Ciclesonide-induced bronchospasm: an important but preventable side effect

Despite recent advances in its management, asthma remains a significant ongoing cause of morbidity1 and mortality2 in Australia. Ciclesonide, a newer inhaled corticosteroid, offers exciting potential to improve both asthma control and longer-term outcomes. This is because of its improved safety profile relative to other asthma medications, and the potential for improved adherence to treatment, given its proven efficacy as a once-daily medication.3 It is administered as a prodrug, activated within the lungs, and has lower oral bioavailability and extensive first-pass metabolism which reduces its systemic side effect profile.4 In Australia, ciclesonide is now available on the Pharmaceutical Benefits Scheme for use in children from the age of 6 years. Despite increasing use of this drug, side effects are infrequently reported.

We highlight an important potential side effect of ciclesonide treatment, which occurred in three adolescent patients with asthma, who recently attended our tertiary paediatric hospital-based clinic with persistent asthma (ranging in severity from mild to moderately severe based on recommended classifications5). Ciclesonide therapy had been commenced in each patient in an attempt to improve both asthma control as well as compliance. All three patients experienced ciclesonide-induced bronchospasm after using ciclesonide, which was confirmed on formal challenge testing (with ciclesonide at the same dose that was being administered for asthma) in a specialised respiratory function laboratory. The bronchospasm was reversed by use of an inhaled bronchodilator (Box), and then prevented during ongoing treatment by use of a bronchodilator before dosing with ciclesonide. Ciclesonide treatment was subsequently shown to improve overall asthma control to within acceptable limits in two of the three patients. In the third, failure to achieve this reflected the severity of the underlying persistent asthma as shown by this patient’s need for daily oral corticosteroid therapy to achieve symptom control. The adverse reactions to ciclesonide in these patients were reported to the manufacturers of ciclesonide (Takeda Pharmaceuticals Australia), and ciclesonide-induced bronchoconstriction is now listed as a recognised side effect in the product information for this drug.

Ciclesonide is an attractive preventer medication for persistent asthma in children aged 6 years and over for several reasons. However, health professionals should be aware of this important potential side effect, which we speculate is currently underrecognised, but easily identified with careful questioning about wheeze and/or chest tightness after ciclesonide dosing. If suspected, we recommend that patients be referred for formal ciclesonide airway challenge testing (at the same ciclesonide dose being administered for treatment) in a specialised respiratory function laboratory. If the patient’s bronchoconstriction can be reversed by administering a bronchodilator, a subsequent trial of pretreatment with a bronchodilator before ciclesonide dosing should be performed before finally evaluating the role of ciclesonide therapy on asthma control.

1  Ciclesonide-induced bronchospasm during ciclesonide-based airway challenge testing

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The green line indicates the reference data for a child of the same age, sex and height. Baseline and post-ciclesonide challenge flow-volume loops are shown by the purple and red lines, respectively. The fall in (forced expiratory volume in one second; FEV₁) from 106% to 86% predicted represented a 19% fall in FEV₁ with ciclesonide administration.