ASMANEX TWISTHALER Inhalation powder Ref.[7527] Active ingredients: Mometasone

Oral candidiasis

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

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 and may vary in individual patients and between different corticosteroid preparations. Possible systemic effects may include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataracts, glaucoma, and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). Therefore, it is important that the dose of inhaled corticosteroid is titrated to the lowest dose at which effective control of asthma is maintained.

Visual disturbance may be reported with systemic and topical (including, intranasal, inhaled and intraocular) corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes of visual disturbances which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

Transferring from systemic corticosteroid therapy

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.

Effects on HPA axis function

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.

Bronchospasm

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.

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.

Immunosuppression

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.

Effects on growth

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.

Effects on adrenal suppression

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.

Dosing considerations

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.

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

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, cobicistat) 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.

Interaction studies have only been performed in adults.

Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects of corticosteroids. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.

Pregnancy

There are no or limited amount of data from the use of mometasone furoate in pregnant women. Studies in animals with mometasone furoate, like other glucocorticoids, have shown reproductive toxicity (see section 5.3).

As with other inhaled corticosteroid preparations, mometasone furoate is not to be used during pregnancy unless the potential benefit to the mother justifies the potential risk to the mother, fetus or infant. Infants born of mothers who received corticosteroids during pregnancy are to be observed carefully for hypoadrenalism.

Breast-feeding

It is unknown whether mometasone furoate/metabolites are excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of mometasone furoate in milk (see section 5.3). A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from mometasone furoate therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility

In reproductive studies in rats, there was no effect on fertility (see section 5.3).

Asmanex Twisthaler 200 micrograms Inhalation Powder has no or negligible influence on the ability to drive and use machines.

Summary of safety profile

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 below.

Tabulated list of adverse reactions

The adverse reactions reported during clinical trials and the post-marketing period are listed in the following table by treatment regimen, severity, System Organ Class and Preferred Term. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

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 (see 4.4 Special warnings and precautions for use). 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.

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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

Not applicable.