This information is intended for use by health professionals

1. Name of the medicinal product

Nizoral 2% cream

2. Qualitative and quantitative composition

Ketoconazole 2% w/w (each gram of cream contains 20mg).

Excipients;

propylene glycol, 20%w/w (each gram of cream contains 200mg).

stearyl alcohol, 7.5%w/w (each gram of cream contains 75mg).

cetyl alcohol, 2.0%w/w (each gram of cream contains 20mg).

For a full list of excipients, see 6.1.

3. Pharmaceutical form

Cream

4. Clinical particulars
4.1 Therapeutic indications

For topical application in the treatment of dermatophyte infections of the skin such as tinea corporis, tinea cruris, tinea manus and tinea pedis infections due to Trichophyton spp, Microsporon spp and Epidermophyton spp. Nizoral 2% cream is also indicated for the treatment of cutaneous candidosis (including vulvitis), tinea (pityriasis) versicolor and seborrhoeic dermatitis caused by Malassezia (previously called Pityrosporum) spp.

4.2 Posology and method of administration

Ketoconazole cream is for use in adults.

Tinea pedis:

Nizoral 2% cream should be applied to the affected areas twice daily. The usual duration of treatment for mild infections is 1 week. For more severe or extensive infections (eg involving the sole or sides of the feet) treatment should be continued until a few days after all signs and symptoms have disappeared in order to prevent relapse.

For other infections:

Nizoral 2% cream should be applied to the affected areas once or twice daily, depending on the severity of the infection.

The treatment should be continued until a few days after the disappearance of all signs and symptoms. The usual duration of treatment is: tinea versicolor 2–3 weeks, tinea corporis 3–4 weeks.

The diagnosis should be reconsidered if no clinical improvement is noted after 4 weeks. General measures in regard to hygiene should be observed to control sources of infection or reinfection.

Seborrhoeic dermatitis is a chronic condition and relapse is highly likely.

Method of administration: Cutaneous administration.

Paediatrics

There are limited data on the use of ketoconazole 2% cream in paediatric patients.

4.3 Contraindications

Nizoral 2% 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

Nizoral 2% cream is not for ophthalmic use.

If coadministered with a topical corticosteroid, 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 Nizoral 2% cream in the evening, and to subsequently and gradually withdraw the topical corticosteroid therapy over a period of 2-3 weeks.

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.

Plasma concentrations of ketoconazole are not detectable after topical application of Nizoral 2% Cream to the skin of non-pregnant humans. (See Pharmacokinetic properties, section 5.2) There are no known risks associated with the use of Nizoral 2% Cream in pregnancy or lactation.

4.7 Effects on ability to drive and use machines

Nizoral 2% cream has no influence on the ability to drive and use machines.

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) adverse reactions were (with % incidence): application site pruritus (2%), skin burning sensation (1.9%), and application site erythema (1%).

Including the above-mentioned adverse reactions, the following table displays adverse reactions 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:

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 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 paresthesia

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:

Yellow Card Scheme

Website: 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: Antifungals for Topical Use,Imidazole and triazole derivatives

ATC Code: D01AC08

Usually ketoconazole cream acts rapidly on pruritus, which is commonly seen in dermatophyte and yeast infections, as well as skin conditions associated with the presence of Malassezia spp. This symptomatic improvement is observed before the first signs of healing are observed.

Ketoconazole, a synthetic imidazole dioxolane derivative, has a potent antimycotic activity against dermatophytes such as Trichophyton spp., Epidermophyton floccosum and Microsporum spp. and against yeasts, including Malassezia spp. and Candida spp. The effect on Malassezia spp. is particularly pronounced.

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 Nizoral 2% Cream in adults on the skin. In one study in infants with seborrhoeic dermatitis (n = 19), where approximately 40 g of Nizoral 2% 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.

6. Pharmaceutical particulars
6.1 List of excipients

Propylene Glycol

Stearyl Alcohol

Cetyl Alcohol

Sorbitan Stearate

Polysorbate 60

Isopropyl Myristate

Sodium Sulphite Anhydrous (E221)

Polysorbate 80

Water purified (Ph. Eur)

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.

Tube of 30g.

6.6 Special precautions for disposal and other handling

No special requirements

7. Marketing authorisation holder

Janssen-Cilag Ltd

50-100 Holmers Farm Way

High Wycombe

Bucks

HP12 4EG

UK

8. Marketing authorisation number(s)

PL 00242/0107

9. Date of first authorisation/renewal of the authorisation

Date of first authorization: 02 December 1983

Renewed 3 December 2002

10. Date of revision of the text

26 March 2015