Ciclesonide

Pronunciation: sye-KLES-oh-nide
Class: Corticosteroid

Trade Names

Alvesco
- Solution, inhalation 80 mcg/actuation
- Solution, inhalation 160 mcg/actuation

Omnaris
- Spray, suspension, intranasal 50 mcg/actuation

Zetonna
- Aerosol, spray, intranasal 37 mcg/actuation

Pharmacology

Anti-inflammatory activity with a high affinity for the glucocorticoid receptor.

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Pharmacokinetics

Absorption

Prodrug converted to active metabolite, des-ciclesonide. Negligible bioavailability. Des-ciclesonide C _max is below 30 pg/mL ( Omnaris intranasal), 59 pg/mL ( Zetonna intranasal), and 1.02 ng/mL (inhalation).

Distribution

Following IV administration, Vd of ciclesonide and des-ciclesonide are approximately 2.9 and 12.1 L/kg, respectively, and protein binding averages at least 99% for ciclesonide and its metabolite.

Metabolism

Des-ciclesonide is metabolized in the liver by the CYP3A4 isozyme and, to a lesser degree, CYP2D6.

Elimination

After IV administration, predominantly excreted in the feces (66%) and approximately 20% or less in the urine. Cl of IV ciclesonide and des-ciclesonide were 152 and 228 L/h, respectively. Mean half-lives of ciclesonide and des-ciclesonide were 0.71 and 6 to 7 h, respectively (inhalation).

Special Populations

Renal Function Impairment

Studies were not conducted because renal excretion is a minor route of elimination.

Hepatic Function Impairment

C _max of des-ciclesonide in patients with moderate to severe liver impairment increased 1.4- to 2.7-fold after oral inhalation. When administered by oral inhalation, dosage adjustments are not needed.

Elderly

Population pharmacokinetics showed that the characteristics of des-ciclesonide after oral inhalation were not influenced by age.

Gender

Population pharmacokinetics showed that the characteristics of des-ciclesonide after oral inhalation were not influenced by gender.

Race

Population pharmacokinetics showed that the characteristics of des-ciclesonide after oral inhalation were not influenced by race.

Weight

Population pharmacokinetics showed that the characteristics of des-ciclesonide after oral inhalation were not influenced by weight.

Indications and Usage

Treatment of nasal symptoms associated with seasonal or perennial allergic rhinitis (intranasal); for the maintenance treatment of asthma as prophylactic therapy (oral inhalation).

Contraindications

Hypersensitivity to ciclesonide or any of the ingredients; treatment of status asthmaticus or other acute episodes of asthma (oral inhalation).

Dosage and Administration

Asthma
Adults and children 12 y and older Patients who receive bronchodilators alone

Oral inhalation Initially 80 mcg twice daily (max, 160 mcg twice daily).

Patients who received inhaled corticosteroids

Oral inhalation Initially 80 mcg twice daily (max, 320 mcg twice daily).

Patients who received oral corticosteroids

Oral inhalation Initially 320 mcg twice daily. Prednisone should be reduced gradually, no faster than 2.5 mg/day on a weekly basis, beginning after at least 1 wk of therapy with ciclesonide.

Perennial Allergic Rhinitis
Omnaris Adults and children 12 y and older

Nasal inhalation 2 sprays (50 mcg/spray) in each nostril once daily (max, 200 mcg/day).

Zetonna Adults and children 12 y and older

1 actuation (37 mcg/actuation) per nostril once daily (max, 74 mcg/day).

Seasonal Allergic Rhinitis
Omnaris Adults and children 6 y and older

Nasal inhalation 2 sprays (50 mcg/spray) in each nostril once daily (max, 200 mcg/day).

Zetonna Adults and children 12 y and older

1 actuation (37 mcg/actuation) per nostril once daily (max, 74 mcg/day).

General Advice

• Nasal inhalation
• Administer by intranasal route only.
• Before use, gently shake the nasal spray, then prime the pump by actuating 8 times ( Omnaris ) or 3 times ( Zetonna ).
• If Omnaris is not used for 4 or more consecutive days, it should be gently shaken and primed with 1 spray or until a fine mist appears.
• If Zetonna is not used for 10 consecutive days, it should be primed by actuating 3 times.
• Advise patients to avoid spraying in the eyes or directly onto the nasal septum.
• Omnaris provides 120 actuations and Zetonna 60 actuations after initial priming.

• Oral inhalation
• For patients who do not respond adequately to the starting dose after 4 wk of therapy, higher doses may provide additional asthma control.
• After asthma stability has been achieved, titrate to the lowest effective dose.
• For oral inhalation only. Avoid spraying into the nose or eyes.
• Prime ciclesonide before using for the first time by actuating 3 times prior to using the first dose from a new canister or when the inhaler has not been used for more than 10 days.

Storage/Stability

Store nasal spray at 59° to 86°F. Do not freeze. Store oral inhalation between 59° and 86°F. Do not puncture Zetonna canister or store near heat or open flame. Exposure to temperatures above 120°F may cause bursting; never throw canister into fire or incinerator.

Drug Interactions

Azole antifungal agents (eg, ketoconazole)

Coadministration of orally inhaled ciclesonide and oral ketoconazole, a potent inhibitor of CYP3A4, may increase exposure (ie, AUC) to the ciclesonide active metabolite, des-ciclesonide, while levels of ciclesonide remain unchanged. Coadminister azole antifungal agents and ciclesonide with caution.

Delavirdine

Plasma concentrations of ciclesonide may be increased when coadministered with delavirdine. Use with caution. Consider alternatives to inhaled ciclesonide, particularly for long-term use.

Protease inhibitors (eg, ritonavir)

Plasma concentrations and pharmacologic effects of ciclesonide may be increased by protease inhibitors. Severe adrenal suppression with resulting iatrogenic Cushing syndrome may occur. Closely monitor for signs of iatrogenic Cushing syndrome. When an inhaled or intranasal steroid is needed, administer the lowest effective dose and a less systemically available agent (eg, budesonide).

Adverse Reactions

CNS

Headache (27%); dizziness, fatigue (3% or more).

EENT

Nasal discomfort (28%); epistaxis (26%); nasopharyngitis (7%); nasal congestion, sinusitis (6%); pharyngeal pain (5%); conjunctivitis, pharyngolaryngeal pain (3% or more); nasal mucosal/septum disorders, oropharyngeal pain, Streptococcal pharyngitis (2% or more); ear pain (2%); nasal septal ulcerations; localized infections of nose or mouth with Candida albicans , nasal ulcer (postmarketing).

GI

Gastroenteritis, oral candidiasis (3% or more); nausea (2% or more).

Hypersensitivity

Immediate or delayed hypersensitivity reactions (postmarketing).

Musculoskeletal

Arthralgia (4%); back pain, musculoskeletal chest pain (3% or more); muscle strain (2% or more).

Respiratory

Upper respiratory tract infection (9%); bronchitis, cough, pneumonia (3% or more); viral upper respiratory tract infection (2%).

Miscellaneous

Face edema, hoarseness, influenza, urticaria, UTI (3% or more); pain in extremity (3%).

Precautions

Monitor Carefully monitor lung function (forced expiratory volume at 1 sec or morning peak expiratory flow rate), beta-agonist use, and asthma symptoms during withdrawal of oral corticosteroids. Closely monitor patients with a change in vision or with a history of glaucoma or cataracts. Routinely monitor (eg, via stadiometry) the growth of children. Periodically examine patients using ciclesonide over several months or longer for evidence of Candida infection or other signs of adverse effects. Carefully monitor patients previously treated for prolonged periods of time with systemic corticosteroids and transferred to topical corticosteroids for acute adrenal insufficiency in response to stress. Monitor patients with major risk factors for decreased bone mineral content.

Pregnancy

Category C .

Lactation

Undetermined.

Children

May cause a reduction in growth velocity when administered to children.

Asthma

Safety and efficacy not established in children younger than 12 y.

Perennial allergic rhinitis

Safety and efficacy not established in children younger than 12 y ( Omnaris and Zetonna ).

Seasonal allergic rhinitis

Safety and efficacy not established in children younger than 6 y ( Omnaris ) and younger than 12 y ( Zetonna ).

Elderly

Use with caution, usually starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Hypersensitivity

Immediate and delayed reactions have occurred.

Acute asthma

Not indicated for rapid relief of bronchospasm or other acute episodes of asthma.

Adrenal insufficiency

Replacement of systemic corticosteroids with topical corticosteroids can be accompanied by signs of adrenal insufficiency. Some patients may experience symptoms of corticosteroid withdrawal (eg, depression, joint or muscular pain, lassitude).

Bone mineral density

Decreases in bone mineral density (BMD) have been observed with long-term use of products containing inhaled corticosteroids.

Bronchospasm

Inhaled ciclesonide may cause bronchospasm with an immediate increase in wheezing after dosing.

Effect on growth

Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to children.

Immunosuppression

Patients receiving immunosuppressant agents (eg, corticosteroids) are more susceptible to infections than healthy individuals. If a patient is exposed to measles or chickenpox, appropriate prophylaxis and treatment may be indicated.

Infection

Use with caution, if at all, in patients with untreated active or quiescent tuberculosis infection of the respiratory tract; untreated systemic fungal, bacterial, parasitic, or viral infections; or ocular herpes simplex. The development of localized infections of the nose and pharynx with C. albicans has rarely occurred.

Long-term use

In patients who have asthma or other clinical conditions requiring long-term systemic corticosteroid treatment, rapid decreases in systemic corticosteroid dosages may cause severe exacerbation of symptoms.

Ophthalmic effects

Glaucoma, increased IOP, and cataracts have been reported following long-term use of inhaled corticosteroids.

Prior corticosteroid use

Transfer from oral corticosteroids to inhaled corticosteroids has resulted in death caused by adrenal insufficiency related to a lower systemic availability. A number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) axis suppression. Patients maintained on prednisone 20 mg or more daily may be at higher risk. Transfer from oral to inhaled or intranasal corticosteroids may unmask allergic conditions previously suppressed by the systemic corticosteroid (eg, eczema, rhinitis).

Wound healing

Because of the inhibitory effect of corticosteroids on wound healing, patients experiencing recent nasal septal ulcers, nasal surgery, or nasal trauma should not use a nasal corticosteroid until healing has occurred.

Overdosage

Symptoms

Signs of hypercorticism.

Patient Information

• Instruct patient on the correct administration technique.
• Review proper administration technique. Have patient demonstrate technique to ensure effective use of the delivery system.
• Warn patients taking immunosuppressant doses of corticosteroids to avoid exposure to measles and chickenpox, and, if exposed, to seek medical advice.
• Instruct patients to contact their health care provider if symptoms do not improve within a reasonable time or if conditions worsen.
• Inform patients that orally inhaled or intranasal corticosteroids may cause a reduction in growth velocity when administered to children.
• Inform patients that glaucoma and cataracts are associated with nasal and inhaled corticosteroid use. Advise patients to inform their health care provider if a change in vision is noted while using ciclesonide.

• Nasal inhalation
• Caution patients not to spray into the eyes or onto the nasal septum.
• Instruct patients not to stop the medication once symptoms have been controlled. Continued daily use is necessary to continue to control symptoms.
• Instruct patients to use with caution if sores develop or injuries occur in nasal passages. Drug may prevent or slow proper healing.
• Advise patients to report the following symptoms to their health care provider: nasal irritation, nasal ulceration, nasal septal perforation, nosebleed, or sneezing.
• Advise patients to discard bottle when labeled number of sprays have been used, even if bottle is not completely empty.

• Oral inhalation
• Warn patient that the drug is an asthma controller and is not to be used to treat an acute asthma attack. Rescue medication (bronchodilator) must be used to obtain rapid relief of asthma symptoms.
• Instruct patients not to stop the medication once symptoms have been controlled. Continued daily use is necessary to continue to control symptoms, and maximum benefit may not be achieved for 4 wk or longer after starting treatment.
• Advise patients who are at an increased risk of decreased BMD that the use of corticosteroids may pose an additional risk and should be monitored.
• If a patient is being converted from oral corticosteroids to inhaled or intranasal corticosteroids, review signs and symptoms of adrenal insufficiency, which may occur days or weeks after conversion is complete. Advise patient to carry medical identification (eg, card, bracelet) indicating the need for supplemental systemic corticosteroids during periods of stress or a severe asthma attack.
• Advise patient to rinse mouth thoroughly with water after using the oral inhalation medication.
• Instruct patient that when the dose indicator display window shows a red zone, approximately 20 inhalations are left and a refill is required. Discard the inhaler when the indicator shows 0.
• Instruct patients who have been withdrawn from oral corticosteroids to resume oral corticosteroids during periods of stress or a severe asthma attack.

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