Corticosteroid

Ciclesonide

1 actuation (delivered dose from the mouthpiece) contains 160 micrograms of ciclesonide

Pressurised inhalation, solution Clear and colourless

Treatment to control persistent asthma in adults (18 years and older).

The medicinal product is for inhalation use only.

Dosing recommendation for adults and adolescents:

The recommended dose of Alvesco^® is 160 micrograms once daily, which leads to asthma control in the majority of patients. However in severe asthmatics, a 12 week study has shown that a dose of 640 micrograms/day (given 320 micrograms twice daily) has demonstrated a reduction in the frequency of exacerbations but without an improvement in lung function. Dose reduction to 80 micrograms once daily may be an effective maintenance dose for some patients.

Alvesco^® should preferably be administered in the evening although morning dosing of Alvesco^® has also been shown to be effective. The final decision on evening or morning dosing should be left to the discretion of the physician.

Symptoms start to improve with Alvesco^® within 24 hours of treatment. Once control is achieved, the dose of Alvesco^® should be individualised and titrated to the minimum dose needed to maintain good asthma control.

Patients with severe asthma are at risk of acute attacks and should have regular assessments of their asthma control including pulmonary function tests. Increasing use of short-acting bronchodilators to relieve asthma symptoms indicates deterioration of asthma control. If patients find that short-acting relief bronchodilator treatment becomes less effective, or they need more inhalations than usual, medical attention must be sought. In this situation, patients should be reassessed and consideration given to the need for increased anti-inflammatory treatment therapy (e.g. a higher dose of Alvesco for a short period or a course of oral corticosteroids). Severe asthma exacerbations should be managed the usual way.

To address specific patient needs, such as finding it difficult to press the inhaler and breathe in at the same time, Alvesco^® can be used with the AeroChamber Plus^TM spacer device.

Specific patient groups:

There is no need to adjust the dose in elderly patients or those with hepatic or renal impairment.

To date, there are insufficient data available in the treatment of children under 12 years of age with ciclesonide.

Instructions for use / handling:

The patient needs to be instructed how to use the inhaler correctly.

If the inhaler is new or has not been used for one week or more, three puffs should be released into the air. No shaking is necessary as this is a solution aerosol.

During inhalation, the patient should preferably sit or stand, and the inhaler should be held upright with the thumb on the base, below the mouthpiece.

Instruct the patient to remove the mouthpiece cover, place the inhaler into their mouth, close their lips around the mouthpiece, and breathe in slowly and deeply. While breathing in through the mouth, the top of the inhaler should be pressed down. Then, patients should remove the inhaler from their mouth, and hold their breath for about 10 seconds, or as long as is comfortable. The patient is not to breathe out into the inhaler. Finally, patients should breathe out slowly and replace the mouthpiece cover.

The mouthpiece should be cleaned with a dry tissue or cloth weekly. The inhaler should not be washed or put in water.

For detailed instructions see Patient Information Leaflet.

To date, there are insufficient data available in the treatment of adolescents and children 17 years and younger with Alvesco.

There is no need to adjust the dose in elderly patients or those with hepatic or renal impairment.

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 M 1 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.

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.

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

In vitro data indicate that CYP3A4 is the major enzyme involved in the metabolism of the active metabolite of ciclesonide M1 in man. The serum levels of ciclesonide and its metabolite M1 are low. However, co-administration with a potent inhibitor of the cytochrome P 450 3A4 system (e.g. ketoconazole, itraconazole and ritonavir or nelfinavir) should be considered with caution because there might be an increase in ciclesonide / metabolite serum levels. The risk of clinical adverse effect (e.g. cushingoid syndrome) cannot be excluded.

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.

* 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

Nycomed GmbH

(POM)

23 November 2011