Miconazolnitraat/Hydrocortison Actavis

For the topical treatment of inflamed dermatoses where infection by susceptible organisms and inflammation co-exist, eg intertrigo and infected eczema.

Moist or dry eczema or dermatitis including atopic eczema, primary irritant or contact allergic eczema or seborrhoeic eczema including that associated with acne.

Intertriginous eczema including inframammary intertrigo, perianal and genital dermatitis.

Organisms which are susceptible to miconazole are dermatophytes and pathogenic yeasts (eg Candida spp.). Also many Gram-positive bacteria including most strains of Streptococcus and Staphylococcus.

For topical administration.

Apply the ointment two or three times a day to the affected area, rubbing in gently until the ointment has been absorbed by the skin.

The properties of Miconazolnitraat/Hydrocortison Actavis indicate its use particularly for the initial stages of treatment. Because of its corticosteroid content avoid long-term treatment with Miconazolnitraat/Hydrocortison Actavis. Once the inflammatory symptoms have disappeared (after about 7 days), treatment can be continued where necessary with miconazole nitrate 20mg/g cream or powder. Treatment should be continued without interruption until the lesion has completely disappeared (usually after 2 to 5 weeks).

If after about 7 days' application, no improvement has occurred, cultural isolation of the offending organism should be followed by appropriate local or systemic antimicrobial therapy.

The same dosage applies to both adults and children.

Elderly

Natural thinning of the skin occurs in the elderly, hence corticosteroids should be used sparingly and for short periods of time.

Paediatrics

In infants and children, caution is advised when Miconazolnitraat/Hydrocortison Actavis Ointment is applied to extensive surface areas or under occlusive dressings including baby napkins (diapers). In infants, long term continuous topical corticosteroid therapy should be avoided.

Severe hypersensitivity reactions, including anaphylaxis and angioedema, have been reported during treatment with Miconazolnitraat/Hydrocortison Actavis and with other miconazole topical formulations. If a reaction suggesting hypersensitivity or irritation should occur, the treatment should be discontinued. Miconazolnitraat/Hydrocortison Actavis must not come into contact with the mucosa of the eyes.

When Miconazolnitraat/Hydrocortison Actavis is used by patients taking oral anticoagulants, the anticoagulant effect should be carefully monitored.

As with any topical corticosteroid, caution is advised with infants and children when Miconazolnitraat/Hydrocortison Actavis is to be applied to extensive surface areas or under occlusive dressings including baby napkins; similarly, application to the face should be avoided.

In infants, long term continuous topical corticosteroid therapy should be avoided.

Adrenal suppression can occur even without occlusion.

Miconazolnitraat/Hydrocortison Actavis can damage certain synthetic materials. Therefore, it is recommended to wear cotton underwear if this clothing comes into contact with the affected area.

The concurrent use of latex condoms or diaphragms with vaginal anti-infective preparations may decrease the effectiveness of latex contraceptive agents. Therefore Miconazolnitraat/Hydrocortison Actavis should not be used concurrently with a latex condom or latex diaphragm.

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.

None known.

Safety information from clinical trial data is not available for Miconazolnitraat/Hydrocortison Actavis Ointment. The following information is available for Miconazolnitraat/Hydrocortison Actavis Cream. As the cream and ointment formulations contain the same active ingredients in the same concentrations, the safety data for the cream formulation is considered applicable to the ointment formulation.

The safety of Miconazolnitraat/Hydrocortison Actavis Cream was evaluated in 480 patients who participated in 13 clinical trials (six double-blind and seven open-label trials) of Miconazolnitraat/Hydrocortison Actavis Cream but not with Miconazolnitraat/Hydrocortison Actavis Ointment. These studies examined patients from 1 month to 95 years of age with infections of the skin caused by dermatophytes or Candida species in which inflammatory symptoms were prominent.

All Patients

No adverse reactions were reported by >1% of the 480 Miconazolnitraat/Hydrocortison Actavis Cream-treated patients (adult and paediatric patients combined).

The frequency categories use the following convention: 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 clinical trial data).

Of the three adverse reactions identified from the 13 clinical trials of Miconazolnitraat/Hydrocortison Actavis Cream, skin irritation was reported in one clinical trial that included patients aged 17 to 84 years, skin burning sensation in two clinical trials that included patients aged 13 to 84 years, and irritability in one clinical trial of infants aged 1 to 34 months.

Paediatric Population

The safety of Miconazolnitraat/Hydrocortison Actavis Cream was evaluated in 63 paediatric patients (1 month to 14 years of age) who were treated with Miconazolnitraat/Hydrocortison Actavis Cream in 3 of the 13 clinical trials noted above. One adverse reaction term (irritability) was reported in these 3 trials. The frequency of irritability in Miconazolnitraat/Hydrocortison Actavis Cream-treated paediatric patients was common (3.2%).

All events of irritability occurred in one clinical trial of infants (aged 1 to 34 months) with napkin (diaper) dermatitis. The frequency, type, and severity of other adverse reactions in paediatric patients are expected to be similar to those in adults. Adverse reactions were reported by >1% of the 480 Miconazolnitraat/Hydrocortison Actavis Cream-treated patients (adult and paediatric patients combined).

Adverse Reactions in Adult and Paediatric Patients Treated With Miconazolnitraat/Hydrocortison Actavis Cream

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.

Prolonged and excessive use can result in skin irritation, which usually disappears after discontinuation of therapy. Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects.

Pharmacotherapeutic group: Imidazole and triazole derivatives, combinations, ATC code: D01AC20

Miconazole nitrate is a potent broad-spectrum antifungal and antibacterial agent with marked activity against dermatophytes, pathogenic yeasts (eg Candida spp) and many Gram-positive bacteria including most strains of Streptococcus and Staphylococcus.

Hydrocortisone is an anti-inflammatory steroid. Its anti-inflammatory action is due to reduction in the vascular component of the inflammatory response, suppression of migration of polymorphonuclear leukocytes, and reversal of increased capillary permeability. The vasoconstrictor action of hydrocortisone may also contribute to its anti-inflammatory activity.

Absorption

Miconazole remains in the skin after topical application for up to 4 days. Systemic absorption of miconazole is limited, with a bioavailability of less than 1% following topical application of miconazole. Plasma concentrations of miconazole and/or its metabolites were measurable 24 and 48 hours after application. Approximately 3% of the dose of hydrocortisone is absorbed after application on the skin.

Distribution

Absorbed miconazole is bound to plasma proteins (88.2%) and red blood cells (10.6%). More than 90% of hydrocortisone is bound to plasma proteins.

Metabolism and elimination

The small amount of miconazole that is absorbed is eliminated predominantly in faeces as both unchanged drug and metabolites over a four-day post-administration period. Smaller amounts of unchanged drug and metabolites also appear in urine.

The half-life of hydrocortisone is about 100 minutes. Metabolism takes place in the liver and tissues and the metabolites are excreted with the urine, mostly as glucuronides, together with a very small fraction of unchanged hydrocortisone.

Preclinical data on the drug product (miconazole nitrate + hydrocortisone) revealed no special hazard for humans based on conventional studies of ocular irritation, dermal sensitization, single dose oral toxicity, primary dermal irritation toxicity, and 21-day repeat dose dermal toxicity. Additional preclinical data on the individual active ingredients in this drug product reveal no special hazard for humans based on conventional studies of local irritation, single and repeated dose toxicity, genotoxicity, and for miconazole toxicity to reproduction. Miconazole has shown no teratogenic effects but is fetotoxic at high oral doses. Reproductive effects (fetotoxicty, reduced weight gain) and developmental abnormalities specifically craniofacial effects including cleft palate have been reported with hydrocortisone in various animal models.

Contact should be avoided between latex products such as contraceptive diaphragms or condoms and Miconazolnitraat/Hydrocortison Actavis since the constituents of Miconazolnitraat/Hydrocortison Actavis may damage the latex.

None.