SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Ketoconazole 2% Shampoo

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Ketoconazole 20mg/g.

For the full list of excipients see section 6.1 3.    PHARMACEUTICAL FORM

Shampoo.

Clear, pink solution.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Prevention and treatment of infections in which the yeast Malassezia (previously called Pityrosporum) is likely to be involved, such as dandruff, seborrhoeic dermatitis and tinea (pityriasis) versicolor.

4.2    Posology and method of administration

For topical administration.

Ketoconazole 2% shampoo is for use in adolescents and adults.

Adults and adolescents

Shake the bottle well. Wash the hair or the infected areas of the skin with the Ketoconazole shampoo. Leave in contact for 3-5 minutes before rinsing thoroughly.

Treatment

Dandruff and seborrhoeic dermatitis: Wash hair twice weekly for 2-4 weeks.

Tinea versicolor:

Once daily for a maximum of 5 days.

Dandruff and seborrhoeic dermatitis:

Use once every 1 - 2 weeks.

Tinea versicolor:

Once daily for a maximum of 3 days in a single treatment course before exposure to sunshine.

4.3    Contraindications

Known hypersensitivity to ketoconazole or any of the other excipients.

4.4    Special warnings and precautions for use

To prevent a rebound effect after stopping prolonged treatment with topical corticosteroids, it is recommended to continue applying the topical corticosteroid together with Ketoconazole shampoo and to subsequently and gradually withdraw the steroid therapy over a period of 2-3 weeks.

Keep out of the eyes. If the shampoo should get into the eyes, they should be bathed with cold water.

4.5    Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

4.6    Fertility, pregnancy and lactation

There are no adequate and well-controlled studies in pregnant or lactating women. 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. No effects on the breastfed newborn/infant are anticipated (See Pharmacokinetic properties, section 5.2)

Plasma concentrations of ketoconazole were not detectable after topical administration of ketoconazole shampoo 2% to the scalp of non-pregnant humans. Plasma levels were detected after topical administration of ketoconazole shampoo 2% on the whole body. There are no known risks associated with the use of ketoconazole shampoo 2% in pregnancy or lactation.

4.7    Effects on ability to drive and use machines

Not relevant.

4.8 Undesirable effects

Seborrhoeic dermatitis and dandruff are often associated with increased hair shedding, and this has also been reported, although rarely, with the use of ketoconazole containing shampoos.

As with other shampoos, a local burning sensation, itching, irritation and oily/dry hair may occur, but are rare, when using shampoos containing ketoconazole.

In some patients with permanently waved, “permed” hair, use of Merazol shampoo results in a loss of curl.

In rare instances, mainly in patients with chemically damaged hair or grey hair, discolouration of the hair has been observed.

The safety of ketoconazole 2% shampoo was evaluated in 2890 subjects who participated in 22 clinical trials. Ketoconazole 2% shampoo was administered topically to the scalp and/or skin. Based on pooled safety data from these clinical trials, there were no ADRs reported with an incidence >1%.

The following table displays ADRs that have been reported with the use of Ketoconazole 2% Shampoo from either clinical trial or postmarketing experiences.

The displayed 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)

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

System Organ Class	Adverse	Drug Reactions Frequency Category
	Uncommon (>1/1,000 to <1/100)	Rare (>1/10,000 to <1/1,000)	Not Known
Immune System disorders		Hypersensitivity
Nervous System disorders		Dysgeusia
Infection and Infestations	Folliculitis
Eye disorders	Increased lacrimation	Eye irritation
Skin and subcutaneous tissue disorders	Alopeica Dry skin Hair texture abnormal Rash Skin burning sensation	Acne Dermatitis contact Skin disorder Skin exfoliation	Angioedema Urticaria Hair colour changes

General disorders and	Application site	Application site
administration site	erythema	hypersensitivity
conditions	Application site	Application site
	irritation	pustules
	Application site pruritus
	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 reaction via the Yellow Card Scheme, Website: www.mhra.gov .uk/yellowcard.

4.9. Overdose

In the event of accidental ingestion, only supportive measures should be carried out. In order to avoid aspiration, neither emesis nor gastric lavage should be instigated.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotherapeutic group: Imidazole and triazole derivatives.

ATC Code: D01A C08 (Topical use).

Ketoconazole is an imidazole-dioxolane antimycotic, active against pathogenic dermatophytes and yeasts including Malassezia. Its broad spectrum of activity is already well known.

5.2 Pharmacokinetic properties

Ketoconazole does not appear to be appreciably absorbed systemically following topical application of a 2% shampoo to skin. Ketoconazole was not detected in plasma of patients receiving topical application of 2% shampoo 410 times weekly for 6 months, or in patients using 2% shampoo 2-3 times weekly for an average of 16 months. Following single topical application, substantial amounts of the drug were detected in hair 12 hours after application; however only 5% of the applied ketoconazole was detected in hair keratin. Following repeated (twice weekly for 2 months) application, 20% of the applied dose was detected in hair keratin.

Plasma levels were detected after topical administration of ketoconazole 2% shampoo on the whole body.

5.3 Preclinical safety data

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

In vitro studies using ketoconazole in a microbial system (i.e. Ames test) have not shown the drug to be mutagenic. In addition, there was no evidence of mutagenicity in any stage of germ cell development in a dominant lethal mutation test in mice who received single oral doses of ketoconazole as high as 80mg/kg. There was no evidence of carcinogenicity in a long-term feeding study in mice and rats. Hepatotoxicity featured prominently in high dose toxicology studies in animals and occurs in about 1 in 10,000 patients.

6. PHARMACEUTICAL PARTICULARS

6.1. List of Excipients

Sodium laureth sulphate, Disodium laureth sulphosuccinate, PEG-120 Methyl glucose dioleate, PEG-7 Glyceryl cocoate, Imidurea, Lauryldimonium hydroxypropyl hydrolysed collagen, Cocamide DEA, Sodium hydroxide, Sodium chloride, Erythrosine C.I. 45430 (E127), Hydrochloric acid concentrated, Purified water

6.2. Incompatibilities

None known

6.3. Shelf life

18 months

6.4. Special Precautions for Storage

Do not store above 25°C

6.5. Nature and Contents of Container

White opaque HDPE bottle with PP closure Pack sizes 60, 80, 100, 120, 125, 150ml

6.6. Instruction for Use/Handling

No special instructions

7.    MARKETING AUTHORISATION HOLDER

Dr. Reddy’s Laboratories (UK) Limited

6 Riverview Road

Beverley

HU17 0LD

United Kingdom

8.    MARKETING AUTHORISATION NUMBER(S)

PL 08553/0051

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

30/01/2009

10    DATE OF REVISION OF THE TEXT

February 2014