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CSP
Drug Substance
Budesonide enema
Date
2 Nov 2011, rev 11 Nov
425May
Nov2011
2010
Supersedes
Proposed Core Safety Profile
Budesonide enema, tablet for rectal suspension, 2 mg (0.02 mg/mL)
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TABLE OF CONTENTS
PAGE
TABLE OF CONTENTS ......................................................................................................... 2
4.3
Contraindications ..................................................................................................... 3
4.4
Special warnings and special precautions for use .................................................... 3
4.5
Interaction with other medicinal products and other forms of interaction ............... 3
4.6
Pregnancy and lactation ........................................................................................... 4
4.7
Effects on ability to drive and use machines............................................................ 4
4.8
Undesirable effects ................................................................................................... 4
4.9
Overdose .................................................................................................................. 5
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4.3
Contraindications
Hypersensitivity to budesonide or to any of the excipients.
4.4
Special warnings and special precautions for use
Side effects typical of systemic corticosteroids may occur. Potential systemic effects include
glaucoma
Caution should be taken in patients with infections or with any other condition where
corticosteroids may have unwanted effects
When patients are transferred from systemic corticosteroid treatment with higher systemic effect
to budesonide enema, they may have adrenocortical suppression.
Some patients feel unwell in a non-specific way during the withdrawal phase, eg, pain in
muscles and joints. A general insufficient corticosteroid effect should be suspected if, in rare
cases, symptoms such as tiredness, headache, nausea and vomiting should occur.
Replacement of high systemic effect corticosteroid treatment with Budesonide enema
sometimes unmasks allergies, eg, rhinitis and eczema that were previously controlled by the
systemic drug.
Reduced liver function affects the elimination of corticosteroids, causing lower elimination
rate and higher systemic exposure. Be aware of possible systemic side effects.
Concomitant use of ketoconazole or other potent CYP3A4 inhibitors 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 (see also section 4.5).
When budesonide enema is used chronically in excessive doses, systemic corticosteroid
effects such as hypercorticism and adrenal suppression may appear. However, the dosage form
- enema - and the route of administration make any prolonged overdosage unlikely.
4.5 Interaction with other medicinal products and other forms of
interaction
The metabolism of budesonide is primarily mediated by CYP3A4.
Inhibitors of this enzyme, eg ketoconazole, itraconazole and HIV protease inhibitors can
therefore increase systemic exposure to budesonide several times, see section 4.4. 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.
Budesonide is unlikely to inhibit other drugs metabolized by CYP3A4 since it has low affinity
to the enzyme.
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Concomitant treatment with CYP3A4 inducers such as carbamazepine probably reduces
budesonide exposure, which may require a dose increase.
Raised plasma concentrations of and enhanced effects of corticosteroids have been observed
in women also treated with estrogens and contraceptive steroids, but no such effect has been
observed with budesonide and concomitant intake of low dose combination oral
contraceptives.
4.6
Pregnancy and lactation
In pregnant animals, administration of budesonide, like other corticosteroids, is associated
with abnormalities in foetal development. The relevance of these findings to humans has not
been established. 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.
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
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 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 budesonide, oral and rectal administrations during
breast-feeding.
4.7
Effects on ability to drive and use machines
Budesonide enema does not affect the ability to drive and use machines
4.8
Undesirable effects
Tabulated list of adverse events
The following definitions apply to the incidence of undesirable effects: 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).
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Adverse drug reactions by frequency and system organ class (SOC)
SOC
Frequency
Reaction
Immune system disorders
Very rare
Anaphylactic reaction
Endocrine disorders
Rare
Signs or symptoms of
systemic glucocorticosteroid
effects, including
hypofunction of the adrenal
gland
Eye distorders
Psychiatric disorders
Unknown
Uncommon
Glaucoma
Agitation, insomnia
Gastrointestinal disorders
Common
Gastrointestinal disturbances,
eg, flatulence, nausea,
diarrhoea
Skin and subcutaneous tissue
disorders
Common
Skin reactions (urticaria,
exanthema)
Description of selected adverse events
In rare cases signs or symptoms of systemic corticosteroid effects, including hypofunction of
the adrenal gland, may occur with rectally administered corticosteroids, probably depending
on dose, treatment time, concomitant and previous corticosteroid intake, and individual
sensitivity.
4.9
Overdose
Reports of acute toxicity or death following overdosage of corticosteroids are rare. Thus, acute
overdosage with budesonide enema, even in excessive doses, is not expected to be a clinical
problem. In the event of acute overdosage, no specific antidote is available.
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