Included as part of the PRECAUTIONS section.
Hypercorticism And Adrenal Axis Suppression
When glucocorticosteroids are used chronically, systemic
effects such as hypercorticism and adrenal suppression may occur.
Glucocorticosteroids can reduce the response of the
hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where
patients are subject to surgery or other stress situations, supplementation
with a systemic glucocorticosteroid is recommended. Since UCERIS is a
glucocorticosteroid, general warnings concerning glucocorticoids should be
Transferring Patients From Systemic Glucocorticosteroid
Care is needed in patients who are transferred from
glucocorticosteroid treatment with higher systemic effects to
glucocorticosteroids with lower systemic effects, such as UCERIS, since symptoms
attributed to withdrawal of steroid therapy, including those of acute adrenal
suppression or benign intracranial hypertension, may develop. Adrenocortical
function monitoring may be required in these patients and the dose of
glucocorticosteroid treatment with high systemic effects should be reduced
Patients who are on drugs that suppress the immune system
are more susceptible to infection than healthy individuals. Chicken pox and
measles, for example, can have a more serious or even fatal course in
susceptible patients or patients on immunosuppressant doses of
glucocorticosteroids. In patients who have not had these diseases, particular
care should be taken to avoid exposure.
How the dose, route, and duration of glucocorticosteroid
administration affect the risk of developing a disseminated infection is not
known. The contribution of the underlying disease and/or prior
glucocorticosteroid treatment to the risk is also not known. If exposed,
therapy with varicella zoster immune globulin (VZIG) or pooled intravenous
immunoglobulin (IVIG), as appropriate, may be indicated. If exposed to measles,
prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated.
(See prescribing information for VZIG and IG.) If chicken pox develops,
treatment with antiviral agents may be considered.
Glucocorticosteroids should be used with caution, if at
all, in patients with active or quiescent tuberculosis infection, untreated
fungal, bacterial, systemic viral or parasitic infections.
Replacement of systemic glucocorticosteroids with UCERIS
tablets may unmask allergies (e.g., rhinitis and eczema), which were previously
controlled by the systemic drug.
Increased Systemic Glucocorticoid Susceptibility
Reduced liver function affects the elimination of
glucocorticosteroids, and increased systemic availability of oral budesonide
has been demonstrated in patients with liver cirrhosis [See Use in Specific
Other Glucocorticosteroid Effects
Caution should be taken in patients with hypertension,
diabetes mellitus, osteoporosis, peptic ulcer, glaucoma or cataracts, or with a
family history of diabetes or glaucoma, or with any other condition where
glucocorticosteroids may have unwanted effects.
Patient And Counseling Information
See FDA-Approved Patient
Labeling (PATIENT INFORMATION).
Patients being treated with UCERIS extended release
tablets should receive the following information and instructions. This
information is intended to aid the patient in the safe and effective use of
Hypercorticism And Adrenal Suppression
Patients should be advised that UCERIS extended release
tablets may cause systemic glucocorticosteroid effects of hypercorticism and
adrenal suppression. Patients should taper slowly from systemic corticosteroids
if transferring to UCERIS extended release tablets [See WARNINGS AND
Patients who are on immunosuppressant doses of
glucocorticosteroids should be warned to avoid exposure to chickenpox or
measles and, if exposed, to consult their physician immediately. If exposure to
such a person occurs, and the patient has not had chicken pox or been properly
vaccinated, a physician should be consulted immediately. Patients should be
informed of potential worsening of existing tuberculosis, fungal, bacterial,
viral, or parasitic infections, or ocular herpes simplex [See WARNINGS AND
How To Take UCERIS Extended Release Tablets
UCERIS extended release tablets should be swallowed whole
with water and NOT CHEWED, CRUSHED, OR BROKEN. Patients should be advised to
avoid the consumption of grapefruit juice for the duration of their UCERIS
therapy [See DOSAGE AND ADMINISTRATION].
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Carcinogenicity studies with budesonide were conducted in
rats and mice. In a two-year study in Sprague-Dawley rats, budesonide caused a
statistically significant increase in the incidence of gliomas in male rats at
an oral dose of 50 mcg/kg (approximately 0.05 times the maximum recommended
human dose on a body surface area basis). In addition, there were increased
incidences of primary hepatocellular tumors in male rats at 25 mcg/kg
(approximately 0.023 times the maximum recommended human dose on a body surface
area basis) and above. No tumorigenicity was seen in female rats at oral doses
up to 50 mcg/kg (approximately 0.05 times the maximum recommended human dose on
a body surface area basis). In an additional two-year study in male
Sprague-Dawley rats, budesonide caused no gliomas at an oral dose of 50 mcg/kg
(approximately 0.05 times the maximum recommended human dose on a body surface
area basis). However, it caused a statistically significant increase in the
incidence of hepatocellular tumors at an oral dose of 50 mcg/kg (approximately
0.05 times the maximum recommended human dose on a body surface area basis).
The concurrent reference glucocorticosteroids (prednisolone and triamcinolone
acetonide) showed similar findings. In a 91-week study in mice, budesonide
caused no treatment-related carcinogenicity at oral doses up to 200 mcg/kg
(approximately 0.1 times the maximum recommended human dose on a body surface
Budesonide was not genotoxic in the Ames test, the mouse
lymphoma cell forward gene mutation (TK+/-) test, the human lymphocyte
chromosome aberration test, the Drosophila melanogaster sex-linked recessive
lethality test, the rat hepatocycte UDS test and the mouse micronucleus test.
Impairment Of Fertility
In rats, budesonide had no effect on fertility at
subcutaneous doses up to 80 mcg/kg (approximately 0.07 times the maximum
recommended human dose on a body surface area basis). However, it caused a
decrease in prenatal viability and viability in pups at birth and during
lactation, along with a decrease in maternal body-weight gain, at subcutaneous
doses of 20 mcg/kg (approximately 0.02 times the maximum recommended human dose
on a body surface area basis) and above. No such effects were noted at 5 mcg/kg
(approximately 0.005 times the maximum recommended human dose on a body surface
Use In Specific Populations
Pregnancy Category C
Budesonide was teratogenic and
embryocidal in rabbits and rats. Budesonide produced fetal loss, decreased pup
weights, and skeletal abnormalities at subcutaneous doses of 25 mcg/kg in
rabbits (approximately 0.05 times the maximum recommended human dose on a body
surface area basis) and 500 mcg/kg in rats (approximately 0.5 times the maximum
recommended human dose on a body surface area basis).
There are no adequate and
well-controlled studies in pregnant women. Budesonide should be used during
pregnancy only if the potential benefit justifies the potential risk to the
Hypoadrenalism may occur in
infants born of mothers receiving glucocorticosteroids during pregnancy. Such
infants should be carefully observed.
The disposition of budesonide when delivered by
inhalation from a dry powder inhaler at doses of 200 or 400 mcg twice daily for
at least 3 months was studied in eight lactating women with asthma from 1 to 6
months postpartum.1 Systemic exposure to budesonide in these women
appears to be comparable to that in non-lactating women with asthma from other
studies. Breast milk obtained over eight hours post-dose revealed that the
maximum budesonide concentration for the 400 and 800 mcg total daily doses was
0.39 and 0.78 nmol/L, respectively, and occurred within 45 minutes after
inhalation. The estimated oral daily dose of budesonide from breast milk to the
infant is approximately 0.007 and 0.014 mcg/kg/day for the two dose regimens
used in this study, which represents approximately 0.3% to 1% of the dose
inhaled by the mother. Budesonide plasma concentrations obtained from five infants
at about 90 minutes after breast feeding (and about 140 minutes after drug
administration to the mother) were below quantifiable levels ( < 0.02 nmol/L
in four infants and < 0.04 nmol/L in one infant).
The recommended daily dose of UCERIS extended release
tablets is higher (9 mg daily) compared with inhaled budesonide (up to 800
μg daily) given to mothers in the above study. The maximum budesonide
plasma concentration following a 9 mg daily dose (in both single-and
repeated-dose pharmacokinetic studies) of oral budesonide is approximately 5-10
nmol/L which is up to 10 times higher than the 1-2 nmol/L for a 800 mcg daily
dose of inhaled budesonide at steady state in the above inhalation study.
Since there are no data from controlled trials on the use
of UCERIS by nursing mothers or their infants, and because of the potential for
serious adverse reactions in nursing infants from UCERIS, a decision should be
made whether to discontinue nursing or to discontinue UCERIS, taking into
account the clinical importance of UCERIS to the mother.
Budesonide is secreted in human milk. Data from
budesonide delivered via dry powder inhaler indicates that the total daily oral
dose of budesonide available in breast milk to the infant is approximately 0.3%
to 1% of the dose inhaled by the mother. Assuming the coefficient of
extrapolation between the inhaled and oral doses is constant across all dose
levels, at therapeutic doses of UCERIS, budesonide exposure to the nursing
child may be up to 10 times higher than that by budesonide inhalation.
Safety and effectiveness of UCERIS in pediatric patients
have not been established. Glucocorticosteroids, such as UCERIS may cause a
reduction of growth velocity in pediatric patients.
Clinical studies of UCERIS did not include sufficient
numbers of subjects aged 65 and over to determine whether they respond
differently from younger subjects. Other reported clinical experience has not
identified differences in responses between the elderly and younger patients.
In general, UCERIS should be used cautiously in elderly patients due to the
potential for decreased hepatic, renal, or cardiac function, and of concomitant
disease or other drug therapy.
Patients with moderate to severe liver disease should be
monitored for increased signs and/or symptoms of hypercorticism. Discontinuing
the use of UCERIS tablets should be considered in these patients [See WARNINGS
1. Falt A, Bengtsson T, Kennedy
B, et al. Exposure of infants to budesonide through breast milk of asthmatic
mothers. J. Allergy Clin Immunol. 2007;120(4):798-802.