No known cases of azelaic acid overdosage resulting from topical administration of Azix-Derm 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.
None known.
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).
| System Organ Class | Very Common | Common | Uncommon | Rare | Not known1 |
| Skin and subcutaneous tissue disorders | seborrhoea, acne, skin depigmentation | cheilitis | Urticaria rash | ||
| General disorders and administration site conditions | application site burning, application site pruritus, application site erythema | application site exfoliation, application site pain, application site dryness, application site discolouration, application site irritation | application site paraesthesia, application site dermatitis, application site discomfort, application site oedema | application site vesicles, application site eczema, application site warmth, application site ulcer, | |
| Immune system disorders | drug hypersensitivity, worsening of asthma | angioedema2, dermatitis contact2 , eye swelling2, swelling face2 |
1 These additional adverse reactions have been reported during post-approval use of Azix-Derm 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.
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 Azix-Derm.
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
Topical treatment of acne vulgaris.
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 Azix-Derm 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.
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 Azix-Derm Cream.
Worsening of asthma in patients treated with azelaic acid has been reported rarely during post-marketing surveillance.
Azix-Derm contains a small amount of benzoic acid, which is mildly irritating to the skin, eyes and mucous membranes.
Azix-Derm also contains propylene glycol, which may cause skin irritation.
Azix-Derm Cream has no influence on the ability to drive and use machines.
Method of administration
Cutaneous use
Dosage regimen
Azix-Derm 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 Azix-Derm only once a day (in the evening) for the first week of treatment and then proceed to twice daily applications.
Before Azix-Derm 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 Azix-Derm Cream can vary from patient to patient and also depends on the severity of the acne.).
It is important to continue to use Azix-Derm 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 Azix-Derm 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 Azix-Derm Cream is administered to adolescents aged 12 - 18 years.
The safety and efficacy of Azix-Derm 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.
No special requirements.
