Download Core Data Sheet

CSP
Drug Substance
Budesonide
Date
13 Oct 2011 rev 11Nov
18 Aug 2011
Supersedes
Agreed Core Safety Profile for
Budesonide nasal spray suspension and
Budesonide nasal powder
TITLE PAGE
Agreed Core Safety Profile for
Budesonide nasal spray suspension and
Budesonide nasal powder
TABLE OF CONTENTS
PAGE
TITLE PAGE ............................................................................................................................ 1
TABLE OF CONTENTS ......................................................................................................... 2
Introduction .............................................................................................................................. 3
CORE SAFETY PROFILE ...................................................................................................... 3
ANNOTATED VERSION ....................................................................................................... 3
4.2 Posology and method of administration ............................................................................. 3
4.3 Contraindications ................................................................................................................ 3
4.4 Special warnings and special precautions for use .............................................................. 4
4.5 Interaction with other medicinal products and other forms of interaction ......................... 4
4.6 Pregnancy and lactation ...................................................................................................... 5
4.7 Effects on ability to drive and use machines ...................................................................... 5
4.8 Undesirable effects ............................................................................................................. 6
4.9 Overdose ............................................................................................................................. 7
CORE SAFETY PROFILE ...................................................................................................... 7
CLEAN VERSION .................................................................................................................. 7
4.2 Posology and method of administration ............................................................................. 7
4.3 Contraindications ................................................................................................................ 7
4.4 Special warnings and special precautions for use .............................................................. 7
4.5 Interaction with other medicinal products and other forms of interaction ......................... 8
4.6 Pregnancy and lactation ...................................................................................................... 8
4.7 Effects on ability to drive and use machines ...................................................................... 9
4.8 Undesirable effects ............................................................................................................. 9
4.9 Overdose ........................................................................................................................... 10
2
Agreed Core Safety Profile for
Budesonide nasal spray suspension and
Budesonide nasal powder
Introduction
Agreed Core Safety Profile for
Budesonide nasal spray suspension and
Budesonide nasal powder
Budesonide for nasal use is available in EU/Norway/Iceland in the following pharmaceutical
forms (by brand leader):
Budesonide nasal spray suspension
Budesonide nasal powder
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.
Budesonide nasal powder
Hypersensitivity to budesonide.
3
Agreed Core Safety Profile for
Budesonide nasal spray suspension and
Budesonide nasal powder
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
Agreed Core Safety Profile for
Budesonide nasal spray suspension and
Budesonide nasal powder
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
Agreed Core Safety Profile for
Budesonide nasal spray suspension and
Budesonide nasal powder
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
Immediate and delayed
hypersensitivity reactions,
including urticaria, rash,
dermatitis, angioedema and
pruritus
Very rare
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
Very rare
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 4.4.
6
Agreed Core Safety Profile for
Budesonide nasal spray suspension and
Budesonide nasal powder
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.
Budesonide nasal powder
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
Agreed Core Safety Profile for
Budesonide nasal spray suspension and
Budesonide nasal powder
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
Agreed Core Safety Profile for
Budesonide nasal spray suspension and
Budesonide nasal powder
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
Immediate and delayed
hypersensitivity reactions,
including urticaria, rash,
dermatitis, angioedema and
pruritus
Very rare
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
Agreed Core Safety Profile for
Budesonide nasal spray suspension and
Budesonide nasal powder
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 4.4.
4.9 Overdose
Acute overdosage with Budesonide even in excessive doses, is not expected to be a clinical
problem.
10