Adapalene Gel is proposed for the cutaneous treatment of mild to moderate acne where comedones,
papules and pustules predominate. Acne of the face, chest or back is appropriate for treatment.

Adapalene Gel should be applied to the acne affected areas once a day before retiring and after
washing. A thin film of gel 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
Adapalene Gel.
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.
The safety and effectiveness of Adapalene Gel have not been studied in children below 12 years of
age. Adapalene Gel should not be used in patients with severe acne.

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, or to discontinue use altogether. Adapalene
Gel should not come into contact with the eyes, mouth, nostrils or mucous membranes.
If product enters the eye, wash immediately with warm water. The product should not be applied to
either broken (cut and abrasions) or eczematous skin, nor should it be used in patients with severe
acne involving large areas of the body.

The excipient propylene glycol (E1520) may cause skin irritation.

There are no known interactions with other medications which might be used cutaneously and
concurrently with Adapalene Gel, 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 5.2 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 Adapalene Gel.
Adapalene Gel has a potential for mild local irritation, and therefore it is possible that concomitant use
of peeling agents, abrasive cleansers, strong drying agents, astringents or irritant products (aromatic
and alcoholic agents) may produce additive irritant effects. However, cutaneous antiacne treatment
(eg 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 Adapalene Gel 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, Adapalene Gel should not be used during pregnancy. In case of unexpected
pregnancy, treatment should be discontinued.
Lactation:
No study on animal or human milk transfer was conducted after cutaneous application of Differin. No
effects on the suckling child are anticipated since the systemic exposure of the breast-feeding woman
to Adapalene Gel is negligible.
Adapalene Gel can be used during breastfeeding. To avoid contact exposure of the infant, application
of Adapalene Gel to the chest should be avoided when used during breast-feeding.

Based upon the pharmodynamic profile and clinical experience, performance related to driving and
using machines should not be affected.

Adapalene gel 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 Adapalene gel required to produce toxic effects in mice is greater that 10
mg/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 keratinization 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 proinflammatory
mediators. This profile suggests that the cell mediated inflammatory component of acne
may be modified by adapalene.

Absorption of adapalene through human skin is low, in clinical trial measurable plasma adapalene
levels where 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.

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 symptom of toxicity found in all animal
species by the oral route were related to a hypervitaminosis A syndrome, and included bone
dissolution, elevated alkaline phosphatase and a slight anaemia. Large oral doses of adapalene
produced no adverse neurological, caridovascular 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 circukating levels of adapalene at least 300 times those demonstrated in
clinical use developed normally.

Carbopol 974P

Propylene Glycol 

Disodium Edetate 

Methylparaben

Propylparaben

Sodium Lauryl Sulphate 

Triethanolamine or Diethanolamine 

Purified water 

Not Known

Do not store above 30 C.

Advice to be used within 3 months of tube opening.

Keep out of the reach of children.

Packed in 30 gm Aluminum collapsible tubes with HDPE screw cap.

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