Ciclesonide

In vitro data indicate that CYP3A4 is the major enzyme involved in the metabolism of the active metabolite of ciclesonide M1 in man. In a drug-drug interaction study at steady state with ciclesonide and ketoconazole as a potent CYP3A4 inhibitor, the exposure to the active metabolite M1 increased approximately 3.5-fold, whereas the exposure to ciclesonide was not affected. Therefore the concomitant administration of potent inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole and ritonavir or nelfinavir) should be avoided unless the benefit outweighs the increased risk of systemic side effects of corticosteroids.

There is no data available in patients with severe hepatic impairment. An increased exposure in patients with severe hepatic impairment is expected and these patients should therefore be monitored for potential systemic effects.

As with all inhaled corticosteroids, ciclesonide should be administered with caution in patients with active or quiescent pulmonary tuberculosis, fungal, viral or bacterial infections, and only if these patients are adequately treated.

Fertility and Pregnancy

There are no adequate and well-controlled studies in pregnant women.

In animal studies glucocorticoids have been shown to induce malformations. This is not likely to be relevant for humans given recommended inhalation doses.

As with other glucocorticoids, ciclesonide should only be used during pregnancy if the potential benefit to the mother justifies the potential risk to the fetus. The lowest effective dose of ciclesonide needed to maintain adequate asthma control should be used.

Infants born of mothers who received corticosteroids during pregnancy are to be observed carefully for hypoadrenalism.

It is unknown whether inhaled ciclesonide is excreted in human breast milk. Administration of ciclesonide to women who are breast-feeding should only be considered if the expected benefit to the mother is greater than any possible risk to the child.

Inhaled ciclesonide has no or negligible influence on the ability to drive and use machines.

Approximately 5% of patients experienced adverse reactions in clinical trials with ciclesonide given in the dose range 40 to 1280 micrograms per day. In the majority of cases, these were mild and did not require discontinuation of treatment with ciclesonide. Uncommon (>1/1.000-<1/100), Rare (1/10.000–1/.1000), Unknown.

Cardiac disorders

Rare: Palpitations**

Gastrointestinal disorders

Uncommon: Nausea, Vomiting*, Bad taste

Rare: Abdominal pain*, Dyspepsia*

General disorders and administration site conditions

Uncommon: Application site reactions, Application site dryness

Immune system disorders

Rare: Angioedema, Hypersensitivity

Infections and infestations

Uncommon: Oral fungal infections*

Nervous system disorders

Uncommon: Headache*

Psychiatric disorders

Unknown: Psychomotor hyperactivity, sleep disorders, anxiety, depression, aggression, behavioural changes (predominantly in children)

Respiratory, thoracic and mediastinal disorders

Uncommon: Dysphonia, Cough after inhalation*, Paradoxical bronchospasm*

Skin and subcutaneous tissue disorders

Uncommon: Eczema and rash

Vascular disorders

Rare: Hypertension

* Similar or lower incidence when compared with placebo
** Palpitations were observed in clinical trials in cases mostly confounded with concomitant medication with known cardiac effects (e.g. theophylline or salbutamol).

Paradoxical bronchospasm may occur immediately after dosing and is an unspecific acute reaction to all inhaled medicinal products, which may be related to the active substance, the excipient, or evaporation cooling in the case of metered dose inhalers. In severe cases, withdrawal of ciclesonide should be considered.

Systemic effects of inhaled corticosteroids may occur, particularly at high doses prescribed for prolonged periods. Possible systemic effects include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract, glaucoma.