Budair 0.25 mg & 0.5 mg Nebuliser Suspension

BUDAIR is indicated for management of asthma in patients inadequately controlled by bronchodilators, thus necessitating additional treatment with steroids and who are unable to use a pressurised metered dose inhaler or unable to inhale the medicine in powder form. BUDAIR is also recommended for use in infants and children with acute laryngotracheobronchitis- croup.

Instruction for correct use of BUDAIR: BUDAIR should be administered via a jet nebuliser equipped with a mouthpiece or suitable face mask. The nebuliser should be connected to an air compressor with an adequate air flow (5-8 litres/minute), and the fill volume should be 2-4 ml. Ultrasonic nebulisers are not suitable for the administration of BUDAIR and therefore are not recommended. For complete instructions for the correct use of BUDAIR please refer to the accompanying patient information leaflet.

The dosage of BUDAIR nebulizing suspension is individual, and should be titrated to the lowest effective maintenance dose once the control of asthma is achieved.

Asthma

Adults

Initial Dose: 0,5-1 mg twice daily. In some cases, the dose may be further increased.

Children

12 months-6 years

6 years and older

Previous therapy

• Bronchodilators alone: 0,25 mg twice daily
• Inhaled corticosteroids: 0,25 mg twice daily
• Oral corticosteroids: 0,5 mg twice daily

Maintenance dose

0,25-0,5 mg twice daily

In patients where an increased therapeutic effect is required, an increased dose of BUDAIR should be considered. Maintenance dose: The maintenance dose is individual. After the desired clinical effect has been obtained, the maintenance dose should be gradually reduced to the smallest amount necessary to control symptoms.

Patients dependent on oral steroids

Initially, BUDAIR should be used concurrently with the patient's usual maintenance dose of oral glucocorticosteroid. After approximately 1 week the oral dose is gradually reduced to the lowest possible level, e.g. by about 2,5 mg prednisolone every two weeks. A slow rate of withdrawal is strongly recommended. In a proportion of cases, it is possible to completely substitute the oral glucocorticosteroid with BUDAIR. During withdrawal some patients may experience symptoms of systemic corticosteroid withdrawal, e.g. joint and/or muscle pain, lassitude and depression, despite maintenance or even in improvement in pulmonary function. Such patients should be encouraged to continue with BUDAIR but should be monitored for objective signs of adrenal insufficiency. If evidence of adrenal insufficiency occurs, the systemic corticosteroid doses should be increased temporarily and thereafter withdrawal should be continued more slowly. During periods of stress or during a severe asthma attack, transfer patients may require supplementary treatment with systemic corticosteroids.

Acute laryngotracheobronchitis croup

In infants and children with croup, the usual dose is 2 mg of nebulised budesonide. This dose is given as a single administration or as two 1 mg doses separated by 30 minutes.

Dosage table

Dosage in mg

Volume of BUDAIR 0,25 mg/ml 0,5 mg/ml

• 0,25 mg: 1 ml -
• 0,5 mg: 2 ml 1 ml
• 0,75 mg: 3 ml -
• 1 mg: - 2 ml
• 1,5 mg: - 3 ml
• 2 mg: - 4 ml

BUDAIR can be mixed with 0,9 % saline and with solutions for nebulisation of terbutaline, salbutamol, fenoterol, acetylcysteine, sodium cromoglycate or ipratropium bromide. The admixture should be used within 30 minutes.

BUDAIR is contraindicated in:

• Hypersensitivity to budesonide and any of the ingredients of BUDAIR listed in section 6.1.
• Lung tuberculosis, fungal and viral infection in airways

Safety and efficacy for children less than 12 months has not been established.

Facial skin irritation may occur when a nebuliser with face mask is used. To prevent irritation, the facial skin should be washed with water after use of face mask. To minimize oropharyngeal thrush, the patient should rinse the mouth out with water after each dosing occasion.

BUDAIR is not intended for rapid relief of acute episodes of asthma where an inhaled short-acting bronchodilator is required. If patients find short-acting bronchodilator treatment ineffective, or they need more inhalations than usual, medical attention must be sought. In this situation consideration should be given to the need for increased anti-inflammatory therapy, e.g. higher doses of inhaled budesonide or a course of oral glucocorticosteroid.

Particular care is needed in patients transferring from oral steroids, since they may remain at risk of impaired adrenal function for a considerable time. Patients who have required high dose emergency corticosteroid therapy or prolonged treatment at the highest recommended dose of inhaled corticosteroids may also be at risk. These patients may exhibit signs and symptoms of adrenal insufficiency when exposed to severe stress. Additional systemic corticosteroid cover should be considered during periods of stress or elective surgery.

Systemic effects may occur with any inhaled corticosteroids, particularly at high doses prescribed for long periods. These effects are much less likely to occur with inhalation treatment than with oral corticosteroids. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract, glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children (see section 4.8). It is important, therefore, that the dose of inhaled corticosteroid is titrated to the lowest dose at which effective control of asthma is maintained.

Some patients feel unwell in a non-specific way during the withdrawal phase, e.g. pain in muscles and joints. A general insufficient glucocorticosteroid effect should be suspected if symptoms such as tiredness, headache, nausea and vomiting should occur. In these cases a temporary increase in the dose of oral glucocorticosteroids is sometimes necessary.

Replacement of systemic steroid treatment with inhaled therapy sometimes unmasks allergies, e.g. rhinitis and eczema, which were previously controlled by systemic medicine. These allergies should be symptomatically controlled with an antihistamine and/or topical preparations.

Reduced liver function may affect the elimination of corticosteroids. This may be clinically relevant in patients with severely compromised liver function. The plasma clearance following an intravenous dose of budesonide was reported to be similar in cirrhotic patients and in healthy subjects. After oral ingestion systemic availability of budesonide was reported to increase by compromised liver function due to decreased first pass metabolism. The clinical relevance of this to treatment with budesonide is unknown as no reported data exist for inhaled budesonide, but increases in plasma levels and hence an increased risk of systemic adverse effects could be expected.

The long-term local and systemic effects of BUDAIR in human subjects are not completely known. The dose should be titrated to the lowest effective maintenance dose once control of asthma is achieved. Medical practitioners should closely monitor the growth of children and adolescents taking corticosteroids by any route and weigh the benefit of corticosteroid therapy and asthma control against the possibility of growth suppression. Special consideration may be needed in patients with active or quiescent pulmonary tuberculosis (see section 4.3)

Non steroid-dependent patients: A therapeutic effect is usually reached within 10 days. In patients with excessive mucus secretion in the bronchi, a short (about 2 weeks) additional oral corticosteroid regimen can be given initially. After the course of the oral medicine, BUDAIR alone should be sufficient therapy.

Steroid-dependent patients: When transfer from oral corticosteroid to treatment with BUDAIR is initiated, the patient should be in a relatively stable phase. BUDAIR is then given, in combination with the previously used oral steroid dose, for about 10 days. After that, the oral steroid dose should be gradually reduced (by, for example, 2,5 mg prednisolone or the equivalent each month), to the lowest possible level. In many cases, it is possible to completely substitute BUDAIR for the oral corticosteroid.

On prolonged administration signs or symptoms of systemic glucocorticosteroid effect, including hypofunction of adrenal gland and reduction of growth velocity, may occur with inhaled glucocorticosteroids, probably depending on dose, exposure time, concomitant and previous steroid exposure, and individual sensitivity.

Paradoxical bronchospasm may occur. (see section 4.8).

Co-treatment with CYP3A inhibitors, e.g. itraconazole, ketoconazole, HIV protease inhibitors and cobicistat-containing products is expected to increase the risk of systemic corticosteroid side effects. Therefore, the combination should be avoided unless the benefit outweighs this increased risk, in which case patients should be monitored for systemic corticosteroid side effects. This is of limited clinical importance for short-term (1-2 weeks) treatment with itraconazole or ketoconazole or other potent CYP3A inhibitors, but should be taken into consideration during long-term treatment.

A reduction in the dose of budesonide should also be considered (see section 4.5).

The nebuliser chamber should be cleaned after every administration. Wash the nebuliser chamber and mouthpiece or face-mask in hot water using a mild detergent. Rinse well and dry, by connecting the nebuliser chamber to the compressor or air inlet.

Oral candidiasis may occur during the therapy with inhaled corticosteroids. This infection may require treatment with appropriate antifungal therapy and in some patients discontinuation of treatment may be necessary.

Pneumonia in patients with chronic obstructive pulmonary disorder (COPD)

An increase in the incidence of pneumonia, including pneumonia requiring hospitalisation, has been reported in patients with COPD receiving inhaled corticosteroids. There is some reported evidence of an increased risk of pneumonia with increasing steroid dose but this has not been demonstrated conclusively across all studies. There is no conclusive reported clinical evidence for intra-class differences in the magnitude of the pneumonia risk among inhaled corticosteroid medicines. Medical practitioners should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of such infections overlap with the symptoms of COPD exacerbations. Risk factors for pneumonia in patients with COPD include current smoking, older age, low body mass index (BMI) and severe COPD.

Visual disturbance

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 (see section 4.8).

Paediatric population

Influence on growth

It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is regularly monitored. If growth is slowed, therapy should be re-evaluated with the aim of reducing the dose of inhaled corticosteroid, if possible, to the lowest dose at which effective control of asthma is maintained. The benefits of the corticosteroid therapy and the possible risks of growth suppression must be carefully weighed. In addition, consideration should be given to referring the patient to a paediatric respiratory specialist.

Budesonide has not been reported to interact with any medicine used for the treatment of asthma. The metabolism of budesonide is primarily mediated by CYP3A4, a subfamily of cytochrome P450. Inhibitors of this enzyme, e.g. ketoconazole, itraconazole, HIV protease inhibitors and cobicistat-containing medicines therefore increase systemic exposure to budesonide and are expected to increase the risk of systemic side effects (see section 4.4. and 5.2). The combination of BUDAIR with potent CYP3A inhibitors 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. If BUDAIR is co-administered with anti-fungals (such as itraconazole and ketoconazole), the period between treatments should be as long as possible. A reduction of the BUDAIR dose could be considered. Limited reported data about this interaction for high-dose inhaled budesonide indicate that marked increases in plasma levels (on average four-fold) may occur if itraconazole, 200 mg once daily, is administered concomitantly with inhaled budesonide (single dose of 1000 u03bcg). Raised plasma concentrations of and enhanced effects of corticosteroids have been reported in women also treated with oestrogens and contraceptive steroids, but no effect has been reported with budesonide and concomitant intake of low dose combination oral contraceptives.

Because adrenal function may be suppressed, an (Adrenocorticotropic hormone) (ACTH) stimulation test for diagnosing pituitary insufficiency might show false results (low values). At recommended doses, cimetidine has slight but clinically insignificant effect on the pharmacokinetics of oral budesonide.

Paediatric population

Interaction studies have only been reported in adults.

Pregnancy

Safety in pregnancy has not been reported. It is important for both foetus and mother to maintain an adequate asthma treatment during pregnancy. Inhaled glucocorticosteroids should be considered in preference to oral glucocorticosteroids because of the lower systemic effects at the doses required to achieve similar pulmonary responses.

Breastfeeding

Safety in lactation has not been reported. Budesonide is excreted in breast milk. However, at maternal therapeutic doses of BUDAIR, the budesonide plasma level in infants are at or below minimal measurable concentrations.

Fertility

There are no fertility data reported for budesonide.

BUDAIR has no effect on ability to drive and use machines. However blurred vision may occur, and patient should be advised not to drive or operate machines until they know how BUDAIR affects them.

The following adverse events have been reported from clinical studies and post-marketing experience by system organ class and frequency.

Table: Adverse Drug Reactions (ADR) by System Organ Class (SOC) and Frequency

SOC Frequency Adverse Drug Reaction

Infections and infestations

Frequent Oropharyngeal candidiasis Pneumonia (in COPD patients)

Immune system disorders

Less frequent Immediate and delayed hypersensitivity reactions* including rash, bronchospasm, contact dermatitis, urticaria, angioedema and anaphylactic reaction

Endocrine disorders

Less frequent Signs and symptoms of systemic corticosteroid effects, including adrenal suppression and growth retardation**

Psychiatric disorders

Less frequent Anxiety, depression, psychomotor hyperactivity, sleep disorders, aggression, behavioural changes (predominantly in children)

Frequency not known Nervousness, restlessness

Nervous system disorders

Less frequent Tremor***

Eye disorders

Less frequent Cataract, blurred vision (see also section 4.4)

Frequency not known Glaucoma

Respiratory, thoracic and mediastinal disorders

Frequent Coughing Hoarseness Throat irritation

Less frequent Bronchospasm, Dysphonia, hoarseness****

Skin and subcutaneous tissue disorders

Less frequent Bruising

Musculoskeletal and connective tissue disorders

Less frequent Muscle spasm

* refer to Description of selected adverse reactions; facial skin irritation, below ** refer to Paediatric population, below *** based on the frequency reported in clinical trials **** rare in children

Occasionally, signs or symptoms of systemic glucocorticosteroid-side effects may occur with inhaled glucocorticosteroids, probably depending on dose, exposure time, concomitant and previous corticosteroid exposure, and individual sensitivity (see section 4.4).

Description of selected adverse reactions

The candida infection in the oropharynx is due to the medicine deposition. Advising the patient to rinse the mouth out with water after each dosing will minimise the risk.

Paradoxical bronchospasm may occur. (see section 4.4).

Facial skin irritation, as an example of a hypersensitivity reaction, has been reported in some cases when a nebuliser with a face mask has been used (see section 4.4). To prevent irritation, the facial skin should be washed with water after use of the face mask.

Paediatric population

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 medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u20186.04 Adverse Drug Reaction Reporting formu2019, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/index/8.

Acute overdosage with BUDAIR, even in excessive doses, is not expected to be a clinical problem. Treatment should be discontinued and appropriate measures taken to protect the patient against stress situations.