BUDESONIDE 64 Aqueous Nasal Spray Ref.[6670] Active ingredients: Budesonide

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).

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 caution is necessary in patients with active or quiescent pulmonary tuberculosis, and in patients with fungal or viral 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.

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

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

Paediatric population

The long-term effects of nasal glucocorticosteroids in children are not fully known. Physicians should closely follow the growth of children taking glucocorticosteroids for longer term by any route, and weigh the benefits of the glucocorticosteroid therapy against the possibility of growth suppression.

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.

Switching from administration route

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

Budesonide has not been observed to interact with any drug used for the treatment of rhinitis.

Concomitant administration of oral ketoconazole 200 mg once daily and oral budesonide (3 mg single dose) increased the plasma concentrations of budesonide on average 6-fold. When ketoconazole 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.: itraconazole, ciclosporin and troleandomycin) is likely to result in a marked increase of budesonide plasma concentrations.

Raised plasma concentrations of and enhanced effects of corticosteroids have been observed in women also treated with oestrogens and contraceptive steroids, but no effect has been observed with budesonide and concomitant intake of low dose combination oral contraceptives.

Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.

Because adrenal function may be suppressed, an ACTH stimulation test for diagnosing pituitary insufficiency might show false results (low values).

Pregnancy

Results from prospective epidemiological studies and from worldwide post marketing experience indicate no increased risk for overall congenital malformations from the use of inhaled or intranasal budesonide during early pregnancy. Animal studies have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. As with other drugs the administration of budesonide during pregnancy requires that the benefits for the mother are weighed against the risks for the foetus.

Breast-feeding

Budesonide is excreted in breast milk. However, at therapeutic doses of budesonide no effects on the suckling child are anticipated. Budesonide can be used during breast feeding.

Maintenance treatment with inhaled budesonide (200 or 400 mcg twice daily) in asthmatic nursing women results in negligible systemic exposure to budesonide in breast-fed infants.

In a pharmacokinetic study, the estimated daily infant dose was 0.3% of the daily maternal dose for both dose levels, and the average plasma concentration in infants was estimated to be 1/600th of the concentrations observed in maternal plasma, assuming complete infant oral bioavailability. Budesonide concentrations in infant plasma samples were all less than the limit of quantification.

Based on data from inhaled budesonide and the fact that budesonide exhibits linear PK properties within the therapeutic dosage intervals after nasal, inhaled, oral and rectal administrations, at therapeutic doses of budesonide, exposure to the suckling child is anticipated to be low.

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.

In rare cases, signs or symptoms of systemic glucocorticosteroid-side effects may occur with nasal glucocorticosteroids, probably depending on dose, exposure time, concomitant and previous corticosteroid exposure, and individual sensitivity

Undesirable effects frequencies were defined as follows:

Very common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)
Very rare (<1/10,000), not known (cannot be estimated from the available data)

Immune system disorders

Uncommon: immediate or delayed hypersensitivity reaction (urticaria, rash, itching, dermatitis, angioedema)

Rare: anaphylactic reaction

Endocrine disorders

Rare: signs and symptoms of systemic corticosteroid effects, including adrenal suppression and growth retardation

Nervous system disorders

Rare: dysphonia

Eye disorders

Rare: glaucoma, cataract (with long-term treatment) vision, blurred (see also section 4.4)

Respiratroy, thoracic and mediastinal disorders

Common: local symptoms like nasal mucosa irritation, slight haemorrhagic secretion, epistaxis (immediately after application)

Rare: nasal ulcer, nasal septum perforation

Musculoskeletal and connective tissue disorders

Uncommon: muscle spasm

Rare: osteoporosis (with long-term treatment), contusion

Paediatric population

Growth retardation has been reported in children receiving intranasal steroids. Due to the risk of growth retardation in the paediatric population, growth should be monitored as described in section 4.4.

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 (www.mhra.gov.uk/yellowcard).

Not applicable.