Agreed Core Safety Profile for Budesonide nasal spray suspension and Budesonide nasal powder

Transcription

1 CSP Drug Budesonide Substance Date 13 Oct 2011 rev 11Nov Supersedes 18 Aug 2011 Agreed Core Safety Profile for DK/H/PSUR/0041/001

2 TABLE OF CONTENTS PAGE TITLE PAGE... 1 TABLE OF CONTENTS... 2 Introduction... 3 CORE SAFETY PROFILE... 3 ANNOTATED VERSION Posology and method of administration Contraindications Special warnings and special precautions for use Interaction with other medicinal products and other forms of interaction Pregnancy and lactation Effects on ability to drive and use machines Undesirable effects Overdose... 7 CORE SAFETY PROFILE... 7 CLEAN VERSION Posology and method of administration Contraindications Special warnings and special precautions for use Interaction with other medicinal products and other forms of interaction Pregnancy and lactation Effects on ability to drive and use machines Undesirable effects Overdose

3 Introduction Agreed Core Safety Profile for Budesonide for nasal use is available in EU/Norway/Iceland in the following pharmaceutical forms (by brand leader): Budesonide nasal spray suspension In the proposed CSP the pharmaceutical forms are referred to as Budesonide, unless the statement is specific to one formulation and hence stated. The parts of the CSP that have been updated with regards to the Draft Final Assessment Report are written in Purple colour. At the end of this document there is also a clean version of the CSP. CORE SAFETY PROFILE ANNOTATED VERSION 4.2 Posology and method of administration Note-only relevant part of section 4.2 presented here The patient should be informed that the full effect of budesonide is not achieved until after a few days treatment. Treatment of seasonal rhinitis should, if possible, start before exposure to allergens. 4.3 Contraindications Budesonide nasal spray Hypersensitivity to budesonide or to any of the excipients. Hypersensitivity to budesonide. 3

4 4.4 Special warnings and special precautions for use 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 and glaucoma. A range of psychological or behavioural effects including restlessness, sleep disturbances, nervousness, depression and agitation may also occur (mainly in children). 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). Reduced liver function affects the elimination of corticosteroids, causing lower elimination rate and higher systemic exposure. Be aware of possible systemic side effects. Special caution is necessary in patients with active or quiescent pulmonary tuberculosis, and in patients with fungal or viral infections in the airways. 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. 4.5 Interaction with other medicinal products and other forms of interaction Budesonide has not been observed to interact with any drug used for the treatment of rhinitis. The metabolism of budesonide is primarily mediated by CYP3A4. Inhibitors of this enzyme, eg, ketoconazole and itraconazole, can therefore increase systemic exposure to budesonide several times. Since there is no data to support a dosage recommendation, the combination should be avoided. If this is not possible, the period between treatments should be as long as possible and a reduction of the budesonide dose could also be considered. 4

5 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. Because adrenal function may be suppressed, an ACTH stimulation test for diagnosing pituitary insufficiency might show false results (low values). 4.6 Pregnancy and lactation 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. 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. 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 microg twice daily) in asthmatic nursing women results in negligible systemic exposure to budesonide in breast-fed infants., milk and plasma samples were collected up to 8 hours after dosing from 8 mothers receiving budesonide maintenance treatment (200 or 400 microg twice daily). Infant exposure was estimated based on average milk budesonide concentrations. A single blood sample was obtained from 5 infants close to expected infant maximum concentration 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. These data support continued use of inhaled budesonide during breast-feeding. 4.7 Effects on ability to drive and use machines Budesonide has no influence on the ability to drive and use machines. 5

6 4.8 Undesirable effects The following definitions apply to the incidence of undesirable effects: Frequencies are defined as: very common ( 1/10); common ( 1/100 to <1/10); uncommon ( 1/1000 to <1/100); rare ( 1/10000 to <1/1000); very rare (<1/10000). SOC Frequency ADR Immune system disorders Uncommon Very rare Immediate and delayed hypersensitivity reactions, including urticaria, rash, dermatitis, angioedema and pruritus Anaphylactic reaction Endocrine disorders Rare Signs and symptoms of systemic corticosteroid effects, including adrenal suppression and growth retardation Eye disorders Unknown Cataract Glaucoma Respiratory, thoracic and mediastinal disorders Common Very rare Haemorrhagic secretion and epistaxis Nasal irritation Ulcerations of the mucous membrane Nasal septum perforation Systemic effects of nasal corticosteroids may occur, particularly at high doses when used for prolonged periods (see section 4.4). 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

7 4.9 Overdose Acute overdosage with Budesonide even in excessive doses, is not expected to be a clinical problem. CORE SAFETY PROFILE CLEAN VERSION 4.2 Posology and method of administration Note-only relevant part of section 4.2 presented here The patient should be informed that the full effect of budesonide is not achieved until after a few days treatment. Treatment of seasonal rhinitis should, if possible, start before exposure to allergens. 4.3 Contraindications Budesonide nasal spray Hypersensitivity to budesonide or to any of the excipients. Hypersensitivity to budesonide. 4.4 Special warnings and special precautions for use 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). Reduced liver function affects the elimination of corticosteroids, causing lower elimination rate and higher systemic exposure. Be aware of possible systemic side effects. 7

8 Special caution is necessary in patients with active or quiescent pulmonary tuberculosis, and in patients with fungal or viral infections in the airways. 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. 4.5 Interaction with other medicinal products and other forms of interaction Budesonide has not been observed to interact with any drug used for the treatment of rhinitis. The metabolism of budesonide is primarily mediated by CYP3A4. Inhibitors of this enzyme, eg, ketoconazole and itraconazole, can therefore increase systemic exposure to budesonide several times. Since there is no data to support a dosage recommendation, the combination should be avoided. If this is not possible, the period between treatments should be as long as possible and a reduction of the budesonide dose could also be considered. 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. Because adrenal function may be suppressed, an ACTH stimulation test for diagnosing pituitary insufficiency might show false results (low values). 4.6 Pregnancy and lactation 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. 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. 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 microg 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 8

9 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. 4.7 Effects on ability to drive and use machines Budesonide has no influence on the ability to drive and use machines. 4.8 Undesirable effects The following definitions apply to the incidence of undesirable effects: Frequencies are defined as: very common ( 1/10); common ( 1/100 to <1/10); uncommon ( 1/1000 to <1/100); rare ( 1/10000 to <1/1000); very rare (<1/10000). SOC Frequency ADR Immune system disorders Uncommon Very rare Immediate and delayed hypersensitivity reactions, including urticaria, rash, dermatitis, angioedema and pruritus Anaphylactic reaction Endocrine disorders Rare Signs and symptoms of systemic corticosteroid effects, including adrenal suppression and growth retardation Eye disorders Unknown Cataract Glaucoma Respiratory, thoracic and mediastinal disorders Common Haemorrhagic secretion and epistaxis Nasal irritation Ulcerations of the mucous 9

10 Very rare membrane Nasal septum perforation Systemic effects of nasal corticosteroids may occur, particularly at high doses when used for prolonged periods (see section 4.4). 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 Overdose Acute overdosage with Budesonide even in excessive doses, is not expected to be a clinical problem. 10