Mometasone

Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. 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.

Co-administration of inhaled mometasone furoate with ketoconazole resulted in an increase in plasma concentrations of mometasone approximately twice.

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

As with other inhaled corticosteroid preparations, mometasone 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.

During pregnancy treatment with mometasone cream should be performed only on the physician’s order. Then however, the application on large body surface areas or over a prolonged period should be avoided. There is inadequate evidence of safety in human pregnancy. Topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate and intra-uterine growth retardation. There are no adequate and well-controlled studies in pregnant women and therefore the risk of such effects to the human foetus is unknown. However as with all topically applied glucocorticoids, the possibility that foetal growth may be affected by glucocorticoid passage through the placental barrier should be considered. There may therefore be a very small risk of such effects in the human foetus. Like other topically applied glucocorticoids, mometasone should be used in pregnant women only if the potential benefit justifies the potential risk to the mother or the foetus.

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

It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Mometasone should be administered to nursing mothers only after careful consideration of the benefit/risk relationship. If treatment with higher doses or long term application is indicated, breast-feeding should be discontinued.

Fertility

In reproductive studies in rats, there was no effect on fertility.

Respiratory / Nasal administration

Mometasone has no or negligible influence on the ability to drive and use machines.

Cutaneous use / Topical administration

None stated.

Respiratory administration

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 mometasone 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 mometasone inhalation powder, 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. Mometasone inhalation powder 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.

Nasal administration

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.

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 below. 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)”.

Infections and infestations

Common: Pharyngitis, Upper respiratory tract infection†

Immune system disorders

Not known: Hypersensitivity including anaphylactic reactions, angioedema, bronchospasm, and dyspnoea

Nervous system disorders

Common: Headache

Eye disorders

Not known: Glaucoma, Increased intraocular pressure, Cataracts, Vision blurred

Respiratory, thoracic and mediastinal disorders

__Very common:__Epistaxis*

Common: Epistaxis, Nasal burning, Nasal irritation, Nasal ulceration

Not known: Nasal septum perforation

Gastrointestinal disorders

Common: Throat irritation*

Not known: Disturbances of taste and smell

* 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.

Cutaneous use / Topical administration

Frequency: Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10 000,); not known (cannot be estimated from available data).

Treatment-related adverse reactions reported by body system and frequency:

Infections and infestations

Not known: Infection, furuncle

Very rare: Folliculitis

Nervous system disorders

Not known: Paraesthesia

Very rare: Burning sensation

Skin and subcutaneous tissue disorders

Not known: Dermatitis contact, skin hypopigmentation, hypertrichosis, skin striae, dermatitis acneiform, skin atrophy

Very rare: Pruritus

General disorders and administration site conditions

Not known: Application site pain, application site reactions

Eye disorders

Not known: Vision blurred

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.