1. Name Of The Medicinal Product
Daktacort™ 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.
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.
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.
4.3 Contraindications
True hypersensitivity to any of the ingredients. 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 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)
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 Pregnancy And Lactation
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.
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 drug reactions (ADRs) were reported by
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
Adverse Drug Reactions in Adult and Paediatric Patients Treated With Daktacort Cream
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4.9 Overdose
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.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Miconazole nitrate is active against dermatophytes and pathogenic yeasts, and many Gram-positive bacteria. Hydrocortisone has 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
Mineral oil
Benzoic acid
Disodium edetate
Butylated hydroxyanisole
Purified water
6.2 Incompatibilities
None.
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
17 November 2011
LEGAL CATEGORY
POM.
