Janssen-Cilag Ltd

Change to section 4.4 - Special warnings and precautions for Use

Nizoral 2% 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 Nizoral 2% cream in the evening, and to subsequently and gradually withdraw the steroid therapy over a period of 2-3 weeks.

Change to section 4.6 - 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.

Change to section 10 - Date of revision of the text

21 June 2011

Change to section 4.6 - Pregnancy and Lactation

Animal studies have shown reproductive toxicity at doses that are not relevant to the topical administration of ketoconazole.

Change to section 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.

Change to section 10 - Date of revision of the text

10 March 2011

Change to section 1 -Name of the Medicinal product

Nizoral 2% cream

Change to section 2 - Qualitative and quantitative composition

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).

Change to section 4.5 - Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed

Change to section 4.7 - Effects on Ability to Drive and Use Machines

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

Change to section 5.1 - Pharmacodynamic Properties

Pharmacotherapeutic group: Imidazole and triazole derivatives

Change to section 6. 6 - Instructions for use, handling and disposal

No special requirements

Change to section 10 - Date of revision of the text

25 June 2010

Change to section 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:

                Very common (³1/10)

Common (³1/100 to <1/10)

Uncommon (³1/1,000 to <1/100)

Rare (³1/10,000 to <1/1,000)

Very rare (<1/10,000)

Change to section 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.

Change to section 10 – Date of revision of the text

30 November 2009

Change to section 1 –Name of the medicinal product

Updated to Nizoral 2% Cream

Change to section 2 – quantitative and qualitative composition

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

For a full list of excipients, see 6.1.

Change to section 10 – Date of revision of the text

22 April 2009

Change to section 4.8 – Undesirable effects

The safety of ketoconazole cream was evaluated in 1117 subjects who participated in 31 clinical trials. Each subject received at least one topical administration of ketoconazole cream.

Commonly observed adverse reactions to Ketoconazole cream in clinical trials were burning sensation, application site erythema and pruritus.

Including the above-mentioned adverse drug reactions (ADRs), the following table displays ADRs that have been reported with the use of ketconoazole cream from either clinical trial or postmarketing experiences. The displayed frequency categories use the following convention:

Very Common             (³1/10)

Common                    (³1/100 to <1/10)

Uncommon                 (³1/1,000 to <1/100)

Rare                           (³1/10,000 to <1/1,000)

Very rare                     (<1/10,000)

Not Known                  (cannot be estimated form the clinical trial data).

Table showing all ADRs

Change to section 10 – Date of revision of the text

February 2009

Change to section 10 – Date of revision of the text

December 2008

Change to section 4.6 – Pregnancy and Lactation

New information:

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 following oral administration of ketoconazole. (see Preclinical safety data, section 5.3). No effects on the breastfed newborn/infant are anticipated. See Pharmacokinetic properties, section 5.2

X

Change to section 4.3 – Contra-indications

Updated information

X

Change to section 5.2 - Pharmacokinetic properties

Updated information