The Food and Drug Administration (FDA) approved ciclesonide (Alvesco) inhalation aerosol for the maintenance treatment of asthma in adults and adolescents 12 years and older on January 10, 2008. Ciclesonide is an inhaled corticosteroid developed with unique release and distribution properties.

Approximately 22 million Americans have asthma. Annually, asthma accounts for nearly 2 million emergency department visits and an estimated $11.5 billion in healthcare costs.1 On a daily basis in the United States, asthma results in 40,000 people missing school or work; 30,000 people experience an asthma attack; 5,000 people visit the emergency department; 1,000 people are admitted to the hospital; and 11 people die.1

Useful Medication

According to the 2007 Guidelines for the Diagnosis and Management of Asthma, corticosteroids are one of the most effective medications for long-term control of persistent asthma. These drugs are effective because of their ability to moderate the underlying inflammation characteristic of asthma. The mechanism of action of corticosteroids helps reduce airway hyperresponsiveness, inhibit inflammatory cell migration and activation, and block late phase reactions to allergens. Inhaled corticosteroids are the most consistently effective long-term control medication at all steps of care for persistent asthma, and improve asthma control more effectively in both children and adults than any other single, long-term control medication.2

Ciclesonide is indicated only for the maintenance treatment of asthma as prophylactic therapy in adult and adolescent patients 12 years of age and older.3 Ciclesonide is not indicated for the relief of acute bronchospasm or for treatment of asthma in patients less than 12 years of age. Unique properties of the drug include:

* a smaller particle size for greater lung deposition and less oral exposure

* greater affinity to the glucocorticoid receptors than current inhaled corticosteroids

* an ozone-safe propellant

* greater than 50% of the inhaled dose delivered directly to the lung

* a conversion to its active form by esterases in the lung

* lipid conjugation for prolonged anti-inflammatory effects and once-daily dosing

* high protein binding for systemic safety

* only 1% available for systemic exposure

* quick metabolization in the liver for first-pass inactivation.4

Mechanism of Action

Following oral inhalation ciclesonide, a prodrug is enzymatically hydrolyzed in the lungs to a pharmacologically active metabolite (des-ciclesonide). Des-ciclesonide has anti-inflammatory activity with an affinity for glucocorticoid receptors that is 120 times greater than the parent compound and 12 times greater than dexamethasone.3

Corticosteroids have a wide range of inhibitory activities against multiple cell types (such as mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils) and mediators (such as histamine, eicosanoids, leukotrienes, and cytokines) involved in the asthmatic inflammatory response.3 The anti-inflammatory actions of corticosteroids are believed to contribute to their efficacy in asthma. However, they do not produce any immediate therapeutic effect on asthma symptoms. Individual patients will experience a variable time to onset and degree of symptom relief. The maximum benefit for those using inhaled corticosteroids may not be achieved for 4 weeks or longer after starting treatment.

Drug Metabolism

Orally inhaled medications such as ciclesonide have minimal systemic absorption. Therefore, the pharmacodynamic effects of absorption, distribution, metabolism, and excretion of these medications are less important than with orally ingested drugs.

In clinical studies, concurrent administration of ciclesonide and other drugs commonly used in the treatment of asthma (albuterol, formoterol) had no effect on pharmacokinetics of desciclesonide.3 Clinical studies to date have indicated that des-ciclesonide has no potential for metabolic drug interactions or protein binding-based drug interactions.

Contraindications and Precautions

Ciclesonide is not indicated for the primary treatment of acute bronchospasm or status asthmaticus. The medication is also contraindicated in patients with known hypersensitivity to ciclesonide or any of the ingredients of ciclesonide. The manufacturer has noted that during worldwide post-marketing use of ciclesonide oral, rare cases of hypersensitivity reactions with manifestations such as angioedema and swelling of the lips, tongue, and pharynx have been reported.3 Because these reactions are voluntarily reported from a population of uncertain size, it is not always possible to reliably approximate their regularity or establish a causal relationship to drug exposure.3

There are no adequate and well-controlled studies in pregnant women. Therefore, ciclesonide, a pregnancy Category C drug, should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.3 Clinical trials with ciclesonide did not include nursing mothers, but as inhaled corticosteroids may be excreted in breast milk, the drug is not recommended for use in nursing women. Studies involving patients 4 to 11 years of age have showed inconsistent results, thus the safety and effectiveness of ciclesonide in children under 12 years of age has not been established.

Clinical studies with other orally inhaled corticosteroids have shown a potential for a reduction in growth velocity in pediatric patients. In these studies, the mean reduction in growth velocity was approximately 1 centimeter per year (range 0.3 to 1.8 centimeters per year) and appears to be related to dose and duration of exposure.3 The long-term effects of growth reduction velocity and the impact on final adult height are still being explored. Providers should titrate the medication to the lowest effective dose and continue to monitor growth in non-adult patients.

The use of ciclesonide in geriatric patients has not demonstrated a significant difference in efficacy or an increase in adverse events. However, dose selection for elderly patients should be chosen cautiously, and should start at the low end of the dosing range due to the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.3

Adverse Reactions

In clinical trials, the most common adverse reactions experienced by patients (>3%) using ciclesonide included headache, nasopharyngitis, sinusitis, pharyngolaryngeal pain, upper respiratory infection, arthralgia, nasal congestion, pain in extremity, and back pain.3 In general, the use of systemic and local corticosteroids have been shown to produce adverse reactions such as:

* bronchospasm

* Candida albicans infection

* immunosuppression

* hypercorticism and adrenal suppression

* decreased bone mineral density

* growth effects

* glaucoma and cataracts.3

Dosage and Administration

Ciclesonide is administered through oral inhalation and is available in 80 mcg/actuation and 160 mcg/actuation strengths. Patients should be instructed to prime the inhaler before using for the first time by actuating three times from a new canister or when the inhaler has not been used for more than 10 days. The maximum beneficial effect of the medication may not be achieved for 4 weeks or longer after initiation. After asthma stability has been achieved and to reduce the possibility of side effects, it is desirable to titrate to the lowest effective dosage. For patients who do not respond adequately to the starting dose after 4 weeks of therapy, higher doses may provide additional asthma control.

Starting and maximum dosages of ciclesonide are based on the patient's current medication regimen. The recommendation for patients currently using only bronchodilators is a starting dose of 80 mcg twice daily and maximum dose of 160 mcg twice daily. For patients using inhaled corticosteroids, a starting dose of 80 twice daily and a maximum dose of 320 mcg twice daily is suggested. Dose adjustment is not necessary with patients that have diminished renal or hepatic function.

With patients currently using oral corticosteroids such as prednisone, a 320 mcg twice daily dose is the recommended starting and maximum dose. Discontinuation of oral steroids when switching to inhaled ciclesonide should be tapered with careful monitoring of the patient's status.

Special Instructions

Patients should be advised to rinse their mouth following inhalation to avoid Candida albicans infection of the mouth and pharynx. Due to some systemic absorption of ciclesonide, the possibility of a suppressed immune system may result in a worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infection; or ocular herpes simplex. Also in susceptible patients, a more serious or even fatal course of chickenpox or measles may arise. Providers should use ciclesonide cautiously in patients with these conditions because of the potential for worsening of these infections.

In patients transferring from oral steroids to inhaled corticosteroids, there is a risk of impaired adrenal function. Providers should taper patients slowly from systemic corticosteroids to the inhaled ciclesonide. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response. Hypercorticism and adrenal suppression may appear in a small number of patients, especially if ciclesonide is administered at higher than recommended doses over prolonged periods of time.3 Corticosteroids also have the potential for suppression of growth in children, and pediatric patients using ciclesonide should have their growth monitored routinely.

Patients who are at an increased risk for decreased bone mineral density should be advised that the use of corticosteroids may pose an additional risk and should be closely monitored. Ciclesonide as well as other inhaled corticosteroids may cause glaucoma, increased intraocular pressure, and cataracts. Practitioners should provide close monitoring in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts.3

Bronchospasm is a potential reaction to the use of inhaled corticosteroids and may result in an immediate increase in wheezing. Patients should be advised to treat bronchospasm episodes with a fast-acting inhaled bronchodilator.

Precautions

As with all inhaled corticosteroids, providers should advise their patients to use these drugs consistently and at regular intervals, since their effectiveness depends on regular use. The patient should not increase the prescribed dosage but should contact their provider if symptoms do not improve or if their condition worsens. Patients should be instructed not to stop ciclesonide abruptly and should contact their provider immediately if use of the drug is discontinued.3

Ciclesonide is dispensed via a multi-dose actuator and can be stored at room temperature. The actuator has a dose indicator display window that shows a red zone when approximately 20 inhalations are left. Patients should request a refill at this time and discard the inhaler when the indicator shows zero.

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