Class: Skin and Mucous Membrane Agents, Miscellaneous
Chemical Name: (4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]-5-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-6-amino-1-[(2S)-2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
Molecular Formula: C78H111N21O19
CAS Number: 75921-69-6
Afamelanotide acetate is a skin or mucous membrane agent.
Uses for Afamelanotide (Topical)
Afamelanotide acetate has the following uses:
Afamelanotide acetate is a melanocortin 1 receptor (MC1-R) agonist indicated to increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP).
Afamelanotide (Topical) Dosage and Administration
Afamelanotide acetate is available in the following dosage form(s) and strength(s):
Implant: 16 mg of afamelanotide.
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Dosage and Administration
Afamelanotide acetate should be administered by a healthcare professional who is proficient in the subcutaneous implantation procedure and has completed training prior to administration.
Insert a single implant, containing 16 mg of afamelanotide, using an SFM Implantation Cannula or other implantation devices that have been determined by the manufacturer to be suitable for implantation of afamelanotide.
Administer afamelanotide acetate subcutaneously every 2 months.
Cautions for Afamelanotide (Topical)
Afamelanotide acetate may lead to generalized increased skin pigmentation and darkening of pre-existing nevi and ephelides because of its pharmacologic effect. A full body skin examination (twice yearly) is recommended to monitor pre-existing and new skin pigmentary lesions.
Risk Summary: There are no data on afamelanotide use in pregnant women to evaluate for any drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcome.
In animal reproductive and development toxicity studies, no adverse developmental effects were observed with afamelanotide administration during the period of organogenesis to pregnant rats at subcutaneous doses up to 12 times the maximum recommended human dose (MRHD).
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Animal Data: In embryofetal development studies in Sprague Dawley and Lister Hooded rats, afamelanotide was administered subcutaneously to pregnant rats at doses of 0.2, 2, or 20 mg/kg/day throughout the period of organogenesis. No adverse embryofetal developmental effects were observed at doses up to 20 mg/kg/day (12 times the MRHD, based on a body surface area comparison).
In an oral pre- and post-natal development study in Sprague Dawley rats, afamelanotide was administered subcutaneously at doses of 0.2, 2, or 20 mg/kg/day during the period of organogenesis through lactation. No treatment-related effects were observed at doses up to 20 mg/kg/day (12 times the MRHD, based on a body surface area comparison).
Risk Summary: There are no data on the presence of afamelanotide or any of its metabolites in human or animal milk, the effects on the breastfed infant, or the effect on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for afamelanotide acetate and any potential adverse effects on the breastfed infant from afamelanotide acetate or from the underlying maternal condition.
The safety and effectiveness of afamelanotide acetate have not been established in pediatric patients.
There were 10 subjects 65 years old and over in the clinical studies for EPP. Of the 125 subjects treated with afamelanotide acetate in these studies, 4 (3%) were 65 years of age and older. Clinical studies of afamelanotide acetate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
Common Adverse Effects
The most common adverse reactions (incidence > 2%) are implant site reaction, nausea, oropharyngeal pain, cough, fatigue, dizziness, skin hyperpigmentation, somnolence, melanocytic nevus, respiratory tract infection, non-acute porphyria, and skin irritation.
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
Please see product labeling for drug interaction information.
Mechanism of Action
Afamelanotide is a synthetic tridecapeptide and a structural analog of α-melanocyte stimulating hormone (α-MSH).
Afamelanotide is a melanocortin receptor agonist and binds predominantly to MC1-R.
Advice to Patients
Advise patients to maintain sun and light protection measures during treatment with afamelanotide to prevent phototoxic reactions related to EPP.
Advise patients that darkening of pre-existing nevi and ephelides may occur with use of afamelanotide. A full body skin examination is recommended twice yearly to monitor pre-existing and new skin pigmentary lesions.
Advise patients to contact their healthcare provider if the implant is expelled.
Advise patients that the dressing can be removed after 24 hours.
Advise patients to monitor the insertion site after dressing removal and to report any reaction observed at the site to their healthcare provider.
AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
16 mg (of afamelanotide)
AHFS Drug Information. © Copyright 2022, Selected Revisions January 13, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
More about afamelanotide
- Side effects
- Dosage information
- During pregnancy
- En español
- Drug class: melanocortin receptor agonists
- Other brands