Azelic

Topical treatment of acne vulgaris.

Method of administration

Cutaneous use

Dosage regimen

Azelic Cream should be applied to the affected areas of skin twice daily (mornings and evenings), and rubbed in gently. As a guide 2.5 cm (approx. 0.5 g) of cream is sufficient for the entire facial area. If other areas of acne, in addition to the face require treatment, for example the chest and back, the amount of cream should be adjusted accordingly.

Patients with sensitive skin should be advised to use Azelic only once a day (in the evening) for the first week of treatment and then proceed to twice daily applications.

Before Azelic Cream is applied, the skin should be thoroughly cleaned with plain water and dried. A mild skin-cleansing agent may be used.

The duration of use of Azelic Cream can vary from patient to patient and also depends on the severity of the acne.).

It is important to continue to use Azelic Cream regularly over the entire period of treatment. However, in the event of intolerable skin irritation , the amount of cream per application should be reduced or the frequency of use of Azelic Cream should be reduced to once a day until the irritation ceases. If required, treatment might have to be temporarily interrupted for a few days.

Additional information on special populations

Paediatric population

Use in adolescents (12 - 18 years of age): dose adjustment is not required when Azelic Cream is administered to adolescents aged 12 - 18 years.

The safety and efficacy of Azelic Cream in children below the age of 12 years have not been established.

Geriatric patients

No targeted studies have been performed in patients aged 65 and over.

Patients with hepatic impairment

No targeted studies have been performed in patients with hepatic impairment.

Patients with renal impairment

No targeted studies have been performed in patients with renal impairment.

For external use only.

). In the event of accidental contact, the eyes, mouth and/or affected mucous membranes should be washed with large amounts of water. If eye irritation persists, patients should consult a physician. The hands should be washed after each application of Azelic Cream.

Worsening of asthma in patients treated with azelaic acid has been reported rarely during post-marketing surveillance.

Azelic contains a small amount of benzoic acid, which is mildly irritating to the skin, eyes and mucous membranes.

Azelic also contains propylene glycol, which may cause skin irritation.

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

From clinical studies and post-marketing surveillance, the most frequently observed side-effects included application site burning, application site pruritus and application site erythema.

Frequencies of side-effects observed in clinical studies and post-marketing surveillance and given in the table below are defined according to the MedDRA frequency convention:

Very common (>1/10), Common (>1/100 to <1/10), Uncommon (>1/1,000 to <1/100), Rare (>1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).

¹ These additional adverse reactions have been reported during post-approval use of Azelic cream (frequency unknown).

² may occur with hypersensitivity

Generally, local skin irritation regresses in the course of treatment.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions 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 adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

No known cases of azelaic acid overdosage resulting from topical administration of Azelic Cream have been reported. Results from acute toxicity studies do not indicate that any risk of acute intoxication is to be expected following a single dermal application of an overdose (application over a large area under conditions favourable to absorption) or inadvertent oral ingestion. Due to the very low local and systemic toxicity of azelaic acid intoxication is unlikely.

Pharmacotherapeutic group: other anti-acne preparations for topical use.

ATC Code: D10AX03

The antimicrobial action and a direct influence on follicular hyperkeratosis are assumed to be the basis for the therapeutic efficacy of Azelic in acne.

Clinically, a significant reduction of the colonization density of Propionibacterium acnes and a significant reduction of the fraction of free fatty acids in the skin surface lipids is observed.

In vitro and in vivo, azelaic acid inhibits the proliferation of keratinocytes and normalizes the disturbed terminal epidermal differentiation processes in acne. In the rabbit ear model, azelaic acid accelerates the comedolysis of tetradecane-induced comedones.

There is clinical experience for a continuous application time period of up to one year.

After dermal administration of the cream, azelaic acid penetrates into all layers of human skin. The penetration is more rapid into damaged skin than into intact skin. A total of 3.6% of the administered dose was absorbed percutaneously after a single topical administration of 1 g azelaic acid (5 g cream).

A portion of the azelaic acid which is absorbed through the skin is eliminated unchanged with the urine. The remaining portion is metabolized through beta- oxidation into short-chained dicarboxylic acids (C₇, C₅ carboxylic acids) which have likewise been found in the urine.

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, contact hypersensitivity, genotoxicity and toxicity to reproduction and development.

Embryofetal developmental studies with oral administration of azelaic acid to rats, rabbits, and cynomolgus monkeys during the period of organogenesis revealed embryotoxicity at doses where some maternal toxicity was noted.).

In a peri- and post-natal developmental study in rats where azelaic acid was administered orally from gestational day 15 to through day 21 postpartum slight disturbances in the post-natal development of fetuses were noted at oral doses that generated some maternal toxicity. The NOAEL was 3 times the MRHD based on BSA. No effects on sexual maturation of the fetuses were noted in this study.

Studies on impairment of fertility in animals have not produced any evidence for such a risk during therapeutic use of Azelic.

If azelaic acid came into contact with the eyes of monkeys and rabbits, signs of moderate to severe irritation became evident. Therefore, contact with the eyes should be avoided.

Azelaic acid administered once intravenously had no effects on the nervous system (Irwin test), cardiovascular function, intermediary metabolism, smooth muscles and liver and kidney function

None known.

No special requirements.