Afamelanotide
Afamelanotide Uses, Dosage, Side Effects, Food Interaction and all others data.
Afamelanotide is a first-in-class, synthetic, 13-amino acid peptide analogue of the endogenous alpha melanocyte-stimulating hormone (α-MSH). It differs structurally from its endogenous counterpart by only two amino acids - these structural differences improve biological efficacy by imparting a greater affinity for its target and a longer biological half-life. Afamelanotide is currently the only approved drug therapy used in the management of erythropoietic protoporphyria, having received approval in the EU in December 2014 and subsequent FDA approval in October 2019. Despite its relatively recent approval, afamelanotide has been available for use as an orphan drug in both the US and EU since 2008.
Afamelanotide increases the production of eumelanin, an endogenous photoprotective agent, to attenuate UV-induced skin damage in patients with a condition that predisposes them to phototoxicity. It has a relatively long duration of therapeutic effect despite its short half-life due to its ability to increase melanosome density and therefore skin pigmentation. As afamelanotide may darken pre-existing skin pigmentary lesions, patients receiving afamelanotide should undergo a full body skin examination every 6 months to monitor for progression or worsening of any skin abnormalities. Standard sun safety measures should continue to be employed during afamelanotide therapy.
| Trade Name | Afamelanotide |
| Availability | Prescription only |
| Generic | Afamelanotide |
| Afamelanotide Other Names | Afamelanotide, Melanotan 1, Melanotan I, Melanotan-1 |
| Related Drugs | Scenesse |
| Weight | 16mg, |
| Type | Subcutaneous Implant, Subcutaneous |
| Formula | C78H111N21O19 |
| Weight | Average: 1646.8452 Monoisotopic: 1645.836510475 |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Afamelanotide is an injectable subcutaneous implant used to mitigate phototoxicity secondary to erythropoietic protoporphyria (EPP).
Afamelanotide is indicated for the prevention of phototoxicity in adult patients with erythropoietic protoporphyria (EPP).
Afamelanotide is also used to associated treatment for these conditions: Phototoxicity reaction
How Afamelanotide works
Patients with erythropoietic porphyria (EPP) have a deficiency of ferrochelatase (FECH), an enzyme involved in the final step of heme biosynthesis. FECH is required to insert iron into protoporphyrin IX (PPIX) to generate heme, and a deficiency in FECH results in accumulation of PPIX (particularly in the liver and superficial skin vasculature). PPIX molecules are photodynamic - exposure to UV radiation causes these molecules to form reactive oxygen species that lead to subsequent tissue damage.
Afamelanotide mimics endogenous alpha melanocyte-stimulating hormone (α-MSH), a hormone typically released in response to UV-induced skin damage. Both afamelanotide and α-MSH bind to the melanocortin-1 receptor (MC1R) on melanocytes which stimulates the synthesis of eumelanin, a photoprotective compound. Eumelanin is incorporated into small vesicles called melanosomes which are then distributed to surrounding keratinocytes. Melanosomes are concentrated above the nucleus of these keratinocytes, thus protecting them from UV-induced damage. While endogenous α-MSH requires UV-induced skin damage in order to be produced, afamelanotide increases eumelanin biosynthesis independent of UV exposure.
Activation of MC1R signalling by afamelanotide also instigates other protective processes, including an increase in antioxidant activity, DNA repair, and secretion of immunomodulatory proteins such as interleukin-10.
Toxicity
Data regarding symptoms or treatment of afamelanotide overdose are currently unavailable.
Food Interaction
No interactions found.Volume of Distribution
The apparent volume of distribution of afamelanotide following intravenous administration is approximately 0.54 L/kg.
Elimination Route
Afamelanotide is administered as a subcutaneous implant that slowly elutes active drug. Most of the dose is released within the first 48 hours, with >90% released by day 5. Plasma levels of afamelanotide decrease slowly over the course of several days following administration - by day 10, plasma levels were undetectable in most clinical trial subjects. Following administration of a single subcutaneous implant, the median Tmax was 36 hours, the mean Cmax was 3.7 ± 1.3 ng/mL, and the mean AUC0-∞ was 138.9 ± 42.6 hr.ng/mL.
Half Life
The half-life of afamelanotide is approximately 30 minutes. The apparent half-life following administration of a slow-release subcutaneous implant is 15 hours.
Clearance
Data regarding plasma clearance of afamelanotide are limited. Plasma drug levels are typically undetectable at day 10 following subcutaneous administration of the afamelanotide implant.
Elimination Route
Minimal amounts of unchanged afamelanotide are recovered in the urine following administration, suggesting the drug is extensively metabolized and most likely eliminated primarily via fecal or biliary route.
Innovators Monograph
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