Ciclesonide

Products

Ciclesonide is administered with a metered-dose inhaler (Alvesco). It has been approved in many countries since 2006. In the United States, it has also been commercially available as a nasal spray for the treatment of allergic rhinitis since 2012 (Zetonna).

Structure and properties

Ciclesonide (C₃₂H₄₄O₇, M_r = 540.7 g/mol) is a prodrug and is hydrolyzed by intracellular esterases in the lung to the active metabolite C21-desisobutyrylciclesonide (= desciclesonide). This provides some selectivity for the lower respiratory tract. Ciclesonide is a non-halogenated glucocorticoid that is structurally closely related to budesonide and exists as an -enantiomer. It is a white to yellowish-white crystalline powder that is practically insoluble in water.

Effects

Ciclesonide (ATC R03BA08) has anti-inflammatory, antiasthmatic, antiallergic, and immunosuppressive properties. The effects are due to binding of the metabolite desciclesonide to the glucocorticoid receptor. The maximum effect is delayed and occurs after about four weeks. Several properties of the compound mediate a selective effect in the lung and are thought to reduce systemic adverse effects:

• Administration of the drug as an inactive prodrug and enantiomer (“on site” activation).
• Low oral bioavailability (< 1%), high first-pass metabolism and rapid elimination.
• High deposition in the lungs
• High protein binding

Indications

• For the long-term treatment of bronchial asthma
• Allergic rhinitis (nasal spray, not yet in many countries).

Dosage

According to the drug label. The drug is intended for regular use and inhaled 1-2 times a day. It is not suitable for the therapy of an acute asthma attack. To reduce the risk of developing oral thrush, use before eating or rinse the mouth after inhalation.

Contraindications

• Hypersensitivity

For complete precautions, see the drug label.

Interactions

Ciclesonide is further metabolized after hydrolysis by CYP3A4 and to a lesser extent by CYP2D6. Because of the low plasma concentrations, relevant pharmacokinetic drug-drug interactions are not expected. Co-administration of potent CYP inhibitors may result in an increase in ciclesonide or its metabolites.

Adverse effects

The most common possible adverse effects that occasionally occur include oral thrush, headache, hoarseness, cough after inhalation, paradoxical bronchospasm, nausea, vomiting, bad taste, rash, and dry mouth. As with other inhaled glucocorticoids, there is a risk for systemic side effects. Oral thrush appears to occur somewhat less frequently compared with other inhaled glucocorticoidem.