Introduction

Synthetic, non-halogenated glucocorticoid.

Uses for Ciclesonide (Systemic, Oral Inhalation)

Asthma

Long-term prevention of bronchospasm in patients with asthma.

In corticosteroid-dependent patients, may permit a reduction in dosage or discontinuance of systemic corticosteroids.

Not indicated for management of acute bronchospasm.

Ciclesonide (Systemic, Oral Inhalation) Dosage and Administration

General

• Adjust dosage carefully according to individual requirements and response.

• Base initial and maximum dosages in adults and children ≥12 years of age on previous asthma therapy.

• After a satisfactory response is obtained, decrease dosage gradually to the lowest dosage that maintains an adequate clinical response. Achieve the lowest effective dosage, particularly in children, since inhaled corticosteroids have the potential to affect growth. (See Pediatric Use under Cautions.)

Conversion to Orally Inhaled Therapy in Patients Receiving Systemic Corticosteroids

• When switching from systemic corticosteroids to orally inhaled ciclesonide, asthma should be reasonably stable before initiating treatment with oral inhalation.

• Initially, administer oral inhalation concurrently with the maintenance dosage of the systemic corticosteroid. After at least 1 week, gradually withdraw the systemic corticosteroid.

• Decrements usually should not exceed 2.5 mg daily of prednisone (or its equivalent) each week in patients receiving the oral inhalation. Once oral corticosteroids are discontinued and symptoms of asthma have been controlled, titrate the dosage to the lowest effective level.

• Death has occurred in some individuals in whom systemic corticosteroids were withdrawn too rapidly. (See Withdrawal of Systemic Corticosteroid Therapy under Cautions.)

Administration

Oral Inhalation

Administer by oral inhalation using an oral aerosol inhaler.

Test-spray aerosol (3 times) before first use or when the inhaler is unused for >10 days.

Oral inhalation aerosol is formulated as a solution, which does not require shaking.

Exhale completely and place the mouthpiece of the inhaler well into the mouth with the lips closed firmly around it; keep the tongue below the mouthpiece. Inhale slowly and deeply through the mouth while pressing the canister down with forefinger. Hold the breath for about 10 seconds, or as long as comfortable, then withdraw the mouthpiece and exhale gently.

Patients receiving oral inhalation of ciclesonide should rinse their mouth with water after each dose to remove residual medication in the oropharyngeal area and to minimize the development of fungal overgrowth and/or infection.

Dosage

Pediatric Patients

Asthma

Oral Inhalation

Children ≥12 years of age receiving bronchodilators alone previously: Initially 80 mcg twice daily. If control of asthma is inadequate after 4 weeks of therapy at the initial dosage, a higher dosage may provide additional asthma control. If required, may increase dosage to a maximum of 160 mcg twice daily.

Children ≥12 years of age receiving inhaled corticosteroids previously: Initially 80 mcg twice daily. If control of asthma is inadequate after 4 weeks of therapy at the initial dosage, a higher dosage may provide additional asthma control. If required, may increase dosage to a maximum of 320 mcg twice daily.

Children ≥12 years of age receiving oral corticosteroids previously: 320 mcg twice daily.

Adults

Asthma

Oral Inhalation

Previously receiving bronchodilators alone: Initially 80 mcg twice daily. If control of asthma is inadequate after 4 weeks of therapy at the initial dosage, a higher dosage may provide additional asthma control. If required, may increase dosage to a maximum of 160 mcg twice daily.

Previously receiving inhaled corticosteroids: Initially 80 mcg twice daily. If control of asthma is inadequate after 4 weeks of therapy at the initial dosage, a higher dosage may provide additional asthma control. If required, may increase dosage to a maximum of 320 mcg twice daily.

Previously receiving oral corticosteroids: 320 mcg twice daily.

Prescribing Limits

Pediatric Patients

Asthma

Oral Inhalation

Children ≥12 years of age receiving bronchodilators alone previously: Maximum 160 mcg twice daily.

Children ≥12 years of age receiving inhaled corticosteroids previously: Maximum 320 mcg twice daily.

Children ≥12 years of age receiving oral corticosteroids previously: Maximum 320 mcg twice daily.

Adults

Asthma

Oral Inhalation

Previously receiving bronchodilators alone: Maximum 160 mcg twice daily.

Previously receiving inhaled corticosteroids: Maximum 320 mcg twice daily.

Previously receiving oral corticosteroids: Maximum 320 mcg twice daily.

Special Populations

Hepatic Impairment

Dosage adjustment not required. (See Hepatic Impairment under Cautions.)

Renal Impairment

No specific dosage recommendations at this time. (See Renal Impairment under Cautions.)

Geriatric Patients

Careful dosage selection, usually initiating therapy at the low end of the dosage range, recommended due to possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Contraindications

• Primary treatment of severe acute asthmatic attacks or status asthmaticus when intensive measures (e.g., oxygen, parenteral bronchodilators, IV corticosteroids) are required.

• Known hypersensitivity to ciclesonide or any ingredient in the formulation.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity reactions, including angioedema with swelling of the lips, tongue, and pharynx, reported.

Infections

Localized candidal infections of the mouth and/or pharynx reported.

If infection occurs, initiate appropriate local or systemic antifungal treatment while still continuing with inhaled ciclesonide therapy. May require interruption of ciclesonide therapy in some patients.

Use with caution, if at all, in patients with clinical or asymptomatic Mycobacterium tuberculosis infections of the respiratory tract; untreated systemic fungal, bacterial, parasitic, or viral infections; or ocular herpes simplex.

Acute Exacerbations of Asthma

Treat acute asthma symptoms with a short-acting β₂-agonist bronchodilator. If symptoms persist, promptly reevaluate asthma therapy and consider initiating systemic corticosteroids.

Immunosuppressed Patients

Increased susceptibility to infections in patients who are taking immunosuppressive drugs compared with healthy individuals. Certain infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome in such patients.

Take particular care to avoid exposure in susceptible patients. If exposure to varicella or measles occurs in susceptible patients, consider administering varicella zoster immune globulin (VZIG) or pooled immune globulin (IG), respectively. Consider treatment with an antiviral agent if varicella develops.

Withdrawal of Systemic Corticosteroid Therapy

Possible life-threatening adrenal insufficiency in patients being switched from systemic corticosteroids to orally inhaled ciclesonide.

Withdraw systemic corticosteroid therapy gradually and monitor carefully for objective signs of adrenal insufficiency (e.g., fatigue, lassitude, weakness, nausea, vomiting, hypotension) during withdrawal of systemic therapy. Lung function (FEV₁ or morning peak expiratory flow rate [PEFR]), adjunctive β₂-adrenergic agonist use, and asthma symptoms also should be carefully monitored. In most patients, several months are required for total recovery of HPA function following withdrawal of systemic corticosteroid therapy. Patients who have been maintained on ≥20 mg of prednisone (or its equivalent) daily may be most susceptible to such adverse events, particularly during the later part of the transfer. (See Conversion to Orally Inhaled Therapy in Patients Receiving Systemic Corticosteroids under Dosage and Administration.)

Corticosteroid withdrawal symptoms (e.g., joint pain, muscular pain, lassitude, depression) may occur; carefully monitor during and for a number of months after withdrawal of systemic corticosteroids.

Acute adrenal insufficiency may occur during exposure to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss.

Possible unmasking of allergic conditions previously controlled by systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions).

Systemic Corticosteroid Effects

Administration of higher than recommended dosages of inhaled ciclesonide over prolonged periods may result in manifestations of hypercorticism and suppression of HPA function. If such changes occur, reduce the dosage of ciclesonide slowly, consistent with accepted procedures for reducing systemic corticosteroid dosage and management of asthma symptoms.

Take particular care in monitoring patients postoperatively or during periods of stress for evidence of inadequate adrenal response. Supplemental therapy with a systemic corticosteroid required during stress or severe asthma attacks.

Musculoskeletal Effects

Long-term use of orally inhaled corticosteroids may affect normal bone metabolism, resulting in a loss of bone mineral density (BMD).

Monitor patients with major risk factors for decreased BMD (e.g., family history of osteoporosis, prolonged immobilization, chronic use of drugs that can reduce bone mass [e.g., anticonvulsants, corticosteroids]) and treat with established standards of care.

Ocular Effects

Glaucoma, increased IOP, and cataracts reported rarely in patients receiving orally inhaled corticosteroids. Carefully monitor patients who have a change in vision and those with a history of increased IOP, glaucoma, and/or cataracts.

Respiratory Effects

Bronchospasm and wheezing may occur with oral inhalation therapy.

If bronchospasm occurs, treat immediately with a short-acting bronchodilator, and discontinue treatment with ciclesonide and institute alternate therapy.

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Caution if used in nursing women.

Pediatric Use

Safety and efficacy not established in children <12 years of age.

With prolonged use, may slow growth rate in children and adolescents. Monitor routinely (e.g., via stadiometry) the growth and development of pediatric patients receiving corticosteroid therapy. Weigh benefits of corticosteroid therapy versus possibility of growth suppression and the risks associated with alternative therapies. Use the lowest possible dosage that effectively controls asthma.

Geriatric Use

Insufficient experience with oral inhalation in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients. (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Increased systemic exposure in patients with moderate to severe hepatic impairment; however, dosage adjustments not necessary.

Renal Impairment

Pharmacokinetics not evaluated but impact of renal impairment should be minimal.

Common Adverse Effects

Headache, nasopharyngitis, sinusitis, pharyngolaryngeal pain, upper respiratory infection, arthralgia, nasal congestion, extremity pain, back pain, hoarseness, oral candidiasis, influenza, pneumonia, musculoskeletal chest pain, urticaria, dizziness, gastroenteritis, facial edema, fatigue, conjunctivitis.

General

• Adjust dosage carefully according to individual requirements and response.

• Base initial and maximum dosages in adults and children ≥12 years of age on previous asthma therapy.

• After a satisfactory response is obtained, decrease dosage gradually to the lowest dosage that maintains an adequate clinical response. Achieve the lowest effective dosage, particularly in children, since inhaled corticosteroids have the potential to affect growth. (See Pediatric Use under Cautions.)

Conversion to Orally Inhaled Therapy in Patients Receiving Systemic Corticosteroids

• When switching from systemic corticosteroids to orally inhaled ciclesonide, asthma should be reasonably stable before initiating treatment with oral inhalation.

• Initially, administer oral inhalation concurrently with the maintenance dosage of the systemic corticosteroid. After at least 1 week, gradually withdraw the systemic corticosteroid.

• Decrements usually should not exceed 2.5 mg daily of prednisone (or its equivalent) each week in patients receiving the oral inhalation. Once oral corticosteroids are discontinued and symptoms of asthma have been controlled, titrate the dosage to the lowest effective level.

• Death has occurred in some individuals in whom systemic corticosteroids were withdrawn too rapidly. (See Withdrawal of Systemic Corticosteroid Therapy under Cautions.)

Administration

Oral Inhalation

Administer by oral inhalation using an oral aerosol inhaler.

Test-spray aerosol (3 times) before first use or when the inhaler is unused for >10 days.

Oral inhalation aerosol is formulated as a solution, which does not require shaking.

Exhale completely and place the mouthpiece of the inhaler well into the mouth with the lips closed firmly around it; keep the tongue below the mouthpiece. Inhale slowly and deeply through the mouth while pressing the canister down with forefinger. Hold the breath for about 10 seconds, or as long as comfortable, then withdraw the mouthpiece and exhale gently.

Patients receiving oral inhalation of ciclesonide should rinse their mouth with water after each dose to remove residual medication in the oropharyngeal area and to minimize the development of fungal overgrowth and/or infection.

Dosage

Pediatric Patients

Asthma

Oral Inhalation

Children ≥12 years of age receiving bronchodilators alone previously: Initially 80 mcg twice daily. If control of asthma is inadequate after 4 weeks of therapy at the initial dosage, a higher dosage may provide additional asthma control. If required, may increase dosage to a maximum of 160 mcg twice daily.

Children ≥12 years of age receiving inhaled corticosteroids previously: Initially 80 mcg twice daily. If control of asthma is inadequate after 4 weeks of therapy at the initial dosage, a higher dosage may provide additional asthma control. If required, may increase dosage to a maximum of 320 mcg twice daily.

Children ≥12 years of age receiving oral corticosteroids previously: 320 mcg twice daily.

Adults

Asthma

Oral Inhalation

Previously receiving bronchodilators alone: Initially 80 mcg twice daily. If control of asthma is inadequate after 4 weeks of therapy at the initial dosage, a higher dosage may provide additional asthma control. If required, may increase dosage to a maximum of 160 mcg twice daily.

Previously receiving inhaled corticosteroids: Initially 80 mcg twice daily. If control of asthma is inadequate after 4 weeks of therapy at the initial dosage, a higher dosage may provide additional asthma control. If required, may increase dosage to a maximum of 320 mcg twice daily.

Previously receiving oral corticosteroids: 320 mcg twice daily.

Prescribing Limits

Pediatric Patients

Asthma

Oral Inhalation

Children ≥12 years of age receiving bronchodilators alone previously: Maximum 160 mcg twice daily.

Children ≥12 years of age receiving inhaled corticosteroids previously: Maximum 320 mcg twice daily.

Children ≥12 years of age receiving oral corticosteroids previously: Maximum 320 mcg twice daily.

Adults

Asthma

Oral Inhalation

Previously receiving bronchodilators alone: Maximum 160 mcg twice daily.

Previously receiving inhaled corticosteroids: Maximum 320 mcg twice daily.

Previously receiving oral corticosteroids: Maximum 320 mcg twice daily.

Special Populations

Hepatic Impairment

Dosage adjustment not required. (See Hepatic Impairment under Cautions.)

Renal Impairment

No specific dosage recommendations at this time. (See Renal Impairment under Cautions.)

Geriatric Patients

Careful dosage selection, usually initiating therapy at the low end of the dosage range, recommended due to possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Inhibitory potential of ciclesonide on CYP isoenzymes not evaluated; however des-ciclesonide (active metabolite) does not inhibit or induce the metabolism of other drugs metabolized by CYP isoenzymes in vitro.

Ciclesonide and des-ciclesonide do not induce CYP isoenzymes in vitro.

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased plasma des-ciclesonide concentrations).

Protein-bound Drugs

Pharmacokinetic interaction unlikely.

Specific Drugs