not freeze.

Amber type III glass bottle fitted with a plastic nasal spray pump and polypropylene nasal applicator: pack size of 1 x120 doses, 3 x 120 doses, 10 x 120 doses

Not all pack sizes may be marketed.

No special requirements.

Sandoz Limited

Frimley Business Park,

Frimley,

Camberley,

Surrey,

GU16 7SR.

United Kingdom

PL 04416/0784

30^th July 2009

06/2011