Ciclesonide

Ciclesonide Advanz Pharma is indicated in treatment to control persistent asthma in adults and adolescents (12 years and older).

The medicinal product is for inhalation use only.

Posology Dosing recommendation for adults and adolescents:

The recommended dose of Ciclesonide Advanz Pharma is 160 micrograms once daily, which leads to asthma control in the majority of patients. 1). Patients should be given a dose of inhaled ciclesonide which is appropriate to the severity of their disease.

Symptoms start to improve with Ciclesonide Advanz Pharma within 24 hours of treatment. Once control is achieved, the dose of Ciclesonide Advanz Pharma should be individualised and titrated to the minimum dose needed to maintain good asthma control.

Dose reduction to 80 micrograms once daily may be an effective maintenance dose for some patients. Ciclesonide Advanz Pharma should preferably be administered in the evening although morning dosing of Ciclesonide Advanz Pharma has also been shown to be effective.

The final decision on evening or morning dosing should be left to the discretion of the physician. Patients with severe asthma are at risk of acute attacks and should have regular assessments of their asthma control including pulmonary function tests.

Increasing use of short-acting bronchodilators to relieve asthma symptoms indicates deterioration of asthma control. If patients find that short-acting relief bronchodilator treatment becomes less effective, or they need more inhalations than usual, medical attention must be sought.

g. 1) or a course of oral corticosteroids). Severe asthma exacerbations should be managed the usual way. To address specific patient needs, such as finding it difficult to press the inhaler and breathe in at the same time, Ciclesonide Advanz Pharma can be used with the AeroChamber Plus Flow-Vu spacer device.

Special populations Elderly and patients with renal or hepatic impairment There is no need to adjust the dose in elderly patients or those with hepatic or renal impairment. Paediatric population The safety and efficacy of ciclesonide in children aged under 12 years have not yet been established.

No sufficient data are available. Method of administration Precautions to be taken before handling or administering the medicinal product The patient needs to be instructed how to use the inhaler correctly. If the inhaler is new or has not been used for one week or more, three puffs should be released into the air.

No shaking is necessary as this is a solution aerosol. During inhalation, the patient should preferably sit or stand, and the inhaler should be held upright with the thumb on the base, below the mouthpiece. Instruct the patient to remove the mouthpiece cover, place the inhaler into their mouth, close their lips around the mouthpiece, and breathe in slowly and deeply.

While breathing in through the mouth, the top of the inhaler should be pressed down. Then, patients should remove the inhaler from their mouth, and hold their breath for about 10 seconds, or as long as is comfortable. The patient is not to breathe out into the inhaler.

Finally, patients should breathe out slowly and replace the mouthpiece cover. The mouthpiece should be cleaned with a dry tissue or cloth weekly. The inhaler should not be washed or put in water. 6.

Approximately 5% of patients experienced adverse reactions in clinical trials with Ciclesonide Advanz Pharma given in the dose range 40 to 1280 micrograms per day. In the majority of cases, these were mild and did not require discontinuation of treatment with Ciclesonide Advanz Pharma.

g. theophylline or salbutamol). Paradoxical bronchospasm may occur immediately after dosing and is an unspecific acute reaction to all inhaled medicinal products, which may be related to the active substance, the excipient, or evaporation cooling in the case of metered dose inhalers.

In severe cases, withdrawal of Ciclesonide Advanz Pharma should be considered. Systemic effects of inhaled corticosteroids may occur, particularly at high doses prescribed for prolonged periods. 4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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AND CLINICAL USE ........................................................................... 3 CONTRAINDICATIONS ................................................................................................. 3 WARNINGS AND PRECAUTIONS ...............................................................................

4 ADVERSE REACTIONS ................................................................................................. 8 DRUG INTERACTIONS ...............................................................................................

12 DOSAGE AND ADMINISTRATION ........................................................................... 13 OVERDOSAGE .............................................................................................................. 15 ACTION AND CLINICAL PHARMACOLOGY ..........................................................

15 STORAGE AND STABILITY ....................................................................................... 18 DOSAGE FORMS, COMPOSITION AND PACKAGING........................................... 18 PART II: SCIENTIFIC INFORMATION..............................................................................

19 PHARMACEUTICAL INFORMATION ....................................................................... 19 CLINICAL TRIALS ....................................................................................................... 19 DETAILED PHARMACOLOGY ..................................................................................

25 REFERENCES ................................................................................................................ 32 PART III: CONSUMER INFORMATION............................................................................

34 COPYRIGHT 2021 COVIS PHARMA GmbH Page 3 of 37 ALVESCO® ciclesonide inhalation aerosol PART I: HEALTH PROFESSIONAL INFORMATION SUMMARY PRODUCT INFORMATION Route of Administration Dosage Form / Strength All Non-medicinal Ingredients Oral Inhalation Metered Dose Inhaler 100 micrograms 200 micrograms per actuation (ex-valve) propellant HFA-134a (norflurane) and ethanol Note: All doses given in this monograph are ex-valve unless specified otherwise.

INDICATIONS AND CLINICAL USE ALVESCO (ciclesonide) is indicated for:  prophylactic management of steroid-responsive bronchial asthma in adults, adolescents and children 6 years of age and older.

Pediatrics:

At present, there is limited data regarding the use of ALVESCO in patients <6 years of age and therefore ALVESCO is not recommended for patients younger than 6 years.

Geriatrics (>65 years of age):

Based on the pharmacokinetic characteristics obtained in patients older than 65 years of age, dose adjustment is not necessary in elderly patients. CONTRAINDICATIONS  ALVESCO (ciclesonide) is contraindicated in patients with known hypersensitivity to any of the ingredients.

For a complete listing, see Dosage Forms, Composition and Packaging section of the PM. COPYRIGHT 2021 COVIS PHARMA GmbH Page 4 of 37  ALVESCO is contraindicated in patients with untreated fungal, bacterial or tuberculosis infections of the respiratory tract  ALVESCO is not to be used in the primary treatment of status asthmaticus or other acute episodes of asthma, or in patients with moderate to severe bronchiectasis.

WARNINGS AND PRECAUTIONS General It is essential that patients be instructed that ALVESCO (ciclesonide) is a preventative agent which must be taken daily at the intervals recommended by their doctors and is not to be used as acute treatment for an asthmatic attack.

Patients should be advised to inform subsequent physicians of the prior use of corticosteroids. Treatment with ALVESCO should not be stopped abruptly, but tapered off gradually.

Monitoring Asthma Control:

Patients with severe asthma are at risk of acute attacks and should have regular assessments of their asthma control including pulmonary function tests. Increasing use of short-acting bronchodilators to relieve asthma symptoms indicate deterioration of asthma control.

If patients find that short-acting relief bronchodilator treatment becomes less effective, or they need more inhalations than usual, medical attention should be sought. In this situation, patients should be reassessed and consideration given to the need for increased anti-inflammatory treatment therapy (either higher doses of ALVESCO or a course of oral corticosteroids).

Severe asthma exacerbations should be managed according to standard medical practice. Carcinogenesis and Mutagenesis See TOXICOLOGY.

Endocrine and Metabolism Hypothyroidism:

There is an enhanced effect of corticosteroids on patients with hypothyroidism.

Hematologic Eosinophilic Conditions:

In rare cases, patients on inhaled corticosteroid therapy may present with systemic eosinophilic conditions, with some patients presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition that is often treated with systemic corticosteroid therapy.

These events usually, but not always, have been associated with the reduction and/or withdrawal of oral corticosteroid therapy following the introduction of inhaled corticosteroids, and cases of serious eosinophilic conditions have been reported in this clinical setting.

COPYRIGHT 2021 COVIS PHARMA GmbH Page 5 of 37 Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal relationship between ciclesonide and these underlying conditions has not been established.

Hypoprothrombinemia:

Acetylsalicyclic acid should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia.

Hepatic/Biliary/Pancreatic Cirrhosis:

There is an enhanced effect of corticosteroids on patients with cirrhosis.

Hepatic Insufficiency:

Based on the pharmacokinetic characteristics obtained in patients with hepatic insufficiency, dose adjustment is not necessary in this […]

Recommended Dose and Dosage Adjustment Adults and adolescents 12 years of age and older  The recommended starting dose of ALVESCO (ciclesonide) therapy for most patients, whether previously maintained on either bronchodilators alone or inhaled corticosteroids, is 400 micrograms once daily.

 The recommended dose range is 100 to 800 micrograms per day.  ALVESCO can be administered as 1 or 2 puffs once daily either in the morning or evening.  Some patients with more severe asthma may be more adequately controlled on 800 micrograms daily (administered as 400 micrograms twice daily).

 As with all inhaled corticosteroids, the dose of ALVESCO should be adjusted according to individual response. Children 6-11 years of age  The recommended starting dose of ALVESCO therapy for most patients, whether previously maintained on either bronchodilators alone or inhaled corticosteroids, is 100 to 200 micrograms once daily.

 The recommended dose range is 100 to 200 micrograms per day, administered as 1 or 2 puffs once daily either in the morning or evening.  As with all inhaled corticosteroids, the dose of ALVESCO should be adjusted according to individual response.

At present there is limited efficacy data regarding the use of ALVESCO in patients <6 years of age and therefore ALVESCO is not recommended for patients younger than 6 years. Symptoms can start to improve with ALVESCO within 24 hours of treatment.

Clinically, ALVESCO has been shown to improve lung function as measured by FEV1, peak expiratory flow, improved asthma symptom control, reduced exacerbations, and decreased need for inhaled beta2-agonists. It is important to gain control of asthma symptoms and optimize pulmonary function as soon as possible.

If there has been no improvement within one to two weeks, the patient should consult with their physician. Due to its prophylactic nature, ALVESCO should be taken regularly even when patients are asymptomatic. The patient should be aware that the benefit COPYRIGHT 2021 COVIS PHARMA GmbH Page 14 of 37 of ALVESCO depends on regular use even when they are experiencing no symptoms.

When patient symptoms remain under satisfactory control, the dose of ALVESCO should be titrated to the lowest dose at which effective control of asthma is maintained. Patients should be instructed to seek medical attention if their asthma symptoms worsen, or if their need for rescue medication increases.

Dose adjustments are not necessary in elderly patients, patients with liver impairment and patients with renal impairment. Missed Dose It is very important that ciclesonide is used regularly. If a dose is missed, the next dose should be taken when it is due.

Administration ALVESCO is for oral inhalation use only. To ensure the proper dosage and administration of the drug, the patient must be instructed by a physician or other health professional in the use of the inhalation aerosol (see CONSUMER INFORMATION).

Inhaler technique of patients should be checked regularly to make sure that correct method is used and inhaler actuation is synchronized with inhalation to ensure optimum delivery to the lungs. In patients who find co-ordination of a pressurized metered dose inhaler difficult, a spacer device (AeroChamber Plus®) may be used with ALVESCO.

If the inhaler is new or has not been used for one week or more, three puffs should be released into the air. No shaking is necessary as ALVESCO is a solution aerosol. The mouthpiece should be cleaned with a dry tissue or cloth weekly.

No part of the inhaler should be washed or put into water. Patients should be instructed to use the following technique to administer their medication:  Instruct the patient to remove the mouthpiece cover, place the inhaler in their mouth, close their lips around the mouthpiece, and breathe in slowly and deeply.

 After starting to breathe in through the mouth, the top of the inhaler should be pressed down.  Then, patients should move the inhaler away from their mouth, and hold their breath for about 10 seconds, or as long as is comfortable.

 The patient should not breathe out into the inhaler.  Finally, patients should breathe out slowly, and replace the mouthpiece cover. COPYRIGHT 2021 COVIS PHARMA GmbH Page 15 of 37 Transferring a patient from an oral steroid to ALVESCO The patient should be in a relatively stable phase.

A high dose of ALVESCO should be given in combination with the oral steroid for about 10 days. Then the oral steroid should be gradually reduced to the lowest possible level. 0 mg of prednisone (or equivalent of another corticosteroid) at seven day intervals if the patient is under close observation.

0 mg of the daily dose of prednisone (or equivalent) every ten days. If withdrawal symptoms appear, the previous dose of the systemic drug should be resumed for a week before any further decrease is attempted. OVERDOSAGE Single doses of up to 3200 micrograms inhaled ALVESCO (ciclesonide) were administered to healthy volunteers and were well tolerated.

The potential for acute toxic effects following overdose of inhaled ciclesonide is low. The only effect that follows inhalation of large amounts of the drug over a short period of time may be temporary suppression of adrenal function, symptoms of which may include: weakness, nausea, and hypotension.

In such cases, treatment with ALVESCO should be continued at a dose sufficient to control asthma. Recovery of adrenal function can be verified by measuring plasma cortisol. If higher than recommended doses are administered continuously over prolonged periods, some degree of adrenal suppression may occur, therefore monitoring of adrenal reserve should be considered.

Gradual reduction of the inhaled dose may be required. Treatment with ALVESCO should be continued at a dose […]

Adverse Drug Reaction Overview Inhaled corticosteroid therapy may be associated with dose dependent increases in incidence of ocular complications, reduced bone density, suppression of HPA axis responsiveness to stress, and inhibition of growth velocity in children.

Although such events have been associated with inhaled corticosteroid therapy, no significant difference was detected between inhaled ALVESCO (ciclesonide) and placebo on HPA function and serum cortisol levels. See DETAILED PHARMACOLOGY.

Glaucoma may be exacerbated by inhaled corticosteroid treatment for asthma or rhinitis. In patients with established glaucoma who require long-term inhaled corticosteroid treatment, it is prudent to measure intraocular pressure before commencing the inhaled corticosteroid and to monitor it subsequently.

In patients without established glaucoma, but with a potential for developing intraocular hypertension, intraocular pressure should be monitored at appropriate intervals. In all patients who are receiving long-term inhaled corticosteroid therapy, intraocular pressure should be monitored at appropriate intervals (see Monitoring and Laboratory Tests).

In elderly patients treated with inhaled corticosteroids, the prevalence of posterior subcapsular and nuclear cataracts is probably low but increases in relation to the daily and cumulative lifetime dose. Cofactors such as smoking, ultraviolet B exposure, or diabetes may increase the risk.

A reduction of growth velocity in children or teenagers may occur as a result of inadequate control of chronic diseases such as asthma or from use of corticosteroids for treatment. Physicians should closely follow growth of all children taking corticosteroids by any route and weigh the benefits of corticosteroid therapy and asthma control against the possibility of growth suppression if any child’s or adolescent’s growth appears slowed.

In a one-year study, ALVESCO was shown to have no effect on growth rates compared to placebo when administered to pediatric patients at doses of up to 200 micrograms per day (see CLINICAL TRIALS). Osteoporosis and bone fracture are complications of long term asthma treatment with parenteral or oral steroids.

Inhaled corticosteroid therapy has also been associated with dose dependent bone loss, although the risk is much less with inhaled therapy than with oral and parenteral therapy. Clinical Trial Adverse Drug Reactions Because clinical trials are conducted under very specific conditions the adverse drug reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse drug reaction information from clinical trials is useful for identifying drug- related adverse events and for approximating rates.

COPYRIGHT 2021 COVIS PHARMA GmbH Page 9 of 37 Use in adolescents and adults:

The clinical trial safety database for ALVESCO consists of a total of 9162 patients (740 adolescents and 8422 adults) treated with ALVESCO, 100 to 1600 micrograms per day, in clinical studies ranging in duration from 2 weeks to 1 year.

The majority of short-term trials had a randomized, blinded design. Three long-term studies were of open-label design. 6% of patients in placebo-controlled clinical trials experienced adverse events assessed as possibly related to treatment with ALVESCO by the investigator and/or sponsor (vs.

5% of patients treated with placebo). 4%), these were mild and did not require discontinuation of treatment with ALVESCO. 2% of patients treated with ALVESCO discontinued clinical trial participation due to an adverse event vs. 4% of patients in the placebo group.

4% vs. 8%). 9 1Assessed as possibly related to the treatment by investigator and/or sponsor. 2Paradoxical bronchospasm refers to a known adverse drug reaction of all inhaled drugs, which may be related to the active drug substance, excipients, or in the case of metered dose inhalers, to the cooling caused by the propellant or evaporation.

Suspected paradoxical bronchospasm includes the preferred terms: chest discomfort, chest pain, asthma, bronchospasm, cough, dyspnea, obstructive airways disorder, wheezing.

Dose Response Information:

The incidence of possibly treatment-related adverse events was generally comparable among the ALVESCO dose groups, with the exception of respiratory, thoracic and mediastinal disorders which showed a trend towards dose dependency. This could be due to the fact that the higher dose groups tended to include patients with more severe asthma.

Special Populations:

No safety signals specific for gender or for age were found in clinical trials. 0%). 1%). 1%). 1%). 1%). 1%). 1%). 4%), […]

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 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. 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.

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. 2 ) • Priming Information: Gently shake and prime OMNARIS Nasal Spray before using for the first time or when not used for four consecutive days.

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 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).

4 )] The most common adverse reactions (>2% incidence) included headache, epistaxis, nasopharyngitis, ear pain, and pharyngolaryngeal pain. gov/medwatch. 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. 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. 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. 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. 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.

3 )] . Patients with a known hypersensitivity to ciclesonide or any of the ingredients of OMNARIS Nasal Spray. ( 4 )