WARNINGS
The replacement of a systemic corticosteroid with a topical
corticosteroid can be accompanied by signs of adrenal insufficiency. In
addition, some patients may experience symptoms of corticosteroid withdrawal,
e.g., joint and/or muscular pain, lassitude, and depression. Patients previously
treated for prolonged periods with systemic corticosteroids and transferred to
topical corticosteroids should be carefully monitored for acute adrenal
insufficiency in response to stress. In those patients who have asthma or other
clinical conditions requiring long-term systemic corticosteroid treatment, rapid
decreases in systemic corticosteroid dosages may cause a severe exacerbation of
their symptoms.
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 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 contribution of the
underlying disease and/or prior corticosteroid treatment to the risk is also not
known. If exposed to chickenpox, prophylaxis with varicella zoster immune
globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled
intramuscular immunoglobulin (IG) may be indicated. (See the respective package
inserts for complete VZIG and IG prescribing information). If chickenpox
develops, treatment with antiviral agents may be considered.
PRECAUTIONS
General
Intranasal corticosteroids may cause a reduction in growth
velocity when administered to pediatric patients (see PRECAUTIONS: Pediatric Use). Rarely, immediate
hypersensitivity reactions or contact dermatitis may occur after the
administration of intranasal corticosteroids. Patients with a known
hypersensitivity reaction to other corticosteroid preparations should use
caution when using ciclesonide nasal spray since cross reactivity to other
corticosteroids including ciclesonide may also occur.
Because of the inhibitory effect of corticosteroids on wound healing,
patients who have experienced recent nasal septal ulcers, nasal surgery, or
nasal trauma should not use a nasal corticosteroid until healing has occurred.
In clinical studies with OMNARIS Nasal Spray, the development of localized
infections of the nose and pharynx with Candida albicans
has rarely occurred. When such an infection develops, it may require
treatment with appropriate local therapy and discontinuation of OMNARIS Nasal
Spray. Therefore, patients using OMNARIS Nasal Spray over several months or
longer should be examined periodically for evidence of Candida infection or other signs of adverse effects on the
nasal mucosa. Intranasal corticosteroids should be used with caution, if at all,
in patients with active or quiescent tuberculosis infections of the respiratory
tract; or in patients with untreated local or systemic fungal or bacterial
infections; systemic viral or parasitic infections; or ocular herpes simplex.
If recommended doses of intranasal corticosteroids are exceeded or if
individuals are particularly sensitive or predisposed by virtue of recent
systemic steroid therapy, symptoms of hypercorticism may occur, including very
rare cases of menstrual irregularities, acneiform lesions, and cushingoid
features. If such changes occur, topical corticosteroids should be discontinued
slowly, consistent with accepted procedures for discontinuing oral steroid
therapy.
The risk of glaucoma was evaluated by assessments of intraocular pressure in
3 studies including 943 patients. Of these, 390 adolescents or adults were
treated for up to 52 weeks and 186 children ages 2 to 11 received treatment with
OMNARIS Nasal Spray 200 mcg daily for up to 12 weeks. In these trials, no
significant differences in intraocular pressure changes were observed between
OMNARIS Nasal Spray 200 mcg and placebo-treated patients. Additionally, no
significant differences between OMNARIS Nasal Spray 200 mcg and placebo-treated
patients were noted during the 52-week study of adults and adolescent patients
in whom thorough ophthalmologic assessments were performed including evaluation
of cataract formation using slit lamp examinations. Rare instances of wheezing,
nasal septum perforation, cataracts, glaucoma, and increased intraocular
pressure have been reported following the intranasal application of
corticosteroids. Close follow-up is warranted in patients with a change in
vision and with a history of glaucoma and/or cataracts.
Information for Patients
Patients being treated with OMNARIS Nasal Spray should receive
the following information and instructions. This information is intended to aid
them in the safe and effective use of this medication. It is not a disclosure of
all possible adverse or intended effects.
Patients who are on immunosuppressive doses of corticosteroids should be
warned to avoid exposure to chickenpox or measles, and if exposed, to obtain
medical advice. Patients should use OMNARIS Nasal Spray at regular intervals
since its effectiveness depends on its regular use (See DOSAGE AND ADMINISTRATION).
In clinical trials, the onset of effect was seen within 24 to 48 hours with
further symptomatic improvement observed over 1 to 2 weeks in seasonal allergic
rhinitis and 5 weeks in perennial allergic rhinitis. Initial assessment of
response should be made during this timeframe and periodically until the
patients symptoms are stabilized.
The patient should take the medication as directed and should not exceed the
prescribed dosage. The patient should contact the physician if symptoms do not
improve by a reasonable time or if the condition worsens. For the proper use of
this unit and to attain maximum improvement, the patients should read and follow
the accompanying patient instructions carefully. Spraying OMNARIS Nasal Spray
directly into the eyes or onto the nasal septum should be avoided. It is
important that the bottle is gently shaken prior to use to ensure that a
consistent amount is dispensed per actuation. The bottle should be discarded
after 120 actuations following initial priming or after 4 months after the
bottle is removed from the foil pouch, whichever occurs first.
Drug Interactions
Based on in vitro studies in human liver microsomes,
des-ciclesonide appears to have no inhibitory or induction potential on the
metabolism of other drugs metabolized by CYP 450 enzymes. The inhibitory
potential of ciclesonide on CYP450 isoenzymes has not been studied. In vitro
studies demonstrated that the plasma protein binding of des-ciclesonide was not
affected by warfarin or salicylic acid, indicating no potential for protein
binding-based drug interactions.
In a drug interaction study, co-administration of orally inhaled ciclesonide
and oral erythromycin, an inhibitor of cytochrome P450 3A4, had no effect on the
pharmacokinetics of either des-ciclesonide or erythromycin. In another drug
interaction study, co-administration of orally inhaled ciclesonide and oral
ketoconazole, a potent inhibitor of cytochrome P450 3A4, increased the exposure
(AUC) of des-ciclesonide by approximately 3.6-fold at steady state, while levels
of ciclesonide remained unchanged. Therefore, ketoconazole should be
administered with caution with intranasal ciclesonide.
Carcinogenesis, Mutagenesis, Impairment of
Fertility
Ciclesonide demonstrated no carcinogenic potential in a study of
oral doses up to 900 mcg/kg (approximately 20 and 10 times the maximum human
daily intranasal dose in adults and children, respectively, based on mcg/m2) in mice for 104 weeks and in a study of inhalation doses up
to 193 mcg/kg (approximately 8 and 5 times the maximum human daily intranasal
dose in adults and children, respectively, based on mcg/m2) in rats for 104 weeks. Ciclesonide was not mutagenic in an
Ames test or in a forward mutation assay and was not clastogenic in a human
lymphocyte assay or in an in vitro micronucleus test. However, ciclesonide was
clastogenic in the in vivo mouse micronucleus test. The concurrent reference
corticosteroid (dexamethasone) in this study showed similar findings. No
evidence of impairment of fertility was observed in a reproductive study
conducted in male and female rats both dosed orally up to 900 mcg/kg/day
(approximately 35 times the maximum human daily intranasal dose in adults based
on mcg/m2).
Pregnancy: Teratogenic Effects
Pregnancy Category C
Oral administration of ciclesonide in rats up to 900 mcg/kg (approximately 35
times the maximum human daily intranasal dose in adults based on mcg/m2) produced no teratogenicity or other fetal effects. However,
subcutaneous administration of ciclesonide in rabbits at 5 mcg/kg (less than the
maximum human daily intranasal dose in adults based on mcg/m2) or greater produced fetal toxicity. This included fetal
loss, reduced fetal weight, cleft palate, skeletal abnormalities including
incomplete ossifications, and skin effects. No toxicity was observed at 1 mcg/kg
(less than the maximum human daily intranasal dose based on mcg/m2).
There are no adequate and well-controlled studies in pregnant women. OMNARIS
Nasal Spray, like other corticosteroids, should be used during pregnancy only if
the potential benefit justifies the potential risk to the fetus. Experience with
oral corticosteroids since their introduction in pharmacologic, as opposed to
physiologic, doses suggests that rodents are more prone to teratogenic effects
from corticosteroids than humans. In addition, because there is a natural
increase in corticosteroid production during pregnancy, most women will require
a lower exogenous corticosteroid dose and many will not need corticosteroid
treatment during pregnancy.
Nonteratogenic effects
Hypoadrenalism may occur in infants born of mothers receiving
corticosteroids during pregnancy. Such infants should be carefully
monitored.
Nursing Mothers
It is not known if ciclesonide is excreted in human milk.
However, other corticosteroids are excreted in human milk. In a study with
lactating rats, minimal but detectable levels of ciclesonide were recovered in
milk. Caution should be used when OMNARIS Nasal Spray is administered to nursing
women.
Pediatric Use
The safety and effectiveness for seasonal and perennial allergic
rhinitis in children 12 years of age and older have been established. The
efficacy of OMNARIS Nasal Spray in patients 6 to 11 years of age for treatment
of the symptoms of seasonal allergic rhinitis is supported by evidence from four
adequate and well-controlled studies in adults and adolescents 12 years of age
and older with seasonal and perennial allergic rhinitis, and one study in
patients 6 to 11 years of age with seasonal allergic rhinitis. The efficacy of
OMNARIS Nasal Spray for the treatment of the symptoms of perennial allergic
rhinitis in patient 6 to 11 years of age has not been established (see CLINICAL TRIALS: Pediatric Patients Aged 6 to 11 Years).
The efficacy of OMNARIS Nasal Spray in children 2 to 5 years of age has not been
established. The safety of OMNARIS Nasal Spray in children 2 to 11 years of age
was evaluated in 4 controlled clinical studies of 2 to 12 weeks duration (See CLINICAL PHARMACOLOGY: Pharmacodynamics, CLINICAL TRIALS, ADVERSE REACTIONS:
Pediatric Patients).
Clinical studies in children less than two years of age have not been
conducted. Studies in children under 2 years of age are waived because of local
and systemic safety concerns.
Controlled clinical studies have shown that intranasal 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 intranasal corticosteroids,
including the impact on final adult height, are unknown. The potential for
"catch-up" growth following discontinuation of treatment with intranasal
corticosteroids has not been adequately studied. The growth of pediatric
patients receiving intranasal corticosteroids, including OMNARIS Nasal Spray,
should be monitored routinely (e.g., via stadiometry). 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 intranasal corticosteroids,
each patient should be titrated to the lowest dose that effectively controls
his/her symptoms.
Geriatric Use
Clinical studies of OMNARIS Nasal Spray did not include
sufficient numbers of subjects age 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, dose selection for an elderly patient should be cautious, usually
starting at the low end of the dosing range, reflecting the greater frequency of
decreased hepatic, renal, or cardiac function, and of concomitant disease or
other drug therapy.
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