This information is intended for use by health professionals

1. Name of the medicinal product

Daktacort 2% / 1% w/w cream.

2. Qualitative and quantitative composition

Miconazole nitrate 2% w/w and hydrocortisone 1% w/w.

3. Pharmaceutical form

White, homogeneous cream.

4. Clinical particulars
4.1 Therapeutic indications

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 inflammatory 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.

4.2 Posology and method of administration

For topical administration.

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

The properties of Daktacort indicate it particularly for the initial stages of treatment. Because of its corticosteroid content avoid long-term treatment with Daktacort. Once the inflammatory symptoms have disappeared (after about 7 days), treatment can be continued where necessary with miconazole nitrate 20 mg/g cream or miconazole nitrate 20 mg/g 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 Daktacort 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 (see Section 4.4).

4.3 Contraindications

True hypersensitivity to miconazole/miconazole nitrate, other imidazole derivatives, hydrocortisone or to any of the excipients listed in section 6.1. Tubercular or viral infections of the skin or those caused by Gram-negative bacteria.

4.4 Special warnings and precautions for use

When Daktacort is used by patients taking oral anticoagulants, the anticoagulant effect should be carefully monitored.

Severe hypersensitivity reactions, including anaphylaxis and angioedema, have been reported during treatment with Daktacort and with other miconazole topical formulations (see section 4.8). If a reaction suggesting hypersensitivity or irritation should occur, the treatment should be discontinued. Daktacort must not come into contact with the mucosa of the eyes.

As with any topical corticosteroid, caution is advised with infants and children when Daktacort 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.

Because of its corticosteroid content avoid long-term treatment with Daktacort. Once the inflammatory symptoms have disappeared treatment may be continued with miconazole nitrate 20mg/g cream or powder. (See Section 4.1)

Daktacort 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 Daktacort 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.

4.5 Interaction with other medicinal products and other forms of interaction

Miconazole administered systemically is known to inhibit CYP3A4/2C9. Due to the limited systemic availability after topical application (see Section 5.2 Pharmacokinetic properties), clinically relevant interactions are rare. However, in patients on oral anticoagulants, such as warfarin, caution should be exercised and anticoagulant effect should be monitored.

Miconazole is a CYP3A4 inhibitor that can decrease the rate of metabolism of hydrocortisone. Serum concentrations of hydrocortisone may be higher with the use of Daktacort compared with topical preparations containing hydrocortisone alone.

4.6 Fertility, pregnancy and lactation

Pregnancy

Clinical data on the use of Daktacort Cream in pregnancy are limited. In animals, corticosteroids are known to cross the placenta and consequently can affect the foetus (see Section 5.3). Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development. The relevance of these findings to humans has not been established.

As a precautionary measure, it is preferable to avoid the use of Daktacort during pregnancy. Treatment of large surfaces and the application under occlusive dressing is not recommended.

Breastfeeding

There are no adequate and well-controlled studies on the topical administration of Daktacort Cream during breastfeeding. It is not known whether concomitant topical administration of Daktacort Cream to the skin could result in sufficient systemic absorption to produce detectable quantities of hydrocortisone and miconazole in breast milk in humans.

A risk to the newborn child cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Daktacort therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. Treatment of large surfaces and the application under occlusive dressing is not recommended.

4.7 Effects on ability to drive and use machines

None known.

4.8 Undesirable effects

The safety of Daktacort Cream was evaluated in 480 patients who participated in 13 clinical trials (six double-blind and seven open-label trials) of Daktacort Cream. 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 Daktacort 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 Daktacort 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 Daktacort Cream was evaluated in 63 paediatric patients (1 month to 14 years of age) who were treated with Daktacort 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 Daktacort 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 Daktacort Cream-treated patients (adult and paediatric patients combined).

Adverse Reactions in Adult and Paediatric Patients Treated With Daktacort Cream

System Organ Class

Adverse reactions

Frequency Category

Uncommon

(≥1/1,000 to <1/100)

Not Known

Immune System Disorders

Anaphylactic reaction, Hypersensitivity

Skin and Subcutaneous Tissue Disorders

Skin irritation, Skin burning sensation, Urticaria, Pruritus

Angioedema, Rash, Contact dermatitis, Erythema, Skin inflammation, Skin hypopigmentation, Application site reaction

General Disorders and Administration Site Conditions

Irritability

Eye disorders

Vision, blurred (see also section 4.4)

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.

4.9 Overdose

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.

5. Pharmacological properties
5.1 Pharmacodynamic properties

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

Miconazole nitrate is active against dermatophytes and pathogenic yeasts, and many Gram-positive bacteria.

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.

5.2 Pharmacokinetic properties

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.

5.3 Preclinical safety data

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.

6. Pharmaceutical particulars
6.1 List of excipients

PEG-6, PEG-32 and glycol stearate

Oleoyl macroglycerides

Liquid paraffin

Benzoic acid (E210)

Disodium edetate

Butylated hydroxyanisole (E320)

Purified water

6.2 Incompatibilities

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

6.3 Shelf life

36 months.

6.4 Special precautions for storage

Store in a refrigerator (2-8°C).

6.5 Nature and contents of container

Aluminium tube with polypropylene cap.

Each tube contains 5 g, 10 g, 15 g, 30 g or 75 g cream.

6.6 Special precautions for disposal and other handling

None.

7. Marketing authorisation holder

Janssen-Cilag Ltd

50-100 Holmers Farm Way

High Wycombe

Buckinghamshire

HP12 4 EG

UK

8. Marketing authorisation number(s)

PL 00242/0042

9. Date of first authorisation/renewal of the authorisation

Date of First Authorisation:

04/02/77

Renewal of Authorisation:

24/02/2009

10. Date of revision of the text

13 April 2018