Abstract

Inhaled steroids are widely used in high doses and for prolonged periods in the prevention and control of asthma in children. The adverse effects and multiple doses make it difficult to maintain good compliance in children due to their daily school and other activities. It would make life a little less cumbersome and rosier if we could give them an option of single dosing MDI. Here we review the drug ciclesonide as an effective and safe, once daily therapy for asthma control.

Introduction

of the airways clinically diagnosed based on symptoms and objective evidence of variable airflow obstruction. Bronchial hyperreactivity in asthma is a consequence of the activity of a wide range of mediators and inflammatory cells that can cause remodeling of the airways through fibrosis and smooth muscle proliferation.

Inhaled corticosteroids have a central role in the treatment of asthma as preventers.1,2 They have been shown to improve lung function and reduce symptoms, exacerbations, hospital readmissions and mortality caused by asthma.2-4 Long term, high doses of inhaled steroids may be associated with reduced bone mineral density, cataracts, glaucoma, hypothalamo-pituitary-adrenal-axis suppression and a decrease in growth velocity in children. Thus alternative drugs which act only locally and have minimal systemic adverse effects are needed.

Ciclesonide is a novel, single dose, nonhalogenated inhaled corticosteroid which is a prodrug. The aim of this article is to review the efficacy, dosage interval and side effects of ciclesonide as compared to other standard inhaled corticosteroids in children.

Mechanism of action

Inhaled ciclesonide is the parent compound that is converted to the active metabolite desisobutyryl-ciclesonide (des-CIC).5 It acts by reducing airway responsiveness to AMP which further reduces the release of spasminogenic mediators from mast cells. It also attenuates both early and late phase allergen induced bronchoconstriction.6 In a study conducted by Hansen et al it was found that treatment with 320 mg/day of ciclesonide caused a significant decrease in the FEV1 from baseline and a higher number of symptom free days as compared to budesonide.5

On inhalation CIC is converted to des-CIC. This is highly protein bound in the plasma with a free fraction of less than 1% and does not accumulate in the red blood cells.7,8 After exiting from the lungs des-CIC undergoes rapid hepatic metabolism by cytochrome P450 enzymes (CYP3A4) to inactive metabolites and is eliminated in the stool. Elimination half-life of ciclesonide is 0.71 hrs and des-CIC 3.5 hrs.7

The anti-inflammatory actions of ciclesonide are similar to commonly used budesonide and fluticasone. In two studies of airway responsiveness, inhaled ciclesoide of 320-1280 mg/day was as effective at reducing airway responsiveness as fluticasone proprionate 1000-2000 mg/day and budesonide 400 mg/day.5,9

In the therapeutic doses used ciclesonide has no action on the hypothalamo-pituitary-adrenal axis. Short term studies using inhaled ciclesonide of 200-1600 mg/day also showed no significant decrease from baseline in serum levels or urinary excretion of cortisol.10,11

Dosage

Ciclesonide is administered once daily as MDI in doses of 80-640 mg depending on the clinical severity and response.

Side-effects

Ciclesonide is generally well tolerated than budesonide according to various clinical trials.5

Local side effects like oral candidiasis occur in only about 4% of patients.12 Other adverse effects include paradoxical bronchospasm, altered taste in mouth, dry mouth, voice alteration, inflammation and irritation in throat.

Systemic side effects are much less as compared to other inhaled corticosteroids as it has been studied that it does not suppress endogenous cortisol release,10,11 though more studies are required to demonstrate the effect of long term therapy.

Inference

Ciclesonide is a cheap, single dose alternative with minimal side effects which is safely used in adults, though its safety in children has to be studied with large scale studies.

Acknowledgement

We thank our Dean Dr. SN Oak and Head of Department of Paediatrics, BYL Nair Hospital for permitting us to publish this article.

References

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