SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Daktarin Intensiv Cream

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Ketoconazole 2% w/w.

Excipients include: propylene glycol, stearyl alcohol, cetyl alcohol.

For full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Cream.

White homogenous cream.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the treatment of the following mycotic infections of the skin: tinea pedis and tinea cruris.

4.2.    Posology and method of administration

Ketoconazole cream is for use in adults.

For the treatment of tinea pedis (athlete’s foot) and tinea cruris (dhobie itch).

For tinea pedis, Daktarin Intensiv cream should be applied thinly to the affected areas twice daily. The infected area should be washed and dried, especially between the toes, before applying the cream. The usual duration of treatment for mild infections is 1 week. For more severe or extensive infections (e.g. involving the sole or sides of the feet), treatment should be continued for 2-3 days after all signs of infection have disappeared to prevent relapse. If no improvement in symptoms is experienced after 7 days treatment, a doctor should be consulted.

For tinea cruris, apply cream to the affected areas once or twice daily until 2-3 days after all signs of infection have disappeared to prevent relapse. Treatment for up to 6 weeks may be necessary. If no improvement in symptoms is experienced after 4 weeks treatment, a doctor should be consulted.

Method of administration: Topical administration

4.3 Contraindications

Ketoconazole cream is contra-indicated in patients with a known hypersensitivity to any of the ingredients or to ketoconazole itself.

4.4    Special warnings and precautions for use

Daktarin Intensiv cream is not for ophthalmic use.

To prevent a rebound effect after stopping a prolonged treatment with topical corticosteroids, it is recommended to continue applying a mild topical corticosteroid in the morning and to apply Daktarin Intensiv cream in the evening, and to subsequently and gradually withdraw the steroid therapy over a period of 2-3 weeks.

4.5    Interaction with other medicinal products and other forms of interaction

None known.

4.6. Fertility, pregnancy and lactation

There are no adequate and well-controlled studies in pregnant or lactating women. To date, no other relevant epidemiological data are available. Data on a limited number of exposed pregnancies indicate no adverse effects of topical ketoconazole on pregnancy or on the health of the foetus/newborn child. Animal studies have shown reproductive toxicity at doses that are not relevant to the topical administration of ketoconazole.

Plasma concentrations of ketoconazole are not detectable after topical application of Daktarin Intensiv cream to the skin of non-pregnant humans (See Pharmacokinetic properties, section 5.2). There are no known risks associated with the use of Daktarin Intensiv cream in pregnancy or lactation.

Effects on ability to drive and use machines

None.

4.8. Undesirable effects

The safety of ketoconazole cream was evaluated in 1079 subjects who participated in 30 clinical trials. Ketoconazole cream was applied topically to the skin.

Based on pooled safety data from these clinical trials, the most commonly reported (>1% incidence) ADRs were (with % incidence): application site pruritus (2%), skin burning sensation (1.9%), and application site erythema (1%). Including the above-mentioned adverse drug reactions (ADRs), the following table displays ADRs that have been reported with the use of ketoconazole cream from either clinical trial or postmarketing experiences. The displayed frequency categories use the following convention:

(>1/100 to <1/10)

(>1/1,000 to <1/100)

(>1/10,000 to <1/1,000)

(<1/10,000)

(cannot be estimated from the available clinical trial data).

System Organ Class	Adverse Drug Reactions
	Frequency Category
	Common (>1/100 to <1/10)	Uncommon (>1/1,000 to <1/100)	Not Known
Immune System Disorders		Hypersensitivity
Skin and Subcutaneous Tissue Disorders	Skin burning sensation	Bullous eruption Dermatitis contact Rash Skin exfoliation Sticky skin	Urticaria
General Disorders and Administration Site Conditions	Application site erythema Application site pruritus	Application site bleeding Application site discomfort Application site dryness Application site inflammation Application site irritation Application site paraesthesia Application site reaction

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.

4.9 Overdose

Topical application

Excessive topical application may lead to erythema, oedema and a burning sensation, which will disappear upon discontinuation of the treatment.

Ingestion

In the event of accidental ingestion, supportive and symptomatic measures should be carried out.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: ATC code: D01AC08

Ketoconazole has a potent antimycotic action against dermatophytes and yeasts. Ketoconazole cream acts rapidly on the pruritus, which is commonly seen in dermatophyte and yeast infections. This symptomatic improvement often occurs before the first signs of healing are observed.

A study in 250 patients has shown that application twice daily for 7 days of ketoconazole 2% cream vs clotrimazole 1% cream for 4 weeks on both feet demonstrated efficacy in patients with tinea pedis (athlete’s foot) presenting lesions between the toes.

The primary efficacy endpoint was negative microscopic KOH examination at 4 weeks.

Ketoconazole 2% treatment showed equivalent efficacy to 4 weeks clotrimazole 1% treatment.

There was no evidence of relapse following treatment with ketoconazole cream at 8 weeks.

5.2 Pharmacokinetic properties

Plasma concentrations of ketoconazole were not detectable after topical administration of ketoconazole Cream in adults on the skin. In one study in infants with seborrhoeic dermatitis (n = 19), where approximately 40 g of ketoconazole cream was applied daily on 40% of the body surface area, plasma levels of ketoconazole were detected in 5 infants, ranging from 32 to 133 ng/mL.

5.3 Preclinical safety data

Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.

PHARMACEUTICAL PARTICULARS

List of excipients

Propylene glycol

Stearyl alcohol

Cetyl alcohol

Sorbitan stearate

Polysorbate 60

Isopropyl myristate

Sodium sulphite anhydrous (E221)

Polysorbate 80

Purified water

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

36 months

6.4    Special precautions for storage

Do not store above 25°C.

6.5    Nature and contents of container

Tube made of 99.7% aluminum, lined on inner side with heat polymerised epoxyphenol resin with a latex coldseal ring at the end of the tube. The cap is made of 60% polypropylene, 30% calcium carbonate and 10% glyceryl monostearate.

Tubes of 5, 15 and 30g.

Not all pack sizes may be marketed.

6.6. Special precautions for disposal and handling

No special requirements.

Any unused medicinal products or waste material should be disposed of in accordance with local requirements.

7    MARKETING AUTHORISATION HOLDER

McNeil Products Limited

Foundation Park

Roxborough Way

Maidenhead

Berkshire

SL6 3UG

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 15513/0181

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

16/12/2009

10 DATE OF REVISION OF THE TEXT

06/11/2013