Daktacort™ Ointment.

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

White, odourless, fatty ointment.

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.

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.

Daktacort Ointment should be applied topically two or three times daily.

The same dosage applies to both adults and children.

Use in elderly:

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

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

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.

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.

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.

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.

In animals, miconazole nitrate has shown no teratogenic effects but is foetotoxic at high oral doses and administration of corticosteroids to pregnant animals can cause abnormalities of foetal development. The relevance of these findings to humans has not been established. However, combinations of topical steroids with imidazoles should be used in pregnant women only if the practitioner considers it to be necessary.

None known.

Rarely, local sensitivity may occur requiring discontinuation of treatment.

Additional adverse drug reactions reported in postmarketing reports with DAKTACORT CREAM but not with DAKTACORT OINTMENT are included in Table 1. The frequencies are based on spontaneous reporting rates, according to the following convention:

Very common	1/10
Common	1/100 and < 1/10
Uncommon	1/1,000 and <1/100
Rare	1/10,000, <1/1,000
Very rare	<1/10,000, including isolated reports

Review of adverse events reported with Daktacort Ointment did not find sufficient evidence to assess any of the events as adverse drug reactions associated with the use of Daktacort Ointment.

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 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 a widely used topical anti-inflammatory of value in the treatment of inflammatory skin conditions including atrophic and infantile eczema, contact sensitivity reactions and intertrigo.

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.

Not applicable.

Polyethylene 5.5% liquid paraffin gel.

None known.

36 months.

Store at or below 25°C.

Aluminium tube with polypropylene cap.

Each tube contains 5 g, 30 g or 75 g ointment.

None.

Janssen-Cilag Ltd

50-100 Holmers Farm Way

High Wycombe

Buckinghamshire

HP12 4EG

UK

PL 00242/0130

2^nd March 2009

POM.