SCENESSE

SCENESSE should only be prescribed by specialist physicians in recognised porphyria centres and administration should be performed by a physician trained and accredited by the marketing authorisation holder to administer the implant.

Posology One implant is administered every 2 months prior to expected and during increased sunlight exposure. 1). 2. 4). Paediatric population The safety and efficacy of afamelanotide in children and adolescents aged 0 to 17 years have not yet been established.

No data are available. Method of administration For subcutaneous use. Instruction for use - Take the packed implant out of the refrigerator and allow the medicinal product to warm up to ambient temperature. - Have the patient sit in a comfortable position or lie on his/her back with the upper part of the body slightly raised.

- Disinfect the skin above the supra-iliac crest. - Anaesthetise the insertion area if deemed necessary and in consultation with the patient. 6 mm inner diameter) catheter with needle. 5 to 2 cm on the catheter shaft using surgical ink.

- Hold the catheter at its base using a sterile technique, pinch and hold the skinfold cranial to, or overlying the patient’s supra-iliac crest with two fingers. 5 to 2 cm into the subcutaneous layer at a 30 to 45 degree angle to the skin surface in one continuous flowing movement.

- With the catheter in place, aseptically remove the implant from the vial. - Remove the needle from within the catheter using a sterile technique. - Transfer the implant to the outlet of the catheter. - Using a suitable device (such as a stylet) gently push the implant down the full length of the catheter lumen.

- Apply some pressure to the insertion area with your finger while removing the stylet and the catheter. - Confirm insertion of the implant by palpating the skin with subcutis cranial to/overlying the suprailiac crest until the implant is located.

Always verify the presence of the implant, if in doubt of its presence, check whether the implant has remained in the catheter. If the implant has not been administered during the procedural steps described above, discard the implant and administer a new implant.

Do not administer a new implant unless it has been unequivocally confirmed that the first one had not been inserted. - Apply a small pressure dressing to the injection site. - Observe the patient for 30 minutes to ensure that you will notice if the patient develops an allergic or hypersensitivity reaction (immediate type).

Summary of the safety profile The safety profile is based on pooled data from clinical studies in 425 patients. The most commonly reported adverse reactions are nausea, experienced by approximately 19% of subjects who received treatment with this medicinal product, headache (20%), and implant site reactions (21%; mainly discolouration, pain, haematoma, erythema).

In most cases these adverse reactions are reported to be mild in severity. 4). Tabulated list of adverse reactions The adverse reactions reported during clinical studies conducted with afamelanotide are listed in the table below by MedDRA system organ class and frequency convention.

Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), and rare (≥1/10,000 to <1/1,000). System Organ Class Very common Common Uncommon Rare Infections and infestations Influenza Upper respiratory tract infection Cystitis Folliculitis Gastrointestinal infection Gastroenteritis Candida infection Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocyte naevus Haemangioma Blood and lymphatic system disorders Leukopenia Immune system disorders Hypersensitivity Anaphylaxis System Organ Class Very common Common Uncommon Rare Metabolism and nutrition disorders Decreased appetite Increased appetite Hypercholesterolaemia Psychiatric disorders Depressed mood including depression Insomnia Confusional state Nervous system disorders Headache Dizziness Migraine Somnolence Balance disorder Hyperaesthesia Lethargy Paraesthesia Poor quality sleep Presyncope Restless leg syndrome Syncope Dysgeusia Post-traumatic headache Eye disorders Dry eye Eye pain Ocular hyperaemia Photophobia Presbyopia Eyelid oedema Ear and labyrinth disorders Tinnitus Cardiac disorders Palpitations Tachycardia Vascular disorders Flushing Hot flush Haemorrhage Haematoma Hypertension Diastolic hypertension Respiratory, thoracic and mediastinal disorders Sinus congestion Gastrointestinal disorders Nausea Abdominal pain including abdominal discomfort Diarrhoea Toothache Vomiting Abdominal distension Defaecation disorders Dyspepsia Flatulence Gastroesophageal reflux disease Gastritis Irritable bowel syndrome Gingival pain Hypoaesthesia oral Lip swelling Bowel movement irregularity Cheilitis Gingival discolouration Lip discolouration Lip oedema Tongue discolouration Skin and subcutaneous tissue disorders Ephelides Erythema Pigmentation disorder Pruritus Rash including rash vesicular, rash Acne Dermatitis contact Dry skin Eczema Hair colour changes Hyperhidrosis Nail pigmentation Lichen planus Vitiligo System Organ Class Very common Common Uncommon Rare erythematous, rash papular and rash pruritic Papule Photosensitivity reaction Pigmentation lip Post inflammatory pigmentation change Pruritus generalised Skin burning sensation Skin discolouration Skin exfoliation Skin hyperpigmentation Skin hypopigmentation Skin irritation Skin lesion Seborrhoea Urticaria Musculoskeletal and connective tissue disorders Musculoskeletal pain including back pain, arthralgia, pain in extremity and groin pain Joint stiffnes Muscle spasm Musculoskeletal stiffness Muscular weakness Limb discomfort Reproductive system and breast disorders Breast tenderness Dysmenorrhoea Menstruation irregular Libido decreased Menorrhagia Vaginal discharge General disorders and administration site conditions Asthenia Fatigue Implant site disorders including implant site bruising, implant site discolouration, implant site erythema, implant site haematoma, implant site haemorrhage, implant site hypersensitivity, implant site hypertrophy, implant site induration, implant site irritation, implant site mass, implant site oedema, implant site pain, implant site pruritus, implant Chills Feeling hot Hangover Malaise Oedema peripheral Oedema mucosal System Organ Class Very common Common Uncommon Rare site reaction, implant site swelling, implant site urticaria, implant site vesicles, implant site warmth Influenza-like illness including cough, nasal congestion, nasopharyngitis, oropharyngeal pain, rhinitis Pain Pyrexia Investigations Alanine aminotransferase increased Aspartate aminotransferase increased Blood creatine phosphokinase increased Blood glucose increased Blood iron decreased Blood urine present Hepatic enzyme increased Liver function test abnormal Transaminases increased Blood pressure diastolic increased Transferrin saturation decreased Weight increased Injury, poisoning and procedural complications Fall Wound Procedural nausea Wound complication Product issues Device expulsion Reporting of suspected adverse reactions Reporting of suspected adverse reactions after authorisation of the medicinal product is important.

Hypersensitivity Uncommon occurrences of hypersensitivity reactions, including anaphylaxis, have been reported following administration of SCENESSE. Appropriate medical support measures should be readily available when SCENESSE is administered.

8). Concomitant disorders not studied Clinically significant disorders of the gastrointestinal, cardiovascular, respiratory, endocrine (including diabetes, Cushing’s disease, Addison’s disease, Peutz-Jeghers syndrome), neurological (including seizures) and haematological (especially anaemia) systems have not been evaluated.

A careful decision must be made whether to treat patients with any of these conditions with this medicinal product. If such patients are treated they must be monitored after each implant administration, including vital signs, routine haematology, and biochemistry.

Sun protection It is recommended that sun protection measures routinely adopted by each patient to manage their photosensitivity related to EPP and in accordance with their skin type (Fitzpatrick scale) are maintained during treatment with this medicinal product.

Skin monitoring Afamelanotide may induce darkening of pre-existing pigmentary lesions due to its pharmacological effect. A regular full body skin examination (every 6 months) is recommended to monitor all pigmentary lesions and other skin abnormalities.

If the skin changes noted are consistent with skin cancer or its precursors, or are ambiguous to the porphyria specialist, dermatology specialist consultation should be sought. The two total full body skin examinations per year are intended to: - detect early any skin cancers and their precursors induced by UV-exposure, as EPP patients can be expected to significantly increase their exposure to sunlight and UV light while on treatment with afamelanotide.

EPP patients with fair skin may be more likely to request treatment and are more prone to developing UV light-associated skin changes, including cancer; - detect and monitor changes in pigmentary lesions, thus allowing early detection of melanoma.

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