Adolin Cream is proposed for the cutaneous treatment of mild to moderate acne vulgaris where comedones,
papules and pustules predominate. Adolin Cream is best suited for use on dry and fair skin. Acne of the face,
chest or back is appropriate for treatment.

Adolin Cream should be applied to the acne affected areas once a day before retiring and after washing. A thin
film of cream should be applied, with the fingertips, avoiding the eyes and lips (see 4.4 Special warnings and
special precautions for use, below). Ensure that the affected areas are dry before application.
Since it is customary to alternate therapies in the treatment of acne, it is recommended that the physician
assess the continued improvement of the patient after three months of treatment with Adolin Cream.
With patients for whom it is necessary to reduce the frequency of application or to temporarily discontinue
treatment, frequency of application may be restored or therapy resumed once it is judged that the patient can
again tolerate the treatment.
If patients use cosmetics, these should be non-comedogenic and non-astringent.
Paediatric population: The safety and effectiveness of Adolin Cream have not been studied in children below
12 years of age.

If a reaction suggesting sensitivity or severe irritation occurs, use of the medication should be discontinued. If
the degree of local irritation warrants, patients should be directed to use the medication less frequently, to
discontinue use temporarily until symptoms subside or to discontinue use altogether. Adolin Cream should not
come into contact with the eyes, mouth, angles of the nose or mucous membranes.
If product enters the eye, wash immediately with warm water. The product should not be applied to either
broken (cuts and abrasions), sunburnt or eczematous skin, nor should it be used in patients with severe acne,
or acne involving large areas of the body.
Exposure to sunlight and artificial UV irradiation, including sunlamps, should be minimised during use of
adapalene. Patients who normally experience high levels of sun exposure and those with inherent sensitivity to
sun, should be warned to exercise caution. Use of sunscreen products and protective clothing over treated
areas is recommended when exposure cannot be avoided.

There are no known interactions with other medications which might be used cutaneously and concurrently with
Adolin Cream; however, other retinoids or drugs with a similar mode of action should not be used concurrently
with adapalene.
Adapalene is essentially stable to oxygen and light and is chemically non-reactive. Whilst extensive studies in
animals and man have shown neither phototoxic nor photoallergic potential for adapalene, the safety of using
adapalene during repeated exposure to sunlight or UV irradiation has not been established in either animals or
man. Exposure to excessive sunlight or UV irradiation should be avoided.
Absorption of adapalene through human skin is low (see Pharmacokinetic Properties) and therefore interaction
with systemic medications is unlikely. There is no evidence that the efficacy of oral drugs such as
contraceptives and antibiotics is influenced by the cutaneous use of Adolin Cream.
Adolin Cream has a potential for mild local irritation, and therefore it is possible that concomitant use of peeling
agents, astringents or irritant products may produce additive irritant effects. However, cutaneous antiacne
treatment e.g. erythromycin (up to 4%) or clindamycin phosphate (1% as the base) solutions or benzoyl
peroxide water based gels up to 10% may be used in the morning when Adolin Cream is used at night as there
is no mutual degradation or cumulative irritation.

Pregnancy:
Animal studies by the oral route have shown reproductive toxicity at high systemic exposure (see section 5.3).
Clinical experience with locally applied adapalene in pregnancy is limited but the few available data do not
indicate harmful effects on pregnancy or on the health of the foetus exposed in early pregnancy. Due to the
limited available data and because a very weak cutaneous passage of adapalene is possible, Adolin should not
be used during pregnancy. In case of unexpected pregnancy, treatment should be discontinued.
Breast-feeding:
No study on animal or human milk transfer was conducted after cutaneous application of Adolin.
No effects on the suckling child are anticipated since the systemic exposure of the breast-feeding woman to
Adolin is negligible. Adolin can be used during breastfeeding. To avoid contact exposure of the infant,
application of Adolin to the chest should be avoided when used during breast-feeding.

Adolin Cream has no influence on the ability to drive and use machines
 

Adolin may cause the following adverse drug reactions:
tissue disorders

Skin and subcutaneous tissue disorders :  

Common (≥1/100 to<1/10) Dry skin, skin irritation, skin burning sensation, erythem
Uncommon (≥1/1000 to <1/100) : Dermatitis contact, skin discomfort, sunburn, pruritus, skin exfoliation, acne
Unknown* Dermatitis allergic (allergic contact dermatitis), pain of skin, skin
swelling,

Eye disorders:

Unknown*eyelid irritation, eyelid erythema, eyelid pruritus, eyelid swelling

*Post marketing surveillance data

− To reports any side effect(s):
Reporting side effect 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 side effects to the relevant competent authority.

Adolin Cream is not to be taken orally and is for cutaneous use only. If the medication is applied excessively,
no more rapid or better results will be obtained and marked redness, peeling or discomfort may occur.
The acute oral dose of Adolin Cream required to produce toxic effects in mice is greater than 10 g/kg.
Nevertheless, unless the amount accidentally ingested is small, an appropriate method of gastric emptying
should be considered.

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).

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 Odemethylation,
hydroxylation and conjugation, and excretion is primarily by the biliary route.

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.

6.1 List of excipients
Carbomer 934P
PEG-20 Methyl Glucose Sesquistearate
Glycerin
Squalane
Methyl Paraben
Propyl Paraben
Disodium EDTA
Phenoxy Ethanol
Methyl Glucose Sesquistearate
Cyclomethicone
Sodium Hydroxide
Purified Water

Not applicable.

Store below 25°C.

Collapsible Aluminium tube and HDPE Screw Cap
Pack sizes 30g

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.