Afamelanotide

Indications

Afamelanotide is used for: Phototoxicity, Anaphylaxis & Erythropoietic, Protoporphyria

Adult Dose

Phototoxicity/Anaphylaxis & Erythropoietic Protoporphyria Indicated for prevention of phototoxicity and anaphylactoid reactions in adults with erythropoietic protoporphyria (EPP) 16 mg implanted SC q2Months

Child Dose

Renal Dose

Administration

SC Implant Preparation Equipment required Afamelanotide implant SFM implantation cannula (contact manufacturer for other suitable implantation devices) Sterile gloves Local anesthetic, needle, and syringe Blunt forceps suitable for removing implant from vial Sterile gauze, adhesive bandage, pressure bandage SC Implant Administration Also see prescribing information for instructions and diagrams Step 1 Remove implant from refrigerator and allow to gradually warm up to ambient temperature Remove the seal and stopper from the glass vial containing implant; remove implant from vial using the blunt forceps under aseptic conditions and place on sterile gauze Step 2 Position patient in a comfortable reclined supine position Identify the insertion site 3-4 cm above the anterior suprailiac crest and disinfect the skin surface Step 3 (optional) Anesthetize insertion area if deemed necessary and in consultation with the patient Step 4 While pinching skin at insertion site, insert the cannula with the bevel facing upwards (away from the abdomen) at a 30-45º angle into the SC layer Advance the cannula 2 cm into the SC layer Step 5 Remove stylet (obturator) from the cannula, maintaining aseptic precautions Load the implant into the cannula Using the stylet (obturator), gently push the implant down the full length of the cannula’s shaft Step 6 Apply pressure to implant site while removing the stylet (obturator) and cannula Verify that no implant or implant portion remains in the cannula Step 7 Verify the correct insertion and placement of the implant by palpating the skin overlying the implant Step 8 Apply dressing to the insertion site Leave dressing in place for 24 hr Step 9 Monitor the patient for 30 minutes after implant administration

Contra Indications

Precautions

Owing to its pharmacologic effect, afamelanotide may lead to generalized increased skin pigmentation and darkening of preexisting nevi and ephelides; twice-yearly full-body skin examination recommended to monitor preexisting and new skin pigmentary lesions

Pregnancy-Lactation

Pregnancy No data are available regarding use in pregnant women to evaluate for any drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcome Animal data In animal reproductive and development toxicity studies, no adverse developmental effects were observed with administration during organogenesis to pregnant rats at SC doses up to 12 times the maximum recommended human dose (MRHD) Lactation No data are available on the presence of afamelanotide or any of its metabolites in human or animal milk, effects on the breastfed infant, or on milk production

Interactions

Adverse Effects

Side effects of Afamelanotide : >10% Implant site reaction (21%) Nausea (19%) 1-10% Oropharyngeal pain (7%) Fatigue (6%) Skin hyperpigmentation (4%) Dizziness (4%) Melanocytic nevus (4%) Respiratory tract infection (4%) Somnolence (2%) Nonacute porphyria (2%) Skin irritation (2%)

Mechanism of Action

Erythropoietic protoporphyria is a rare disorder caused by mutations leading to impaired activity of ferrochelatase, an enzyme involved in heme production; decreased ferrochelatase activity leads to protoporphyrin IX (PPIX) accumulation in the body; light reaching the skin can react with PPIX, causing intense skin pain and skin changes (eg, redness, thickening) Afamelanotide, a melanocortin-1 receptor (MC1-R) agonist, increases production of eumelanin (the most common type of melanin) in the skin independent of exposure to sunlight or artificial light sources