Skinoren Cream

1. Name Of The Medicinal Product

Skinoren Cream.

2. Qualitative And Quantitative Composition

Skinoren cream 1 g contains 200 mg (20%) micronised azelaic acid.

For excipients, see 6.1.

3. Pharmaceutical Form

Cream.

4. Clinical Particulars

4.1 Therapeutic Indications

Topical treatment of acne vulgaris.

4.2 Posology And Method Of Administration

Skinoren should be applied to the affected areas twice daily (mornings and evenings), and rubbed in well. Regular use is important.

Patients with sensitive skin should be advised to use Skinoren only once a day (in the evening) for the first week of treatment and then proceed to twice daily applications.

Before Skinoren is applied, the skin should be thoroughly washed with water alone or, if necessary, with a mild cleansing agent.

The amount of Skinoren to be applied will depend on the size of the affected area. As a guide a daily dose of 2 g (1 g per application) will be sufficient for the treatment of the entire facial area (1 g = 4 cm cream).

If other areas of acne, in addition to the face require treatment, for example the chest and back, a daily dose of 10 g of cream should not, in general, be exceeded.

The duration of use of Skinoren will vary from person to person and also depends on the severity of the acne. In general, a distinct improvement becomes apparent after about 4 weeks. To obtain the best results, Skinoren should be applied over a period of several months but not for more than 6 months.

4.3 Contraindications

Hypersensitivity to any ingredient of the cream, in particular propylene glycol.

4.4 Special Warnings And Precautions For Use

For external use only.

Avoid contact with the eyes. If Skinoren comes into contact with the eyes they should immediately be thoroughly rinsed with copious amounts of water.

Skinoren contains a small amount of benzoic acid, which is mildly irritating to the skin, eyes and mucous membrane.

Skinoren also contains propylene glycol, which may cause skin irritation.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

None known.

4.6 Pregnancy And Lactation

There is no evidence of the safety of azelaic acid during human pregnancy or lactation. It is therefore advisable to avoid using Skinoren during pregnancy or lactation unless essential and no suitable alternative treatment is available. Animal studies have however produced no evidence that would suggest any risk to a foetus from use by a pregnant woman.

4.7 Effects On Ability To Drive And Use Machines

None.

4.8 Undesirable Effects

Local skin irritation (e.g. erythema, scaling, itching or burning) occurs in occasional cases, usually at the start of treatment. However, in the majority of cases the irritation is mild and regresses as treatment continues. If marked skin irritation persists, the amount of cream per application should be reduced, the frequency of application should be reduced, or the treatment temporarily interrupted until the symptoms regress.

Photosensitivity reactions have been reported very rarely during the use of Skinoren.

Also, in very rare cases, allergic skin reactions (e.g. rash) may occur (see also “Section 4.3 Contraindications”).

4.9 Overdose

Not applicable.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Azelaic acid inhibits the growth of the propionibacteria involved in the development of acne and their production of acne-promoting fatty acids. Azelaic acid also reduces the multiplication of keratinocytes and their keratinization, and therefore restricts the formation of comedones.

5.2 Pharmacokinetic Properties

After dermal administration of the cream, azelaic acid penetrates to all layers of the human skin. The penetration is more rapid into damaged skin than intact skin. A total of 3.6% of the administered dose was absorbed percutaneously after a single administration of 5 g cream to the face, upper back and chest, which are typical regions for acne lesions. Applying 5 g of cream twice daily results in a systemic burden ranging from 1 to 1.5 mg per kg body weight.

43% of azelaic acid is bound to plasma proteins.

Due to the low percutaneous absorption, the amount of azelaic acid reaching the infant via the mother's milk should be negligible i.e. less than 200 μg per day which corresponds to 0.01% of the two 5 g doses.

A part of the azelaic acid which is absorbed through the skin is eliminated in its original form with urine. The other part is metabolized through ß-oxidation into short-chained dicarboxylic acids (C7, C5 carboxylic acids) which were found in urine as well.

5.3 Preclinical Safety Data

In vitro and in vivo studies with the active substance produced no evidence for genotoxic effects on germinal and somatic cells.

No signs that azelaic acid has sensitising properties were found in the maximization test in the guinea-pig.

6. Pharmaceutical Particulars

6.1 List Of Excipients

• Arlatone 983S (polyoxyethylene fatty acid ester)

• Cutina CBS (mixture of mono-diglyceridene, fatty alcohols, triglycerides and wax

esters)

• Cetearyl octanoate

• Propylene glycol

• Glycerol 85% (E 422)

• Benzoic acid (E 210)

• Purifed water.

6.2 Incompatibilities

None known.

6.3 Shelf Life

5 years.

6.4 Special Precautions For Storage

Do not store above 30°C.

6.5 Nature And Contents Of Container

Tubes containing 20, 30 or 50 g. Not all pack sizes are marketed.

Standard aluminium tube with membrane closure and screw cap. The internal coating is epoxide and the screw cap is made of high-density polyethylene.

6.6 Special Precautions For Disposal And Other Handling

Store all medicines properly and keep them out of the reach of children.

7. Marketing Authorisation Holder

Intendis GmbH

Max-Dohrn-Strasse 10

D-10589

Berlin

Germany

8. Marketing Authorisation Number(S)

PL 28428/0005

9. Date Of First Authorisation/Renewal Of The Authorisation

24 November 2005

10. Date Of Revision Of The Text

29 September 2006