Mometasone Furoate 0.1% W/W Ointment
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Mometasone furoate 0.1% w/w Ointment
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
One gram of ointment contains 1 mg of mometasone furoate (0.1 % mometasone furoate).
Excipients: 25.00 mg propylene glycol monopalmitostearate and 50.00 mg emulsifying cetostearyl alcohol (type A)/ 1 g ointment.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Ointment
An off-white, transparent ointment.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Mometasone furoate 0.1% w/w Ointment is indicated for the symptomatic treatment of inflammatory skin conditions which respond to external treatment with glucocorticoids, such as atopic dermatitis and psoriasis (excluding widespread plaque psoriasis).
Mometasone furoate 0.1% w/w Ointment should be preferably used to treat very dry, scaly and cracked skin complaints where a topical mometasone preparation is indicated.
4.2 Posology and method of administration
For application on the skin (cutaneous use).
Adults, including elderly patients and children aged 6 years and over :
A thin film of Mometasone furoate 0.1% w/w Ointment should be applied to the affected skin area once daily.
Strong topical corticosteroids generally should not be applied to the face without close monitoring by the physician.
Mometasone furoate 0.1% w/w Ointment should not be used for long periods (over 3 weeks) or on large areas (over 20% of body surface area).
In children aged 6 years and over a maximum of 10% of the body surface area should be treated. It should not be used occlusively or intertriginously. Treatment duration is limited to a maximum of 3 weeks.
Use of a weaker corticosteroid is often advisable when there is a clinical improvement.
Children below 6years:
Mometasone furoate 0.1% w/w Ointment is a potent group III glucocorticoid. It is not recommended for use in children below 6 years due to insufficient data on safety.
4.3 Contraindications
Mometasone furoate 0.1% w/w Ointment is contraindicated in patients with
• hypersensitivity to the active substance mometasone furoate or to any of the excipients
• facial rosacea
• acne vulgaris
• perioral dermatitis
• perianal and genital pruritus
• napkin eruptions
• bacterial (e.g. impetigo), viral (e.g. herpes simplex, herpes zoster, chickenpox (varicella)) and fungal (e.g. candida or dermatophyte) infections
• tuberculosis
• syphilis
• post-vaccine reactions
The use of Mometasone furoate 0.1% w/w Ointment on the eyelids is contraindicated.
4.4 Special warnings and precautions for use
Any contact with the eyes, and use on the eyelids should be avoided.
Mometasone furoate 0.1% w/w Ointment should not be applied to broken skin and mucous membranes.
Caution should be observed in patients who are hypersensitive to any other corticosteroid. If irritation or sensitization develops with the use of Mometasone furoate 0.1% w/w Ointment, 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 favorable response does not occur promptly, the corticosteroid should be discontinued until the infection is adequately controlled.
Local and systemic toxicity is common especially following long continued use on large areas of damaged skin, in flexures and with occlusion. Caution should be exercised when large areas of the body are treated and 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 centralized 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 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.
Hyperglycaemia and glucosuria can occur in some patients after topical application due to systemic absorption.
Glucocorticoids can change the appearance of some lesions and make it difficult to establish an adequate diagnosis and can also delay the healing.
Mometasone furoate 0.1% w/w Ointment contains propylene glycol monopalmitostearate which may cause skin irritations and also cetostearyl alcohol, which may cause local skin reactions (e.g. contact dermatitis).
Mometasone furoate 0.1% w/w Ointment should not be used in children under 6 years of age, as there is insufficient clinical experience.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.
4.6 Pregnancy and lactation
Pregnancy
Corticosteroids cross the placenta. There is very limited data on the use of topical mometasone during pregnancy. After systemic use of high dose corticosteroids, effects on the foetus/neonate has been described (intra-uterine growth retardation, adrenocortical suppression, cleft palate).
Animal studies have shown reproduction toxicity and teratogenicity (see section 5.3). The potential risk for humans is unknown.
Although systemic exposure is limited, Mometasone furoate 0.1% w/w Ointment should only be used during pregnancy after careful consideration of the benefit/risk assessment.
Lactation
It is not known whether mometasone is excreted into breast milk. Mometasone furoate 0.1% w/w Ointment should only be administered to nursing mothers after careful consideration of the benefit/risk assessment. During the lactation period, Mometasone furoate 0.1% w/w Ointment must not be applied in the breast area. No interaction studies have been performed.
4.7 Effects on ability to drive and use machines
Mometasone furoate 0.1% w/w Ointment has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
Adverse reactions are listed in Table 1 according to MedDRA system organ class and in decreasing frequency defined as follows:
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)
Not known (frequency cannot be estimated from the available data)
Undesirable effects that have been reported in connection with external corticosteroid treatment include:
Table 1: Treatment-related adverse reactions reported by body system and frequency
|
Skin and subcutaneous tissue disorders Common: Uncommon: |
Mild to moderate burning sensations at the application site, tingling/stinging, pruritus, bacterial infections, paraesthesia, furunculosis, local skin atrophy. Striae, irritation, hypertrichosis, hypopigmentation, perioral dermatitis, maceration of the skin, allergic contact dermatitis, papulous rosacea like dermatitis (facial skin), acneiform reactions, capillary brittleness (ecchymoses), miliaria, dryness, sensitisation (mometasone), folliculitis. |
|
Infections and infestations | |
|
Uncommon: |
Secondary infection. |
|
Vascular disorders | |
|
Very rare: |
Telangiectasis. |
An increased risk of systemic effects and local undesirable effects exists with frequent dosing, treatment of large areas or in the long term and also the treatment of intertriginous areas or with occlusive dressings. Hypopigmentation or hyperpigmentation has been reported in isolated cases (rare) in connection with other steroids and may therefore occur with Mometasone furoate 0.1% w/w Ointment.
Side effects which have been reported with systemic glucocorticoids - including adrenal suppression - may also occur with topically applied glucocorticoids.
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 to body weight ratio. Chronic corticosteroids therapy may interfere with the growth and development of children.
Intracranial hypertension has been reported in paediatric patients receiving topical corticosteroids. Manifestations of intracranial hypertension include bulging fontanelles, headaches and bilateral papilloedema.
4.9 Overdose
Excessive long-term use of external corticosteroids may suppress HPA axis function and give rise to secondary adrenocortical insufficiency. If suppression of the HPA axis has been reported, it should be endeavoured, with the usual caution being exercised in these situations, to reduce the frequency of applications or to try to withdraw the drug.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Corticosteriods, potent (Group III)
ATC Code: D07AC13
Mometasone furoate 0.1% w/w Ointment is a potent glucocorticoid, group III.
The active substance, mometasone furoate, is a synthetic, non-fluorinated glucocorticoid with a furoate ester in position 17.
Like other corticosteroids for external use, mometasone furoate exhibits marked antiinflammatory activity and marked anti-psoriatic activity in standard animal predictive models.
Mometasone furoate 0.1% w/w Ointment was shown to have an equivalent pharmacodynamic (vasoconstriction) response profile to the reference ointment product containing 1mg/g mometasone furoate when applied to normal skin. The calculated AUC ratio of Mometasone furoate 0.1% w/w Ointment to the reference product in the vasoconstrictor assay was 101.5%.
The therapeutic index of mometasone furoate (a ratio of desired to unwanted effects) determined from relevant literature data suggests that mometasone belongs to a category of topical glucocorticoids, in which desired effects clearly outweigh unwanted effects.
In the croton oil assay in mice, mometasone (ED50 = 0.2 pg/ear) was equipotent to betamethasone valerate after single application and about 8 times as potent after five applications (ED50 = 0.002 pg/ear /day versus 0.014 pg/ear/day).
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.
5.2 Pharmacokinetic properties
Results from percutaneous absorption studies have indicated that systemic absorption following topical application of mometasone furoate ointment 0.1% is minimal. The results show that about 0.7% of the active ingredient is absorbed by the intact skin in 8 hours (without using an occlusive dressing).
Characterization of metabolites was not feasible owing to the small amounts present in plasma and excreta.
5.3 Preclinical safety data
Acute Toxicity
|
Type of Animal |
Type of Application |
LD50 (mg/kg) |
|
Mouse |
subcutaneous |
200 - 2000 |
|
Rat |
subcutaneous |
200 |
|
Dog |
subcutaneous |
>200 |
|
Mouse |
oral |
>2000 |
|
Rat |
oral |
>2000 |
Chronic Toxicity
In various toxicity studies with chronic use in which excessive quantities of the active ingredient (670 times the therapeutic dose) were applied over 6 months, only symptoms typical of corticoid overdose were found: reduced weight gain; muscular atrophy; distended abdomen; decrease in lymphocytes and eosinophilic granulocytes and increase in neutrophilic leucocytes; increase in serum transaminases (SGPT and SGOT), cholesterol and triglycerides; lipidaemia; organ changes (atrophy of the spleen and thymus, local skin atrophy, increases in liver and kidney weight and reduced osteogenesis).
These changes were generally more pronounced and more frequent in animals which were given the comparison substance, betamethasone valerate. Neither of the two substances exhibited unusual systemic effects.
Genotoxicity
Tests on gene mutations were negative. However, mometasone induced chromosome mutations in-vitro but only at cell-toxic concentrations. Similar effects were not observed in thorough in-vivo tests, so a mutagenic risk can be ruled out with sufficient certainty.
Carcinogenicity
Long-term carcinogenicity studies of mometasone furoate have been conducted by the inhalation route in rats (2 years) and mice (19 months). No statistically significant increase in the incident of tumours was observed at doses up to 67 mcg/kg in rats or 160 mcg/kg in mice.
Reproduction Toxicity
Animal tests on the effect of mometasone furoate on embryonic development in rabbits revealed depressed body weight from 0.15 mg/kg/BWT upwards.
After topical treatment of rabbits, the progeny suffered various types of malformation, such as crooked front paws, cleft palate, gallbladder agenesis and umbilical hernia. In the rat, embryo-lethal effects from 7.5 frg//kg/BWT (subcutaneous) and poor development from 0.3 mg/kg/BWT (topical) (depressed body weight, delayed ossification) and substance-related increase in umbilical hernia were observed. When the drug was administered to mothers close to the birth date, protracted labour and difficult births were observed.
Mometasone furoate had no effects on the fertility of rats.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
White soft paraffin Liquid paraffin 2-Methylpentane-2,4-diol
Emulsifying cetostearyl alcohol (type A, contains disodium/potassium hydrogen phosphate for pH adjustment)
Propylene glycol monopalmitostearate
White beeswax
Purified water
Anhydrous citric acid
Sodium citrate
6.2 Incompatibilities
When treating the genital or anal area with Mometasone furoate 0.1% w/w Ointment, the ingredients white soft paraffin and liquid paraffin can lead to a reduction in the functional capability of latex products (e.g. condoms, diaphragms) when used simultaneously and might thereby impair the safety of these products.
6.3 Shelf life
2 years
After first opening: 6 months
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5. Nature and contents of container
The ointment is filled in aluminium tubes fitted with a white high density polyethylene piercing screw cap in a cardboard carton. Carton of 1 tube.
Pack sizes:
Tubes with 10g, 15g, 20g, 25g, 30g, 35g 50g, 60g, 70g, 90g and 100g of ointment Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Almirall Hermal GmbH ScholtzstraBe 3 21465 Reinbek Germany
8 MARKETING AUTHORISATION NUMBER(S)
PL 33016/0001
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
30/03/2011
10 DATE OF REVISION OF THE TEXT
30/08/2013