Budesonide nebuliser suspension is indicated for the treatment of persistent bronchial asthma in patients for whom the use of pressurized inhalers or dry powder inhalers is not suitable or effective. It is also indicated in severe cases of pseudocroup (subglottic laryngitis) where hospitalization is required.

Budesonide is a synthetic corticosteroid with strong glucocorticoid activity and minimal mineralocorticoid effects. It has a high affinity for glucocorticoid receptors and demonstrates significantly greater topical anti-inflammatory activity compared to cortisol. Corticosteroids act by inhibiting various inflammatory cells (such as mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (including histamine, eicosanoids, leukotrienes, and cytokines), thereby reducing allergic inflammation.

Asthma: The dose should be given twice daily. Administration once daily may be considered in cases of mild to moderate stable asthma.

Initial dosage: The initial dose should be tailored to the severity of the disease and thereafter should be adjusted on an individual basis. The following doses are recommended but the minimum effective dose should always be sought.

• Children aged 6 months and above: 0.25-1.0 mg daily. For patients in maintenance therapy with oral steroids a higher initial dosage up to 2.0 mg daily should be considered.
• Adults (including the elderly) and children/adolescents over 12 years of age: 0.5-2 mg daily. In very severe cases the dosage may be increased further.

Maintenance dose: The maintenance dose should be adjusted to meet the requirements of the individual patient taking account of the severity of the disease and the clinical response of the patient. When the desired clinical effect has been obtained, the maintenance dose should be reduced to the minimum required for control of the symptoms.

• Children aged 6 months and above: 0.25-1.0 mg daily.
• Adults (including the elderly) and children/adolescents over 12 years of age: 0.5-2.0 mg daily. In very severe cases the dosage may be further increased.

Administration once daily: Administration once daily should be considered for children and adults with mild to moderate stable asthma and with a maintenance dose between 0.25 mg and 1 mg budesonide daily. Once-daily administration may be initiated both in patients who are not receiving corticosteroid treatment and in well-controlled patients who are already taking inhaled steroids. The dose may be given in the morning or in the evening. If a worsening of the asthma occurs, the daily dose should be increased by administering the dose twice daily.

Onset of effect: An improvement of the asthma following administration of budesonide may occur within 3 days after initiation of therapy. The maximum effect will only be obtained after 2-4 weeks of treatment.

Patients in maintenance therapy with oral glucocorticosteroids:

Asthma: Budesonide Nebuliser suspension may permit replacement or significant reduction in dosage of oral glucocorticosteroids while maintaining asthma control. When transferring from oral steroids to budesonide Nebuliser suspension is started, the patient should be in a relatively stable phase. A high dose of budesonide Nebuliser suspension 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 milligrams prednisolone or the equivalent each month) to the lowest possible level. In many cases, it is possible to completely substitute the oral steroid with budesonide Nebuliser suspension. For further information on the withdrawal of corticosteroids, when tapering off systemic corticosteroids some patients will experience steroid withdrawal symptoms, e.g. joint and/or muscle pain, lack of energy and depression or even a decreased lung function. Such patients must be advised to continue the inhaled budesonide therapy, but they should be examined for any objective signs of adrenocortical insufficiency. If such signs are present, the dose of the systemic corticosteroid should be temporarily increased and then tapered off even more slowly. In periods of stress or severe asthma attacks, patients in the transition phase may require treatment with systemic corticosteroids.

Pseudocroup: In infants and children with pseudocroup, the commonly used dose is 2 mg of nebulised budesonide. This is given as a single administration, or as two 1 mg doses separated by 30 minutes. Dosing can be repeated every 12 hours for a maximum of 36 hours or until clinical improvement.

Administration

Should be mixed with 0.9 % saline to a volume of 2 ml.

Division of the dose and miscibility: The contents of the single-dose container may be divided for adjustment of the dose. Half the ampoule contents should be placed in the Nebuliser cup and mixed with an equal volume of 0.9% sodium chloride solution. To ensure accurate dosing the use of a measuring syringe is recommended. Budesonide Nebuliser Suspension may be mixed with 0.9% sodium chloride solution and with solutions for inhalation containing terbutaline, salbutamol, sodium cromoglycate or ipratropium.

Nebuliser: Budesonide Nebuliser Suspension must be administered with a jet Nebuliser supplied with a mouthpiece or mask. The Nebuliser should be connected to an air compressor with adequate air flow (5-8 l/min), and the filling volume should be 2-4 ml. There can be variation in the performance (dose delivered) between nebulisers, even those of the same make and model.

Instruction for use-

• The spray container should be shaken before use.
• To minimise the risk of oropharyngeal candida infection, the patient should rinse their mouth out with water after inhaling.
• To prevent irritation of the facial skin the face should be washed after using the Nebuliser with a mask.
• The Nebuliser should be cleaned after each use.
• Wash the Nebuliser container and mouthpiece or face-mask in warm water using a mild detergent in accordance with the manufacturer’s instructions. Rinse well and dry it by connecting the Nebuliser container to the compressor or the air inlet.

Budesonide nebuliser suspension may enhance the bronchodilatory effect of inhaled beta-2 agonists.

Co-administration with CYP3A inhibitors, including cobicistat-containing products, may increase the risk of systemic corticosteroid adverse effects. This combination should generally be avoided unless the expected benefit outweighs the risk, and patients should be carefully monitored.

Budesonide is mainly metabolized by CYP3A4. Strong inhibitors of this enzyme, such as ketoconazole and itraconazole, can markedly increase systemic exposure to budesonide. If co-administration is unavoidable, increasing the interval between doses and reducing the budesonide dose should be considered.

Other CYP3A4 inhibitors, including erythromycin, clarithromycin, ritonavir, and saquinavir, may also significantly raise budesonide plasma levels.

Cimetidine has only a minor and clinically insignificant effect on the hepatic metabolism of budesonide.

Elevated plasma levels and enhanced corticosteroid effects have been reported in patients receiving estrogens and contraceptive steroids, although no significant interaction has been observed with low-dose oral contraceptives.

Concurrent use with systemic or intranasal corticosteroids may lead to additive suppression of adrenal function.

Because budesonide can suppress adrenal activity, diagnostic tests such as the ACTH stimulation test may produce falsely low results.

Budesonide is not indicated for the treatment of acute dyspnea or status asthmaticus. These conditions require fast-acting bronchodilators such as beta-agonists.

Adverse effects are categorized based on frequency: 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), and not known (cannot be estimated from available data).

Facial irritation, as a manifestation of hypersensitivity, has been reported in some cases, particularly when a face mask is used with a nebuliser. Washing the face after use can help prevent this irritation.

In placebo-controlled studies, cataract has been reported occasionally in placebo-treated patients.

Pooled data from clinical trials involving 13,119 patients treated with inhaled budesonide and 7,278 patients receiving placebo showed similar rates of anxiety (0.52% vs 0.63%) and depression (0.67% vs 1.15%).

An increased risk of pneumonia has been observed in patients with COPD initiating inhaled corticosteroid therapy. However, combined analyses of multiple studies have not consistently demonstrated a significant increase in risk.

Oropharyngeal candidiasis may occur during treatment. This can be reduced by inhaling before meals and rinsing the mouth after use. Most cases respond to topical antifungal treatment without discontinuing budesonide.

Coughing may be minimized by administering a short-acting beta-2 agonist (e.g., terbutaline) 5–10 minutes before using budesonide nebuliser suspension.

Systemic corticosteroid-related effects may occasionally occur, depending on dose, duration, prior exposure, and individual sensitivity. These may include adrenal suppression, growth retardation in children and adolescents, reduced bone mineral density, cataract, glaucoma, increased susceptibility to infections, and impaired stress response. However, these effects are less frequent with inhaled budesonide compared to oral corticosteroids.

Pregnancy: There are no adequate and well-controlled studies in pregnant women. It is important to maintain proper asthma control during pregnancy for the health of both the mother and the fetus. As with other medications, the use of budesonide during pregnancy should be considered only if the potential benefit to the mother outweighs the possible risk to the fetus.

Breastfeeding: Budesonide is excreted into breast milk; however, at therapeutic doses, no adverse effects on the nursing infant are expected. Budesonide can be used during breastfeeding, as maintenance doses (e.g., 200–400 micrograms twice daily) result in minimal systemic exposure in breastfed infants. Pharmacokinetic data suggest that the infant receives approximately 0.3% of the maternal daily dose, with very low plasma levels observed in infants. Overall, exposure of the breastfed infant to budesonide is considered negligible at standard therapeutic doses.

Transitioning patients from oral corticosteroids to inhaled budesonide requires careful management. Patients should be in a stable condition before initiating higher doses of inhaled corticosteroids alongside their maintenance oral dose. After approximately 10 days, oral corticosteroids should be gradually tapered to the lowest effective dose. In some cases, oral therapy can be fully replaced by inhaled budesonide.
Patients with impaired adrenal function may require additional systemic corticosteroids during periods of stress such as surgery, infections, or severe asthma exacerbations.

Patients who have received high-dose corticosteroids or prolonged therapy may be at risk of adrenal insufficiency, especially during stress. Additional systemic corticosteroids may be required in such situations.

During the transition from oral corticosteroids, previously suppressed conditions such as allergic rhinitis, eczema, or musculoskeletal pain may reappear and require appropriate treatment.

Some patients may feel unwell during withdrawal despite stable or improved lung function. These patients should continue inhaled therapy unless signs of adrenal insufficiency occur.

Paradoxical bronchospasm may rarely occur after inhalation, presenting as increased wheezing or breathlessness. If this happens, treatment should be stopped immediately and appropriate therapy initiated.

In acute worsening of asthma symptoms, rapid-acting bronchodilators should be used. If symptoms remain uncontrolled, short-term systemic corticosteroids may be necessary.

Systemic effects may occur with prolonged or high-dose use, although less frequently than with oral corticosteroids.

Possible systemic effects include Cushing’s syndrome, adrenal suppression, growth retardation in children and adolescents, decreased bone density, cataract, glaucoma, and psychological or behavioral changes such as anxiety, depression, or hyperactivity.

Children receiving long-term therapy should have their growth monitored regularly. Dose adjustments should be considered if growth suppression occurs.

Patients previously dependent on oral corticosteroids may experience prolonged adrenal suppression and should be monitored regularly.

Oral candidiasis may develop and may require antifungal treatment or discontinuation of therapy in severe cases.

Asthma symptoms may worsen due to infections, requiring appropriate treatment including antibiotics if necessary.

Patients with tuberculosis or other infections should receive appropriate therapy and careful monitoring.

In cases of excessive mucus production, short-term oral corticosteroids may be required.

Severe hepatic impairment may reduce clearance of budesonide and increase systemic exposure.

Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, HIV protease inhibitors) should be avoided or managed with caution.

Patients with COPD using inhaled corticosteroids may have an increased risk of pneumonia.

Visual disturbances such as blurred vision may occur; ophthalmologic evaluation may be necessary.

Budesonide nebuliser suspension should be administered using a jet nebuliser; ultrasonic nebulisers are not suitable.

Pediatric Population: Growth should be monitored due to potential growth suppression with long-term use.

Nasal Decongestants & Other Nasal Preparations, Respiratory corticosteroids

Store below 30°C, protected from light and moisture. Keep out of reach of children.