| 1. What
are the systemic effects of budesonide? |
Systemic
effects of intranasally administered steroids have centred around
influence on the hypothalamic-pituitary-adrenal axis and growth in
children, both of which have been investigated with Rhinocort®.
Rhinocort® Aqua™ 64 µg once daily had no
suppressive effects on stimulated plasma cortisol levels during a
6-week, placebo-controlled study in 78 children (2–5 years)
with allergic rhinitis (Figure 1; Kim et al
2004). In an open trial of 78 children (5–15
years) with allergic rhinitis, 18 months of treatment with
Rhinocort® pMDI treatment did not affect 24-h urinary cortisol or
basal morning plasma cortisol (Möller et al
2003). Doses ranged from 256 to 400 µg/day. No changes
in urinary cortisol were seen during a further 6-month extension
period using 400 µg/day. Furthermore, 5.5 years of treatment
with Rhinocort® pMDI 200–400 µg/day, in adult
patients with allergic rhinitis, had no influence
on the hypothalamic-pituitary-adrenal axis,
as assessed by basal and stimulated morning cortisol (Figure
2; Pipkorn et al 1988).
Figure
1. Mean sycontropin (10 µg) stimulated plasma cortisol levels
at baseline and end of study in 78 paediatric patients following 6
weeks’ treatment with Rhinocort®
Aqua™ 64 µg once daily or placebo (Kim et al
2004)
Figure 2. Mean plasma cortisol levels before and 30 min
after stimulation with adrenocorticotrophic hormone in 24 adult
patients with allergic rhinitis treated with Rhinocort®
pMDI 200–400 µg (Pipkorn et al 1988).
|
| 2. Is
Rhinocort® associated with any local adverse effects? |
Although
there are known adverse effects associated with topical application
of corticosteroids (Trangsrud et al 2002), currently available
intranasal corticosteroids are well tolerated, but local effects,
such as crusting, dryness and minor epistaxis, may occur in some
patients (Bousquet et al 2001). Long-term studies with Rhinocort®
have shown no histological changes in the nasal mucosa, as assessed
by regular nasal biopsy, after 1 year (Lindqvist et al 1986) and 5.5
years (Pipkorn et al 1988) of treatment. In addition, a recent study
by Mastruzzo and colleagues (2003) has documented epithelial
restitution of the nasal mucosa after treatment with Rhinocort®
in patients suffering from nasal polyposis.
Nasal
corticosteroid treatment has also been linked to nasal septum
perforation. This is a rare complication with a few cases being
reported for Rhinocort® as well as for other intranasal
corticosteroids (Cervin & Andersson 1998). The risk appears to
be higher in women during the first year of treatment and with
concomitant use of nasal decongestants. Rhinocort® should not be
used if pronounced septum deviation is observed, and if epistaxis or
crusting occurs.
|
| 3. Is
Rhinocort® suitable for use in children as well as adults? |
The
tolerability of Rhinocort® in adults has been well documented
(Pipkorn et al 1988). A recent 1-year study in 229 children aged 4–8
years with perennial allergic rhinitis showed no difference in growth
velocity between the group treated once daily with Rhinocort®
Aqua™ 64 µg compared with the placebo group (Murphy et al
2004).
Furthermore,
an open study in 78 children (aged 5–15 years) with perennial
allergic rhinitis demonstrated that Rhinocort® 256–400 µg
had no significant changes in haematological
parameters, blood chemistry tests, urinalysis, bone age or growth
after 1–2 years of treatment (Möller
et al 2003).
|
| 4. What
happens if a patient administers more than
the prescribed dose of Rhinocort®? |
High
doses of glucocorticosteroids have a low toxicity and are virtually
without harmful effects, even following multiple administrations at
very high doses (Haynes 1990; Costa 2000). Occasional overdosing of
intranasally or orally inhaled corticosteroids is not considered to
have any significant impact on patient safety. The majority of
intranasally administered budesonide is not systemically absorbed,
but cleared from the nasal mucosa by mucociliary activity and
subsequently swallowed, thereafter undergoing first pass
de-activation in the liver. The highest dose of oral inhaled
budesonide that has been studied in healthy volunteers was 7200 µg,
given as a series of inhalations on one occasion (AstraDraco 1988).
Apart from an expected temporary lowering of the plasma concentration
of endogenous cortisol, there were no adverse effects of clinical
importance. As with all inhaled corticosteroids, systemic
glucocorticoid effects may appear if used chronically in excessive
doses.
|
| 5. References |
AstraDraco,
Clinical Study Report 850-CR-0116. 1988.
Bousquet
J, van Cauwenberge P, Khaltaev N, Aria Workshop Group, World Health
Organization. Allergic Rhinitis and its impact on Asthma. J
Allergy Clin Immunol 2001; 108 (suppl): S147–S334.
Cervin
A, Andersson M. Intranasal
steroids and septum perforation – an overlooked complication?
A description of the course of events and a discussion of the causes.
Rhinology
1998; 36: 128–132.
Costa
J. Corticotropins and corticosteroids, in Meyler´s side
effects of drugs, M. Dukes and J. Aronson, Editors. 2000, Elsevier:
Amsterdam. p. 1364–1395.
Haynes
Jr R. Adrenocorticotropic hormone;
adrenocortical steroids and their synthetic analogs; inhibitors of
the synthesis and actions of adrenocortical hormones in Goodman and
Gilman’s The Pharmacological Basis of Therapeutics, A. Goodman
Gilman, et al., Editors. 1990, Pergamon Press: New York. p.
1431–1462.
Kim KT, Rabinovitch N, Uryniak T, Simpson B, O'Dowd L, Casty F. Effect of budesonide aqueous nasal spray on hypothalamic-pituitary-adrenal axis function in children with allergic rhinitis. Annals of Allergy, Asthma, & Immunology 2004;93(1):61-7.
Lindqvist
N, Balle VH, Karma P, et al. Long-term
safety and efficacy of budesonide nasal aerosol in perennial
rhinitis. A 12-month multicentre study. Allergy
1986; 41: 179–186.
Mastruzzo
C, Greco LR, Nakano K, et al. Impact of intranasal budesonide on
immune inflammatory responses and epithelial remodeling in chronic
upper airway inflammation. J Allergy Clin Immunol 2003; 112:
37–44.
Möller
C, Ahlström H, Henricson K-Å, et al. Safety of
nasal budesonide in the long-term treatment of children with
perennial rhinitis. Clin Exp Allergy 2003; 33: 816–822.
Murphy
KR, Uryniak T, Simpson B, et al. Recommended once-daily dose of
budesonide aqueous nasal spray (Rhinocort® Aqua™) does not
suppress growth velocity in paediatric patients with perennial
allergic rhinitis. J All Clin Immunol 2004; 13: S175.
Pipkorn
U, Pukander J, SuonpääJ, Makinen J, Lindqvist N. Long-term
safety of budesonide nasal aerosol: a 5.5-year follow-up study.
Clin Allergy 1988; 18: 253–259.
Trangsrud
AJ, Whitaker AL, Small RE. Intranasal corticosteroids for allergic
rhinitis. Pharmacotherapy 2002; 22: 1458–1467.
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