Source: FDA, National Drug Code (US) Revision Year: 2019
OMNARIS Nasal Spray is contraindicated in patients with a known hypersensitivity to ciclesonide or any of the ingredients of OMNARIS Nasal Spray [see Warnings and Precautions (5.3)].
Epistaxis: In clinical studies of 2 to 52 weeks' duration, epistaxis was observed more frequently in patients treated with OMNARIS Nasal Spray than those who received placebo [see Adverse Reactions (6)].
Candida Infection: In clinical studies with OMNARIS Nasal Spray, the development of localized infections of the nose and pharynx with Candida albicans has 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.
Nasal Septal Perforation: Instances of nasal septal perforation have been reported in patients following the intranasal application of corticosteroids. No cases of nasal septal perforation were identified in clinical studies with OMNARIS Nasal Spray. Avoid spraying OMNARIS Nasal Spray directly onto the nasal septum.
Impaired Wound Healing: 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.
Nasal and inhaled corticosteroids may result in the development of glaucoma and/or cataracts. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts.
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 studies, 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.
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 contribution of the underlying disease and/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 package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered.
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 because of the potential for worsening of these infections.
Hypercorticism and Adrenal Suppression: When intranasal corticosteroids are used at higher than recommended dosages or in susceptible individuals at recommended dosages, systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear. If such changes occur, the dosage of OMNARIS Nasal Spray should be discontinued slowly, consistent with accepted procedures for discontinuing oral steroid therapy.
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.
Corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth routinely (e.g., via stadiometry) in pediatric patients receiving OMNARIS Nasal Spray.
Systemic and local corticosteroid use may result in the following:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety data described below for adults and adolescents 12 years of age and older are based on 3 clinical trials of 2 to 6 weeks duration and one 52-week trial. In the 3 trials of 2 to 6 weeks duration, 1524 patients (495 males and 1029 females, ages 12 to 86 years old) with seasonal or perennial allergic rhinitis were treated with OMNARIS Nasal Spray 200, 100, 50, or 25 mcg or placebo once daily. The racial distribution in these three trials included 1374 Caucasians, 69 Blacks, 31 Asians, and 50 patients classified as Other. The 52-week trial was conducted in 663 patients (227 males and 436 females, ages 12 to 73 years old) treated with OMNARIS Nasal Spray 200 mcg or placebo once daily. The racial distribution in this trial included 538 Caucasians, 69 Blacks, 16 Asians, and 40 patients classified as Other. The data from pediatric patients are based upon 4 clinical trials in which 1541 children (871 males and 670 females, ages 2 to 11 years old) with seasonal or perennial allergic rhinitis were treated with OMNARIS Nasal Spray 200, 100, or 25 mcg or placebo once daily for 2 to 12 weeks. The racial distribution in these four trials included 1136 Caucasians, 273 Blacks, 20 Asians, and 112 patients classified as Other.
In three short-term trials conducted in the US and Canada, 546 patients were treated with OMNARIS Nasal Spray 200 mcg daily. Adverse reactions did not differ appreciably based on age, gender, or race. Approximately 2% of patients treated with OMNARIS Nasal Spray 200 mcg in clinical trials discontinued because of adverse reactions; this rate was similar for patients treated with placebo. The table below displays reactions that occurred with an incidence of 2% or greater and more frequently with OMNARIS Nasal Spray 200 mcg than with placebo in clinical trials of 2 to 6 weeks in duration.
Table 1. Adverse Events from Controlled Clinical Trials 2 to 6 Weeks in Duration in Patients 12 Years of Age and Older with Seasonal or Perennial Allergic Rhinitis:
| Adverse Event | OMNARIS Nasal Spray 200 mcg Once Daily (N=546) % | Placebo (N=544) % |
|---|---|---|
| Headache | 6.0 | 4.6 |
| Epistaxis | 4.9 | 2.9 |
| Nasopharyngitis | 3.7 | 3.3 |
| Ear Pain | 2.2 | 0.6 |
In two short-term trials, conducted in the US and Canada, 913 patients were treated with OMNARIS Nasal Spray 200 mcg, 100 mcg or 25 mcg daily. Adverse events did not differ appreciably based on age, gender, or race. In clinical trials, 1.6% and 2.7% of patients treated with OMNARIS Nasal Spray 200 mcg or 100 mcg, respectively, discontinued because of adverse reactions; these rates were lower than the rate in patients treated with placebo (2.8%). Table 2 displays adverse events that occurred with an incidence of 3% or greater and more frequently with OMNARIS Nasal Spray 200 mcg than with placebo.
Table 2. Adverse Events from Controlled Clinical Trials 2 to 12 Weeks in Duration in Patients 6 to 11 Years of Age and Older with Seasonal or Perennial Allergic Rhinitis:
| Adverse Event | OMNARIS Nasal Spray 200 mcg Once Daily (N=380) % | Placebo (N=369) % |
|---|---|---|
| Headache | 6.6 | 5.7 |
| Nasopharyngitis | 6.6 | 5.4 |
| Pharyngolaryngeal pain | 3.4 | 3.3 |
In two short-term trials conducted in the US, 183 patients were treated with OMNARIS Nasal Spray 200 mcg, 100 mcg or 25 mcg daily. The distribution of adverse events was similar to that seen in the 6 to 11 year old children.
In a 52-week double-blind, placebo-controlled safety trial that included 663 adults and adolescent patients (441 treated with ciclesonide: 227 males and 436 females) with perennial allergic rhinitis, the adverse reaction profile over the treatment period was similar to the adverse event profile in trials of shorter duration. Adverse reactions, irrespective of drug relationship, that occurred with an incidence of 3% or greater and more frequently with OMNARIS Nasal Spray 200 mcg than with placebo were epistaxis, pharyngolaryngeal pain, sinusitis, headache, nasal discomfort, cough, bronchitis, influenza, back pain, and urinary tract infection. No patient experienced a nasal septal perforation or nasal ulcer during this long-term trial of OMNARIS Nasal Spray.
The following adverse reactions have been reported in association with post-marketing use of OMNARIS Nasal Spray and are not listed above: nasal congestion, nasal ulcer and dizziness. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure.
In vitro studies and clinical pharmacology studies suggested that des-ciclesonide has no potential for metabolic drug interactions or protein binding-based drug interactions [see Clinical Pharmacology (12.3)].
In a 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. Erythromycin, a moderate inhibitor of cytochrome P450 3A4, had no effect on the pharmacokinetics of either des-ciclesonide or erythromycin following oral inhalation of ciclesonide [see Clinical Pharmacology (12.3)].
There are no data on ONMARIS nasal spray use in pregnant women to assess a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There is low systemic exposure following OMNARIS nasal spray administration at the recommended dose [see Clinical Pharmacology (12.3)].
In animal reproduction studies, ciclesonide, administered by the oral route to pregnant rats, during the period of organogenesis, did not cause any evidence of fetal harm at doses up 45 times the maximum recommended human daily intranasal dose (MRHDID) of 200 mcg/day. Teratogenicity, characteristic of corticosteroids, decreased body weight and/or skeletal variations were observed in rabbit fetuses following administration of ciclesonide to pregnant rabbits by the subcutaneous route during the period of organogenesis at doses 0.5 times the MRHDID and higher on a mcg/m² basis (see Data). No evidence of fetal harm was observed in rabbits at doses 0.1 times the MRHDID.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
In an embryo-fetal development study in pregnant rats dosed by the oral route during the period of organogenesis from gestation days 6 to 15, ciclesonide did not cause any evidence of fetal harm at doses up to 45 times the MRHDID in adults (on a mcg/m² basis with maternal oral dose up to 900 mcg/kg/day). Maternal toxicity, as evidenced by decreased body weight gain, was observed at 45 times the MRHDID in adults (on a mcg/m² basis at a maternal dose of 900 mcg/kg/day); however, no adverse effects were observed at doses 15 times the MRHDID and lower (on a mcg/m² basis with maternal oral doses of 300 mcg/kg/day and lower).
In two embryo-fetal development studies in pregnant rabbits dosed by the subcutaneous route during the period of organogenesis from gestation days 6 to 18, ciclesonide caused acampsia (flexures of legs) in fetuses at doses 0.5 times the MRHDID and higher (on a mcg/m² basis with maternal oral doses of 5 mcg/kg/day and higher), decreased body weight, cleft palate, enlarged fontanelle, parchment-like skin, and incomplete ossification of bones in fetuses at doses 2 times the MRHDID (on a mcg/m² basis with a maternal subcutaneous dose of 25 µg/kg/day) and embryo-fetal death at doses 10 times the MRHDID and higher (on a mcg/m² basis at maternal subcutaneous doses of 100 mcg/kg/day and higher). No evidence of fetal harm was observed at a dose 0.1 times the MRHDID in adults (on a mcg/m² basis at a maternal subcutaneous dose of 1 mcg/kg/day). Maternal toxicity was observed at doses 10 times the MRHDID in adults (on a mcg/m² basis with maternal subcutaneous doses of 100 mcg/kg/day and lower); however, no evidence of toxicity was observed at doses 2 times the MRHDID and lower (on a mcg/m² basis with maternal subcutaneous doses of 25 mcg/kg/day and lower).
In a prenatal and postnatal development study in pregnant rats dosed by the oral route from gestation day 6 to lactation day 20, ciclesonide produced no adverse developmental effects on offspring at doses up to approximately 45 times the MRHDID (on mcg/m² bases at maternal oral doses up to 900 mcg/kg/day).
There are no data on the presence of ciclesonide in human milk, the effects on the breastfed child, or on milk production. It is not known whether nasal spray administration of ciclesonide at the recommended dose could result in sufficient systemic absorption to produce detectable quantities in human milk [see Clinical Pharmacology (12.3)]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for OMNARIS Nasal Spray, and any potential adverse effects on the breastfed child from OMNARIS Nasal Spray, or from the underlying maternal condition.
The pharmacokinetics of intranasally administered ciclesonide have not been assessed in patient subpopulations because the resulting blood levels of ciclesonide and des-ciclesonide are insufficient for pharmacokinetic calculations [see Clinical Pharmacology (12.3)].
The molecular weight of the prodrug ciclesonide (approximately 541 g/mol) is small enough to be excreted into breast milk; however, its high plasma protein binding affinity and very short half-life suggest that minimal amounts will be present within the milk. Conversely, the half-life of the active metabolite des-ciclesonide (approximately 471 g/mol) suggests that exposure to the nursing infant will be greater than that of the prodrug ciclesonide. Although ciclesonide and des-ciclesonide have negligible oral bioavailability (both less than 1% for each) due to low gastrointestinal absorption and high first-pass metabolism, the relative anti‑inflammatory activity of des-ciclesonide is 12-times greater than that of dexamethasone. The effects of this exposure on a nursing infant are unknown, however, like all corticosteroids, suppression of the HPA function is a potential complication.
At recommended doses, the intranasal administration of ciclesonide results in negligible serum concentrations of ciclesonide. However, the known active metabolite (des‑ciclesonide) is detected in the serum of some patients after nasal inhalation of ciclesonide. The bioanalytical assay used has a lower limit of quantification of 25 pg/mL and 10 pg/mL, for ciclesonide and des-ciclesonide, respectively.
In healthy adults treated for 2 weeks with 50 to 800 mcg of ciclesonide nasal spray daily (n=6 in each treatment group), the peak serum concentrations of des-ciclesonide in all subjects were found to be below 30 pg/mL. Of those treated with 800 mcg and 400 mcg daily, 100% and 67% had detectable levels of des-ciclesonide, respectively. With daily doses of ≤200 mcg, detectable serum levels of des-ciclesonide were not observed. The low systemic exposure following ciclesonide nasal spray administration was confirmed in a crossover study in 29 healthy adults. The median maximum observed concentration was less than 10 pg/mL and 602 pg/mL following a single dose of ciclesonide nasal spray (300 mcg) and orally inhaled ciclesonide (320 mcg), respectively.
A study with 14C-ciclesonide showed milk exposure of rat pups to 0.006% of the dose secreted in milk.
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 was demonstrated in 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 seasonal allergic rhinitis in patients 5 years of age and younger has not been established. The efficacy of OMNARIS Nasal Spray for the treatment of the symptoms of perennial allergic rhinitis in patients 11 years of age and younger has not been established [see Clinical Studies (14.1)]. 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 (12.2), Clinical Studies (14.1), and Adverse Reactions (6)].
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). A 52-week, multicenter, double-blind, randomized, placebo-controlled parallel-group study was conducted to assess the effect of orally inhaled ciclesonide 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 study 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 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 intranasal corticosteroids, each patient should be titrated to the lowest dose that effectively controls his/her symptoms.
Clinical studies of OMNARIS Nasal Spray 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, 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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