Daktacort 2&1% W/W Ointment
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Daktacort 2% / 1% w/w ointment.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Miconazole nitrate 2% w/w and hydrocortisone 1% w/w.
3. PHARMACEUTICAL FORM
White, odourless, fatty ointment.
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 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.
4.2 Posology and method of administration
For topical administration.
Apply the ointment two or three times a day to the affected area, rubbing in gently until the ointment has been absorbed by the skin.
The properties of Daktacort indicate its use 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 20mg/g cream or 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 Ointment 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
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.
When Daktacort is used by patients taking oral anticoagulants, the anticoagulant effect should be carefully monitored.
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.
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.
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 Ointment 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 Ointment during breastfeeding. It is not known whether concomitant topical administration of Daktacort Ointment 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
Safety information from clinical trial data is not available for Daktacort Ointment. The following information is available for Daktacort Cream. As the cream and ointment formulations contain the same active ingredients in the same concentrations, the safety data for the cream formulation is considered applicable to the ointment formulation.
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 but not with Daktacort Ointment. 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 | |
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.
Overdose
4.9
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 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 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
Polyethylene 5.5% liquid paraffin gel.
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
Do not store above 25°C
Aluminium tube with polypropylene cap. Each tube contains 5 g, 30 g or 75 g ointment.
6.6. Instructions for Use, Handling and Disposal
None.
7 MARKETING AUTHORISATION HOLDER
Janssen-Cilag Limited 50-100 Holmers Farm Way High Wycombe Buckinghamshire HP12 4EG UK
8. MARKETING AUTHORISATION NUMBER(S)
PL 00242/0130
9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION
05/03/1987 / 28/03/2003
10 DATE OF REVISION OF THE TEXT
10/11/2015