Daktacort™ Cream.

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

White, homogeneous cream.

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.

The properties of Daktacort indicate it particularly for the initial stages of treatment. Once the inflammatory symptoms have disappeared (after about 7 days), treatment can be continued where necessary with Daktarin™ Cream or Daktarin™ Powder.

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.

True hypersensitivity to any of the ingredients. Tubercular or viral infections of the skin or those caused by Gram-negative bacteria.

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 miconazole topical formulations.

If a reaction suggesting hypersensitivity or irritation should occur, the treatment should be discontinued.

As with any topical corticosteroid, care 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 Daktarin cream or Daktarin Powder. (See Section 4.1)

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

Pregnancy

Clinical data on the use of Daktacort Cream in pregnancy are limited. 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 lactation. 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.

None known.

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 drug reactions (ADRs) 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 ADRs 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 ADR 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 ADRs in paediatric patients are expected to be similar to those in adults.reactions (ADRs) were reported by 1% of the 480 Daktacort Cream-treated patients (adult and paediatric patients combined)

Adverse Drug Reactions in Adult and Paediatric Patients Treated With Daktacort Cream

Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects. If accidental ingestion of large quantities of the product occurs, an appropriate method of gastric emptying may be used if considered necessary.

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

PEG-6, PEG-32 and glycol stearate

Oleoyl macroglycerides

Mineral oil

Benzoic acid

Disodium edetate

Butylated hydroxyanisole

Purified water

None.

36 months.

Store in a refrigerator (2-8°C).

Aluminium tube with polypropylene cap.

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

None.

Janssen-Cilag Ltd

50-100 Holmers Farm Way

High Wycombe

Buckinghamshire

HP12 4 EG

UK

PL 00242/0042

17 November 2011

POM.