Differin Gel
Adapalene 0.1%
Presentation
Differin gel is a smooth white gel containing 1 mg/g adapalene. The gel contains carbomer 980, propylene glycol, poloxamer, disodium edetate, methyl hydroxybenzoate, phenoxyethanol, sodium hydroxide and purified water.
Actions
Adapalene is a chemically stable retinoid-like compound. Although the exact mode of action of adapalene is unknown, evidence suggests that adapalene normalises the differentiation of follicular epithelial cells by binding to specific retinoic acid receptors thereby decreasing microcomedone formation. Biochemical and pharmacological profile studies have demonstrated that adapalene is a potent modulator of cellular differentiation, keratinisation and inflammatory processes all of which represent important features in the pathology of acne vulgaris.
Mechanistically, adapalene binds to specific retinoic acid nuclear receptors but unlike tretinoin, does not bind to the cytosolic receptor protein. Adapalene inhibits the chemotactic (directional) and chemokinetic (random) responses of human polymorphonuclear leucocytes in in vitro assay models. It also inhibits the metabolism of arachidonic acid by lipoxidation, to inflammatory mediators.This profile suggests that the cell mediated inflammatory components of acne is modified by adapalene. Studies on Differin Gel in human patients provide clinical evidence that adapalene is effective in reducing the inflammatory components of acne (i.e. papules and pustules).
Pharmacokinetics
Absorption through the human skin is low; in clinical trials adapalene was seldom detected in plasma, and then only in trace amounts following chronic topical application with an analytical limit of quantification of 0.25 nanograms/mL. After administration of (14C)-adapalene to rats, rabbits and dogs, radioactivity was distributed in several tissues, the highest levels being found in liver, spleen, adrenals and ovaries. Metabolism in animals is maintained by O-demethylation, hydroxylation and conjugation, and excretion is primarily by the biliary route.
Indications
Differin gel 0.1% is proposed for the topical treatment of Grade II - Grade III acne (acne vulgaris) where comedones, papules and pustules predominate.
Safety and effectiveness have not been established in severe pustular and deep cystic nodular acne (acne conglobulata ).
Dosage and Administration
Differin Gel should be applied to the affected areas once a day before retiring and after washing. A thin film of gel should be applied to the dried areas using the fingertips and avoiding the eyes and lips (see Warnings and Precautions below).
Clinical improvement is expected to be clearly evident after four to eight weeks of treatment, with further improvement expected with continued use. The cutaneous safety of Differin gel has been demonstrated in 181 patients over six months of treatment. Since it is customary to alternate therapies in the treatment of acne, it is recommended that the physician assess the improvement of the patient after three months of treatment with Differin Gel.
In 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. Only oil-free moisturisers should be used to relieve dry facial skin.
The safety and effectiveness of Differin gel has not been studied in neonates and young children.
Contraindications
Hypersensitivity to any ingredient of the product.
Warnings and Precautions
If severe irritation occurs, patients should be directed to use the medication less frequently, to temporarily discontinue use or to discontinue use altogether.
Differin gel is for external use only and should not come into contact with the eyes, mouth, angles of the nose or mucous membranes. If product enters the eye, wash with warm water.The product should not be applied to broken skin (cuts or abrasions) or to eczematous or psoriatic skin.
Because of a potential for increased irritation Differin gel should not be used by patients with eczema or seborrhoeic dermatitis.
Adapalene is essentially stable to oxygen and light and is chemically non-reactive. Animal studies on compounds with a similar mode of action to adapalene have suggested that these may enhance the development of skin cancers caused by UV light. Whilst short term studies have shown no phototoxic to photoallergic potential of adapalene, small numbers of reactions consistent with phototoxicity were reported in clinical studies, the safety of using adapalene during long or repeated exposures to sunlight or UV radiation has not been established in animals or humans. Exposure to excessive sunlight or UV irradiation (including sunlamps) should be avoided during treatment with adapalene.
Use in pregnancy
There are no adequate or well controlled reproduction studies in pregnant women. Because of the potential risk of adverse effects on foetal development at high systemic exposure levels, it is prudent to avoid use of this drug during pregnancy unless clearly needed.
In rats and rabbits, adapalene administered orally at relatively high doses (25 mg/kg or greater) was found to induce foetal abnormalities. In addition the incidences of various skeletal variations were increased at lower oral dose in rats. Topical administration at doses up to 6 mg/kg resulted in exposure levels lower than those associated with teratogenicity following oral administration. Nevertheless, increased incidences of various naturally occurring skeletal variations were still observed following topical administration to rats 2mg/kg and to rabbits at 6 mg/kg; topical no effect levels were 0.6 and 2 mg/kg respectively. Adapalene is not mutagenic. Large oral doses of adapalene produced no adverse neurological, cardiovascular or respiratory effects in animals.
Use in lactation
It is not known whether this drug is excreted in human milk. Differin gel should be avoided in lactating women.
Adverse Effects
In clinical trials of efficacy and safety with Differin Gel the total incidence of adverse reactions related to treatment was 4.2% (28 reports from 661 participants). The most frequent adverse reactions reported were erythema (0.9%), dry skin (0.9%), skin irritation (0.6%), burning and stinging (0.6%) and acne flare (0.5%). Other adverse experiences which were attributed to treatment or were possibly related to treatment but occurred less frequently (in less than 0.5% of patients) were pruritis and one case of sunburn. None of the reactions was severe and most occurred within one month of the initiation of therapy and were observed to resolve with continued use of the product or temporary adjustment of the treatment schedule.
The major side effect of Differin Gel is skin irritation which is reversible when treatment is discontinued or reduced in frequency. A feeling of burning, pruritis, dryness, scaling or stinging may occur following application.
Interactions
There are no known interactions with other medications which might be used topically and concurrently with Differin topical gel; however other retinoids or drugs with a similar mode of action should not be used concurrently with adapalene.
Absorption of adapalene through human skin is low (see Pharmacokinetic properties) and therefore interaction with systemic medication is unlikely.
Differin topical gel has potential for local irritation and it is possible that concomitant use of peeling agents, astringents or irritant products may produce additive irritant effects. However cutaneous antiacne treatments e.g. erythromycin, clindamycin phosphate (1% as the base) solutions or benzoyl peroxide water based gels up to 10% may be used in the morning when Differin gel is used at night since no mutual degradation or cumulative irritation occurs with these products.
Overdosage
Differin gel is intended 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 Differin gel required to produce toxic effects in mice and rats is greater than 10mL.kg-1. Nevertheless unless the amount accidentally ingested is small, an appropriate method of gastric emptying should be considered.
Pharmaceutical Precautions
Store below 25°C (77°F). Keep out of reach of children. Do not freeze.
Package Quantities
Product is packaged in a low density polyethylene tube containing 30g of gel and fitted with a white polypropylene screw cap.
Further Information
Nil.
| 
