AHFS Class:

• Corticosteroids 52:08.08

Generic Name(s):

• Ciclesonide

Ciclesonide is a synthetic, nonhalogenated corticosteroid that has glucocorticoid activity.1,3,4,7,9

Allergic Rhinitis

Ciclesonide nasal spray is used for the symptomatic management of seasonal or perennial allergic rhinitis.1,2,6

Efficacy of ciclesonide in the symptomatic management of seasonal allergic rhinitis was established in several randomized, double-blind, placebo-controlled studies of 2-4 weeks' duration in more than 1600 patients (6-86 years of age) with seasonal allergic rhinitis.1,3,4,5,9 In these studies, treatment with ciclesonide 200 mcg once daily was more effective than placebo in reducing nasal symptoms (i.e., rhinorrhea, nasal itching, sneezing, nasal congestion), as assessed by reduction in total nasal symptom scores.1,3,4,5

Efficacy of ciclesonide in the symptomatic management of perennial allergic rhinitis was established in a randomized, double-blind, placebo-controlled study of 6 weeks' duration in more than 400 patients (12-75 years of age) with perennial allergic rhinitis.1,3,7,9 In this study, treatment with ciclesonide 200 mcg once daily was more effective than placebo in reducing nasal symptoms (i.e., rhinorrhea, nasal itching, sneezing, nasal congestion), as assessed by reduction in total nasal symptom scores.1,3,7 In another randomized, double-blind, placebo-controlled study in children 6-11 years of age, ciclesonide was found not to be more effective than placebo in reducing nasal symptoms of perennial allergic rhinitis.1

In adults and children 12 years of age and older, onset of response occurs within 24-48 hours following initiation of intranasal ciclesonide,1,2,4,5 with further symptomatic improvement in 1-2 weeks in patients with seasonal allergic rhinitis or 5 weeks in patients with perennial allergic rhinitis.1,2

Administration

Ciclesonide is administered by nasal inhalation as a hypotonic aqueous suspension using a metered-dose spray pump.1,2,3,9

Prior to initial use of the inhaler, the bottle should be shaken gently, and the pump should be primed by pressing downward on the shoulders of the applicator 8 times.1,2 After initial priming (8 sprays), the nasal spray delivers about 50 mcg of ciclesonide per metered spray and about 120 metered sprays.1,3 If the pump is unused for 4 consecutive days, the bottle should be shaken gently, and the pump should be reprimed by actuating once or until a fine spray appears.1,2

Prior to administration of the nasal suspension using the spray pump, patients should blow the nose as needed to clear their nasal passages.2 The bottle should be shaken gently.2 Patients should tilt the head slightly forward and insert the spray tip into one nostril, keeping the bottle upright.2 The drug suspension should be sprayed quickly and firmly into one nostril (away from the nasal septum) while holding the other nostril closed and concurrently inspiring through the nose.2 This procedure should be repeated for the other nostril.2 The applicator should be wiped with a clean tissue after daily use.2

To unblock or thoroughly clean the applicator, patients should be advised to remove the dust cap and gently pull upward to free the applicator.2 The dust cap and applicator should be washed in warm water and then dried, and then the applicator should be replaced on the bottle.2 The pump should be reprimed by actuating once or until a fine spray appears; then the dust cap should be replaced.2

Dosage

For the symptomatic management of seasonal allergic rhinitis, the recommended dosage of intranasal ciclesonide in adults and children 6 years of age and older is 100 mcg (2 sprays) in each nostril once daily (total daily dosage of 200 mcg).1,2,3

For the symptomatic management of perennial allergic rhinitis, the recommended dosage of intranasal ciclesonide in adults and children 12 years of age and older is 100 mcg (2 sprays) in each nostril once daily (total daily dosage of 200 mcg).1,2,3

The maximum dosage should not exceed 200 mcg daily (2 sprays in each nostril once daily).1

Special Populations

No dosage adjustment is required in patients with hepatic impairment.1

Contraindications

Known hypersensitivity to ciclesonide or any ingredient of the formulation.1

Warnings/Precautions

Warnings

Withdrawal of Systemic Corticosteroid Therapy

Patients being switched from systemic corticosteroids to topical corticosteroids should be carefully monitored, since corticosteroid withdrawal symptoms (e.g., joint pain, muscular pain, lassitude, depression), acute adrenal insufficiency, or severe symptomatic exacerbation of asthma or other clinical conditions may occur.1 For additional information, see Discontinuance of Therapy under Dosage and Administration: Dosage, in the Corticosteroids General Statement 68:04.

Immunosuppressed Patients

Patients who are taking immunosuppressant drugs have increased susceptibility to infections compared with healthy individuals, and certain infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome in such patients.1 In patients who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure.1 It is not known how the dosage, route, and duration of administration of a corticosteroid or the contribution of the underlying disease and/or prior corticosteroid therapy affect the risk of developing a disseminated infection.1 If exposure to varicella (chickenpox) or measles occurs in such individuals, administration of varicella zoster immune globulin (VZIG) or pooled IM immune globulin (IG), respectively, may be initiated.1 If varicella (chickenpox) develops, treatment with an antiviral agent may be considered.1 For additional information, see Cautions: Increased Susceptibility to Infection and also see Precautions and Contraindications, in the Corticosteroids General Statement 68:04.

Sensitivity Reactions

Rarely, immediate hypersensitivity reactions or contact dermatitis may occur following intranasal administration of corticosteroids.1 Wheezing has been reported rarely with intranasal corticosteroids.1

Ciclesonide nasal spray should be used with caution in patients hypersensitive to other corticosteroids since cross-sensitivity may occur.1

General Precautions

Systemic Corticosteroid Effects

Intranasal corticosteroids such as ciclesonide may cause growth suppression in children and adolescents.1 (See Pediatric Use under Warnings/Precautions: Specific Populations, in Cautions.)

To minimize the systemic effects of intranasal corticosteroids, including ciclesonide, dosage should be titrated to the lowest possible effective level.1

Manifestations of hypercorticism, including very rare cases of menstrual irregularities, acneiform lesions, and cushingoid features, may occur in patients who are particularly sensitive or predisposed to corticosteroid effects because of recent systemic corticosteroid therapy or when recommended dosages of intranasal corticosteroids are exceeded.1 If such changes occur, intranasal ciclesonide should be discontinued gradually according to accepted procedures for discontinuing oral corticosteroid therapy.1

Nasopharyngeal Effects

Localized candidal infections of the nose and pharynx have occurred rarely during ciclesonide therapy.1 When infection occurs, appropriate local treatment of the infection may be necessary, and discontinuance of intranasal ciclesonide therapy may be required.1 Patients receiving the drug for several months or longer should be examined periodically for candidal infections or other signs of adverse effects on the nasal mucosa.1

Nasal septum perforation has been reported rarely in patients receiving intranasal corticosteroid therapy.1

Because corticosteroid therapy may inhibit wound healing, patients with recent nasal septum ulcers, nasal surgery, or nasal trauma should not use nasal corticosteroids until healing has occurred.1

Concomitant Infections

Intranasal corticosteroid therapy should be used with caution, if at all, in patients with clinical or asymptomatic Mycobacterium tuberculosis infections of the respiratory tract, untreated local or systemic fungal or bacterial infections, ocular herpes simplex, or systemic viral or parasitic infections.1

Ophthalmic Effects

No ophthalmologic abnormalities (i.e., elevation in intraocular pressure, cataracts) have been observed with intranasal ciclesonide therapy when slit-lamp examinations were conducted in studies of up to 12 months' duration.1 However, cataracts, glaucoma, and increased intraocular pressure have been reported rarely in patients receiving intranasal corticosteroids, and careful monitoring is recommended in patients who have a change in vision and in those with a history of glaucoma and/or cataracts.1

Specific Populations

Pregnancy

Category C.1 (See Users Guide.) Hypoadrenalism may occur in infants of mothers receiving corticosteroid therapy during pregnancy.1 These infants should be carefully monitored.1

Lactation

Ciclesonide is distributed into milk in rats.1 It is not known whether ciclesonide is distributed into human milk.1 Because other corticosteroids are distributed into human milk, caution is advised if ciclesonide is administered in nursing women.1

Pediatric Use

Safety of intranasal ciclesonide has not been established in children younger than 2 years of age.1

Efficacy of intranasal ciclesonide has not been established in children younger than 6 years of age for the treatment of seasonal allergic rhinitis or younger than 12 years of age for the treatment of perennial allergic rhinitis.1

Intranasal corticosteroids may cause growth suppression in children or adolescents, and clinicians should routinely monitor (e.g., via stadiometry) the growth of pediatric patients receiving these drugs.1 See Cautions: Pediatric Precautions, in the Corticosteroids General Statement 68:04.

Geriatric Use

Clinical studies of ciclesonide nasal spray did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients.1 Other reported clinical experience has not revealed age-related differences in response.1 In general, dosage should be selected cautiously in geriatric patients because of age-related decreases in hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy.1

Hepatic Impairment

Following oral inhalation, systemic exposure (i.e., peak plasma concentrations, area under the plasma concentration-time curve [AUC]) in patients with hepatic impairment increased 1.4- to 2.7-fold.1 However, the manufacturer states that dosage adjustment is not necessary in these patients.1

Common Adverse Effects

Adverse effects occurring in 1% or more of patients receiving ciclesonide nasal spray and more frequently than with placebo include headache,1,3 epistaxis,1,3,8 nasopharyngitis,1,3,8 nasal discomfort,1 pharyngolaryngeal pain,1,8 and ear pain.1,3

Based on results of in vitro studies, des-ciclesonide does not appear to inhibit or induce the metabolism of other drugs metabolized by cytochrome P-450 (CYP) isoenzymes.1,3 The inhibitory potential of ciclesonide on CYP isoenzymes has not been studied.1

Drugs Affecting Hepatic Microsomal Enzymes

Concomitant use of orally inhaled ciclesonide with oral ketoconazole (a potent inhibitor of the CYP3A4 isoenzyme) resulted in a more than threefold increase in the area under the plasma concentration-time curve (AUC) of des-ciclesonide, while ciclesonide concentrations remained unchanged.1,3 Therefore, caution is advised when intranasal ciclesonide is used concomitantly with ketoconazole.1

Concomitant use of orally inhaled ciclesonide with oral erythromycin (an inhibitor of the CYP3A4 isoenzyme) had no effect on the pharmacokinetics of des-ciclesonide or erythromycin.1,3

Protein-bound Drugs

Results of in vitro studies indicate that warfarin and salicylic acid do not alter plasma protein binding of des-ciclesonide.1,3 Therefore, pharmacokinetic interactions with protein-bound drugs appear unlikely.1

Description

Ciclesonide is a synthetic, nonhalogenated corticosteroid.1,3,4,7,9 Ciclesonide is a prodrug that is hydrolyzed by esterases in the nasal mucosa to its major active metabolite C21-desisobutyryl-ciclesonide (des-ciclesonide).1,3,4,5,6,7,8 Des-ciclesonide exhibits anti-inflammatory activity, with affinity for glucocorticoid receptors that is 120 times that of the parent compound.1,3

The exact mechanism(s) of action of ciclesonide in allergic rhinitis remains unknown.1,3 However, corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) involved in allergic inflammation.1,3 In adults and children 12 years of age and older receiving intranasal ciclesonide, reductions in nasal symptoms occurred within 24-48 hours following initiation of therapy and persisted throughout the 24-hour dosing interval.1,2,3,6,7

Ciclesonide may alter adrenal function in pediatric patients.1 In several studies, decreases in 24-hour urinary free cortisol concentrations and/or mean morning plasma cortisol concentrations were numerically larger in children 2-11 years of age receiving intranasal ciclesonide (25, 100, or 200 mcg daily) compared with those receiving placebo.1 Effects of ciclesonide nasal spray on adrenal function in adults and adolescents have not been established.1

Following intranasal administration at recommended dosages (200 mcg daily), only negligible concentrations (less than 1%) of ciclesonide and des-ciclesonide were detected in adults;1,3,6,7 however, des-ciclesonide was detected in 50% of children 6-11 years of age receiving recommended intranasal dosages of the drug.1 Ciclesonide and des-ciclesonide are extensively (at least 99%) bound to plasma proteins (mainly albumin and α₁-acid glycoprotein);1,3 des-ciclesonide is not appreciably bound to human transcortin.1 Des-ciclesonide, the major active metabolite of ciclesonide, is metabolized by the cytochrome P-450 (CYP) microsomal enzyme system, principally by the isoenzyme 3A4 (CYP3A4) and, to a lesser extent, by CYP2D6.1,3 Other potentially active metabolites of ciclesonide have not been fully characterized.1,3 Following IV or oral administration of ciclesonide, the terminal elimination half-life of des-ciclesonide is 2.7 or 5.9 hours, respectively.9 Following IV administration of 800 mcg of ciclesonide, approximately 66% of radiolabeled ciclesonide was detected in feces and 20% or less detected in urine.1

Advice to Patients

Patients should be carefully instructed in the use of the nasal spray pump.1,2 To obtain optimum results, patients should read and follow the accompanying patient instructions (provided by the manufacturer) carefully.1,2

Importance of adherence to the prescribed directions for use at regular intervals and not exceeding prescribed dosage.1,2

Advise that the drug usually will provide symptomatic relief within 24-48 hours, with further symptomatic improvement in 1-2 weeks for seasonal allergic rhinitis or 5 weeks for perennial allergic rhinitis.1

Importance of contacting a clinician if symptoms worsen or fail to improve within a reasonable time (i.e., 2 weeks for seasonal allergic rhinitis, 5 weeks for perennial allergic rhinitis).1,2,9

Importance of shaking containers of ciclesonide nasal spray gently prior to each use.1 Importance of discarding the container after 120 actuations following initial priming or after 4 months following removal from the foil pouch, whichever occurs first.1

Avoid spraying drug into eyes or directly on the nasal septum.1,2

Importance of reporting recurrent epistaxis or nasal septum discomfort to clinicians.9

Importance of avoiding exposure to chickenpox or measles in patients receiving immunosuppressive doses of corticosteroids and, if exposure occurs, consulting a clinician.1

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

Importance of advising patients of other important precautionary information.1 (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

1. Sepracor Inc. Omnaris^® (ciclesonide) nasal spray prescribing information. Marlborough, MA; 2007 Nov.

2. Sepracor Inc. Omnaris^® (ciclesonide) nasal spray patient's instructions for use. Marlborough, MA; 2007 Nov.

3. Dhillon S, Wagstaff AJ. Ciclesonide nasal spray: in allergic rhinitis. Drugs . 2008; 68:875-83. [PubMed 18416590]

4. Ratner PH, Wingertzahn MA, van Bavel JH et al. Effectiveness of ciclesonide nasal spray in the treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol . 2006; 97:657-63. [PubMed 17165276]

5. Ratner PH, Wingertzahn MA, van Bavel JH et al. Efficacy and safety of ciclesonide nasal spray for the treatment of seasonal allergic rhinitis. J Allergy Clin Immunol . 2006; 118:1142-8. [PubMed 17088141]

6. Patel P, Patel D, Kunjibettu S et al. Onset of action of ciclesonide once daily in the treatment of seasonal allergic rhinitis. Ear Nose Throat J . 2008; 87:340-53. [PubMed 18561117]

7. Meltzer EO, Kunjibettu S, Hall N et al. Efficacy and safety of ciclesonide, 200 microg once daily, for the treatment of perennial allergic rhinitis. Ann Allergy Asthma Immunol . 2007; 98:175-81. [PubMed 17304887]

8. Chervinsky P, Kunjibettu S, Miller DL et al. Long-term safety and efficacy of intranasal ciclesonide in adult and adolescent patients with perennial allergic rhinitis. Ann Allergy Asthma Immunol . 2007; 99:69-76. [PubMed 17650833]

9. Sepracor Inc, Marlborough, MA: Personal communication.