Text draft from 26.08.2015 <invented name> 1 mg/g cream Page 1 cream Dokument1 __________________________________________________________________________ SUMMARY OF PRODUCT CHARACTERISTICS / SmPC 1. NAME OF THE MEDICINAL PRODUCT <invented name> 1 mg/g cream 2. QUALITATIVE AND QUANTITATIVE COMPOSITION 1 g cream contains 1 mg adapalene Excipients with known effect: 2 mg methylparahydroxybenzoate, 1 mg propylparahydroxybenzoate. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Cream White cream 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Topical facial treatment of acne vulgaris where comedones predominate and papules and pustules are present. 4.2 Posology and method of administration <invented name> should be applied thinly once a day to the affected areas before retiring and after washing. Before application of <invented name>, the skin should be washed and thoroughly dried. The cream should be applied thinly with the fingertips to the affected areas. <invented name> is only for external use. Clinical improvement is seen within a time period of 4 to 8 weeks and continues during further treatment. Sufficient clinical experience is available for up to a 12 week treatment period. The duration of treatment is decided by the doctor depending on the clinical picture. With patients for whom it was necessary to temporarily discontinue treatment or reduce frequency of application, therapy may be resumed or the frequency of application may be restored when the reasons for previously mentioned measures no longer apply. Paediatric population The safety and efficacy of <invented name> in children below 12 years of age have not been established. No data are available. 4.3 Contraindications Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Text draft from 26.08.2015 <invented name> 1 mg/g cream Page 2 cream Dokument1 __________________________________________________________________________ 4.4 Special warnings and precautions for use For external use only. If a reaction suggesting sensitivity or severe irritation occurs, use of the medication should be discontinued. If the degree of local irritation warrants, the patient should be directed to use the medication less frequently, to discontinue use temporarily until symptoms subside or to discontinue use altogether. Frequency of application may be restored or therapy resumed once it is judged that the patient can again tolerate the treatment. <invented name> should not come into contact with the eyes, mouth, angles of the nose, mucous membranes or open wounds. If product enters the eye, wash immediately with warm water. The product should not be applied to either broken (cuts and abrasions), sunburnt or eczematous skin, or in cases of dermatitis. <invented name> should not be used in patients with severe cases of acne vulgaris or secondary types of acne such as chloracne as the efficacy and tolerance have not been investigated. Patients should be informed that an increase in the frequency of use (more than twice daily) will not improve the therapeutic effect but will increase skin erythema and skin exfoliation. These symptoms are reversible. Exposure to sunlight and artificial UV irradiation, including sunlamps, should be minimized during use of adapalene. Use of sunscreen products and protective clothing over treated areas is recommended when exposure cannot be avoided. <invented name> may cause local irritation, therefore it is possible that concomitant use of peeling agents, abrasive cleansers, desiccating or irritant products may produce additive irritant effect (see section 4.5). Concomitant use of <invented name> and epilation (waxing) may in very rare cases lead to skin lesions. Epilation (waxing) should therefore be avoided on <invented name> treated areas of the skin. Paediatric population The safety and efficacy of <invented name> in children below 12 years of age has not been established. No data are available. Methyl parahydroxybenzoate and propyl parahydroxybenzoate may cause allergic reactions (possibly delayed). 4.5 Interaction with other medicinal products and other forms of interaction Absorption of adapalene through human skin is low, and therefore interaction with systemic medications is unlikely. Adapalene is essentially stable to oxygen and light and is chemically non-reactive. Cutaneous antiacne treatments such as erythromycin (up to 4%) or clindamycin phosphate (1% as the base) solutions or benzoyl peroxide water based gels (up to 10%) may be used in the morning when <invented name> is used at night as there is no mutual degradation or cumulative irritation. However, other retinoids or drugs with a similar mode of action should not be used concurrently with <invented name>. Text draft from 26.08.2015 <invented name> 1 mg/g cream Page 3 cream Dokument1 __________________________________________________________________________ <invented name>has a potential for mild local irritation, and therefore it is possible that concomitant use of peeling agents, abrasive cleansers, strong drying agents, astringents or irritant products (aromatic and alcoholic agents) may produce additive irritant effects (see section 4.4). 4.6 Fertility, pregnancy and lactation Pregnancy Animal studies by the oral route have shown reproductive toxicity at high systemic exposure (see section 5.3). Clinical experience with locally applied adapalene in pregnancy is limited but the few available data do not indicate harmful effects on early pregnancy or on the health of the foetus. Due to the limited available data and because a very weak cutaneous passage of adapalene is possible, adapalene should not be used during pregnancy. In case of unexpected pregnancy, treatment should be discontinued. Lactation No study on animal or human milk transfer was conducted after cutaneous application of adapalene. No effects on the suckling child are anticipated since the systemic exposure of the breast- feeding woman to adapalene is negligible. Adapalene can be used during breastfeeding. To avoid contact exposure of the infant, application of adapalene to the chest should be avoided when used during breast-feeding. 4.7 Effects on ability to drive and use machines Adapalene has no or negligible influence on the ability to drive and use machines. 4.8 Undesirable effects System organ Frequency Adverse Drug Reaction class Skin and Common (≥1/100 Dry skin, skin irritation, skin burning sensation, subcutaneous to <1/10) erythema tissue disorders Uncommon Contact dermatitis, skin discomfort, sunburn, (≥1/1000 to pruritus, skin exfoliation, acne <1/100) Rare (≥1/10,000 to Pain of skin, skin swelling, <1/1000) Not known (cannot be estimated from Hypopigmentation, hyperpigmentation the available data)* Eye disorder Rare (≥1/10,000 to Eyelid irritation, eyelid erythema, eyelid <1/1000) pruritus, eyelid swelling Text draft from 26.08.2015 <invented name> 1 mg/g cream Page 4 cream Dokument1 __________________________________________________________________________ *Post marketing surveillance data In the case of moderate side effects, the frequency of use of <invented name> can be reduced to every second day for a two week period. If necessary, use of <invented name> can be temporarily discontinued until the symptoms have subsided. Methyl parahydroxybenzoate and Propyl parahydroxybenzoate may cause allergic reactions (possibly delayed). 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 national reporting system listed in Appendix V. 4.9 Overdose Adapalene products are not to be taken orally and are 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. Following accidental contact of <invented name> with the eyes, they should be washed with lukewarm water. The acute oral dose of <invented name> required to produce toxic effects in mice and rats is greater than 10 g/kg. Nevertheless, unless the amount accidentally ingested is small, an appropriate method of gastric emptying should be considered. 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Anti-acne preparations for topical use, retinoids for topical use in acne ATC code: D10 AD03 Adapalene is an effective, chemically stable, retinoid-like compound with additional anti- inflammatory properties. Adapalene binds like tretinoin to specific nuclear receptors but, unlike tretinoin, not to cytosolic receptor binding proteins which are located outside of the nucleus. Adapalene applied cutaneously is comedolytic in an experimental acne-animal model (rhino-mouse). The rhino-mouse is characterized through occurrence of numerous comedoyltic-similar structures in the skin. Adapalene also has effects on the abnormal processes of epidermal keratinisation and differentiation, both of which play a fundamental role in the pathogenesis of acne vulgaris. The mode of action of adapalene is suggested to be a normalisation of differentiation of follicular epithelial cells resulting in decreased microcomedone formation. Text draft from 26.08.2015 <invented name> 1 mg/g cream Page 5 cream Dokument1 __________________________________________________________________________ Adapalene is more anti-inflammatory than reference