MometaHEXAL

MometaHEXAL 200 micrograms Inhalation Powder is indicated in adults and adolescents 12 years of age and older for regular treatment to control persistent asthma.

MometaHEXAL Furoate 1mg/g Cream is indicated for the treatment of inflammatory and pruritic manifestations of psoriasis (excluding widespread plaque psoriasis) and atopic dermatitis.

This medicinal product is indicated in adults and children above 6 years of age.

MometaHEXAL Nasal Spray is indicated for use in adults and children 3 years of age and older to treat the symptoms of seasonal allergic or perennial rhinitis.

MometaHEXAL Nasal Spray is indicated for the treatment of nasal polyps in adults 18 years of age and older.

MometaHEXAL 1mg/g Cream is indicated for the treatment of inflammatory and pruritic manifestations of psoriasis (excluding widespread plaque psoriasis) and atopic dermatitis.

This medicinal product is indicated in adults and children above 6 years of age.

Posology

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 MometaHEXAL 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 MometaHEXAL 200 micrograms Inhalation Powder to the lowest effective dose.

In patients with severe asthma and previously receiving oral corticosteroids, MometaHEXAL 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 MometaHEXAL 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

Paediatric population

The safety and efficacy of MometaHEXAL 200 mcg in children less than 12 years of age have not been established. No data are available.

Elderly patients older than 65 years of age

No dosage adjustment is necessary.

Method of administration

This product is for inhalation use only.

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

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 Package Leaflet.

Posology

Adults, including elderly patients, adolescents and children aged 6 years and over: A thin film of MometaHEXAL Furoate 1mg/g Cream should be applied to the affected areas of skin once daily. One fingertip unit (a line from the tip of an adult index finger to the first crease) is enough to cover an area twice the size of an adult hand.

Use of a weaker corticosteroid is often advisable when there is a clinical improvement.

Paediatric population

MometaHEXAL Furoate 1mg/g Cream should not be used for long periods (over 3 weeks) or on large areas (over 20% of body surface area). In children a maximum of 10% of body surface area should be treated.

Use of topical corticosteroids in children aged 6 years and over, or on the face should be limited to the least amount compatible with an effective therapeutic regimen and duration of treatment should be no more than 5 days.

Children below 6 years: MometaHEXAL Furoate 1mg/g Cream is not recommended for use in children below 6 years of age due to insufficient data on safety.

After initial priming of the MometaHEXAL Nasal Spray pump, each actuation delivers approximately 100 mg of mometasone furoate suspension, containing mometasone furoate monohydrate equivalent to 50 micrograms mometasone furoate.

Posology

Seasonal Allergic or Perennial Rhinitis

Adults (including older patients) and children 12 years of age and older: The usual recommended dose is two actuations (50 micrograms/actuation) in each nostril once daily (total dose 200 micrograms). Once symptoms are controlled, dose reduction to one actuation in each nostril (total dose 100 micrograms) may be effective for maintenance. If symptoms are inadequately controlled, the dose may be increased to a maximum daily dose of four actuations in each nostril once daily (total dose 400 micrograms). Dose reduction is recommended following control of symptoms.

Children between the ages of 3 and 11 years: The usual recommended dose is one actuation (50 micrograms/actuation) in each nostril once daily (total dose 100 micrograms).

MometaHEXAL Nasal Spray demonstrated a clinically significant onset of action within 12 hours after the first dose in some patients with seasonal allergic rhinitis; however, full benefit of treatment may not be achieved in the first 48 hours. Therefore, the patient should continue regular use to achieve full therapeutic benefit.

Treatment with MometaHEXAL Nasal Spray may need to be initiated some days before the expected start of the pollen season in patients who have a history of moderate to severe symptoms of seasonal allergic rhinitis.

Nasal Polyposis

The usual recommended starting dose for polyposis is two actuations (50 micrograms/actuation) in each nostril once daily (total daily dose of 200 micrograms). If after 5 to 6 weeks symptoms are inadequately controlled, the dose may be increased to a daily dose of two sprays in each nostril twice daily (total daily dose of 400 micrograms). The dose should be titrated to the lowest dose at which effective control of symptoms is maintained. If no improvement in symptoms is seen after 5 to 6 weeks of twice daily administration, the patient should be re-evaluated and treatment strategy reconsidered.

Efficacy and Safety studies of MometaHEXAL Nasal Spray for the treatment of nasal polyposis were four months in duration.

Paediatric population

Seasonal Allergic Rhinitis and Perennial Rhinitis

The safety and efficacy of MometaHEXAL Nasal Spray in children under 3 years of age have not been established.

Nasal Polyposis

The safety and efficacy of MometaHEXAL Nasal Spray in children and adolescents under 18 years of age have not been established.

Method of administration

Prior to administration of the first dose, shake container well and actuate the pump 10 times (until a uniform spray is obtained). If the pump is not used for 14 days or longer, reprime the pump with 2 actuations until a uniform spray is observed, before next use.

Shake container well before each use. The bottle should be discarded after the labelled number of actuations or within 2 months of first use.

Posology

Adults, including elderly patients, adolescents and children aged 6 years and over: A thin film of MometaHEXAL 1mg/g Cream should be applied to the affected areas of skin once daily. One fingertip unit (a line from the tip of an adult index finger to the first crease) is enough to cover an area twice the size of an adult hand.

Use of a weaker corticosteroid is often advisable when there is a clinical improvement.

Paediatric population

MometaHEXAL 1mg/g Cream should not be used for long periods (over 3 weeks) or on large areas (over 20% of body surface area). In children a maximum of 10% of body surface area should be treated.

Use of topical corticosteroids in children aged 6 years and over, or on the face should be limited to the least amount compatible with an effective therapeutic regimen and duration of treatment should be no more than 5 days.

Children below 6 years: MometaHEXAL 1mg/g Cream is not recommended for use in children below 6 years of age due to insufficient data on safety.

MometaHEXAL Furoate 1mg/g Cream is contraindicated in facial rosacea, acne vulgaris, skin atrophy, perioral dermatitis, perianal and genital pruritis, napkin eruptions, bacterial (e.g. impetigo, pyodermas), viral (e.g. herpes simplex, herpes zoster, chickenpox, verrucae vulgares, condylomata acuminate and molluscum contagiosum), parasitical and fungal (e.g. candida or dermatophyte) infections, varicella, tuberculosis, syphilis or post-vaccine reactions. MometaHEXAL Furoate 1mg/g Cream should not be used on wounds or on skin which is ulcerated.

MometaHEXAL Nasal Spray should not be used in the presence of untreated localised infection involving the nasal mucosa, such as herpes simplex.

Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal surgery or trauma should not use a nasal corticosteroid until healing has occurred.

MometaHEXAL 1mg/g Cream is contraindicated in facial rosacea, acne vulgaris, skin atrophy, perioral dermatitis, perianal and genital pruritis, napkin eruptions, bacterial (e.g. impetigo, pyodermas), viral (e.g. herpes simplex, herpes zoster, chickenpox, verrucae vulgares, condylomata acuminate and molluscum contagiosum), parasitical and fungal (e.g. candida or dermatophyte) infections, varicella, tuberculosis, syphilis or post-vaccine reactions. MometaHEXAL 1mg/g Cream should not be used on wounds or on skin which is ulcerated.

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 MometaHEXAL 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 MometaHEXAL 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 MometaHEXAL 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 MometaHEXAL 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 MometaHEXAL 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 MometaHEXAL 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 MometaHEXAL 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 MometaHEXAL 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.

If irritation or sensitisation develop with the use of MometaHEXAL Furoate 1mg/g Cream, treatment should be withdrawn and appropriate therapy instituted.

Should an infection develop, use of an appropriate antifungal or antibacterial agent should be instituted. If a favourable response does not occur promptly, the corticosteroid should be discontinued until the infection is adequately controlled.

Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitaryadrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Manifestations of Cushing's syndrome, hyperglycaemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on treatment. Patients applying a topical steroid to a large surface area or areas under occlusion should be evaluated periodically for evidence of HPA axis suppression.

Any of the side effects that are reported following systemic use of corticosteroids, including adrenal suppression, may also occur with topical corticosteroids, especially in infants and children.

Paediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios. As the safety and efficacy of MometaHEXAL Furoate in paediatric patients below 6 years of age have not been established, its use in this age group is not recommended.

Local and systemic toxicity is common especially following long continued use on large areas of damaged skin, in flexures and with polythene occlusion. If used in childhood, or on the face, occlusion should not be used. If used on the face, courses should be limited to 5 days and occlusion should not be used. Long term continuous therapy should be avoided in all patients irrespective of age.

Topical steroids may be hazardous in psoriasis for a number of reasons including rebound relapses following development of tolerance, risk of centralised pustular psoriasis and development of local or systemic toxicity due to impaired barrier function of the skin. If used in psoriasis careful patient supervision is important.

As with all potent topical glucocorticoids, avoid sudden discontinuation of treatment. When long term topical treatment with potent glucocorticoids is stopped, a rebound phenomenon can develop which takes the form of a dermatitis with intense redness, stinging and burning. This can be prevented by slow reduction of the treatment, for instance continue treatment on an intermittent basis before discontinuing treatment.

Glucocorticoids can change the appearance of some lesions and make it difficult to establish an adequate diagnosis and can also delay the healing.

MometaHEXAL Furoate 1mg/g Cream contains propylene glycol which may cause skin irritation. MometaHEXAL Furoate 1mg/g Cream contains stearyl alcohol which may cause local skin reactions (e.g. contact dermatitis).

MometaHEXAL Furoate 1mg/g Cream topical preparations are not for ophthalmic use, including the eyelids, because of the very rare risk of glaucoma simplex or subcapsular cataract.

Visual disturbance

Visual disturbance may be reported with systemic and topical 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 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.

Immunosuppression

MometaHEXAL Nasal Spray should be used with caution, if at all, in patients with active or quiescent tuberculous infections of the respiratory tract, or in untreated fungal, bacterial, or systemic viral infections.

Patients receiving corticosteroids who are potentially immunosuppressed should be warned of the risk of exposure to certain infections (e.g., chickenpox, measles) and of the importance of obtaining medical advice if such exposure occurs.

Local Nasal Effects

Following 12 months of treatment with MometaHEXAL Nasal Spray in a study of patients with perennial rhinitis, there was no evidence of atrophy of the nasal mucosa; also, mometasone furoate tended to reverse the nasal mucosa closer to a normal histologic phenotype. Nevertheless, patients using MometaHEXAL Nasal Spray over several months or longer should be examined periodically for possible changes in the nasal mucosa. If localised fungal infection of the nose or pharynx develops, discontinuance of MometaHEXAL Nasal Spray therapy or appropriate treatment may be required. Persistence of nasopharyngeal irritation may be an indication for discontinuing MometaHEXAL Nasal Spray.

MometaHEXAL is not recommended in case of nasal septum perforation.

In clinical studies, epistaxis occurred at a higher incidence compared to placebo. Epistaxis was generally self-limiting and mild in severity.

MometaHEXAL Nasal Spray contains benzalkonium chloride which may cause nasal irritation.

Systemic Effects of Corticosteroids

Systemic effects of nasal 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. Potential systemic effects may include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).

Following the use of intranasal corticosteroids, instances of increased intraocular pressure have been reported.

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.

Patients who are transferred from long-term administration of systemically active corticosteroids to MometaHEXAL Nasal Spray require careful attention. Systemic corticosteroid withdrawal in such patients may result in adrenal insufficiency for a number of months until recovery of HPA axis function. If these patients exhibit signs and symptoms of adrenal insufficiency or symptoms of withdrawal (e.g., joint and/or muscular pain, lassitude, and depression initially) despite relief from nasal symptoms, systemic corticosteroid administration should be resumed and other modes of therapy and appropriate measures instituted. Such transfer may also unmask pre-existing allergic conditions, such as allergic conjunctivitis and eczema, previously suppressed by systemic corticosteroid therapy.

Treatment with higher than recommended doses may result in clinically significant adrenal suppression. If there is evidence for higher than recommended doses being used, then additional systemic corticosteroid cover should be considered during periods of stress or elective surgery.

Nasal Polyps

The safety and efficacy of MometaHEXAL Nasal Spray has not been studied for use in the treatment of unilateral polyps, polyps associated with cystic fibrosis, or polyps that completely obstruct the nasal cavities.

Unilateral polyps that are unusual or irregular in appearance, especially if ulcerating or bleeding, should be further evaluated.

Effect on Growth in Paediatric Population

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

Non-nasal Symptoms

Although MometaHEXAL Nasal Spray will control the nasal symptoms in most patients, the concomitant use of appropriate additional therapy may provide additional relief of other symptoms, particularly ocular symptoms.

If irritation or sensitisation develop with the use of MometaHEXAL 1mg/g Cream, treatment should be withdrawn and appropriate therapy instituted.

Should an infection develop, use of an appropriate antifungal or antibacterial agent should be instituted. If a favourable response does not occur promptly, the corticosteroid should be discontinued until the infection is adequately controlled.

Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitaryadrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Manifestations of Cushing's syndrome, hyperglycaemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on treatment. Patients applying a topical steroid to a large surface area or areas under occlusion should be evaluated periodically for evidence of HPA axis suppression.

Any of the side effects that are reported following systemic use of corticosteroids, including adrenal suppression, may also occur with topical corticosteroids, especially in infants and children.

Paediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios. As the safety and efficacy of MometaHEXAL in paediatric patients below 6 years of age have not been established, its use in this age group is not recommended.

Local and systemic toxicity is common especially following long continued use on large areas of damaged skin, in flexures and with polythene occlusion. If used in childhood, or on the face, occlusion should not be used. If used on the face, courses should be limited to 5 days and occlusion should not be used. Long term continuous therapy should be avoided in all patients irrespective of age.

Topical steroids may be hazardous in psoriasis for a number of reasons including rebound relapses following development of tolerance, risk of centralised pustular psoriasis and development of local or systemic toxicity due to impaired barrier function of the skin. If used in psoriasis careful patient supervision is important.

As with all potent topical glucocorticoids, avoid sudden discontinuation of treatment. When long term topical treatment with potent glucocorticoids is stopped, a rebound phenomenon can develop which takes the form of a dermatitis with intense redness, stinging and burning. This can be prevented by slow reduction of the treatment, for instance continue treatment on an intermittent basis before discontinuing treatment.

Glucocorticoids can change the appearance of some lesions and make it difficult to establish an adequate diagnosis and can also delay the healing.

MometaHEXAL 1mg/g Cream contains propylene glycol which may cause skin irritation. MometaHEXAL 1mg/g Cream contains stearyl alcohol which may cause local skin reactions (e.g. contact dermatitis).

MometaHEXAL 1mg/g Cream topical preparations are not for ophthalmic use, including the eyelids, because of the very rare risk of glaucoma simplex or subcapsular cataract.

Visual disturbance

Visual disturbance may be reported with systemic and topical 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 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.

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 MometaHEXAL 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 MometaHEXAL 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.

Local adverse reactions reported infrequently with topical dermatalogic corticosteroids include: skin dryness, irritation, dermatitis, perioral dermatitis, maceration of the skin, miliaria and telangiectasiae.

Paediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced hypothalamic-pituitary-adrenal axis suppression and Cushing's syndrome than mature patients because of a larger skin surface area to body weight ratio.

Chronic corticosteroids therapy may interfere with the growth and development of children.

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 Website: www.mhra.gov.uk/yellowcard.

Summary of the safety profile

Epistaxis was generally self-limiting and mild in severity, and occurred at a higher incidence compared to placebo (5%), but at a comparable or lower incidence when compared to the active control nasal corticosteroids studied (up to 15%) as reported in clinical studies for allergic rhinitis. The incidence of all other adverse events was comparable with that of placebo. In patients treated for nasal polyposis, the overall incidence of adverse events was similar to that observed for patients with allergic rhinitis.

Systemic effects of nasal corticosteroids may occur, particularly when prescribed at high doses for prolonged periods.

Tabulated list of adverse reactions

Treatment related adverse reactions (>1%) reported in clinical trials in patients with allergic rhinitis or nasal polyposis and post-marketing regardless of indication are presented in Table 1. Adverse reactions are listed according to MedDRA primary system organ class. Within each system organ class, adverse reactions are ranked by frequency. Frequencies were defined as follows: Very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1,000 to <1/100). The frequency of post-marketing adverse events are considered as “not known (cannot be estimated from the available data)”.

*recorded for twice daily dosing for nasal polyposis

^†recorded at uncommon frequency for twice daily dosing for nasal polyposis

Paediatric population

In the paediatric population, the incidence of recorded adverse events in clinical studies, e.g., epistaxis (6%), headache (3%), nasal irritation (2%) and sneezing (2%) was comparable to placebo.

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.

Local adverse reactions reported infrequently with topical dermatalogic corticosteroids include: skin dryness, irritation, dermatitis, perioral dermatitis, maceration of the skin, miliaria and telangiectasiae.

Paediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced hypothalamic-pituitary-adrenal axis suppression and Cushing's syndrome than mature patients because of a larger skin surface area to body weight ratio.

Chronic corticosteroids therapy may interfere with the growth and development of children.

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 Website: www.mhra.gov.uk/yellowcard.

Pharmacotherapeutic group: Other Antiasthmatics, Inhalants, - Glucocorticoids, ATC code R03B A07

Mechanism of action

Mometasone furoate is a topical glucocorticoid with local anti-inflammatory properties.

It is likely that much of the mechanism for the effects of mometasone furoate lies in its ability to inhibit the release of mediators of the inflammatory cascade.In vitro, mometasone furoate inhibits the release of leukotrienes from leukocytes of allergic patients. In cell culture, mometasone furoate demonstrated high potency in inhibition of synthesis and release of IL-1, IL-5, IL-6, and TNF-alpha; it is also a potent inhibitor of LT production and in addition it is an extremely potent inhibitor of the production of the Th₂ cytokines, IL-4 and IL-5, from human CD4+ T-cells.

Pharmacodynamic effects

Mometasone furoate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor which is approximately 12 times that of dexamethasone, 7 times that of triamcinolone acetonide, 5 times that of budesonide, and 1.5 times that of fluticasone.

In a clinical trial, inhaled mometasone furoate has been shown to reduce airway reactivity to adenosine monophosphate in hyperreactive patients. In another trial, pretreatment using the MometaHEXAL for five days significantly attenuated the early and late phase reactions following inhaled allergen challenge and also reduced allergen-induced hyperresponsiveness to methacholine.

Inhaled mometasone furoate treatment was also shown to attenuate the increase in inflammatory cells (total and activated eosinophils) in induced sputum following allergen and methacholine challenge. The clinical significance of these findings is not known.

Clinical efficacy and safety

In asthmatic patients, repeated administration of inhaled mometasone furoate for 4 weeks at doses of 200 micrograms twice daily to 1200 micrograms once daily showed no evidence of clinically relevant HPA-axis suppression at any dose level and was associated with detectable systemic activity only at a dose of 1600 micrograms per day.

In long-term clinical trials using doses up to 800 micrograms per day, there was no evidence of HPA axis suppression, as assessed by reductions in morning plasma cortisol levels or abnormal responses to cosyntropin.

In a 28 day clinical trial involving 60 asthmatic patients, administration of MometaHEXAL at doses of 400 micrograms, 800 micrograms or 1200 micrograms once daily, or 200 micrograms twice daily, did not result in a statistically significant decrease in 24-hour plasma cortisol AUC.

The potential systemic effect of twice daily dosing of mometasone furoate was evaluated in an active and placebo controlled trial that compared 24-hour plasma cortisol AUC in 64 adult asthmatic patients treated for 28 days with mometasone furoate 400 micrograms twice daily, 800 micrograms twice daily, or prednisone 10 mg once daily. Mometasone furoate 400 micrograms twice daily treatment reduced plasma cortisol AUC_(0-24) values from placebo values by 10 - 25 %. Mometasone furoate 800 micrograms twice daily reduced plasma cortisol AUC_(0-24) from placebo values by 21 - 40 %. Reduction in cortisol was significantly greater after prednisone 10 mg once daily than with placebo or either of the mometasone treatment groups.

Double-blind placebo-controlled trials of 12-weeks duration have shown that treatment with MometaHEXAL at delivered doses within the range of 200 micrograms (once-daily in the evening) - 800 micrograms per day resulted in improved lung function as measured by FEV₁ and peak expiratory flow, improved asthma symptom control, and decreased need for inhaled beta_2--agonist. Improved lung function was observed within 24 hours of the start of treatment in some patients, although maximum benefit was not achieved before 1 to 2 weeks or longer. Improved lung function was maintained for the duration of treatment.

MometaHEXAL furoate exhibits marked anti-inflammatory activity and marked anti-psoriatic activity in standard animal predictive models.

In the croton oil assay in mice, MometaHEXAL was equipotent to betamethasone valerate after single application and about 8 times as potent after five applications.

In guinea pigs, MometaHEXAL was approximately twice as potent as betamethasone valerate in reducing m.ovalis-induced epidermal acanthosis (i.e. anti-psoriatic activity) after 14 applications.

Pharmacotherapeutic group: Decongestants and Other Nasal Preparations for Topical Use-Corticosteroids, ATC code: R01A D09

Mechanism of action

Mometasone furoate is a topical glucocorticosteroid with local anti-inflammatory properties at doses that are not systemically active.

It is likely that much of the mechanism for the anti-allergic and anti-inflammatory effects of mometasone furoate lies in its ability to inhibit the release of mediators of allergic reactions. Mometasone furoate significantly inhibits the release of leukotrienes from leucocytes of allergic patients. In cell culture, mometasone furoate demonstrated high potency in inhibition of synthesis and release of IL-1, IL-5, IL-6 and TNFα; it is also a potent inhibitor of leukotriene production. In addition, it is an extremely potent inhibitor of the production of the Th2 cytokines, IL-4 and IL-5, from human CD4+ T-cells.

Pharmacodynamic effects

In studies utilising nasal antigen challenge, MometaHEXAL Nasal Spray has shown anti-inflammatory activity in both the early- and late- phase allergic responses. This has been demonstrated by decreases (vs placebo) in histamine and eosinophil activity and reductions (vs baseline) in eosinophils, neutrophils, and epithelial cell adhesion proteins.

In 28% of the patients with seasonal allergic rhinitis, MometaHEXAL Nasal Spray demonstrated a clinically significant onset of action within 12 hours after the first dose. The median (50%) onset time of relief was 35.9 hours.

Paediatric population

In a placebo-controlled clinical trial in which paediatric patients (n=49/group) were administered MometaHEXAL Nasal Spray 100 micrograms daily for one year, no reduction in growth velocity was observed.

There are limited data available on the safety and efficacy of MometaHEXAL Nasal Spray in the paediatric population aged 3 to 5 years, and an appropriate dosage range cannot be established. In a study involving 48 children aged 3 to 5 years treated with intranasal mometasone furoate 50, 100 or 200 μg/day for 14 days, there was no significant differences from placebo in the mean change in plasma cortisol level in response to the tetracosactrin stimulation test.

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MometaHEXAL exhibits marked anti-inflammatory activity and marked anti-psoriatic activity in standard animal predictive models.

In the croton oil assay in mice, mometasone was equipotent to betamethasone valerate after single application and about 8 times as potent after five applications.

In guinea pigs, mometasone was approximately twice as potent as betamethasone valerate in reducing m.ovalis-induced epidermal acanthosis (i.e. anti-psoriatic activity) after 14 applications.

Absorption

The systemic bioavailability of mometasone furoate following oral inhalation in healthy volunteers is low, due to poor absorption from the lungs and the gut and extensive pre-systemic metabolism. Plasma concentrations of mometasone following inhalation at the recommended doses of 200 micrograms to 400 micrograms per day were generally near or below the limit of quantification (50 pg/ml) of the analytical assay and were highly variable.

Distribution

After intravenous bolus administration, the V_d is 332 l. The in vitro protein binding for mometasone furoate is high, 98 % to 99 % in concentration range of 5 to 500 ng/ml.

Biotransformation

The portion of an inhaled mometasone furoate dose that is swallowed and absorbed in the gastrointestinal tract undergoes extensive metabolism to multiple metabolites. There are no major metabolites detectable in plasma. In human liver microsomes, mometasone is metabolised by cytochrome P-450 3A4 (CYP3A4).

Elimination

After intravenous bolus administration, mometasone furoate has a terminal elimination T_1/2 of approximately 4.5 hours. A radiolabelled, orally inhaled dose is excreted mainly in the feces (74 %) and to a lesser extent in the urine (8 %).

Pharmacokinetic studies have indicated that systemic absorption following topical application of MometaHEXAL furoate cream 1mg/g is minimal, approximately 0.4% of the applied dose in man, the majority of which is excreted within 72 hours following application. Characterisation of metabolites was not feasible owing to the small amounts present in plasma and excreta.

Absorption

Mometasone furoate, administered as an aqueous nasal spray, has a systemic bioavailability of <1% in plasma, using a sensitive assay with a lower quantitation limit of 0.25 pg/ml.

Distribution

Not applicable as mometasone is poorly absorbed via the nasal route.

Biotransformation

The small amount that may be swallowed and absorbed undergoes extensive first-pass hepatic metabolism.

Elimination

Absorbed mometasone furoate is extensively metabolized and the metabolites are excreted in urine and bile.

Pharmacokinetic studies have indicated that systemic absorption following topical application of MometaHEXAL cream 1mg/g is minimal, approximately 0.4% of the applied dose in man, the majority of which is excreted within 72 hours following application. Characterisation of metabolites was not feasible owing to the small amounts present in plasma and excreta.