afamelanotide (Rx)

>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%)

Contraindications

None

Cautions

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

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

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

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

Absorption

Peak plasma time: 36 hr

Peak plasma concentration: 3.7 ng/mL

AUC: 42.6 hr⋅ng/mL

Metabolism

Not fully characterized; may undergo hydrolysis

Elimination

Half-life: 15 hr

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

Storage

Refrigerate at 2-8ºC (36-46ºF)

Protect from light