Janssen-Cilag Ltd

Daktacort 2% / 1% w/w Cream.

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

Contains 0.2% w/w benzoic acid (E210) and 0.0052% butylated hydroxyanisole (E320).

For full list of excipients, see section 6.1.

Cream.

White, homogeneous, odourless cream.

Daktacort is used for the topical treatment of skin conditions where inflammation and infection by susceptible organisms co-exist. The properties of Daktacort indicate it particularly for the initial stages of treatment. Once the inflammatory symptoms have disappeared, treatment can be continued with miconazole nitrate (Daktarin) cream.

For cutaneous administration

Apply one to three times daily to the affected area or as directed by the physician.

1. Hypersensitivity to miconazole, hydrocortisone or any of the ingredients in Daktacort cream.

2. Use in infants in conjunction with occlusion.

3. Use in the presence of infections of viral, tuberculous or treponemal origin, or of bacterial infections due to Gram-negative organisms.

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.

Continuous treatment for longer than three weeks should be avoided in infants because of the possibility of adrenocortical suppression. Adrenal suppression can occur even without the use of occlusive dressings.

Daktacort cream contains benzoic acid, which is mildly irritant to the skin, eyes and mucous membranes. Daktacort cream also contains butylated hydroxanisole, which may cause local skin reactions (e.g. contact dermatitis), or irritation to the eyes and mucous membranes.

Daktacort must not come into contact with the mucosa of the eyes.

Because of its corticosteroid content avoid long-term treatment with Daktacort. Once the inflammatory symptoms have disappeared treatment may be continued with Daktarin cream. (See Section 4.1)

Daktacort can damage certain synthetic materials. Therefore, it is recommended to wear cottonunderwear if this clothing comes into contact with the affected area.

Miconazole administered systemically is known to inhibit CYP3A4/2C9. Due to the limited systemic availability after cutaneous application, (see Section 5.2 Pharmacokinetic properties), clinically relevant interactions are unlikely to occur. However, in patients on oral anticoagulants, such as warfarin, caution should be exercised and anticoagulant effect should be monitored. The effects and side effects of some other drugs (e.g., certain oral hypoglycemics and phenytoin), when co-administered with miconazole, can be increased and caution should be exercised.

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.

The product should not be used during pregnancy unless considered essential by the physician. Caution is also recommended during lactation. Treatment of large surfaces and the application under occlusive dressing should be avoided during that time.

Miconazole has not been observed to be embryotoxic or teratogenic in animals, Corticosteroids are known to cross the placenta and consequently can affect the foetus. (See Section 5.3)

None.

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 (>/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 to be necessary.

Miconazole nitrate is a synthetic imidazole with a broad spectrum of activity against pathogenic fungi (including yeasts and dermatophytes) and Gram-positive bacteria (Staphylococcus and Streptococcus spp.). Hydrocortisone is a widely used topical anti-inflammatory of value in the treatment of inflammatory skin conditions.

Absorption

Miconazole remains in the skin for up to 4 days. after topical application. 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. Systemic absorption has also been demonstrated after repeated application of miconazole to infants with napkin dermatitis. Plasma levels of miconazole were undetectable or low. 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. Reproductive effects and developmental abnormalities have been reported with hydrocortisone in various animal models.

Macrogol ester

Oleoyl macroglycerides .

Liquid paraffin

Benzoic acid (E210)

Disodium edentate .

Butylated hydroxyanisole (E320)

Purified water

Not applicable..

Three years.

Store in a refrigerator ( 2-8°C).

Aluminium tube lined on inside with heat polymerized epoxy-phenol resin, with a latex cold-seal ring. Cap: polypropylene.

Daktacort cream is supplied in tubes of 5 g, 10 g, 15 g, 30 g and 75 g.

Not all pack sizes are marketed

No special requirements.

Janssen-Cilag Ltd

50-100 Holmers Farm Way

High Wycombe

Buckinghamshire

HP12 4EG

UK

PA 748/26/1

16 December 1996 / 16 December 2006

June 2011