ALVESCO 80 Pressurised inhalation, solution Ref.[6668] Active ingredients: Ciclesonide

As with all inhaled corticosteroids, Alvesco 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.

As with all inhaled corticosteroids, Alvesco is not indicated in the treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required.

As with all inhaled corticosteroids, Alvesco is not designed to relieve acute asthma symptoms for which an inhaled short-acting bronchodilator is required. Patients should be advised to have such rescue medication available.

Systemic effects of inhaled corticosteroids may occur, particularly at high doses prescribed for prolonged periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma, and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). It is therefore important that the dose of inhaled corticosteroid is titrated to the lowest dose at which effective control of asthma is maintained.

It is recommended that the height of children and adolescents receiving prolonged treatment with inhaled corticosteroids is regularly monitored. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of inhaled corticosteroid, if possible to the lowest dose at which effective control of asthma is maintained. In addition, consideration should be given to referring the patient to a paediatric respiratory specialist.

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.

The benefits of inhaled ciclesonide should minimise the need for oral steroids. However, patients transferred from oral steroids remain at risk of impaired adrenal reserve for a considerable time after transferring to inhaled ciclesonide. The possibility of respective symptoms may persist for some time.

These patients may require specialised advice to determine the extent of adrenal impairment before elective procedures. The possibility of residual impaired adrenal response should always be considered in an emergency (medical or surgical) and elective situations likely to produce stress, and appropriate corticosteroid treatment considered.

For the transfer of patients being treated with oral corticosteroids:

The transfer of oral steroid-dependent patients to inhaled ciclesonide, and their subsequent management, needs special care as recovery from impaired adrenocortical function, caused by prolonged systemic steroid therapy, may take a considerable time.

Patients who have been treated with systemic steroids for long periods of time, or at a high dose, may have adrenocortical suppression. With these patients adrenocortical function should be monitored regularly and their dose of systemic steroid reduced cautiously.

After approximately a week, gradual withdrawal of the systemic steroid is started by reducing the dose by 1 mg prednisolone per week, or its equivalent. For maintenance doses of prednisolone in excess of 10 mg daily, it may be appropriate to cautiously use larger reductions in dose at weekly intervals.

Some patients feel unwell in a non-specific way during the withdrawal phase despite maintenance or even improvement of respiratory function. They should be encouraged to persevere with inhaled ciclesonide and to continue withdrawal of systemic steroid, unless there are objective signs of adrenal insufficiency.

Patients transferred from oral steroids whose adrenocortical function is still impaired should carry a steroid warning card indicating that they need supplementary systemic steroid during periods of stress, e.g. worsening asthma attacks, chest infections, major intercurrent illness, surgery, trauma, etc.

Replacement of systemic steroid treatment with inhaled therapy sometimes unmasks allergies such as allergic rhinitis or eczema previously controlled by systemic drug.

Paradoxical bronchospasm with an immediate increase of wheezing or other symptoms of bronchoconstriction after dosing should be treated with an inhaled short-acting bronchodilator, which usually results in quick relief. The patient should be assessed and therapy with Alvesco should only be continued, if after careful consideration the expected benefit is greater than the possible risk. Correlation between severity of asthma and general susceptibility for acute bronchial reactions should be kept in mind (see section 4.8).

Patients inhaler technique should be checked regularly to make sure that inhaler actuation is synchronised with inhaling to ensure optimum delivery to the lungs.

Concomitant treatment with ketoconazole or other potent CYP3A4 inhibitors should be avoided unless the benefit outweighs the increased risk of systemic side effects of corticosteroids (see section 4.5).

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 CYP 3A4 (e.g. ketoconazole, itraconazole and ritonavir or nelfinavir) should be avoided unless the benefit outweighs the increased risk of systemic side effects of corticosteroids.

Fertility and Pregnancy

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

In animal studies glucocorticoids have been shown to induce malformations (see section 5.3). 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.

Breast-feeding

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 Alvesco 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 Alvesco.

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 Alvesco 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 (see also section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

Not applicable.