Scenesse

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 

See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
SCENESSE 16 mg implant 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
The implant contains 16 mg of afamelanotide. 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Implant. 
Solid white to off-white rod approximately 1.7 cm in length and 1.5 mm in diameter. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
SCENESSE is indicated for prevention of phototoxicity in adult patients with erythropoietic 
protoporphyria (EPP). 
 
4.2 Posology and method of administration 
 
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, 
e.g. from spring to early autumn. Three implants per year are recommended, depending on the length 
of protection required. The recommended maximum number of implants is four per year. The overall 
duration of treatment is at the specialist physician’s discretion (see section 4.4). 
 
Special populations 
 
For patients with renal or hepatic impairment see sections 4.3 and  5.2. 
 
Elderly population 
 
Due to limited data in treatment of elderly patients, the use of afamelanotide is not recommended (see 
section 4.4). 
 
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. 
 



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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. 
- Select a 14 gauge (1.6 mm inner diameter) catheter with needle. 
- Mark 1.5 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. 
- With the bevel of the needle facing upwards, insert the catheter laterally 1.5 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). 
 
The implant can be surgically removed if needed. 
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 
- Presence of severe hepatic disease 
- Hepatic impairment (see section 5.2) 
- Renal impairment (see section 5.2) 

 
4.4 Special warnings and precautions for use 
 
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 



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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. 
 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
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. 
 
4.6 Fertility, pregnancy and lactation 
 
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. 



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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. 
 
4.7 Effects on ability to drive and use machines 
 
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. 
 
4.8 Undesirable effects 
 
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) 
 
System Organ Class  Very common Common  Uncommon  
Infections and 
infestations 

  
Upper respiratory tract 
infection 
 

Influenza 
Gastrointestinal infection 
Gastroenteritis 
Folliculitis 
Candidiasis 
Nasopharyngitis 

Neoplasms benign, 
malignant and 

  Haemangioma 



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System Organ Class  Very common Common  Uncommon  
unspecified (incl cysts 
and polyps) 
Blood and lymphatic 
system disorders  

  Leukopenia 

Metabolism and 
nutrition disorders  

 Decreased appetite  Hypercholesterolaemia 
Increased appetite  

Psychiatric disorders   Depression 
Depressed mood 
Insomnia 

Nervous system 
disorders 

Headache 
 

Migraine 
Dizziness 
Lethargy 
Somnolence 
 

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

Eye disorders   Eyelid oedema 
Ocular hyperaemia 
Dry eye 
Presbyopia 

Ear and labyrinth 
disorders 

  Tinnitus 

Cardiac disorders   Palpitations 
Tachycardia 

Vascular disorders  Flushing 
Hot flush 

Haematoma 
Diastolic hypertension 
Hypertension 

Respiratory, thoracic 
and mediastinal 
disorders 

  Dysphonia 
Sinus congestion 
Rhinitis 
Nasal congestion  

Gastrointestinal 
disorders 

Nausea Abdominal pain 
Abdominal pain upper 
Diarrhoea 
Vomiting 

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 



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System Organ Class  Very common Common  Uncommon  
Hypoaesthesia oral 
Lip discolouration 
Tongue discoloration 

Skin and subcutaneous 
tissue disorders 

 Erythema 
Melanocytic naevus 
Pigmentation disorder 
Skin discolouration 
Skin 
hyperpigmentation 
Ephelides 
Pruritus 
 

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 

 Back pain 
 

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

Renal and urinary 
disorders  

  Cystitis  

Reproductive system 
and breast disorders 

  Menorrhagia 
Dysmenorrhoea 
Breast tenderness 
Menstruation irregular 
Vaginal discharge 
Libido decreased 

General disorders and 
administration site 
conditions 

 Implant site 
hypersensitivity 
Implant site reaction 
Implant site pain 
Implant site 
haematoma 
Implant site erythema 
Implant site irritation 
Asthenia 

Oedema peripheral 
Oedema mucosal 
Pain 
Implant site oedema 
Pyrexia 
Chills 
Injection site haematoma 
Injection site irritation 



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System Organ Class  Very common Common  Uncommon  
Fatigue 
Implant site 
discolouration 
Feeling hot 
 

Implant site hypertrophy 
Implant site pruritus 
Device expulsion 
Application site 
discolouration 
Hangover 
Influenza like illness 

Investigations  Blood creatine 
phosphokinase 
increased 
 

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 

  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 
 
4.9 Overdose 
 
There are no data available on symptoms or treatment of overdose with afamelanotide. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Emollients and protectives, protectives against UV-radiation for systemic 
use, ATC code: D02BB02 
 
Mechanism of action 
 
Afamelanotide is a synthetic tridecapeptide and a structural analogue of α-melanocyte stimulating 
hormone (α-MSH). Afamelanotide is a melanocortin receptor agonist and binds predominantly to the 
melanocortin-1 receptor (MC1R). Its binding lasts longer than that of α-MSH. This results in part from 
afamelanotide’s resistance to immediate degradation by serum or proteolytic enzymes (see section 



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5.2). It presumably undergoes hydrolysis within a short time; its metabolites’ pharmacokinetics and 
pharmacodynamics are not understood yet. 
Afamelanotide is thought to mimic the endogenous compound’s pharmacological activity by 
activating the synthesis of eumelanin mediated by the MC1R receptor. 
Eumelanin contributes to photoprotection through different mechanisms including: 
- strong broadband absorption of UV and visible light, where eumelanin acts as a filter 
- antioxidant activity through scavenging of free radicals; and 
- inactivation of the superoxide anion and increased availability of superoxide dismutase to 

reduce oxidative stress. 
 
Pharmacodynamic effects 
 
Administration of afamelanotide may, therefore, result in increased production of eumelanin in the 
skin of the EPP patient independently of exposure to sunlight or artificial UV light. This can be 
accompanied by a darkening of the skin pigmentation in areas with melanocytes which gradually fades 
unless a further implant is administered. 
 
Clinical efficacy and safety 
 
It has been demonstrated that EPP patients receiving afamelanotide had more exposure to direct 
sunlight (10:00 to 18:00 hours) during a 180 day trial period compared to placebo recipients (p=0.044; 
afamelanotide arithmetic mean: 115.6 h, median 69.4h; placebo mean 60.6h, median 40.8h). 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
SCENESSE in one or more subsets of the paediatric population in erythropoietic protoporphyria (see 
section 4.2 for information on paediatric use). 
 
This medicinal product has been authorised under ‘exceptional circumstances’. This means that due to 
the rarity of the disease it has not been possible to obtain complete information on this medicinal 
product. 
The European Medicines Agency will review any new information which may become available every 
year and this SmPC will be updated as necessary. 
 
5.2 Pharmacokinetic properties 
 
Dose-finding studies have not been conducted. 
The pharmacokinetics of afamelanotide have not been fully characterised yet, i.e. distribution, 
metabolism or excretion are not clear. No pharmacokinetic information is available on any of its 
metabolites (active or inactive). 
Half-life is approximately 30 minutes. 
Following subcutaneous administration of the implant, most of the active substance is released within 
the first 48 hours with over 90% released by day 5. Plasma levels of afamelanotide are maintained 
over a number of days. In most clinical studies afamelanotide plasma levels were below the limit of 
quantitation by day 10. The implant is absorbed by the body within 50 to 60 days after administration. 
 
Data on possible interactions or effects in special populations, e.g. in patients with hepatic or renal 
impairment are not available. 
 
Paediatric population 
 
No data are available. 
 
5.3 Preclinical safety data 
 



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Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity, toxicity to reproduction and development. 
 
In repeated dose toxicity studies, the only finding of relevance was an increase in melanin 
pigmentation in the dog, which is consistent with the active substance’s pharmacological activity. This 
effect was observed only at exposure levels approximately 8 times higher than human exposure. 
Inflammation was observed in the Harderian gland in the rat. This finding is not considered relevant to 
human safety since the Harderian gland is not present in man. 
 
In a fertility study no effects on the reproductive function of male or female Sprague-Dawley rats were 
observed after subcutaneous application of afamelanotide. A study in Sprague-Dawley rats showed no 
adverse effects on embryo-fetal development at exposures approximately 135-fold the human 
exposure (based on Cmax). A second study on embryo-fetal development in Lister-Hooded rats did not 
achieve sufficient exposure. Pre- and post-natal development of Sprague-Dawley rats was not affected 
at exposures of about 135-times the human exposure (based on Cmax). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Poly (DL-lactide-co-glycolide) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
4 years.  
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2˚C - 8˚C) 
 
6.5 Nature and contents of container 
 
Type I amber glass vial sealed with a PTFE coated rubber stopper. 
Pack of one vial containing one implant. 
 
6.6 Special precautions for disposal and other handling 
 
For instructions on correct administration and preparation see section 4.2. 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
CLINUVEL EUROPE LIMITED 
10 Earlsfort Terrace 
Dublin 2 
D02 T380 
Ireland 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 



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EU/1/14/969/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 22 December 2014 
Date of latest renewal: 19 November 2019 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 



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ANNEX II 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 
E. SPECIFIC OBLIGATIONS TO COMPLETE POST-

AUTHORISATION MEASURES FOR THE MARKETING 
AUTHORISATION UNDER EXCEPTIONAL 
CIRCUMSTANCES 



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A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
CLINUVEL EUROPE LIMITED 
Alexandra House 
The Sweepstakes 
Ballsbridge 
Dublin 4 
D04 C7H2 
Ireland 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 
marketing authorisation and any agreed subsequent updates of the RMP. 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

• Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being 
reached 

 

• Additional risk minimisation measures 
 
Education and training programme for physicians 
 
Prior to launch of SCENESSE in each Member State, the Marketing Authorisation Holder (MAH) 
must agree the content and format of the educational package, including communication media, 
distribution modalities, and any other aspects, with the National Competent Authority. The MAH shall 
also agree the details of the controlled access programme to ensure distribution of SCENESSE only to 
centres where the physicians received the educational materials and have been trained. 



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The MAH shall ensure that in each Member State where SCENESSE is marketed, all healthcare 
professionals who are expected to use the product are provided with the following educational package 
and trained: 
• Summary of product characteristics, 
• Face to face training material, 
• Educational video, 
• Registry information sheet. 
The face to face training material, including the educational video, shall contain the following key 
messages: 
• Demonstration of the correct application technique, highlighting the measures needed to ensure 

the implant is not damaged during use. 
• The importance of maintaining aseptic conditions. 
• Methods to prevent or minimise application errors and application site reactions 
Registry information sheet shall contain the following key messages: 
• The importance of recruiting and entering patients in the EU Registry, 
• How to access and use the EU Registry. 
 
• Obligation to conduct post-authorisation measures 
 
The MAH shall complete, within the stated timeframe, the below measures: 

Description Due date 
Retrospective chart review study 
The MAH shall conduct a retrospective study comparing long term 
safety data and outcome endpoints in patients receiving and not 
receiving SCENESSE, or having discontinued SCENESSE use. 
The second primary objective of the study should be the assessment 
of the compliance with risk minimization recommendations and the 
controlled access program for patients receiving SCENESSE. 

Final report: 6 years after 
approval. 

 
 
E. SPECIFIC OBLIGATIONS TO COMPLETE POST-AUTHORISATION MEASURES 

FOR THE MARKETING AUTHORISATION UNDER EXCEPTIONAL 
CIRCUMSTANCES 

 
This being an approval under exceptional circumstances and pursuant to Article 14(8) of Regulation 
(EC) No 726/2004, the MAH shall conduct, within the stated timeframe, the following measures: 
Description Due date 

Disease registry 
Prior to launch in Member States, the MAH shall establish a disease 
registry to gather long term safety data and outcome endpoints in 
patients with EPP. The registry should collect data from both patients 
and physicians.  

Draft protocol to be submitted 
2 months after notification of 
the European Commission 
decision 
Intermediate reports: annual 
submission. 



15 

ANNEX III 
  

LABELLING AND PACKAGE LEAFLET 



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A. LABELLING 

 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
SCENESSE 16 mg implant 
afamelanotide 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each implant contains 16 mg afamelanotide. 
 
 
3. LIST OF EXCIPIENTS 
 
Poly (DL-lactide-co-glycolide). 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
1 implant 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Subcutaneous use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY  
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
 
 



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10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CLINUVEL EUROPE LIMITED 
10 Earlsfort Terrace 
Dublin 2 
D02 T380 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/14/969/001 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
SCENESSE 16 mg implant 
afamelanotide 
Subcutaneous use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
BN 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 implant 
 
 
6. OTHER 



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B. PACKAGE LEAFLET 
 



21 

 
Package leaflet: Information for the patient 

 
SCENESSE 16 mg implant 

afamelanotide 
 

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of 
section 4 for how to report side effects. 
 
Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor. 
- If you get any side effects, talk to your doctor. This includes any possible side effects not listed 

in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What SCENESSE is and what it is used for 
2. What you need to know before you receive SCENESSE 
3. How SCENESSE is given 
4. Possible side effects 
5. How SCENESSE is stored 
6. Contents of the pack and other information 
 
 
1. What SCENESSE is and what it is used for 
 
SCENESSE contains the active substance afamelanotide. Afamelanotide is a synthetic form of a body 
hormone called alpha-melanocyte stimulating hormone (α-MSH). Afamelanotide works in a way 
similar to the natural hormone, by making skin cells produce eumelanin which is a brown-black type 
of melanin pigment in the body. 
 
Afamelanotide is used to increase the tolerance to sunlight in adults with a confirmed diagnosis of 
erythropoietic protoporphyria (EPP). EPP is a condition in which patients have an increased sensitivity 
to sunlight, which can cause toxic effects such as pain and burning. By increasing the amount of 
eumelanin, SCENESSE can help to delay the onset of pain due to skin photosensitivity (sensitive to 
sunlight). 
 
 
2. What you need to know before you receive SCENESSE 
 
Do not use SCENESSE 
 
- if you are allergic to afamelanotide or any of the other ingredients of this medicine (listed in 

section 6). 
- if you have any severe condition of the liver. 
- if you have liver problems. 
- if you have kidney problems. 
 
Warnings and precautions 
 
Talk to your doctor before receiving SCENESSE if you have or have ever had: 
- heart problems or severe breathing problems; 
- gastrointestinal problems; 
- diabetes; 



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- Cushing’s disease (a hormone disorder where the body produces too much of the hormone 
cortisol); 

- Addison’s disease (a disorder of the adrenal glands causing a lack of some hormones); 
- Peutz-Jeghers syndrome (a disorder that causes blockage of the bowel and where your hands, 

soles of your feet and surface of your lips may have brown freckles); 
- epilepsy (or have been told that you are at risk of having fits); 
- anaemia (low counts of red blood cells in your blood); 
- melanoma (an aggressive type of skin cancer), including in-situ melanoma, e.g. lentigo maligna; 

or if you have certain inherited conditions that increase the risk of developing a melanoma; 
- skin cancer of the types, basal cell carcinoma or squamous cell carcinoma (inclusive of 

carcinoma in situ, e.g. Bowen’s disease), Merkel cell carcinoma or other malignant or 
premalignant skin problems. 

 
Talk to your doctor before receiving SCENESSE if you are over 70 years of age. 
 
If you have ever had any of these conditions your doctor may have to monitor you more closely during 
your treatment. 
 
Sun protection 
 
Do not change the sun protection measures you normally follow to manage your EPP and according to 
your skin phototype (UV sensitivity). Keep in mind that increased exposure to UV light will contribute 
to skin cancer development. 
 
Skin monitoring 
 
Because this medicine increases eumelanin, in most treated patients the skin will darken. This is an 
expected response to this medicine, and the darkening will slowly fade unless another implant is used. 
 
Your doctor will need to regularly check your skin (full body) to monitor changes in moles (e.g. 
darkening) or other skin abnormalities. This is recommended to be performed every 6 months. 
 
Please inform your doctor about new or changing skin abnormalities. Arrange for an early 
appointment with your porphyria specialist if pigmented lesions like moles grow or if other growing, 
non-healing, weeping, plaque-like, wart-like, or ulcerated lesions appear. A referral to a dermatology 
specialist might be necessary. 
 
Children and adolescents 
 
This medicine should not be given to children and adolescents under 18 years of age because it has not 
been tested in this age group. 
 
Other medicines and SCENESSE 
 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
 
Tell your doctor if you are taking anticoagulant medicines used to prevent blood clots. These may 
include warfarin, acetylsalicylic acid (a substance present in many medicines used to relieve pain and 
lower fever or to prevent blood clotting) and a group of medicines called non-steroidal anti-
inflammatory drug (NSAIDs), used to treat common ailments, such as arthritis, headaches, mild fever, 
rheumatism and sore throats. This is because patients taking such medicines may experience increased 
bruising or bleeding at the site of the implant. 
 
Pregnancy and breastfeeding 
 



23 

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, you 
should not receive SCENESSE, since it is not known how it will affect your unborn baby or the 
breastfed infant. 
 
Women who could become pregnant should use adequate contraception such as oral contraceptives, 
diaphragm plus spermicide, intrauterine device (also known as a coil) during treatment and for three 
months after the last SCENESSE implantation. 
 
Driving and using machines 
 
There is a risk of feeling drowsy and tired when using this medicine, especially within 72 hours of 
administration. If you are affected, do not drive or use any tools or machines. If you suffer from 
continued drowsiness, then you should speak to your doctor. 
 
 
3. How to use SCENESSE 
 
The implant will be inserted by a doctor who has been trained in the administration procedure. The 
doctor will decide with you the most suitable time and the site for inserting the implant. 
 
One implant is injected every 2 months during the spring and summer months. Three implants per year 
are recommended, depending on the length of effect required. However, this number should not 
exceed more than 4 per year. 
 
The implant is given as injection under your skin using a catheter tube and needle (subcutaneous use). 
Before inserting this medicine, your doctor may decide to give you a local anaesthetic to numb the 
area where the implant is to be inserted. The implant is inserted directly under the skin folds on your 
waist or abdomen in an area known as the supra-iliac crest. 
 
At the end of the insertion procedure, you may be able to feel the implant under your skin. Over time 
the implant will be absorbed by the body, this will happen within 50 to 60 days after implantation. 
 
If you experience discomfort and are concerned, speak to your doctor. The implant may be removed 
by a simple surgical procedure if needed. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The following side effects are considered to be: 
 
Very common (may affect more than 1 in 10 people): 
- Nausea (feeling sick), 
- headache; 
- reactions at the implant site including pain, redness, itching, bruising and changes to colour of 
overlying skin. 
 
Common (may affect up to 1 in 10 people): 
 
- General changes to the skin including freckles and skin darkening; 
- migraine (a severe headache); 
- back pain; 
- abdominal (tummy) pain, 
- diarrhoea and vomiting, 



24 

- decreased appetite; 
- fatigue (tiredness), 
- dizziness, drowsiness and weakness; 
- hot flushes; 
- upper respiratory tract infections (colds). 
 
Uncommon (may affect up to 1 in 100 people): 
 
- Infected hair follicle, fungal infection, urinary tract infection 

 
- Chills, fever, flu, flu-like illness, blocked nose, blocked sinuses, inflamed nose and throat, nose 

inflammation 
 
- Depression, inability to sleep, poor quality sleep, fainting, fainting sensation, fall, hangover, 

weakness, inability to get legs comfortable, increased sensitivity to touch, headache following 
injury, burning sensation, abnormal taste sensation 

 
- Swollen eye lids, red eyes, dry eye, difficulty focusing on close objects, ringing in ears 

 
- Palpitations, fast heart rate, bruising, high blood pressure, difficulty to make some sounds 

 
- Inflamed lips, lip swelling, colouration on lip, gum pain, toothache, discoloured gums, reduced 

sense of touch in mouth, lip discolouration, tongue discolouration 
 

- Increased hunger, nausea following implant insertion, indigestion, infection in stomach and 
intestines, inflamed stomach and intestines, heartburn, inflamed stomach, irregular bowel 
movements, wind, bloated tummy, tummy pain 

 
- Irregularity of skin, rash with small blisters, itch, rash, red rash, red swelling on skin, rash with 

small bumps, itchy rash, skin irritation, lighter skin patches, acne, eczema, secretions on skin, skin 
peeling, skin with loss of colour, hair colour changes, excessive sweating 

 
- Joint pain, muscle pain, pain in arms and legs, sudden muscle contraction, pain in muscles and 

bones, stiffness of muscles and bones, joint stiffness, groin pain, feeling of heaviness, swelling in 
lower limbs 

 
- Heavy and prolonged period, abnormal period, breast tenderness, irregular periods, discharge from 

vagina, decreased sex drive 
 
- Pain, swelling around site of implantation, bruising at injection site, irritation at injection site, 

enlargement at implant site, itching at implant site, implant falling out, change in colour of skin at 
implant site 

 
- Decrease white blood cells, abnormal liver function tests, decreased iron binding, increased 

cholesterol, increased sugar level, decreased blood iron level, increased blood pressure, blood in 
urine 

 
- Wound complication, open wound 
 
Reporting of side effects 
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this 
leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. 
By reporting side effects you can help provide more information on the safety of this medicine. 



25 

 
 
5. How SCENESSE is stored 
 
Keep this medicine out of the sight and reach of children. 
 
This medicine must not be used after the expiry date which is stated on the vial and the outer carton. 
Your doctor will check the expiry date before an implant is used. 
 
Store in a refrigerator (2oC - 8oC). 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What SCENESSE contains 
 
- The active substance is afamelanotide. One implant contains 16 mg of afamelanotide. 
- The other ingredient is poly (D,L-lactide-co-glycolide). 
 
What SCENESSE looks like and contents of the pack 
 
The implant is a solid white to off-white rod approximately 1.7 cm in length and 1.5 mm in diameter 
in an amber glass vial sealed with a PTFE coated rubber stopper. 
Pack size of one vial containing one implant. 
 
Marketing Authorisation Holder 
 
CLINUVEL EUROPE LIMITED 
10 Earlsfort Terrace 
Dublin 2 
D02 T380 
Ireland 
Tel: +353 768 888 035 
mail@clinuvel.com 
 
Manufacturer 
 
CLINUVEL EUROPE LIMITED 
Alexandra House 
The Sweepstakes 
Ballsbridge 
Dublin 4 
D04 C7H2 
Ireland 
 
This leaflet was last revised in  
 
This medicine has been authorised under ‘exceptional circumstances’. This means that because of the 
rarity of this disease, for scientific reasons, and for ethical reasons it has been impossible to get 
complete information on this medicine. 
The European Medicines Agency will review any new information on this medicine every year and 
this leaflet will be updated as necessary. 
 
Other sources of information 



26 

 
Detailed information on this medicine is available on the European Medicines Agency web 
site: http://www.ema.europa.eu. There are also links to other websites about rare diseases and 
treatments. 
 
--------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
Method of administration 
 
SCENESSE is administered subcutaneously under aseptic conditions as described below. 
Administration should be performed by a physician trained and accredited by the marketing 
authorisation holder to administer the implant. 
 
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. 
- Anaesthetize the insertion area if deemed necessary and in consultation with the patient. 
- Select a 14 gauge (1.6 mm inner diameter) catheter with needle. 
- Mark 1.5 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. 
- With the bevel of the needle facing upwards, insert the catheter laterally 1.5 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). 
 

The implant can be surgically removed if needed. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	E. SPECIFIC OBLIGATIONS TO COMPLETE POST-AUTHORISATION MEASURES FOR THE MARKETING AUTHORISATION UNDER EXCEPTIONAL CIRCUMSTANCES
	A. LABELLING
	B. PACKAGE LEAFLET