Budesonide 0,125mg 0,25mg & 0,5 mg Cipla Respules

BUDESONIDE RESPULES CIPLA 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. BUDESONIDE RESPULES CIPLA Nebuliser Suspension is also recommended for use in infants and children with acute laryngotracheobronchitis-croup.

Asthma

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

Children

• 12 months to 6 years
• 6 years and older

Previous therapy

• Recommended starting dose

• 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 to 0,5 mg twice daily

In patients where an increased therapeutic effect is required, an increased dose of BUDESONIDE RESPULES CIPLA should be considered. 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, BUDESONIDE RESPULES CIPLA 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 2 weeks. A slow rate of withdrawal is strongly recommended. In a proportion of cases, it is possible to completely substitute the oral glucocorticosteroid with BUDESONIDE RESPULES CIPLA. During withdrawal, some patients may experience symptoms of systemic corticosteroid withdrawal, e.g., joint and/or muscular pain, lassitude and depression, despite maintenance or even improvement in pulmonary function. Such patients should be encouraged to continue with BUDESONIDE RESPULES CIPLA 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.

BUDESONIDE RESPULES CIPLA is contraindicated in:

• Patients with known hypersensitivity to budesonide or to any of the excipients in BUDESONIDE RESPULES CIPLA (see section 6.1).
• Patients with lung tuberculosis, fungal and viral infections in the airways.
• Safety and efficacy for children less than 12 months have not been established.
• Primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required.

Special consideration may be needed in patients with active or quiescent pulmonary tuberculosis and in patients with fungal or viral infections in the airways.

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, BUDESONIDE RESPULES CIPLA alone should be sufficient therapy.

Steroid-dependent patients

When transfer from oral corticosteroid to treatment with BUDESONIDE RESPULES CIPLA is initiated, the patient should be in a relatively stable phase. BUDESONIDE RESPULES CIPLA 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 BUDESONIDE RESPULES CIPLA for the oral corticosteroid. Replacement of systemic steroid treatment with inhaled therapy sometimes unmasks allergies, e.g., rhinitis and eczema, which were previously controlled by the systemic medicine. These allergies should be symptomatically controlled with an antihistamine and/or topical preparations.

Particular care is needed in patients transferring from oral steroids, since they may remain at risk of impaired adrenal function for a considerable time. 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.

Paradoxical bronchospasm may occur, manifested by an immediate increase in wheezing after dosing. If this occurs, treatment with inhaled budesonide should be discontinued immediately, the patient assessed and, if necessary, alternative treatment instituted.

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 corticosteroid, 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 less frequently, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). It is important, therefore, that the dose of inhaled corticosteroid is titrated to the lowest dose at which effective control of asthma is maintained.

BUDESONIDE RESPULES CIPLA 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.

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 however can be similar in cirrhotic patients and in healthy subjects. After oral ingestion systemic availability of budesonide can be increased by compromised liver function due to decreased first pass metabolism. The relevance of this to treatment with BUDESONIDE RESPULES CIPLA is unknown as no data exist for inhaled budesonide but increases in plasma levels and hence an increased risk of systemic adverse effects could be expected.

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 to 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 facemask 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 (see also section 4.2). To minimise oral candidiasis, the patient should rinse the mouth out with water after each occasion.

Pneumonia in patients with COPD

An increase in the incidence of pneumonia, including pneumonia requiring hospitalisation, can be observed in patients with COPD receiving inhaled corticosteroids. Increased risk of pneumonia with increasing steroid dose can be observed in some patients with COPD. There is no conclusive evidence for intra-class differences in the magnitude of the pneumonia risk among inhaled corticosteroid products. Medical practitioners should remain vigilant for the possible development of pneumonia in patients with COPD as the 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 serious chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

Facial skin irritation:

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 the face mask. To minimise oropharyngeal thrush, the patient should rinse the mouth out with water after each dosing occasion.

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.

The long-term local and systemic effects of BUDESONIDE RESPULES CIPLA 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.

Budesonide has not been observed 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 and itraconazole, therefore increase systemic exposure to budesonide. At recommended doses, cimetidine has slight but insignificant effect on the pharmacokinetics of oral budesonide. The combination of BUDESONIDE RESPULES CIPLA 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 BUDESONIDE RESPULES CIPLA is co-administered with anti-fungal (such as itraconazole and ketoconazole), the period between treatments should be as long as possible. A reduction of the budesonide dose could be considered. Few incidents 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 can be 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. Because adrenal function may be suppressed, an ACTH stimulation test for diagnosing pituitary insufficiency might show false results (low values).

Pregnancy: Safety in pregnancy has not been established. 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 breastfeeding has not been established. Budesonide is excreted in breast milk. However, at maternal therapeutic doses of BUDESONIDE RESPULES CIPLA, the budesonide plasma levels in infants are at or below minimal measurable concentrations.

BUDESONIDE RESPULES CIPLA has no effect on the ability to drive and use machines.

a) Tabulated list of adverse reactions

Table 1: Adverse Drug Reactions (ADR) by System Organ Class (SOC) and Frequency

MedDRA system organ class Frequency Side effects

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 unknown Nervousness, restlessness

Nervous system disorders Less frequent Tremor ***

Eye Disorders Less frequent Cataract, Vision, blurred (see also section 4.4)

Frequency unknown Glaucoma

Respiratory, thoracic and mediastinal disorders Frequent Hoarseness, cough, throat irritation

Less frequent Dysphonia, hoarseness****

Skin and subcutaneous tissue disorders Less frequent Bruising

Musculoskeletal and connective tissue disorders Less frequent Muscle Spasms

* refer to Description of selected adverse reactions: facial skin irritation, below ** refer to Paediatric population, below *** based on the frequency reported in clinical trials **** less frequent 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 medicine deposition. Advising the patient to rinse the mouth out with water after each dosing will minimise the risk.

Paradoxical bronchospasm may occur in less frequent cases (see section 4.4).

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 the face mask. To minimise oropharyngeal thrush, the patient should rinse the mouth out with water after each dosing occasion.

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 requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on the SAHPRA website, or to Cipla Medpro (Pty) Ltd. by email: [email protected] or telephone: 080 222 6662 (toll free).

Symptoms

Acute overdose with BUDESONIDE RESPULES CIPLA, even in excessive doses, is not expected to constitute a medical problem. Treatment should be discontinued, and appropriate measures should be taken to protect the patient against stress situations.