1 g Skinoren cream contains 0.2 g (20% w/w) micronized azelaic acid.
Pharmacology: Pharmacodynamics: The antimicrobial action and a direct influence on follicular hyperkeratosis are assumed to be the basis for the therapeutic efficacy of Skinoren in acne.
Clinically, a significant reduction of the colonization density of Propionibacterium acnes and a significant reduction of the fraction of free fatty acids in the skin surface lipids is observed.
In vitro and in vivo, azelaic acid inhibits the proliferation of keratinocytes and normalizes the disturbed terminal epidermal differentiation processes in acne. In the rabbit ear model, azelaic acid accelerates the comedolysis of tetradecane-induced comedones.
Experimental results demonstrate that azelaic acid exerts a dose- and time-dependent inhibitory effect on the growth and viability of abnormal melanocytes.
The molecular mechanisms by which this is accomplished are not entirely clarified.
Currently available data suggest that the main effects of azelaic acid in the treatment of melasma are brought about by an inhibition of the DNA synthesis and/or an inhibition of the cellular respiration of the abnormal melanocytes.
Pharmacokinetics: Azelaic acid penetrates into all layers of human skin after topical application of the cream.
Penetration is faster into damaged skin than into intact skin. A total of 3.6 % of the dose applied is absorbed percutaneously after a single topical application of 1 g azelaic acid (5 g cream).
A portion of the azelaic acid absorbed through the skin is excreted in unchanged form in the urine. The remaining portion is broken down by β-oxidation into dicarboxylic acids with shorter chain length (C7, C5) which have likewise been found in the urine.
Skinoren should be applied to the affected areas of skin twice a day (morning and evening) and rubbed gently into the skin.
Before Skinoren cream is applied, the skin should be thoroughly cleaned with clear water, or if applicable, a mild skin-cleansing agent.
It is important to continue to use Skinoren regularly over the entire period of treatment.
The duration of use of Skinoren can vary from patient to patient and also depends on the severity of the acne. In patients with acne, in general, a distinct improvement becomes apparent after about 4 weeks. To obtain the best results, however, Skinoren should be used regularly over several months. However, Skinoren should not be used continuously for more than 12 months at any time.
The amount of Skinoren to be applied will depend on the size of the affected area. As a guide, a daily dose of approximately 2.5cm/1inch of cream is sufficient for the entire facial area. Excessive amounts of cream must be avoided.
In the event of excessive irritation of the skin (see "Adverse Reactions"), the amount of cream per application should be reduced or the frequency of use of Skinoren should be reduced to once a day until the irritation ceases, or the treatment should be temporarily interrupted for a few days.
Skinoren is intended for external use only. Findings from animal experiments show that vomiting may occur after ingestion of large amounts. No organotoxic changes are likely though no human data on overdosage are available.
Results from acute toxicity studies do not indicate that any risk of acute intoxication is to be expected following a single dermal application of an overdose (application over a large area under conditions favourable to absorption) or inadvertent oral ingestion.
Hypersensitivity to any ingredients of the cream, in particular propylene glycol.
For external use only.
Care must be taken when using Skinoren cream to avoid contact with the eyes, mouth and other mucous membranes, and patients should be instructed accordingly. In the event of accidental contact, the eyes, mouth and/or affected mucous membranes should be washed with large amount of water. If eye irritation persists, patients should consult a physician. The hands should be washed after each application of the Skinoren cream.
Benzoic acid is mildly irritant to the skin, eyes and mucous membranes. Propylene glycol may cause skin irritation.
Pregnancy: There are no adequate and well-controlled studies of topically administered azelaic acid in pregnant women.
Animal studies do indicate the potential for effects with respect to pregnancy, embryo-fetal development, parturition or postnatal development. However, the dose levels without observed adverse effects in animals ranged across studies from 3-32 times the maximum recommended human dose based on body surface area. It is advisable to avoid Skinoren cream during pregnancy unless the benefit outweighs the risk.
Lactation: It is not known if azelaic acid is secreted in human milk in vivo. However an in vitro equilibrium dialysis experiment demonstrated that passage of drug into maternal milk may occur. But the distribution of azelaic acid into maternal milk is not expected to cause a significant change from baseline azelaic acid levels in the milk since azelaic acid is not concentrated in milk and less than 4% of topically applied azelaic acid is systemically absorbed not increasing endogenous azelaic acid exposure above physiological levels. However, Skinoren cream should not be used by lactating woman unless the benefit outweighs the risk.
In clinical studies, most frequently observed side effects included application site burning, application site pruritus, and application site erythema.
Frequencies of side effects observed in clinical studies and given in the table as follows are defined according to the MedDRA frequency 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 data). (See table.)
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Generally, local skin irritation regresses in the course of treatment.
The following additional adverse reactions have been reported during post-approval use of Skinoren cream (frequency unknown): Angioedema, Dermatitis contact, Eye swelling, Swelling face (which may occur with Hypersensitivity); Rash; Urticaria; Worsening of Asthma.
There have been no interaction studies of Skinoren cream with other drugs.
Store below 30°C.
Shelf-Life: After first opening of the container, the in-use stability is 6 months.
D10AX03 - azelaic acid ; Belongs to the class of other topical preparations used in the treatment of acne.
Cream 20% w/w (white, opaque) x 30 g.