Adapalene
DESCRIPTION:
Deriva Aqueous Gel, containing adapalene, is used for the
topical treatment of acne vulgaris.
COMPOSITION:
Adapalene 0.1%w/w
in a aqueous gel base.
Preservatives:
Methyl paraben IP 0.1%w/w
Phenoxyethanol BP 0.25% w/w
CLINICAL PHARMACOLOGY:
Adapalene is a chemically stable, retinoid-like compound.
Biochemical and pharmacological profile studies twice
demonstrated that adapalene is a modulator of cellular
differentiation, keratinization, 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 does not bind to the cytosolic receptor
protein. Although the exact mode of action of adapalene is
unknown, it is suggested that topical adapalene may normalize
the differentiation of follicular epithelial cells resulting in
decreased microcomedone formation.
PHARMACOKINETICS: Absorption of adapalene through
human skin is low. Only trace amounts (<0.25 ng/ml) of parent
substance have been found in the plasma of acne patients
following chronic topical application of adapalene in controlled
trials. Excretion appears to be primarily by biliary route.
INDICATIONS AND USAGE:
Deriva Aqueous Gel is indicated for the topical treatment of
acne vulgaris.
CONTRAINDICATIONS:
Deriva Aqueous Gel should not be administered to individuals
who are hypersensitive to adapalene or any of the components
in the vehicle gel.
WARNINGS:
Use of Deriva Aqueous Gel should be discontinued if
hypersensitivity to any of the ingredients is noted. Patients
with sunburn should be advised not to use the product until
fully recovered.
PRECAUTIONS:
General: If a reaction suggesting sensitivity or chemical
irritation occurs, use of the medication should be discontinued.
Exposure to sunlight, including sunlamps, should be minimized'
during the 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. Weather
extremes, such as wind or cold, also may be irritating to
patients under treatment with adapalene.
Avoid contact with the eyes, lips, angles of the nose, and
mucous membranes. The product should not be applied to
cuts, abrasions, eczematous skins, or sunburned skin.
Certain cutaneous signs and symptoms such as erythema,
dryness, scaling, burning or pruritus may be experienced
during treatment. These are most likely to occur during the
first two to four weeks and will usually lessen with continued
use of the medication. Depending upon the severity of adverse
events, patients should be instructed to reduce the frequency
of application or discontinue use.
Drug Interactions: As Deriva Aqueous Gel has the potential
to produce local irritation in some patients, concomitant use
of other potentially irritation topical products (medicated or
abrasive soaps, and cleansers , soaps and cosmetics that
have a strong drying effect, and products with high
concentrations of alcohol, astringents, spices, or lime) should
be approached with caution. Particular caution should be
exercised in using preparations containing sulfur, resorcinol,
or salicylic acid in combination with Deriva Aqueous Gel. If
these preparations have been used, it is advisable not to start
therapy with Deriva Aqueous Gel until the effects of such
preparations in the skin have subsided.
Carcinogenesis, mutagenesis , impairment of fertility :
Carcinogenicity studies with adapalene have been conducted
in mice at topical doses 0f 0.3,0.9 and 2.6 mg/kg/day and in
rats at oral doses of 0.15,0.5 and 1.5 mg/kg/day, approximately-
4-75 times the maximal daily human topical dose. In the oral-
study, positive linear trends were observed in the incidence
of follicular cell adenomas and carcinomas in the thyroid
glands of female rats and in the incidence of benign and
malignant pheochromocytoma in the adrenal medullas of
male rats.
No photocarcinogenicity studies were conducted. Animal
studies have shown as increased tumorigenic risk with the
use of pharmacologically similar drugs (e.g., retinoids) when
exposed to UV irradiation in the laboratory or to sunlight.
Although the significance of these studies to human use is
not clear, patients should be advised to avoid or minimize
exposure to either sunlight or artificial UV irradiation sources.
In a series of in vivo and vitro studies, adapalene did not
exhibit mutagenic or genotoxic activities.
Pregnancy: Teratogenic effects. Pregnancy category C.
No teratogenic effects were seen in rats at oral doses of
adapalene 0.15 to 5.0 mg/kg/day, up to 120 times the maximal
daily human, topical dose. Cutaneous route teratology studies
conducted in rats and rabbits at doses of 0.6, 2.0 and 6.0
mg/kg/day, up to 150 times the maximal daily human topical
dose exhibited no fetotoxicity and only minimal increases in
supernumerary ribs in rats. There are no adequate and well-
controlled studies in pregnant women. Adapalene should be
used during pregnancy only if the potential benefit justifies
the potential risk to the fetus.
Nursing Mothers: It is not known whether this drug is excreted
in human milk. Because many drugs are excreted in human
milk, caution should be exercised when Deriva Aqueous Gel
is administered to a nursing woman.
Pediatric Use: Safety and effectiveness in pediatric patients
below the age of 12 have not been established.
ADVERSE REACTIONS:
Some adverse effects such as erythema, scaling, dryness,
pruritus and burning will occur in 10-40% of patients. Pruritus
or burning immediately after application also occurs in
approximately 20% of patients. The following additional
adverse experiences were reported in approximately 1 % or
sunburn, and acne flares. These are most commonly seen
during the first month of therapy and decrease in frequency
and severity thereafter. All adverse effects with use of Deriva
Aqueous Gel during clinical trials were reversible upon
discontinuation of therapy.
OVERDOSAGE:
Deriva Aqueous Gel is intended for cutaneous use only. If
the medication is applied excessively, no more rapid or better
results will be contained and marked redness, peeling or
discomfort may occur. The acute oral toxicity of Deriva Aqueous
Gel in mice and rats is greater than 10 mL/kg. Chronic ingestion
of the drug may lead to the same side effects as those
associated with excessive oral intake of Vitamin A.
DOSAGE AND ADMINISTRATION:
Deriva Aqueous Gel should be applied once a day to affected
areas after washing in the evening before retiring. A thin film
of the gel should be applied, avoiding eyes, lips and mucous
membranes.
During the early weeks of therapy, an apparent exacerbation
of acne may occur. This is due to the action of the medication
on previously unseen lesions and should not be considered
a reason to discontinue therapy. Therapeutic results should
be noticed after eight to twelve weeks of treatment.