SCENESSE Implant Ref.[7589] Active ingredients: Afamelanotide

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.

Special caution is warranted in patients with an:

• individual or family history of melanoma (inclusive of in-situ melanoma, e.g. lentigo maligna) or suspected or confirmed susceptibility to cutaneous melanoma (CMM1, MIM #155600, synonyms: familial atypical mole-malignant melanoma syndrome, FAMMM; dysplastic naevus syndrome, DNS; B-K mole syndrome; CMM2 MIM #155601)

and/or an

• individual history of basal cell carcinoma, squamous cell carcinoma (inclusive of carcinoma in situ, e.g. Bowen’s disease), Merkel cell carcinoma, or other malignant or premalignant skin lesions.

Long-term use

Long-term safety data for afamelanotide are limited. The safety of this medicinal product has not been evaluated in clinical trials of duration longer than 2 years (see section 4.2).

Elderly

Since available data in treatment of the elderly are limited, afamelanotide should not be used in patients over 70 years of age. If such patients are treated they must be monitored after administration of every implant, including vital signs, routine haematology and biochemistry

No specific interaction studies have been performed with this medicinal product.

Pharmacokinetic data for afamelanotide or any of its metabolites are very limited. As an oligopeptide with a short half-life, afamelanotide is expected to be rapidly hydrolysed into shorter peptide fragments and into its individual amino acids. However, due to the lack of data caution is warranted.

Patients taking substances which reduce coagulation, such as vitamin K antagonists (e.g. warfarin), acetylsalicylic acid and non-steroidal anti-inflammatory drug (NSAIDs) may experience increased bruising or bleeding at the site of implantation.

Women of childbearing potential/contraception in females

Women of childbearing potential have to use effective contraception during treatment with SCENESSE and for a period of three months thereafter.

Pregnancy

There are no or limited amounts of data from the use of afamelanotide in pregnant women. Animal studies are insufficient with respect to developmental toxicity (see section 5.3). A risk to newborns/infants cannot be excluded.

SCENESSE should not be used during pregnancy and in women of childbearing potential not using effective contraception.

Breast-feeding

It is unknown whether afamelanotide or any of its metabolites are excreted in breast milk.

No clinical data are available on the use of afamelanotide in breastfeeding women.

A risk to newborns/infants cannot be excluded. SCENESSE should not be used during breastfeeding.

Fertility

There are no clinical data on the effects of afamelanotide on fertility. Animal studies have not shown any harmful effect on fertility and reproduction.

Afamelanotide has moderate influence on the ability to drive and use machines, especially within 72 hours of administration. Following administration of this medicinal product, somnolence, fatigue, dizziness, and nausea have been reported. Patients should not drive or use machines in case they are affected by these symptoms.

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.

Tabulated list of adverse reactions

The adverse reactions reported during clinical trials 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), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

Infections and infestations

Common: Upper respiratory tract infection

Uncommon: Influenza, Gastrointestinal infection, Gastroenteritis, Folliculitis, Candidiasis, Nasopharyngitis

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Uncommon: Haemangioma

Blood and lymphatic system disorders

Uncommon: Leukopenia

Metabolism and nutrition disorders

Common: Decreased appetite

Uncommon: Hypercholesterolaemia, Increased appetite

Psychiatric disorders

Uncommon: Depression, Depressed mood, Insomnia

Nervous system disorders

Very common: Headache

Common: Migraine, Dizziness, Lethargy, Somnolence

Uncommon: Syncope,Restless leg syndrome, Hyperaesthesia, Presyncope, Post-traumatic headache, Burning sensation, Poor quality sleep, Dysgeusia

Eye disorders

Uncommon: Eyelid oedema, Ocular hyperaemia, Dry eye, Presbyopia

Ear and labyrinth disorders

Uncommon: Tinnitus

Cardiac disorders

Uncommon: Palpitations, Tachycardia

Vascular disorders

Common: Flushing, Hot flush

Uncommon: Haematoma, Diastolic hypertension, Hypertension

Respiratory, thoracic and mediastinal disorders

Uncommon: Dysphonia, Sinus congestion, Rhinitis, Nasal congestion

Gastrointestinal disorders

Very common: Nausea

Common: Abdominal pain, Abdominal pain upper, Diarrhoea, Vomiting

Uncommon: Lip oedema, Lip swelling, Gastroesophageal reflux disease, Gastritis, Dyspepsia, Cheilitis, Abdominal distension, Gingival pain, Abdominal discomfort, Toothache, Abdominal symptom, Bowel movement irregularity, Flatulence, Gingival discolouration, Hypoaesthesia oral, Lip discolouration, Tongue discoloration

Skin and subcutaneous tissue disorders

Common: Erythema, Melanocytic naevus, Pigmentation disorder, Skin discolouration, Skin hyperpigmentation, Ephelides, Pruritus

Uncommon: Lichen planus, Rash vesicular, Pruritus generalised, Rash, Rash erythematous, Rash papular, Rash pruritic, Skin irritation, Vitiligo, Acne, Eczema, Pigmentation lip, Post inflammatory pigmentation change Seborrhoea, Skin exfoliation, Skin hypopigmentation, Hair colour changes, Hyperhidrosis

Musculoskeletal and connective tissue disorders

Common: Back pain

Uncommon: Arthralgia, Myalgia, Pain in extremity, Muscle spasm, Musculoskeletal pain, Musculoskeletal stiffness, Joint stiffness, Groin pain, Sensation of heaviness

Renal and urinary disorders

Uncommon: Cystitis

Reproductive system and breast disorders

Uncommon: Menorrhagia, Dysmenorrhoea, Breast tenderness, Menstruation irregular, Vaginal discharge, Libido decreased

General disorders and administration site conditions

Common: Implant site, hypersensitivity, Implant site reaction, Implant site pain, Implant site, haematoma, Implant site erythema, Implant site irritation, Asthenia, Fatigue, Implant site discolouration, Feeling hot

Uncommon: Oedema peripheral, Oedema mucosal, Pain, Implant site oedema, Pyrexia, Chills, Injection site haematoma, Injection site irritation, Implant site hypertrophy, Implant site pruritus, Device expulsion, Application site discolouration, Hangover, Influenza like illness

Investigations

Common: Blood creatine phosphokinase increased

Uncommon: Alanine aminotransferase increased, Aspartate aminotransferase increased, Liver function test abnormal, Transaminases increased, Transferrin saturation decreased, Blood cholesterol increased, Blood glucose increased, Blood iron decreased, Blood pressure diastolic increased, Blood urine present, Biopsy skin

Injury, poisoning and procedural complications

Uncommon: Wound complication, Open wound, Fall, Procedural nausea

Reporting of suspected adverse reactions

Reporting of 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.

Not applicable.