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Components:
Adapalene
Method of action:
Antiacne, Anti-Inflammatory, Comedonolitic
Medically reviewed by Kovalenko Svetlana Olegovna, PharmD. Last updated on 2020.03.30

Pharmacodynamic properties

Pharmacotherapeutic Group: D10A Anti-Acne Preparations for Topical Use

ATC code: D10AD03

Adapalene is a retinoid-like compound which in, in vivo and in vitro models of inflammation, has been demonstrated to possess anti-inflammatory properties. Adapalene is essentially stable to oxygen and light and is chemically non-reactive. Mechanically, adapalene binds like tretinoin to specific retinoic acid nuclear receptors but, unlike tretinoin not to cytosolic receptor binding proteins.

Adapalene applied cutaneously is comedolytic in the rhino mouse model and also has effects on the abnormal processes of epidermal keratinisation and differentiation, both of which are present in the pathogenesis of acne vulgaris. The mode of action of adapalene is suggested to be a normalisation of differentiation of follicular epithelial cells resulting in decreased microcomedone formation.

Adapalene is superior to reference retinoids in standard anti-inflammatory assays, both in vivo and in vitro. Mechanistically, it inhibits chemotactic and chemokinetic responses of human polymorphonuclear leucocytes and also the metabolism by lipoxidation of arachidonic acid to pro-inflammatory mediators. This profile suggests that the cell mediated inflammatory component of acne may be modified by adapalene. Studies in human patients provide clinical evidence that cutaneous adapalene is effective in reducing the inflammatory components of acne (papules and pustules).

Pharmacokinetic properties

Absorption of adapalene through human skin is low, in clinical trials measurable plasma adapalene levels were not found following chronic cutaneous application to large areas of acneic skin with an analytical sensitivity of 0.15 ng/ml.

After administration of [14C]-adapalene in rats (IV, IP, oral and cutaneous), rabbits (IV, oral and cutaneous) and dogs (IV and oral), radioactivity was distributed in several tissues, the highest levels being found in liver, spleen, adrenals and ovaries. Metabolism in animals has been tentatively identified as being mainly by O-demethylation, hydroxylation and conjugation, and excretion is primarily by the biliary route.

Pharmacotherapeutic group

D10A Anti-Acne Preparations for Topical Use

Preclinical safety data

In animal studies, adapalene was well tolerated on cutaneous application for periods of up to six months in rabbits and for up to two years in mice. The major symptoms of toxicity found in all animal species by the oral route were related to an hypervitaminosis A syndrome, and included bone dissolution, elevated alkaline phosphatase and a slight anaemia. Large oral doses of adapalene produced no adverse neurological, cardiovascular or respiratory effects in animals. Adapalene is not mutagenic. Lifetime studies with adapalene have been completed in mice at cutaneous doses of 0.6, 2 and 6 mg/kg/day and in rats at oral doses of 0.15, 0.5 and 1.5 mg/kg/day. The only significant finding was a statistically significant increase of benign phaeochromocytomas of the adrenal medulla among male rats receiving adapalene at 1.5 mg/kg/day. These changes are unlikely to be of relevance to the cutaneous use of adapalene.

Adapalene produces teratogenic effects by the oral route in rats and rabbits. At cutaneous doses up to 200 fold the therapeutic dose, producing circulating plasma levels of adapalene at least 35 to 120 times higher than plasma levels demonstrated in therapeutic use, adapalene increased the incidence of additional ribs in rats and rabbits, without increasing the incidence of major malformations.

It is not known whether adapalene is secreted in animal or human milk. In animal studies, infant rats suckled by mother with circulating levels of adapalene at least 300 times those demonstrated in clinical use developed normally.

List of excipients

Carbomer 934P

Macrogol-20 methyl glucose sesquistearate

Glycerol (E422)

Natural squalane

Methyl parahydroxybenzoate (E218)

Propyl parahydroxybenzoate (E216)

Disodium edetate

Methyl glucose sesquistearate

Phenoxyethanol

Cyclomethicone

Sodium hydroxide

Purified water

Incompatibilities

Not applicable

Shelf life

3 years.

Special precautions for storage

Do not store above 25°C.

Do not freeze.

Keep out of the sight and reach of children.

Nature and contents of container

Collapsible Aluminium tube coated internally with an epoxy-phenolic resin and fitted with a white Polypropylene screw cap. Pack sizes 5g (Sample Pack), 30g, 45g and 50g.

Not all pack sizes may be marketed.

Special precautions for disposal and other handling

A thin film of the cream should be applied, avoiding eyes, lips and mucous membranes.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Marketing authorisation holder

Galderma (UK) Limited

Meridien House

69-71 Clarendon Road

Watford

Herts.

WD17 1DS

UK

Marketing authorisation number(s)

PL 10590/0029

Date of first authorisation/renewal of the authorisation

9 January 1998

Date of revision of the text

August 2017

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