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| Product NDC Code | 70515-701 | ||||
|---|---|---|---|---|---|
| Drug Name | Omnaris |
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| Type | Brand | ||||
| Active Ingredients |
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| Route | NASAL | ||||
| Dosage Form | SPRAY | ||||
| RxCUI drug identifier | 1797841, 1797843 |
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| Application Number | NDA022004 | ||||
| Labeler Name | Covis Pharma US, Inc | ||||
| Packages |
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Overdosage of Omnaris
Information about signs, symptoms, and laboratory findings of acute ovedosage and the general principles of overdose treatment.10 OVERDOSAGE Chronic overdosage may result in signs or symptoms of hypercorticism [see Warnings and Precautions ( 5.4 )] . There are no data available on the effects of acute or chronic overdosage with OMNARIS Nasal Spray.
Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.6 ADVERSE REACTIONS Systemic and local corticosteroid use may result in the following: • Epistaxis, nasal septal perforations, Candida albicans infection, impaired wound healing [see Warnings and Precautions ( 5.1 )] • Cataracts and glaucoma [see Warnings and Precautions ( 5.2 )] • Immunosuppression [see Warnings and Precautions ( 5.3 )] • Hypothalamic-pituitary-adrenal (HPA) axis effects, including growth reduction [see Warnings and Precautions ( 5.4 , 5.5 ), Use in Specific Populations ( 8.4 )] The most common adverse reactions (>2% incidence) included headache, epistaxis, nasopharyngitis, ear pain, and pharyngolaryngeal pain. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Covis Pharma at 1-866-488-4423 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience 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. Adults and Adolescents 12 Years of Age and Older in Short-Term (2-6 weeks) Trials: 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 Pediatric Patients Aged 6 to 11 Years in Short-Term (2-12 weeks) Trials: 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 Pediatric Patients Aged 2 to 5 Years in Short-Term (6-12 weeks) Trials: 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. Long-Term (52-Week) Safety Trial: 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. 6.2 Post-Marketing Experience 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.
Omnaris Drug Interactions
Information about and practical guidance on preventing clinically significant drug/drug and drug/food interactions that may occur in people taking the drug.7 DRUG INTERACTIONS 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 )] .
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Ciclesonide is a pro-drug that is enzymatically hydrolyzed to a pharmacologically active metabolite, C21-desisobutyryl-ciclesonide (des-ciclesonide or RM1) following intranasal application. Des-ciclesonide has anti-inflammatory activity with affinity for the glucocorticoid receptor that is 120-times higher than the parent compound. The precise mechanism through which ciclesonide affects allergic rhinitis symptoms is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic inflammation. 12.2 Pharmacodynamics Adrenal Function : In a 6-week trial in adolescents and adults 12-73 years of age with perennial allergic rhinitis, a daily dose of 200 mcg of OMNARIS Nasal Spray was compared to placebo nasal spray. Dexamethasone 6 mg was used as an active control during the last 4 days of the treatment period. Adrenal function was assessed by measurement of 24-hour serum cortisol levels before and after 6 consecutive weeks of treatment. The difference from placebo for the change from baseline in serum cortisol AUC (0-24) was 10.4 mcg•hour/dL (95% CI: -4.7, 25.5) for 200 mcg of OMNARIS Nasal Spray. The effects observed with the active control (dexamethasone, n=18) validate the sensitivity of the study to assess the effect of ciclesonide on the HPA axis. In a 12-week study in children 6 to 11 years of age with perennial allergic rhinitis, daily doses of 200 mcg, 100 mcg, and 25 mcg of OMNARIS Nasal Spray were compared to placebo nasal spray. Adrenal function was assessed by measurement of 24-hour urinary-free cortisol (in 32 to 44 patients per group) and morning plasma cortisol levels (in 45 to 61 patients per group) before and after 12 consecutive weeks of treatment. The ciclesonide-treated groups had a numerically greater decline in 24-hour urinary-free cortisol compared to the placebo-treated group. The differences (and 95% confidence intervals) from placebo in the mean change from baseline to 12 weeks were -0.81 (-4.0, 2.4), -0.08 (-3.1, 2.9), and ‑2.11 (‑5.3, 1.1) mcg/day for 200 mcg, 100 mcg, and 25 mcg dose groups, respectively. The mean AM plasma cortisol value did not show any consistent treatment effect with differences (and 95% confidence intervals) from placebo in the mean change from baseline to 12 weeks of 0.35 (‑1.4, 2.1), 0.12 (-1.5, 1.7), and -0.38 (-2.1, 1.3) mcg/dL for 200 mcg, 100 mcg, and 25 mcg dose groups, respectively. In this study, serum was assayed for ciclesonide and des‑ciclesonide [see Clinical Pharmacology ( 12.3 )] . In a 6-week study in children 2 to 5 years of age with perennial allergic rhinitis, daily doses of 200 mcg, 100 mcg, and 25 mcg of OMNARIS Nasal Spray were compared to placebo nasal spray. Adrenal function was assessed by measurement of 24-hour urinary-free cortisol (in 15 to 22 patients per group) and morning plasma cortisol levels (in 28 to 30 patients per group) before and after 6 consecutive weeks of treatment. The ciclesonide-treated groups had a numerically greater decline in 24-hour urinary-free cortisol compared to the placebo-treated group. The differences (and 95% confidence intervals) from placebo in the mean change from baseline to 6 weeks were ‑2.04 (-4.4, 0.3), -1.96 (-4.5, 0.6), and ‑1.76 (‑4.3, 0.8) mcg/day for the 200 mcg, 100 mcg, and 25 mcg dose groups, respectively. The plasma cortisol also decreased numerically after treatment with ciclesonide. The differences (and 95% confidence intervals) from placebo in the mean change in plasma cortisol from baseline to 6 weeks were ‑1.04 (‑2.7, 0.7), -0.36 (-2.1, 1.4), and ‑0.12 (‑1.8, 1.6) mcg/dL for the 200 mcg, 100 mcg, and 25 mcg dose groups, respectively. In this study, serum was assayed for ciclesonide and des-ciclesonide [see Clinical Pharmacology ( 12.3 )] . 12.3 Pharmacokinetics Absorption : Ciclesonide and des-ciclesonide have negligible oral bioavailability (both less than 1%) due to low gastrointestinal absorption and high first-pass metabolism. The intranasal administration of ciclesonide at recommended doses 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 two 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 or less, 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 twenty-nine healthy adults. The median C max 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. Distribution : Following intravenous administration of 800 mcg of ciclesonide, the volumes of distribution of ciclesonide and des-ciclesonide were approximately 2.9 L/kg and 12.1 L/kg, respectively. The percentage of ciclesonide and des-ciclesonide bound to human plasma proteins averaged ≥ 99% each, with ≤ 1% of unbound drug detected in the systemic circulation. Des‑ciclesonide is not significantly bound to human transcortin. Metabolism : Ciclesonide is hydrolyzed to a biologically active metabolite, des-ciclesonide, by esterases. Des-ciclesonide undergoes further metabolism in the liver to additional metabolites mainly by the cytochrome P450 (CYP) 3A4 isozyme and to a lesser extent by CYP 2D6. The full range of potentially active metabolites of ciclesonide has not been characterized. After intravenous administration of 14 C-ciclesonide, 19.3% of the resulting radioactivity in the plasma is accounted for by ciclesonide or des-ciclesonide; the remainder may be a result of other, as yet, unidentified multiple metabolites. Elimination : Following intravenous administration of 800 mcg of ciclesonide, the clearance values of ciclesonide and des-ciclesonide were high (approximately 152 L/h and 228 L/h, respectively). 14 C-labeled ciclesonide was predominantly excreted via the feces after intravenous administration (66%) indicating that excretion through bile is the major route of elimination. Approximately 20% or less of drug-related radioactivity was excreted in the urine. Special Populations : 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. However, population pharmacokinetic analysis showed that characteristics of des-ciclesonide after oral inhalation of ciclesonide were not appreciably influenced by a variety of subject characteristics such as body weight, age, race, and gender. Hepatic Impairment : Compared to healthy subjects, the systemic exposure (Cmax and AUC) in patients with liver impairment increased in the range of 1.4 to 2.7-fold after ex-actuator administration of 1280 mcg ciclesonide via oral inhalation. Dose adjustment in liver impairment is not necessary. Renal Impairment : Studies in renally-impaired patients were not conducted since renal excretion of des-ciclesonide is a minor route of elimination (≤ 20%). Pediatric : In pediatric subjects treated with 25 to 200 mcg of ciclesonide nasal spray daily, serum concentrations of des-ciclesonide were below 45 pg/mL, with the exception of one value of 64.5 pg/mL. In a 12-week study in children 6 to 11 years of age with perennial allergic rhinitis, des-ciclesonide was detected in 50% of the subjects treated with 200 mcg and in 5% of those treated with 100 mcg ciclesonide nasal spray daily. In a 6-week study in children 2 to 5 years of age with perennial allergic rhinitis, des-ciclesonide was detected in 41%, 22%, and 13% of the subjects treated with 200 mcg, 100 mcg, and 25 mcg ciclesonide nasal spray daily, respectively. Drug-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 cytochrome P450 enzymes. The inhibitory potential of ciclesonide on cytochrome P450 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 ketoconazole, a strong inhibitor of cytochrome P450 3A4, increased the exposure (AUC) of the active metabolite of ciclesonide, des-ciclesonide, by approximately 3.6-fold at steady state, while levels of ciclesonide remained unchanged. In another drug interaction study, co-administration of orally inhaled ciclesonide and oral erythromycin, a moderate inhibitor of cytochrome P450 3A4, had no effect on the pharmacokinetics of either des-ciclesonide or erythromycin.
Mechanism of action
Information about the established mechanism(s) of the drugÕs action in humans at various levels (for example receptor, membrane, tissue, organ, whole body). If the mechanism of action is not known, this field contains a statement about the lack of information.12.1 Mechanism of Action Ciclesonide is a pro-drug that is enzymatically hydrolyzed to a pharmacologically active metabolite, C21-desisobutyryl-ciclesonide (des-ciclesonide or RM1) following intranasal application. Des-ciclesonide has anti-inflammatory activity with affinity for the glucocorticoid receptor that is 120-times higher than the parent compound. The precise mechanism through which ciclesonide affects allergic rhinitis symptoms is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic inflammation.
Pharmacodynamics
Information about any biochemical or physiologic pharmacologic effects of the drug or active metabolites related to the drugÕs clinical effect in preventing, diagnosing, mitigating, curing, or treating disease, or those related to adverse effects or toxicity.12.2 Pharmacodynamics Adrenal Function : In a 6-week trial in adolescents and adults 12-73 years of age with perennial allergic rhinitis, a daily dose of 200 mcg of OMNARIS Nasal Spray was compared to placebo nasal spray. Dexamethasone 6 mg was used as an active control during the last 4 days of the treatment period. Adrenal function was assessed by measurement of 24-hour serum cortisol levels before and after 6 consecutive weeks of treatment. The difference from placebo for the change from baseline in serum cortisol AUC (0-24) was 10.4 mcg•hour/dL (95% CI: -4.7, 25.5) for 200 mcg of OMNARIS Nasal Spray. The effects observed with the active control (dexamethasone, n=18) validate the sensitivity of the study to assess the effect of ciclesonide on the HPA axis. In a 12-week study in children 6 to 11 years of age with perennial allergic rhinitis, daily doses of 200 mcg, 100 mcg, and 25 mcg of OMNARIS Nasal Spray were compared to placebo nasal spray. Adrenal function was assessed by measurement of 24-hour urinary-free cortisol (in 32 to 44 patients per group) and morning plasma cortisol levels (in 45 to 61 patients per group) before and after 12 consecutive weeks of treatment. The ciclesonide-treated groups had a numerically greater decline in 24-hour urinary-free cortisol compared to the placebo-treated group. The differences (and 95% confidence intervals) from placebo in the mean change from baseline to 12 weeks were -0.81 (-4.0, 2.4), -0.08 (-3.1, 2.9), and ‑2.11 (‑5.3, 1.1) mcg/day for 200 mcg, 100 mcg, and 25 mcg dose groups, respectively. The mean AM plasma cortisol value did not show any consistent treatment effect with differences (and 95% confidence intervals) from placebo in the mean change from baseline to 12 weeks of 0.35 (‑1.4, 2.1), 0.12 (-1.5, 1.7), and -0.38 (-2.1, 1.3) mcg/dL for 200 mcg, 100 mcg, and 25 mcg dose groups, respectively. In this study, serum was assayed for ciclesonide and des‑ciclesonide [see Clinical Pharmacology ( 12.3 )] . In a 6-week study in children 2 to 5 years of age with perennial allergic rhinitis, daily doses of 200 mcg, 100 mcg, and 25 mcg of OMNARIS Nasal Spray were compared to placebo nasal spray. Adrenal function was assessed by measurement of 24-hour urinary-free cortisol (in 15 to 22 patients per group) and morning plasma cortisol levels (in 28 to 30 patients per group) before and after 6 consecutive weeks of treatment. The ciclesonide-treated groups had a numerically greater decline in 24-hour urinary-free cortisol compared to the placebo-treated group. The differences (and 95% confidence intervals) from placebo in the mean change from baseline to 6 weeks were ‑2.04 (-4.4, 0.3), -1.96 (-4.5, 0.6), and ‑1.76 (‑4.3, 0.8) mcg/day for the 200 mcg, 100 mcg, and 25 mcg dose groups, respectively. The plasma cortisol also decreased numerically after treatment with ciclesonide. The differences (and 95% confidence intervals) from placebo in the mean change in plasma cortisol from baseline to 6 weeks were ‑1.04 (‑2.7, 0.7), -0.36 (-2.1, 1.4), and ‑0.12 (‑1.8, 1.6) mcg/dL for the 200 mcg, 100 mcg, and 25 mcg dose groups, respectively. In this study, serum was assayed for ciclesonide and des-ciclesonide [see Clinical Pharmacology ( 12.3 )] .
Pharmacokinetics
Information about the clinically significant pharmacokinetics of a drug or active metabolites, for instance pertinent absorption, distribution, metabolism, and excretion parameters.12.3 Pharmacokinetics Absorption : Ciclesonide and des-ciclesonide have negligible oral bioavailability (both less than 1%) due to low gastrointestinal absorption and high first-pass metabolism. The intranasal administration of ciclesonide at recommended doses 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 two 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 or less, 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 twenty-nine healthy adults. The median C max 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. Distribution : Following intravenous administration of 800 mcg of ciclesonide, the volumes of distribution of ciclesonide and des-ciclesonide were approximately 2.9 L/kg and 12.1 L/kg, respectively. The percentage of ciclesonide and des-ciclesonide bound to human plasma proteins averaged ≥ 99% each, with ≤ 1% of unbound drug detected in the systemic circulation. Des‑ciclesonide is not significantly bound to human transcortin. Metabolism : Ciclesonide is hydrolyzed to a biologically active metabolite, des-ciclesonide, by esterases. Des-ciclesonide undergoes further metabolism in the liver to additional metabolites mainly by the cytochrome P450 (CYP) 3A4 isozyme and to a lesser extent by CYP 2D6. The full range of potentially active metabolites of ciclesonide has not been characterized. After intravenous administration of 14 C-ciclesonide, 19.3% of the resulting radioactivity in the plasma is accounted for by ciclesonide or des-ciclesonide; the remainder may be a result of other, as yet, unidentified multiple metabolites. Elimination : Following intravenous administration of 800 mcg of ciclesonide, the clearance values of ciclesonide and des-ciclesonide were high (approximately 152 L/h and 228 L/h, respectively). 14 C-labeled ciclesonide was predominantly excreted via the feces after intravenous administration (66%) indicating that excretion through bile is the major route of elimination. Approximately 20% or less of drug-related radioactivity was excreted in the urine. Special Populations : 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. However, population pharmacokinetic analysis showed that characteristics of des-ciclesonide after oral inhalation of ciclesonide were not appreciably influenced by a variety of subject characteristics such as body weight, age, race, and gender. Hepatic Impairment : Compared to healthy subjects, the systemic exposure (Cmax and AUC) in patients with liver impairment increased in the range of 1.4 to 2.7-fold after ex-actuator administration of 1280 mcg ciclesonide via oral inhalation. Dose adjustment in liver impairment is not necessary. Renal Impairment : Studies in renally-impaired patients were not conducted since renal excretion of des-ciclesonide is a minor route of elimination (≤ 20%). Pediatric : In pediatric subjects treated with 25 to 200 mcg of ciclesonide nasal spray daily, serum concentrations of des-ciclesonide were below 45 pg/mL, with the exception of one value of 64.5 pg/mL. In a 12-week study in children 6 to 11 years of age with perennial allergic rhinitis, des-ciclesonide was detected in 50% of the subjects treated with 200 mcg and in 5% of those treated with 100 mcg ciclesonide nasal spray daily. In a 6-week study in children 2 to 5 years of age with perennial allergic rhinitis, des-ciclesonide was detected in 41%, 22%, and 13% of the subjects treated with 200 mcg, 100 mcg, and 25 mcg ciclesonide nasal spray daily, respectively. Drug-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 cytochrome P450 enzymes. The inhibitory potential of ciclesonide on cytochrome P450 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 ketoconazole, a strong inhibitor of cytochrome P450 3A4, increased the exposure (AUC) of the active metabolite of ciclesonide, des-ciclesonide, by approximately 3.6-fold at steady state, while levels of ciclesonide remained unchanged. In another drug interaction study, co-administration of orally inhaled ciclesonide and oral erythromycin, a moderate inhibitor of cytochrome P450 3A4, had no effect on the pharmacokinetics of either des-ciclesonide or erythromycin.
Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.4 CONTRAINDICATIONS 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 )] . Patients with a known hypersensitivity to ciclesonide or any of the ingredients of OMNARIS Nasal Spray. ( 4 )
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.11 DESCRIPTION The active component of OMNARIS Nasal Spray is ciclesonide, a non-halogenated glucocorticoid having the chemical name pregna -1,4-diene-3,20-dione, 16,17-[[R-cyclohexylmethylene]bis(oxy)]-11-hydroxy-21-(2-methyl-1-oxopropoxy)-,(11β,16α)-. Ciclesonide is delivered as the R-epimer. The empirical formula is C 32 H 44 O 7 and its molecular weight is 540.7. Its structural formula is as follows: Ciclesonide is a white to yellow-white powder, practically insoluble in water and freely soluble in ethanol and acetone. OMNARIS Nasal Spray is a metered-dose, manual-pump spray formulation containing a hypotonic aqueous suspension of ciclesonide. OMNARIS Nasal Spray also contains microcrystalline cellulose, carboxymethylcellulose sodium, hypromellose, potassium sorbate and edetate sodium; and hydrochloric acid to adjust the pH to 4.5. Structural Formula
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.2 DOSAGE AND ADMINISTRATION Administer OMNARIS Nasal Spray by the intranasal route only. Prior to initial use, OMNARIS Nasal Spray must be gently shaken and then the pump must be primed by actuating eight times. If the product is not used for four consecutive days, it should be gently shaken and reprimed with one spray or until a fine mist appears. Illustrated patient’s instructions for proper use accompany each package of OMNARIS Nasal Spray. For Intranasal Use Only • 2 sprays per nostril once daily. (200 mcg) ( 2.1 , 2.2 ) • Priming Information: Gently shake and prime OMNARIS Nasal Spray before using for the first time or when not used for four consecutive days. ( 2 ) 2.1 Seasonal Allergic Rhinitis Adults and Children (6 Years of Age and Older): The recommended dose of OMNARIS Nasal Spray is 2 sprays per nostril once daily (200 mcg). The maximum total daily dosage should not exceed 2 sprays in each nostril (200 mcg/day). 2.2 Perennial Allergic Rhinitis Adults and Adolescents (12 Years of Age and Older): The recommended dose of OMNARIS Nasal Spray is 2 sprays per nostril once daily (200 mcg). The maximum total daily dosage should not exceed 2 sprays in each nostril (200 mcg/day).
Dosage forms and strengths
Information about all available dosage forms and strengths for the drug product to which the labeling applies. This field may contain descriptions of product appearance.3 DOSAGE FORMS AND STRENGTHS OMNARIS Nasal Spray is a metered-dose, manual-pump spray formulation containing a hypotonic aqueous suspension of ciclesonide. Once primed, each actuation of the pump delivers 50 mcg ciclesonide in a volume of 70 microliters from the nasal actuator. Nasal Spray: 50 mcg of ciclesonide in each 70-microliter spray. ( 3 )
Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.1 INDICATIONS AND USAGE OMNARIS Nasal Spray is a corticosteroid indicated for treatment of nasal symptoms associated with seasonal allergic rhinitis in adults and children 6 years of age and older and perennial allergic rhinitis in adults and adolescents 12 years of age and older. ( 1.1 , 1.2 ) 1.1 Treatment of Seasonal Allergic Rhinitis OMNARIS Nasal Spray is indicated for the treatment of nasal symptoms associated with seasonal allergic rhinitis in adults and children 6 years of age and older. 1.2 Treatment of Perennial Allergic Rhinitis OMNARIS Nasal Spray is indicated for the treatment of nasal symptoms associated with perennial allergic rhinitis in adults and adolescents 12 years of age and older.
Spl product data elements
Usually a list of ingredients in a drug product.Omnaris ciclesonide CICLESONIDE CICLESONIDE MICROCRYSTALLINE CELLULOSE CARBOXYMETHYLCELLULOSE SODIUM, UNSPECIFIED FORM HYPROMELLOSE, UNSPECIFIED POTASSIUM SORBATE EDETATE DISODIUM HYDROCHLORIC ACID WATER
Carcinogenesis and mutagenesis and impairment of fertility
Information about carcinogenic, mutagenic, or fertility impairment potential revealed by studies in animals. Information from human data about such potential is part of the warnings field.13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Two-year carcinogenicity studies in B6C3F1 mice and Wistar rats were conducted to assess the carcinogenic potential of ciclesonide. Ciclesonide demonstrated no tumorigenic potential in a study with mice that received oral doses up to 900 mcg/kg/day (approximately 20 and 10 times the MRHDID in adults and adolescents ≥ 12 years of age and children 6 to 11 years of age, respectively, on a mcg/m 2 basis) and a study with rats that received inhalation doses up to 193 mcg/kg/day (approximately 9 and 4 times the MRHDID in adults and adolescents ≥ 12 years of age and children 6 to 11 years of age, respectively, on a mcg/m 2 basis). Ciclesonide was not mutagenic in an Ames test or in the Chinese hamster lung V79 cell/hypoxanthine-guanine phosphoribosyl transferase (HGPRT) forward mutation assay and was not clastogenic in a human lymphocyte chromosomal aberration assay or in an in vitro micronucleus test. However, ciclesonide was clastogenic in an in vivo mouse micronucleus test. The concurrent reference corticosteroid (dexamethasone) in this study showed similar findings. Fertility and reproductive performance were unaffected in male and female rats dosed by the oral route up to 900 mcg/kg/day (approximately 45 times the MRHDID in adults based on mcg/m 2 ).
Nonclinical toxicology
Information about toxicology in non-human subjects.13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Two-year carcinogenicity studies in B6C3F1 mice and Wistar rats were conducted to assess the carcinogenic potential of ciclesonide. Ciclesonide demonstrated no tumorigenic potential in a study with mice that received oral doses up to 900 mcg/kg/day (approximately 20 and 10 times the MRHDID in adults and adolescents ≥ 12 years of age and children 6 to 11 years of age, respectively, on a mcg/m 2 basis) and a study with rats that received inhalation doses up to 193 mcg/kg/day (approximately 9 and 4 times the MRHDID in adults and adolescents ≥ 12 years of age and children 6 to 11 years of age, respectively, on a mcg/m 2 basis). Ciclesonide was not mutagenic in an Ames test or in the Chinese hamster lung V79 cell/hypoxanthine-guanine phosphoribosyl transferase (HGPRT) forward mutation assay and was not clastogenic in a human lymphocyte chromosomal aberration assay or in an in vitro micronucleus test. However, ciclesonide was clastogenic in an in vivo mouse micronucleus test. The concurrent reference corticosteroid (dexamethasone) in this study showed similar findings. Fertility and reproductive performance were unaffected in male and female rats dosed by the oral route up to 900 mcg/kg/day (approximately 45 times the MRHDID in adults based on mcg/m 2 ).
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.PRINCIPAL DISPLAY PANEL - 50 mcg Carton Label 50 mcg Carton Label NDC 70515-701-01 Net Contents: 12.5 g omnaris ® (ciclesonide) Nasal Spray, 50 mcg 120 Metered Actuations FOR INTRANASAL USE ONLY Rx Only FRAGILE: Glass bottle inside. Attention Pharmacist: Dispense with accompanying Patient’s Instructions for Use . Attention Patient: See Patient’s Instructions for Use and cleaning instructions before using this product. Discard OMNARIS ® 4 months after opening foil pouch. COVIS GTIN: 00370515701014 LOT: XXXXXX EXP: MM-YYYY SERIAL NO:XXXXXXXXXXXXXX Discard OMNARIS ® 4 months after opening foil pouch. Discard After Date: ___/___/___ Peel off and place directly on nasal spray bottle. Manufactured for Covis Pharma Zug, 6300 Switzerland Made in Germany © 2019 Covis Pharma All rights reserved. Contents: A manual metered pump spray unit containing a hypotonic aqueous suspension of ciclesonide; microcrystalline cellulose, carboxymethylcellulose sodium, hypromellose, potassium sorbate, edetate sodium adjusted to a target pH of 4.5 with hydrochloric acid. Usual Dosage: See package insert. Avoid spraying in eyes. Keep out of reach of children. Shake gently before use. Store at 25°C (77°F); excursions permitted to 15°–30°C (59°–86°F) [see USP Controlled Room Temperature]. Do not freeze. Principal Display Panel - 50 mcg Carton Label
Omnaris: Information for patients
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling ( Patient Information and Instructions for Use). 17.1 Local Nasal Effects Patients should be informed that treatment with OMNARIS Nasal Spray may lead to adverse reactions, which include epistaxis and nasal ulceration. Candida infection may also occur with treatment with OMNARIS Nasal Spray. In addition, nasal corticosteroids are associated with nasal septal perforation and impaired wound healing. Avoid spraying OMNARIS Nasal Spray directly onto the nasal septum. Patients who have experienced recent nasal ulcers, nasal surgery, or nasal trauma should not use OMNARIS Nasal Spray until healing has occurred [see Warnings and Precautions ( 5.1 )] . 17.2 Cataracts and Glaucoma Patients should be informed that glaucoma and cataracts are associated with nasal and inhaled corticosteroid use. The patient should inform his/her health care provider if a change in vision is noted while using OMNARIS Nasal Spray [see Warnings and Precautions ( 5.2 )] . 17.3 Immunosuppression Patients who are on immunosuppressive doses of corticosteroids should be warned to avoid exposure to chickenpox or measles, and if exposed, to consult their physician without delay. Patients should be informed of potential worsening of existing tuberculosis, fungal, bacterial, viral or parasitic infections, or ocular herpes simplex [see Warnings and Precautions ( 5.3 )] . 17.4 Use Daily Patients should use OMNARIS Nasal Spray at regular intervals since its effectiveness depends on its regular use. 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 time frame and periodically until the patient’s 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. 17.5 Keep Spray Out of Eyes Patients should be informed to avoid spraying OMNARIS Nasal Spray in their eyes. 17.6 Storage and Handling 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. Manufactured for Covis Pharma Zug, 6300 Switzerland Made in Germany © 2018 Covis Pharma and AstraZeneca group of companies. All rights reserved OMNARIS is a registered trademark of AstraZeneca group of companies and is used under license. May 2019
Spl patient package insert
Information necessary for patients to use the drug safely and effectively.Patient Information OMNARIS ® [Ŏm-nĕ’-rĭs] (ciclesonide) Nasal Spray, 50 mcg Important Note: For Intranasal Use Only. Avoid spraying in eyes or directly onto the nasal septum (the wall between the two nostrils). Read this leaflet before you start using OMNARIS Nasal Spray and each time you refill your prescription. This leaflet does not take the place of talking with your healthcare provider about your medical condition or your treatment. If you have any questions about OMNARIS Nasal Spray, ask your healthcare provider or pharmacist. What is OMNARIS Nasal Spray? OMNARIS Nasal Spray contains a medicine called ciclesonide, which is a synthetic corticosteroid (a substance that reduces inflammation). This medicine is used to treat nasal symptoms (i.e., runny nose, itchy nose, sneezing, and nasal congestion) that happen with: • Seasonal nasal allergy in adults and children 6 years of age and older. • Year-round nasal allergy symptoms in adults and adolescents 12 years of age and older. How do I use OMNARIS Nasal Spray? Use your nasal spray exactly as prescribed by your healthcare provider. Seasonal allergy symptoms may improve over 1 to 2 weeks; year-round allergy symptoms may improve over 5 weeks. If your symptoms do not improve or get worse, call your healthcare provider. Dosage • OMNARIS Nasal Spray is used 1 time each day, 2 sprays in each nostril. • Do not use more than a total of 2 sprays in each nostril each day. Before using OMNARIS Nasal Spray, tell your healthcare provider about all of your medical conditions, including if you: • have or have had nasal sores, nasal surgery, or nasal injury. Do not use OMNARIS Nasal Spray until your nose has healed. • have eye problems, including glaucoma and cataracts. You should have regular eye exams. • have an immune system problem. • have any type of viral, bacterial, or fungal infection. • are exposed to chickenpox or measles. • are pregnant or plan to become pregnant. It is not known if OMNARIS Nasal Spray may harm your unborn baby. • are breastfeeding or plan to breastfeed. It is not known if the medicine in OMNARIS Nasal Spray passes into your breast milk and if it can harm your baby. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. OMNARIS Nasal Spray and other medicines may interact with each other. This may cause serious side effects. Especially tell your healthcare provider if you take antifungal or anti-HIV medicines. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. What are the possible side effects of OMNARIS Nasal Spray? OMNARIS Nasal Spray may cause serious side effects, including: • Nasal Problems . Symptoms of nasal problems may include: o Nose bleeds. o Crusting in the nose. o Sores (ulcers) in the nose. o Hole in the cartilage of the nose (nasal septal perforation). A whistling sound when you breathe may be a symptom of nasal septum perforation. o Thrush (candida), a fungal infection in your nose and throat. Tell your healthcare provider if you have any redness or white colored patches in your nose or mouth. o Slow wound healing. You should not use OMNARIS Nasal Spray until your nose has healed if you have a sore in your nose, have had surgery on your nose, or if your nose has been injured. • Eye problems, including glaucoma and cataracts . You should have regular eye exams while you use OMNARIS Nasal Spray. • Serious allergic reactions . Call your healthcare provider or get emergency medical care if you get any of the following signs of a serious allergic reaction: o rash o hives o swelling of your face, mouth, and tongue o breathing problems o low blood pressure • Weakened immune system and increased chance of getting infections (immunosuppression) . Taking medicines that weaken your immune system makes you more likely to get infections and can make certain infections worse. These infections may include tuberculosis (TB), herpes simplex infections of the eyes (ocular herpes simplex infections), and infections caused by fungi, bacteria, viruses, and parasites. You should avoid contact with people who have a contagious disease such as chickenpox or measles while using OMNARIS Nasal Spray. If you come in contact with someone who has chickenpox or measles, call your healthcare provider right away. Symptoms of an infection may include: o fever o pain o aches o chills o feeling tired o nausea o vomiting • Reduced adrenal function (adrenal insufficiency) . Adrenal insufficiency happens when your adrenal glands do not make enough steroid hormones. This can happen when you stop taking oral corticosteroid medicines (such as prednisone) and start taking medicine containing a steroid inhaled into the lungs or for use in the nose. Symptoms of adrenal insufficiency may include: o Tiredness o Weakness o Nausea and vomiting o Low blood pressure • Slowed growth in children . A child taking OMNARIS Nasal Spray should have their growth checked regularly. The most common side effects of OMNARIS Nasal Spray include : • headache • nose bleeds • stuffy nose • ear pain • sore throat • dizziness These are not all the possible side effects of OMNARIS Nasal Spray. Tell your healthcare provider about any side effects that bother you or do not go away. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. What are the ingredients in OMNARIS Nasal Spray? Active ingredient: ciclesonide Inactive ingredients: purified water, microcrystalline cellulose, carboxymethylcellulose sodium, hypromellose, potassium sorbate and edetate sodium; and hydrochloric acid to adjust the pH to 4.5. This leaflet does not contain all of the information about your medicine. If you have any questions, ask your healthcare provider or pharmacist. You may want to read this leaflet again. Please DO NOT THROW IT AWAY until you have finished your medicine. Patient’s Instructions for Use OMNARIS Nasal Spray is supplied in an amber glass bottle in a protective plastic sleeve and should be handled with care. Preparing for Use 1. Remove OMNARIS Nasal Spray from its foil pouch. Count 4 months from today and write this new date on the sticker on the carton (the date that is 4 months after removing the bottle from the foil pouch). Peel off the sticker and place it in the space on your nasal spray bottle. It is important that you throw away the nasal spray bottle after this date. 2. Priming OMNARIS Nasal Spray. Before you use OMNARIS Nasal Spray for the first time, you will need to prime the bottle. Hold the bottle upright and shake the bottle gently. To prime OMNARIS Nasal Spray, fully press down on the finger rests of the applicator eight times (See Figure 1 and Figure 2 ). If you do not use the nasal spray for 4 days, you will need to shake the bottle gently, and prime the pump again by spraying one time, or until you see a fine mist. Figure 1 Using the Spray 1. Blow your nose to clear your nostrils, if needed. 2. Shake the bottle gently and remove the dust cap (See Figure 1 ). 3. Hold the bottle firmly with your index and middle finger on either side of the applicator (on finger rests) while supporting the base of the bottle with your thumb (See Figure 2 ). Figure 2 4. Insert applicator tip into one nostril, and close the other nostril with your finger (See Figure 3 ). Figure 3 5. Tilt your head forward slightly. Keep the bottle upright, and press the finger rests quickly and firmly to activate the pump. Breathe in (inhale) through your nose as you spray (See Figure 4 ). Try not to get any spray in your eyes or directly on your nasal septum (the wall between the two nostrils). Figure 4 6. Repeat steps 3-5 for the second spray in the same nostril and for each spray in the other nostril. How do I store OMNARIS Nasal Spray? a. Keep OMNARIS Nasal Spray clean and dry at all times. b. Store OMNARIS Nasal Spray between 59°F and 86°F. c. Do not freeze. d. Keep OMNARIS Nasal Spray and all medicines out of the reach of children. How do I know when the OMNARIS Nasal Spray bottle is empty? Each bottle of OMNARIS Nasal Spray contains enough medicine for you to spray medicine from the bottle 120 times. Do not use a bottle of OMNARIS Nasal Spray after 120 sprays (not counting the priming sprays) have been used or after the “discard by date” you wrote on the sticker when you opened the foil pouch. You may still see some medicine in the bottle. Talk with your healthcare provider before your supply of OMNARIS Nasal Spray runs out to see if you should get a refill of your medicine. Applicator Cleaning Instructions Wipe the applicator tip with a clean tissue and replace the dust cap, after you use your nasal spray each day (See Figure 5 ). Figure 5 If the applicator is clogged or needs more thorough cleaning, use the following cleaning instructions; (Do not try to unblock the tiny spray hole on the applicator with a pin or other sharp object. Do not twist or try to remove the white plastic pump attached to the medicine bottle.) 1. Remove the dust cap, hold the white plastic pump firmly with one hand and then carefully pull upwards to free the applicator (See Figure 6 ). Figure 6 2. Wash the dust cap and applicator with warm water (See Figure 7 ). Figure 7 3. Dry the applicator, and put it back on the bottle. The applicator will snap into place when properly positioned (See Figure 8 ). Figure 8 4. Prime the unit with one spray or until you see a fine mist. 5. Put the dust cap back on the applicator. Manufactured for Covis Pharma. Zug, 6300 Switzerland Made in Germany © 2018 Covis Pharma and AstraZeneca group of companies. All rights reserved. OMNARIS is a registered trademark of AstraZeneca group of companies and is used under license. Revised: June 2018 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8
Clinical studies
This field may contain references to clinical studies in place of detailed discussion in other sections of the labeling.14 CLINICAL STUDIES 14.1 Seasonal and Perennial Allergic Rhinitis Adults and Adolescent Patients 12 Years of Age and Older: The efficacy of OMNARIS Nasal Spray was evaluated in 3 randomized, double‑blind, parallel-group, multicenter, placebo-controlled clinical trials of 2 to 6 weeks duration conducted in the United States and Canada in adolescents and adults with allergic rhinitis. The three trials included a total of 1524 patients (495 males and 1029 females) of whom 79 were adolescents, ages 12 to 17 years. The racial distribution in these three trials included 1374 Caucasians, 69 Blacks, 31 Asians, and 50 patients classified as Other. Of the 1524 patients, 546 patients received OMNARIS Nasal Spray 200 mcg once daily administered as 2 sprays in each nostril. Patients enrolled in the studies were 12 to 86 years of age with a history of seasonal or perennial allergic rhinitis, a positive skin test to at least one relevant allergen, and active symptoms of allergic rhinitis at study entry. Assessment of efficacy in these trials was based on patient recording of four nasal symptoms (runny nose, nasal itching, sneezing, and nasal congestion) on a 0-3 categorical severity scale (0=absent, 1=mild, 2=moderate, and 3=severe) as reflective or instantaneous scores. Reflective scoring required the patients to record symptom severity over the previous 12 hours; the instantaneous scoring required patients to record symptom severity at the time of recording. The results of these trials showed that patients treated with OMNARIS Nasal Spray 200 mcg once daily exhibited statistically significantly greater decreases in total nasal symptom scores than placebo-treated patients. Secondary measures of efficacy were also generally supportive. Dose-Ranging Trial: One of the three trials was a 2-week dose-ranging trial that evaluated efficacy of four doses of OMNARIS Nasal Spray in patients with seasonal allergic rhinitis. The primary efficacy endpoint was the difference from placebo in the change from baseline of the sum of morning and evening reflective total nasal symptom score averaged over the 2-week treatment period. Results of the primary efficacy endpoint are shown in Table 3 . In this trial OMNARIS Nasal Spray 200 mcg once daily was statistically significantly different from placebo, but the lower doses were not statistically significantly different from placebo. Table 3 Mean change in reflective total nasal symptom score over 2 weeks in patients with seasonal allergic rhinitis * Sum of AM and PM Scores; Maximum score = 24 ** Estimates, 95% Confidence Intervals, and p-values were obtained from repeated measures ANCOVA analysis with treatment, baseline, day, and treatment by day interaction effects included in the model. Treatment N Baseline* Change from Baseline Difference from Placebo** Estimate 95% CI p-value Seasonal Allergic Rhinitis Trial – Reflective total nasal symptom score Ciclesonide 200 mcg 144 18.8 -5.73 -1.35 (-2.43, -0.28) 0.014 Ciclesonide 100 mcg 145 18.7 -5.26 -0.88 (-1.96, 0.19) 0.11 Ciclesonide 50 mcg 143 18.4 -4.82 -0.44 (-1.52, 0.63) 0.42 Ciclesonide 25 mcg 146 18.7 -4.74 -0.35 (-1.42, 0.71) 0.51 Placebo 148 17.8 -4.38 Seasonal Allergic Rhinitis Trial: The second trial was a 4-week single dose level trial conducted in patients with seasonal allergic rhinitis. The primary efficacy endpoint in the seasonal allergic rhinitis trial was the difference from placebo in the change from baseline of the average of morning and evening reflective total nasal symptom score averaged over the first 2 weeks of treatment. In this trial, OMNARIS Nasal Spray 200 mcg once daily was statistically significantly different from placebo ( Table 4 ). Statistically significant differences in the morning pre-dose instantaneous total nasal symptom score indicate that the effect was maintained over the full 24-hour dosing interval. Perennial Allergic Rhinitis Trial: The third trial was a 6-week single dose level trial conducted in patients with perennial allergic rhinitis. The primary efficacy endpoint in the perennial allergic rhinitis trial was the difference from placebo in the change from baseline of the average of morning and evening reflective total nasal symptom score averaged over the 6 weeks of treatment. In this trial, OMNARIS Nasal Spray 200 mcg once daily was statistically significantly different from placebo ( Table 4 ). Statistically significant differences in the morning pre-dose instantaneous total nasal symptom score indicate that the effect was maintained over the full 24-hour dosing interval. Table 4 Mean changes in reflective total nasal symptom score and instantaneous total nasal symptom score in allergic rhinitis trials * Mean of AM and PM score from reflective total nasal symptom score; Mean of AM score for instantaneous total nasal symptom score; Maximum = 12 ** Estimates, 95% Confidence Intervals, and p-values were obtained from repeated measures ANCOVA analysis with treatment, baseline, day, and treatment by day interaction effects included in the model. Treatment N Baseline* Change from Baseline Difference from Placebo** Estimate 95% CI p-value Seasonal Allergic Rhinitis Trial – Reflective total nasal symptom score Ciclesonide 200 mcg 162 8.96 -2.40 -0.90 (-1.36, -0.45) <0.001 Placebo 162 8.83 -1.50 Seasonal Allergic Rhinitis Trial – Instantaneous total nasal symptom score Ciclesonide 200 mcg 162 8.45 -1.87 -0.84 (-1.30, -0.39) <0.001 Placebo 162 8.33 -1.03 Perennial Allergic Rhinitis Trial – Reflective total nasal symptom score Ciclesonide 200 mcg 232 7.59 -2.51 -0.62 (-0.97, -0.28) <0.001 Placebo 229 7.72 -1.89 Perennial Allergic Rhinitis Trial – Instantaneous total nasal symptom score Ciclesonide 200 mcg 232 7.05 -1.99 -0.53 (-0.90, -0.17) 0.004 Placebo 229 7.05 -1.46 Onset of action: Onset of action was evaluated in two environmental exposure unit studies in patients with seasonal allergic rhinitis receiving a single dose of OMNARIS Nasal Spray 200 mcg. Results from these two studies did not demonstrate a replicate onset of action within the assessment period. Onset of action was also evaluated in the 4-week seasonal allergic rhinitis and in the 6-week perennial allergic rhinitis trial by frequent recording of instantaneous symptom score after the first dose. In these trials, 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. Pediatric Patients Aged 6 to 11 Years: The efficacy of OMNARIS Nasal Spray was evaluated in two randomized, double-blind, parallel-group, multicenter, placebo-controlled clinical trials in 1282 patients 6 to 11 years of age with allergic rhinitis. Of the two trials, one was 2 weeks in duration conducted in patients with seasonal allergic rhinitis that evaluated efficacy of 200 mcg and 100 mcg of OMNARIS Nasal Spray once daily. The other trial was 12 weeks in duration conducted in patients with perennial allergic rhinitis that evaluated efficacy of 200 mcg, 100 mcg, and 25 mcg of OMNARIS Nasal Spray once daily. Of the total number of patients enrolled in the 2 studies, 380 were treated with 200 mcg of OMNARIS Nasal Spray once daily. The primary efficacy endpoint was the difference from placebo in the change from baseline of the average of morning and evening reflective total nasal symptom score 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, the OMNARIS Nasal Spray 200 mcg once daily dose was statistically significantly different from placebo, but the 100 mcg once daily dose was not statistically significantly different from placebo. The efficacy results for the seasonal allergic rhinitis trial are shown in Table 5 . Table 5 Mean changes in reflective total nasal symptom score in 1 seasonal allergic rhinitis trial in children 6 to 11 years of age * Mean of AM and PM score from reflective total nasal symptom score; Maximum = 12 ** Estimates, 95% Confidence Intervals, and p-values were obtained from repeated measures ANCOVA analysis with treatment, baseline, day, and treatment by day interaction effects included in the model. Treatment N Baseline* Change from Baseline Difference from Placebo** Estimate 95% CI p-value Reflective total nasal symptom score Ciclesonide 200 mcg 215 8.25 -2.46 -0.39 (-0.76, -0.02) 0.040 Ciclesonide 100 mcg 199 8.41 -2.38 -0.32 (-0.69, 0.06) 0.103 Placebo 204 8.41 -2.07 In the 12-week trial in patients with perennial allergic rhinitis, none of the ciclesonide doses were statistically significantly different from placebo. The means and 95% confidence intervals for the differences (OMNARIS Nasal Spray minus placebo) between OMNARIS Nasal Spray 200 mcg, 100 mcg, and 25 mcg treatment groups and placebo were ‑0.31 (-0.75, 0.13), 0.02 (-0.41, 0.46), and 0.09 (-0.35, 0.53), respectively. Pediatric Patients Aged 2 to 5 Years: Efficacy of OMNARIS Nasal Spray in patients 2 to 5 years of age has not been established [see Pediatric Use ( 8.4 )] .
| * Sum of AM and PM Scores; Maximum score = 24 ** Estimates, 95% Confidence Intervals, and p-values were obtained from repeated measures ANCOVA analysis with treatment, baseline, day, and treatment by day interaction effects included in the model. | ||||||
| * Mean of AM and PM score from reflective total nasal symptom score; Mean of AM score for instantaneous total nasal symptom score; Maximum = 12 ** Estimates, 95% Confidence Intervals, and p-values were obtained from repeated measures ANCOVA analysis with treatment, baseline, day, and treatment by day interaction effects included in the model. | |||||||||||||
| * Mean of AM and PM score from reflective total nasal symptom score; Maximum = 12 ** Estimates, 95% Confidence Intervals, and p-values were obtained from repeated measures ANCOVA analysis with treatment, baseline, day, and treatment by day interaction effects included in the model. | ||||||||||||||||||||
Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.8.5 Geriatric Use 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.
Pediatric use
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.8.4 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 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.
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)8.1 Pregnancy Risk Summary 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/m 2 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. Data Animal Data 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 bases at maternal oral doses up to 900 mcg/kg/day).
Use in specific populations
Information about use of the drug by patients in specific populations, including pregnant women and nursing mothers, pediatric patients, and geriatric patients.8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary 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/m 2 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. Data Animal Data 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 bases at maternal oral doses up to 900 mcg/kg/day). 8.2 Lactation Risk Summary 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. Clinical Considerations 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. Data Human Data 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. Animal Data A study with 14 C-ciclesonide showed milk exposure of rat pups to 0.006% of the dose secreted in milk. 8.4 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 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. 8.5 Geriatric Use 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.
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.16 HOW SUPPLIED/STORAGE AND HANDLING OMNARIS is supplied in an amber glass bottle and provides for nasal delivery with a manual metered pump. OMNARIS Nasal Spray is supplied with an oxygen absorber sachet and enclosed in a foil pouch. The contents of one 12.5 gram bottle provide 120 actuations, after initial priming. Each spray delivers 50 mcg of ciclesonide from the nasal actuator. Prior to initial use, OMNARIS Nasal Spray must be gently shaken and then the pump must be primed by actuating eight times. The OMNARIS Nasal Spray bottle has been filled with an excess to accommodate the priming activity. The bottle should be discarded after removal from the foil pouch either after 120 sprays following initial priming (since the amount of ciclesonide delivered per spray thereafter may be substantially less than the labeled dose) or after 4 months. Patient instructions are also provided. Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [See USP Controlled Room Temperature] . Do not freeze. Shake gently before use. Keep out of reach of children. Omnaris Nasal Spray 50 mcg, 120 metered sprays; net fill weight 12.5 g. NDC 70515-701-01
Disclaimer: Do not rely on openFDA or Phanrmacy Near Me to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. Source: OpenFDA, Healthporta Drugs API