Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Local
Nasal Adverse Reactions
(Additions and/or
revisions underlined)
Epistaxis and Nasal
Ulceration:
In clinical trials of 2 to 26 weeks in duration, epistaxis was observed more frequently in patients treated
with ZETONNA than those who received placebo. In the 26-week open-label
extension of the perennial allergic rhinitis trial, nasal ulceration was
identified in 4 of 824 patients administered ZETONNA (148 mcg) [see Adverse
Reactions (6)].
The occurrence of local nasal adverse events
was further evaluated in a separate, postmarketing 26-week randomized, open-label, active-controlled
nasal and ocular safety trial conducted in patients with perennial allergic
rhinitis. In this study epistaxis was
observed in 6% of patients treated with ZETONNA and nasal ulceration was
identified in 3 of 367 patients administered ZETONNA. [see Adverse
Reactions (6)].
Nasal Septal
Perforation:
Nasal septal perforation has been reported in patients following the nasal application
of ZETONNA. Three short-term
placebo-controlled trials (2 weeks) and one long-term (26 weeks with placebo
control and 26 weeks open-label extension without placebo control) trial were
conducted in patients with seasonal and perennial allergic rhinitis. Nasal septal perforations were reported in
2 patients out of 2335 patients treated with ZETONNA compared with none
of 892 patients treated with placebo.
No nasal septal perforations were reported in 367 patients
treated with ZETONNA
in a postmarketing 26-week, open-label, active- controlled trial in patients with perennial allergic
rhinitis [see Adverse Reactions (6)].
Before starting ZETONNA
conduct a nasal examination to ensure that patients are free of nasal disease other
than allergic rhinitis. Periodically monitor patients
with nasal examinations during treatment for adverse effects in the nasal cavity. If an adverse reaction (e.g. erosion,
ulceration, perforation) is noted, discontinue ZETONNA. Avoid spraying ZETONNA directly onto the nasal septum.
Candida Infection: Localized infections
of the nose or pharynx with Candida albicans has occurred from
the use of ciclesonide. If such an infection occurs with ZETONNA, treat it with appropriate
local therapy and discontinue ZETONNA.
5.2 Glaucoma and
Cataracts
(Additions and/or
revisions underlined)
Nasal and inhaled
corticosteroids, including ZETONNA, can result in the development of
glaucoma and cataracts. Therefore, close
monitoring is warranted in patients with a change
in vision or with a history of increased intraocular pressure, glaucoma,
or cataracts.
5.3
Hypersensitivity Reactions
(Additions and/or
revisions underlined)
ZETONNA is contraindicated in patients with a known
hypersensitivity to ciclesonide or any of the ingredients of ZETONNA. Hypersensitivity reactions including angioedema, with swelling of
the lips, tongue
and pharynx, have occurred after
nasal administration of ZETONNA.
Discontinue ZETONNA if such reactions occur.
5.4
Immunosuppression and Risk of Infections
(Additions and/or
revisions underlined)
Patients who are using
drugs that suppress the immune system are more susceptible to infections than healthy
individuals. Chickenpox and measles, for example, can have a more serious
or even fatal course in
susceptible children or adults using corticosteroids. In children or adults who have
not had these
diseases or been properly immunized, particular care should
be taken to avoid
exposure. How the dose, route, and
duration of corticosteroid administration affect the risk of developing a
disseminated infection is not known. The safety and effectiveness of ZETONNA
have not been established in pediatric patients less than 12 years of age and
ZETONNA is not indicated for use in this population. The contribution of
the underlying disease or prior corticosteroid treatment to the risk is also
not known. If a patient is exposed to
chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may
be indicated. If a patient is exposed
to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be
indicated (see the respective Prescribing Information for VZIG and IG). If chickenpox develops, treatment with antiviral agents may be considered.
…
5.5
Hypercorticism and Adrenal
Suppression
(Additions and/or
revisions underlined)
Hypercorticism and adrenal suppression may occur when nasal
corticosteroids, including ZETONNA, are used at higher-than-recommended dosages
[see Dosage and Administration (2)] or thepatients at risk for
such effects.
5.6 Effect
on Growth
(Additions and/or
revisions underlined)
Corticosteroids, including
ZETONNA, may cause a reduction in growth velocity when administered to
pediatric patients. The safety and effectiveness of ZETONNA have not been
established in pediatric patients less than 12 years of age and ZETONNA is not indicated
for use in this population.
Monitor the growth routinely (e.g., via stadiometry) in pediatric patients
receiving ZETONNA [see Pediatric Use (8.4)].
6
Adverse Reactions
(Additions and/or
revisions underlined)
The following clinically significant adverse reactions are described elsewhere in the labeling:
· Epistaxis, Ulcerations, Nasal Septal Perforations, Candida albicans Infection, Impaired Wound Healing [see Warnings and Precautions (5.1)]
·
Glaucoma and Cataracts [see
Warnings and Precautions (5.2)]
·
Immunosuppression and
Risk of Infections [see Warnings and Precautions (5.4)]
· Hypercorticism and Adrenal Suppression, including Growth Reduction [see Warnings and
Precautions (5.5, 5.6), Use in Specific Populations (8.4)]
6.1 Clinical Trials
Experience
(Additions and/or
revisions underlined)
The safety data
described below for adult and pediatric patients 12 years of age
and older are based on 4 clinical trials evaluating doses of ciclesonide from
74 to 282 mcg. Three of the clinical
trials were 2 to 6 weeks in duration and one trial was 26 weeks in duration
with an additional 26-week open-label extension. Data from the first
6 weeks of the 26-week
trial were pooled with data
from the three 2-week trials. Short-term
data (2 to 6 weeks) included
…
Table 1 displays reactions that occurred with an incidence of at least
2.0% and more frequently
with ZETONNA 74 mcg than with placebo
in seasonal or perennial allergic rhinitis clinical trials of 2 to 6 weeks
duration.
…
In one 26-week
double-blind, placebo-controlled safety trial that included 1110 adult and pediatric
patients (12 to 17 years of age) with perennial allergic rhinitis,
additional adverse reactions, with an incidence of at least
2%, that occurred
more frequently with ZETONNA than with placebo were upper respiratory
tract infection, urinary tract infection, oropharyngeal pain, nasal
mucosal/septum disorders, viral upper respiratory tract infection, cough,
influenza, bronchitis, streptococcal pharyngitis, muscle strain, and nausea. Nasal discomfort (5.7%) and epistaxis (11.4%) were also more frequent in the 26-week safety trial compared to clinical trials 2 to 6 weeks in duration. Nasal mucosal/septum
disorders and cough demonstrated a dose response.
…
Nasal and ocular safety
was evaluated in one 26-week,
postmarketing, randomized, open-label, active-controlled trial, in
adult and
pediatric patients 12-74 years of age with a history of perennial
allergic rhinitis…
8
Use in Specific Populations
8.1
Pregnancy
(Pregnancy
Lactation Labeling Rule (PLLR) conversion; please refer to label for complete
information)
8.2
Lactation
(Pregnancy
Lactation Labeling Rule (PLLR) conversion; please refer to label for complete
information)
8.4 Pediatric Use
(Additions and/or
revisions underlined)
The safety
and effectiveness for seasonal and perennial allergic
rhinitis in pediatric patients 12 years of age and older have been established. Use of ZETONNA for this
indication is supported by evidence
from placebo-controlled, double-blind trials in patients
12 years and older
with allergic rhinitis [see Clinical Studies (14)].
The safety and effectiveness of ZETONNA have not been established in pediatric patients younger than 12 years of age.
Effectiveness was not demonstrated for ZETONNA in pediatric patients
6 through 11 years of age. These patients were
evaluated in 2 randomized, double blind, parallel placebo-controlled clinical
trials in 1693 pediatric patients with allergic rhinitis. Of the 2 trials, 1 was 2
weeks in duration and evaluated the efficacy of 2 doses of ZETONNA (37
mcg and 74 mcg once daily) in 847 patients with seasonal allergic rhinitis. The second clinical trial was 12 weeks in
duration and evaluated the efficacy of 2 doses of ZETONNA (37 mcg and 74
mcg once daily) in 846 patients with perennial
allergic rhinitis. The trials were similar in design to the trials
conducted in pediatric
patients 12 years and older and adults. The
primary efficacy endpoint was the difference from placebo in the change from
baseline of the average morning and evening reflective total nasal symptom
scores (rTNSS) averaged over 2 weeks of treatment in the seasonal allergic rhinitis trial and over the first 6 weeks of
treatment in the perennial allergic rhinitis trial. In the 2-week trial in patients with seasonal allergic rhinitis,
treatment with ZETONNA at either dose failed to demonstrate efficacy. In the 12-week trial in patients with
perennial allergic rhinitis, both ZETONNA 37 mcg and 74 mcg once daily
demonstrated significant improvement in rTNSS compared to placebo with
treatment differences of 0.59 (95% CI: 0.23, 0.95) and 0.47 (95% CI: 0.11,
0.83), respectively.
The effect
of ZETONNA on the HPA axis was evaluated in one placebo-controlled clinical study of 6
weeks in duration in children 6 to11 years of age with perennial allergic
rhinitis [see Clinical
Pharmacology (12.2)].
Studies in pediatric patients under 6 years
of age have not been
conducted.
Effect on Growth
Controlled clinical
trials have shown that nasal corticosteroids may cause a reduction in
growth velocity in pediatric patients. This
effect has been observed in the absence of laboratory evidence of
hypothalamic-pituitary-adrenal (HPA)-axis suppression, suggesting that growth
velocity is a more sensitive indicator of systemic corticosteroid exposure in
pediatric patients than some commonly
used tests of HPA-axis function. The long-term effects
of this reduction in growth
velocity associated with nasal corticosteroids, including the impact on
final adult height, are unknown. The
potential for “catch-up” growth following discontinuation of treatment with nasal corticosteroids has not been adequately studied.
The growth of pediatric patients
receiving nasal corticosteroids, including ZETONNA, should be
monitored routinely (e.g., via stadiometry).
A 52-week, multi-center, double-blind, randomized, placebo-controlled
parallel- group trial was conducted to assess the effect of orally inhaled
ciclesonide (ALVESCO® Inhalation Aerosol) on growth rate in 609
pediatric patients with mild persistent asthma, aged 5 to 8.5 years. Treatment groups included orally inhaled
ciclesonide 40 mcg or 160 mcg or placebo given once daily. Growth was measured by stadiometer height
during the baseline, treatment and follow-up periods. The primary comparison was the difference in growth rates
between ciclesonide 40 and 160 mcg and placebo groups. Conclusions cannot be drawn from this trial because compliance
could not be assured. Ciclesonide
blood levels were also not measured during the one-year treatment period. There was no difference in efficacy
measures between the placebo
and the orally
inhaled ciclesonide (ALVESCO® Inhalation Aerosol) groups.
The potential
growth effects of prolonged treatment
should be weighed
against clinical benefits obtained and the availability of
safe and effective noncorticosteroid treatment alternatives. To minimize the systemic effects of nasal
corticosteroids, each patient should be titrated to the lowest dose that
effectively controls his/her symptoms…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions and/or
revisions underlined)
Advise the patient to read the FDA-approved patient
labeling (Patient Information and Instructions for Use).
Local
Nasal Adverse Reactions
Inform patients that
treatment with ZETONNA may lead to adverse reactions, which include nasal
septal perforation, epistaxis, and nasal ulceration. In addition, ciclesonide is associated with candidal infection,
and nasal corticosteroids are associated with impaired wound healing. Do not
spray ZETONNA directly onto the nasal septum.
Patients who have experienced recent nasal septal perforation, nasal
erosion, nasal ulcers,
nasal surgery, or nasal trauma
should not use ZETONNA until healing has occurred [see
Warnings and Precautions (5.1)].
…
Immunosuppression and Risk of Infections
Warn patients who are
on immunosuppressive doses of corticosteroids to avoid exposure to chickenpox or measles, and if exposed,
to consult their
physician without delay. Inform patients of potential worsening of
existing tuberculosis, fungal, bacterial, viral or parasitic infections, or
ocular herpes simplex [see Warnings and Precautions (5.4)]…
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