Systemic side effects

Since Alvesco^® targets the lung, it has a very low incidence of systemic side effects:¹

1. Protein-binding ensures that only a small proportion of Alvesco^® reaches the systemic circulation, and that most of the drug is unavailable to exert pharmacological effects.²
2. It undergoes high first-pass metabolism.³
3. It is rapidly cleared from the systemic circulation.⁴

High lung deposition and peripheral distribution can lead to an increased bioavailability of inhaled coricosteroid, potentially leading to a higher systemic exposure. Thanks to high protein-binding and rapid clearance however, the effects of Alvesco^® on cortisol suppression are comparable to that of placebo¹ (Figure 1).

Figure 1: The effect of Alvesco^® on serum cortisol levels is comparable to placebo¹
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References:

1. Derom E, Van De Velde V, Marissens S, et al. Effects of inhaled ciclesonide and fluticasone propionate on cortisol secretion and airway responsiveness to adenosine 5' monophosphate in asthmatic patients. Pulm Pharmacol Ther 2005;18:328-336
2. Nave R, Meyer W, Fuhst R, et al. Formation of fatty acid conjugates of ciclesonide active metabolite in the rat lung after 4 week inhalation of ciclesonide. Pulm Pharmacol Ther 2005; 18:390-396
3. Rohatagi S, Krishnaswami S, Pfister M, et al. Model-based covariate pharmacokinetic analysis and lack of cortisol suppression by the new inhaled corticosteroid ciclesonide using a novel cortisol release model. Am J Ther 2005;12:385-397
4. EU SmPC Alvesco^®, 2011.