Regular treatment to control persistent asthma

Inhalation powder. White to off-white powder agglomerates

Regular treatment to control persistent asthma

This product is for inhalation use only.

For use in adult and adolescent patients 12 years of age and older.

Dosage recommendations are based on severity of asthma (see criteria below).

Patients with persistent mild to moderate asthma: The recommended starting dose for most of these patients is 400 micrograms once daily. Data suggest that better asthma control is achieved if once daily dosing is administered in the evening. Some patients may be more adequately controlled on 400 micrograms daily, given in two divided doses (200 micrograms twice daily).

The dose of Asmanex Twisthaler 200 micrograms Inhalation Powder should be individualised and titrated to the lowest dose at which effective control of asthma is maintained. Dose reduction to 200 micrograms once daily given in the evening may be an effective maintenance dose for some patients.

Patients with severe asthma: The recommended starting dose is 400 micrograms twice daily, which is the maximum recommended dose. When symptoms are controlled, titrate Asmanex Twisthaler 200 micrograms Inhalation Powder to the lowest effective dose.

In patients with severe asthma and previously receiving oral corticosteroids, Asmanex Twisthaler 200 micrograms Inhalation Powder will be initiated concurrently with the patient's usual maintenance dose of systemic corticosteroid. After approximately one week, gradual withdrawal of the systemic corticosteroid can be initiated by reducing the daily or alternate daily dose. The next reduction is made after an interval of one to two weeks, depending on the response of the patient. Generally, these decrements are not to exceed 2.5 mg of prednisone daily, or its equivalent.

A slow rate of withdrawal is strongly recommended. During withdrawal of oral corticosteroids, patients must be carefully monitored for signs of unstable asthma, including objective measures of airway function, and for adrenal insufficiency (see 4.4).

The patient should be instructed that Asmanex Twisthaler 200 micrograms Inhalation Powder is not intended to be used "on demand" as a reliever medication to treat acute symptoms and that this product must be taken regularly to maintain therapeutic benefit even when he or she is asymptomatic.

Criteria:

Mild asthma: symptoms > 1 time a week but < 1 time per day; exacerbations may affect activity and sleep; night-time asthma symptoms > 2 times a month; PEF or FEV₁ > 80 % predicted, variability 20 – 30 %

Moderate asthma: symptoms daily; exacerbations affect activity and sleep; night-time asthma symptoms > 1 time a week; daily use of short-acting beta₂ –agonist; PEF or FEV₁ > 60-< 80 % predicted, variability > 30 %

Severe asthma: continuous symptoms; frequent exacerbations; frequent night-time asthma symptoms; physical activities limited by asthma symptoms; PEF or FEV₁ 60% predicted, variability > 30%

Special populations

Children less than 12 years of age: Clinical data are not available to recommend use in this age group.

Elderly patients older than 65 years of age: No dosage adjustment is necessary.

The patient needs to be instructed how to use the inhaler correctly (see below).

Method of administration

Patients should be in an upright position when inhaling the product.

Prior to removing the cap, be sure the counter and the pointer on the cap are aligned. The inhaler can be opened by removing the white cap while holding unit upright (the pink-coloured base down), gripping the base, and twisting the cap counterclockwise. The counter will register the number down by one count. Instruct the patient to place the inhaler in the mouth, closing the lips around the mouthpiece, and to breathe in rapidly and deeply. Then, the inhaler is removed from the mouth, and the breath held for about 10 seconds, or as long as is comfortable. The patient is not to breathe out through the inhaler. To close, while holding the unit in an upright position, replace the cap immediately after each inhalation, loading for the next dose by rotating the cap clockwise while gently pressing down until a click sound is heard and the cap is fully closed. The arrow on the cap will be fully aligned with the counter window. After inhalation, patients are advised to rinse the mouth and spit out the water. This helps to reduce the risk of candidiasis.

The digital display will indicate when the last dose has been delivered; after dose 01, the counter will read 00 and the cap will lock, at which time the unit must be discarded. The inhaler is to be kept clean and dry at all times. The outside of the mouthpiece can be cleaned with a dry cloth or tissue; do not wash the inhaler; avoid contact with water.

For detailed instructions see Patient Leaflet.

Hypersensitivity (allergy) to the active substance or to the excipient (see 6.1 List of excipients).

During clinical trials, oral candidiasis, which is associated with the use of this class of medicinal product, occurred in some patients. This infection may require treatment with appropriate antifungal therapy and in some patients discontinuance of Asmanex Twisthaler 200 micrograms Inhalation Powder may be necessary (see 4.8).

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, cataracts and glaucoma. Therefore, it is important that the dose of inhaled corticosteroid is titrated to the lowest dose at which effective control of asthma is maintained.

Particular care is needed for patients who are transferred from systemically active corticosteroids to inhaled mometasone furoate, because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) axis function.

During dose reduction some patients may experience symptoms of systemic corticosteroid withdrawal, e.g. joint and/or muscular pain, lassitude and depression, despite maintenance or even improvement in pulmonary function. Such patients are to be encouraged to continue with both Asmanex Twisthaler 200 micrograms Inhalation Powder treatment and withdrawal of the systemic corticosteroids, unless objective signs of adrenal insufficiency are present. If evidence of adrenal insufficiency occurs, increase the systemic corticosteroid doses temporarily and thereafter continue withdrawal more slowly.

During periods of stress, including trauma, surgery, or infection, or a severe asthma attack, patients transferred from systemic corticosteroids will require supplementary treatment with a short course of systemic corticosteroids, which is gradually tapered as symptoms subside.

It is recommended that such patients carry a supply of oral corticosteroids and a warning card indicating their need and recommended dosage of systemic corticosteroids during stressful periods. Periodic testing of adrenocortical function, particularly measurement of early morning plasma cortisol levels, is recommended.

Transfer of patients from systemic corticosteroid therapy to Asmanex Twisthaler 200 micrograms Inhalation Powder may unmask pre-existing allergic conditions previously suppressed by systemic corticosteroid therapy. If this occurs, symptomatic treatment is recommended.

Mometasone furoate is not to be regarded as a bronchodilator and is not indicated for rapid relief of bronchospasm or asthma attacks; thus, patients should be instructed to keep an appropriate short-acting bronchodilator inhaler on hand for use when needed.

Instruct patients to contact their physician immediately when asthmatic episodes are not responsive to bronchodilators during treatment with this product or if peak-flow falls. This may indicate worsening asthma. During such episodes, patients may require systemic corticosteroid therapy. In these patients, dose titration to the maximum recommended maintenance dose of inhaled mometasone furoate may be considered.

Use of Asmanex Twisthaler 200 micrograms Inhalation Powder will often permit control of asthma symptoms with less suppression of HPA axis function than therapeutically equivalent oral doses of prednisone. Although mometasone furoate has demonstrated low systemic bioavailability at the recommended dosage, it is absorbed into the circulation and can be systemically active at higher doses. Thus, to maintain its profile of limited potential for HPA axis suppression, recommended doses of this product must not be exceeded, and must be titrated to the lowest effective dose for each individual patient.

As with other inhaled asthma medications, bronchospasm may occur with an immediate increase in wheezing after dosing. If bronchospasm occurs following dosing with the Asmanex Twisthaler 200 micrograms Inhalation Powder, immediate treatment with a fast-acting inhaled bronchodilator is recommended; thus, the patient should be told to keep an appropriate bronchodilator inhaler on hand at all times. In such cases, treatment with Asmanex Twisthaler 200 micrograms Inhalation Powder is then discontinued immediately and alternative therapy instituted.

There is no evidence that the administration of this product in amounts greater than recommended doses increases efficacy.

Use Asmanex Twisthaler 200 micrograms Inhalation Powder with caution, if at all, in patients with untreated active or quiescent tuberculous infections of the respiratory tract, or in untreated fungal, bacterial, systemic viral infections or ocular herpes simplex.

Advise patients who are receiving corticosteroids or other immunosuppressant medicines of the risk of exposure to certain infections (e.g., chickenpox, measles) and of the importance of obtaining medical advice if such exposure occurs. This is of particular importance in children.

A reduction of growth velocity in children or adolescents may occur as a result of inadequate control of chronic diseases such as asthma or from use of corticosteroids for treatment. Physicians are advised to closely follow the growth of adolescents taking corticosteroids by any route and weigh the benefits of corticosteroid therapy and asthma control against the possibility of growth suppression if an adolescent's growth appears slowed.

If growth is slowed, review therapy with the aim of reducing the dose of inhaled corticosteroids if possible, to the lowest dose at which effective control of symptoms is achieved. In addition, consideration should be given to referring the patient to a paediatric respiratory specialist.

When using inhaled corticosteroids, the possibility for clinically significant adrenal suppression may occur, especially after prolonged treatment with high doses and particularly with higher than recommended doses. This is to be considered during periods of stress or elective surgery, when additional systemic corticosteroids may be needed. However, during clinical trials there was no evidence of HPA axis suppression after prolonged treatment with inhaled mometasone furoate at doses of 800 micrograms per day.

Lack of response or severe exacerbations of asthma should be treated by increasing the maintenance dose of inhaled mometasone furoate, and if necessary, by giving a systemic corticosteroid and/or an antibiotic if infection is suspected, and by use of beta-agonist therapy.

The patient should be advised against abrupt discontinuation of therapy with Asmanex Twisthaler 200 micrograms Inhalation Powder.

Patients with lactose intolerance: The maximum recommended daily dose contains lactose 4.64 mg per day. This amount does not normally cause problems in lactose intolerant people.

Due to the very low plasma concentration achieved after inhaled dosing, clinically significant drug interactions are unlikely. However, there may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors (eg ketoconazole, itraconazole, nelfinavir, ritonavir) are co-administered. Co-administration of inhaled mometasone furoate with the potent CYP3A4 enzyme inhibitor ketoconazole causes small but marginally significant (p= 0.09) decreases in serum cortisol AUC _(0-24) and resulted in approximately a 2-fold increase in plasma concentration of mometasone furoate.

In placebo-controlled clinical trials, oral candidiasis was very common (> 10%) in the 400 micrograms twice daily treatment group; other common (1-10%), treatment-related undesirable effects were pharyngitis, headache and dysphonia. Treatment related undesirable effects seen in clinical trials and post-marketing reporting with Asmanex Twisthaler Inhalation Powder use are listed in Table 1.

In patients dependent on oral corticosteroids, who were treated with Asmanex Twisthaler 400 micrograms twice daily for 12 weeks, oral candidiasis occurred in 20 %, and dysphonia in 7 %. These effects were considered treatment-related.

Uncommonly reported adverse events were dry mouth and throat, dyspepsia, weight increase and palpitations.

As with other inhalation therapy, bronchospasm may occur. This should be treated immediately with a fast-acting inhaled bronchodilator. Asmanex should be discontinued immediately, the patient assessed, and if necessary alternative therapy instituted.

Systemic effects of inhaled corticosteroids may occur, particularly when prescribed at high doses for prolonged periods. These may include adrenal suppression, growth retardation in children and adolescents, and decrease in bone mineral density.

As with other inhaled corticosteroids, rare cases of glaucoma, increased intraocular pressure and/or cataracts have been reported.

As with other glucocorticoid products, the potential for hypersensitivity reactions including rashes, urticaria, pruritus and erythema and oedema of the eyes, face, lips and throat should be considered.In placebo-controlled clinical trials, oral candidiasis was very common (> 10%) in the 400 micrograms twice daily treatment group; other common (1-10%), treatment-related undesirable effects were pharyngitis, headache and dysphonia. Treatment related undesirable effects seen in clinical trials and post-marketing reporting with Asmanex Twisthaler Inhalation Powder use are listed in Table 1.

In patients dependent on oral corticosteroids, who were treated with Asmanex Twisthaler 400 micrograms twice daily for 12 weeks, oral candidiasis occurred in 20 %, and dysphonia in 7 %. These effects were considered treatment-related.

Uncommonly reported adverse events were dry mouth and throat, dyspepsia, weight increase and palpitations.

As with other inhalation therapy, bronchospasm may occur. This should be treated immediately with a fast-acting inhaled bronchodilator. Asmanex should be discontinued immediately, the patient assessed, and if necessary alternative therapy instituted.

Systemic effects of inhaled corticosteroids may occur, particularly when prescribed at high doses for prolonged periods. These may include adrenal suppression, growth retardation in children and adolescents, and decrease in bone mineral density.

As with other inhaled corticosteroids, rare cases of glaucoma, increased intraocular pressure and/or cataracts have been reported.

As with other glucocorticoid products, the potential for hypersensitivity reactions including rashes, urticaria, pruritus and erythema and oedema of the eyes, face, lips and throat should be considered.

Merck Sharp & Dohme Limited

Merck Sharp & Dohme Limited

POM

23 November 2011