Cutaneous treatment of Acne vulgaris when comedones, papules and pustules are present (See
section 5.1).
Adzoy is indicated in adults, adolescents and children aged 9 years and over.

Adzoy should be applied to the entire acne affected areas once a day in the evening on a clean and
dry skin. A thin film of gel should be applied, with the fingertips, avoiding the eyes and lips (see
section 4.4).
If irritation occurs, the patient should be directed to apply non-comedogenic moisturizers, to use
the medication less frequently (e.g. every other day), to suspend use temporarily, or to discontinue
use altogether.
The duration of treatment should be determined by the Doctor on the basis of the clinical condition.
Early signs of clinical improvement usually appear after 1 to 4 weeks of treatment.
The safety and effectiveness of Adzoy have not been studied in children below 9 years of age.

Adzoy Gel should not be applied to damaged skin, either broken (cuts or abrasions), eczematous
or sunburned.
Adzoy should not come into contact with the eyes, mouth, nostrils or mucous membranes. If
product enters the eye, wash immediately with warm water.
This product contains propylene glycol (E1520) that may cause skin irritation.

If a reaction suggesting sensitivity to any component of the formula occurs, the use of Adzoy
should be discontinued.
Excessive exposure to sunlight or UV radiation should be avoided.
Adzoy should not come into contact with any coloured material including hair and dyed fabrics as
this may result in bleaching and discoloration.

No interaction studies have been performed.
From previous experience with adapalene and benzoyl peroxide, there are no known interactions
with other medicinal products which might be used cutaneously and concurrently with Adzoy.
However, other retinoids or benzoyl peroxide or drugs with a similar mode of action should not be
used concurrently. Caution should be exercised if cosmetics with desquamative, irritant or drying
effects are used, as they may produce additive irritant effects with Adzoy.
Absorption of adapalene through human skin is low (see section 5.2), and therefore interaction
with systemic medicinal products is unlikely.
The percutaneous penetration of benzoyl peroxide in the skin is low and the drug substance is
completely metabolised into benzoic acid which is rapidly eliminated. Therefore, the potential
interaction of benzoic acid with systemic medicinal products is unlikely to occur.

Orally administered retinoids have been associated with congenital abnormalities. When used in
accordance with the prescribing information, topically administered retinoids are generally
assumed to result into low systemic exposure due to minimal dermal absorption. However, there could be individual factors (e.g. damaged skin barrier, excessive use) that contribute to an
increased systemic exposure.
Pregnancy
Adzoy is contraindicated (see section 4.3) in pregnancy, or in women planning a pregnancy.
There are no or limited amount of data from the use of adapalene topically in pregnant women.
Animal studies by the oral route have shown reproductive toxicity at high systemic exposure (see
section 5.3).
Clinical experience with locally applied adapalene and benzoyl peroxide in pregnancy is limited.
If the product is used during pregnancy, or if the patient becomes pregnant while taking this drug,
treatment should be discontinued.
Breastfeeding
No study on animal or human milk transfer was conducted after cutaneous application of Adzoy
(adapalene / benzoyl peroxide) Gel.
No effects on the suckling child are anticipated since the systemic exposure of the breast-feeding
woman to Adzoy is negligible. Adzoy can be used during breast-feeding.
To avoid contact exposure of the infant, application of Adzoy to the chest should be avoided when
used during breast-feeding.
Fertility
No human fertility studies were conducted with Adzoy gel.
However, no effects of adapalene or benzoyl peroxide on fertility were found in rats in
reproductive studies (See section 5.3).

Not relevant.

Adzoy may cause the following adverse reactions at the site of application:

*Post marketing surveillance data
**Most of the cases of “application site burn” were superficial burns but cases with second degree
burn or severe burn reactions have been reported.
If skin irritation appears after application of Adzoy, the intensity is generally mild or moderate,
with local tolerability signs and symptoms (erythema, dryness, scaling, burning and pain of skin
(stinging pain) peaking during the first week and then subsiding spontaneously.
To report any side effect(s):
• Saudi Arabia:
The National Pharmacovigilance and Drug Safety Centre (NPC)
Fax: +966-11-205-7662
SFDA Call Center: 19999
E-mail: npc.drug@sfda.gov.sa
Website: https://ade.sfda.gov.sa
• Other GCC States:
− Please contact the relevant competent authority

Adzoy is for once-daily cutaneous use only.
In case of accidental ingestion, appropriate symptomatic measures should be taken.

Pharmacotherapeutic group: Anti-Acne Preparations for Topical Use, D10AD Retinoids for
topical use in acne;
ATC code: D10AD53
Mechanism of action and Pharmacodynamic effects
Adzoy combines two active substances, which act through different, but complementary,
mechanisms of action.
- Adapalene: Adapalene is a chemically stable, naphthoic acid derivative with retinoid-like
activity. Biochemical and pharmacological profile studies have demonstrated that adapalene acts
in the pathology of Acne vulgaris: it is a potent modulator of cellular differentiation and
keratinisation and it has anti-inflammatory properties. Mechanistically, adapalene binds to specific
retinoic acid nuclear receptors. Current evidence suggests that topical adapalene normalizes the
differentiation of follicular epithelial cells resulting in decreased microcomedone formation.
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 to inflammatory mediators. In vitro studies have shown inhibition of the AP-1
factors and the inhibition of the expression of toll like receptors 2. This profile suggests that the
cell mediated inflammatory component of acne is reduced by adapalene.
- Benzoyl peroxide: Benzoyl peroxide has been shown to have antimicrobial activity; particularly
against P. acnes, which is abnormally present in the acne-affected pilosebaceous unit. Additionally
benzoyl peroxide has demonstrated exfoliative and keratolytic activities. Benzoyl peroxide is also
sebostatic, counteracting the excessive sebum production associated with acne.

Clinical efficacy of Adzoy in patients aged 12 years and older
The safety and efficacy of Adzoy applied once daily for the treatment of acne vulgaris were
assessed in two 12-week, multicenter, controlled clinical studies of similar design, comparing
Adzoy to its individual active components, adapalene and benzoyl peroxide, and to the gel vehicle
in acne patients. A total of 2185 patients were enrolled in Study 1 and Study 2. The distribution of
patients in the two studies was approximately 49% male and 51% female, 12 years of age or older
(mean age: 18.3 years; range 12 – 50), presenting 20 to 50 inflammatory lesions and 30 to 100
noninflammatory lesions at baseline. The patients treated the face and other acne affected areas as
needed once daily in the evening.
The efficacy criteria were:
Success rate, percentage of patients rated 'Clear' and 'Almost Clear' at Week 12 based on the
Investigator's Global Assessment (IGA);
Change and Percent Change from baseline at Week 12 in:
Inflammatory lesion counts
Non-inflammatory lesion counts
Total lesion count
The efficacy results are presented for each study in Table 1 and combined results in Table 2. Adzoy
was shown to be more effective compared to its monads and gel vehicle in both studies. Overall,
the net beneficial effect (active minus vehicle) obtained from Adzoy was greater than the sum of
the net benefits obtained from the individual components, thus indicating a potentiation of the
therapeutic activities of these substances when used in a fixed-dose combination. An early
treatment effect of Adzoy was consistently observed in Study 1 and Study 2 for Inflammatory
Lesions at Week 1 of treatment. Noninflammatory lesions (open and closed comedones) noticeably
responded between the first and fourth week of treatment. The benefit on nodules in acne has not
been established.

Table 1 Clinical efficacy in two comparative trials

Study 1

Table 2 Clinical efficacy in combined comparative trials

Clinical efficacy of Adzoy in children 9 to 11 years old
During a paediatric clinical trial, 285 children with acne vulgaris, aged 9 – 11 years (53% of the
subjects were 11 years old, 33% were 10 years old and 14% were 9 years old) with a score of 3
(moderate) on the IGA scale and a minimum of 20 but not more than 100 total lesions
(Noninflammatory and/or Inflammatory) on the face (including the nose) at baseline were treated
with Adzoy Gel once daily for 12 weeks.

The study concludes that the efficacy and safety profiles of Adzoy Gel in the treatment of facial
acne in this specific younger age group are consistent with results of other pivotal studies in
subjects with acne vulgaris aged 12 years and older showing significant efficacy with an acceptable
tolerability. A sustained early treatment effect of Adzoy Gel compared to Gel Vehicle was
consistently observed for all Lesions (Inflammatory, Non-Inflammatory, and Total) at Week 1 and
continuing to Week 12.

The pharmacokinetic (PK) properties of Adzoy are similar to the PK profile of Adapalene 0.1%
gel alone.
In a 30-day clinical PK study, conducted in patients with acne who were tested with either the
fixed-combination gel or with an adapalene 0.1% matched formula under maximised conditions
(with application of 2 g gel per day), adapalene was not quantifiable in the majority of plasma
samples (limit of quantification 0.1 ng/ml). Low levels of adapalene (Cmax between 0.1 and 0.2
ng/ml) were measured in two blood samples taken from the subjects treated with Adzoy and in
three samples from the subjects treated with Adapalene 0.1% Gel. The highest adapalene AUC 0-
24h determined in the fixed-combination group was 1.99 ng.h/ml.

These results are comparable to those obtained in previous clinical PK studies on various
Adapalene 0.1% formulations, where systemic exposure to adapalene was consistently low.
The percutaneous penetration of benzoyl peroxide is low; when applied on the skin, it is completely
converted into benzoic acid which is rapidly eliminated.

Preclinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, genotoxicity, phototoxicity or carcinogenicity.
Reproductive toxicology studies with adapalene have been performed by the oral and dermal
routes of administration in the rat and rabbit. A teratogenic effect has been demonstrated at high
systemic exposures (oral doses from 25 mg/kg/day). At lower exposures (dermal dose of 6
mg/kg/day), changes in the numbers of ribs or vertebrae were seen.
Animal studies performed with Adzoy include local tolerance studies and dermal repeat-dose
toxicity studies in rat, dog and minipig up to 13 weeks and demonstrated local irritation and a
potential for sensitisation, as expected for a combination containing benzoyl peroxide. Systemic
exposure to adapalene following repeat dermal application of the fixed combination in animals is
very low, consistent with clinical pharmacokinetic data. Benzoyl peroxide is rapidly and
completely converted to benzoic acid in the skin and after absorption is eliminated in the urine,
with limited systemic exposure.
Reproductive toxicity of adapalene was tested by the oral route in rats for fertility.
There were no adverse effects upon reproductive performance and fertility, F1 litter survival,
growth and development to weaning, and subsequent reproductive performance following
treatment with adapalene oral at doses up to 20 mg/kg/day.
A reproductive and developmental toxicity study conducted in rats exposed groups to oral doses
of benzoyl peroxide of up 1000 mg/kg/day (5 mL/kg) showed that Benzoyl peroxide did not induce
teratogenicity or effects on reproductive function at doses up to 500 mg/kg/day.

 Glycerol
 Propylene glycol
 Edetate Disodium (EDTA)
 Docusate Sodium
 Poloxamer 124 Ph. Eur (Kollisolv P 124)
 Sepineo P600
 Purified water

Not applicable.

Do not store above 30°C.

Pack Size: 1X60 gm.

No special requirements.