Afamelanotide (SCENESSE) is a synthetic α-melanocyte stimulating hormone analog and first-in-class melanocortin-1 receptor agonist that is approved in the EU for the prevention of phototoxicity in adults with erythropoietic protoporphyria. Afamelanotide differs from endogenous α-melanocyte stimulating hormone at the fourth and seventh amino acid residues, increasing its resistance to immediate degradation and increasing its binding time to melanocortin-1 receptor. Afamelanotide is mimic the pharmacological activity of α-melanocyte stimulating hormone by binding to the melanocortin-1 receptor on melanocytes and activating the synthesis of eumelanin. Eumelanin provides photoprotection through mechanisms including, but not limited to, the absorption and scattering of visible and UV light and antioxidant activity. Afamelanotide increases eumelanin density in healthy volunteers and patients with erythropoietic protoporphyria. In healthy, fair-skinned volunteers, a significant increase in melanin density and skin darkening in both sun-exposed and non-sun-exposed sites was seen with subcutaneous injections of afamelanotide. The most common afamelanotide adverse events included headache and nausea. Common adverse effects include back pain, upper respiratory tract infections, decreased appetite, migraine, and dizziness.

Uridine triacetate is used to treat an overdose of capecitabine or fluorouracil. In addition, it is used as a pyrimidine analog for uridine replacement indicated for the treatment of hereditary orotic aciduria. Following oral administration, uridine triacetate is deacetylated by nonspecific esterases present throughout the body, yielding uridine in the circulation. Uridine competitively inhibits cell damage and cell death caused by fluorouracil. Uridine can be used by essentially all cells to make uridine nucleotides, compensating for the genetic deficiency in synthesis in patients with hereditary orotic aciduria. When intracellular uridine nucleotides are restored into the normal range, overproduction of orotic acid is reduced by feedback inhibition, so that urinary excretion of orotic acid is also reduced. Adverse reactions occurring in >2% of patients receiving uridine triacetate included vomiting, nausea, and diarrhea. In vitro data showed that uridine triacetate was a weak substrate for P-glycoprotein. Due to the potential for high local (gut) concentrations of the drug after dosing, the interaction of uridine triacetate with orally administered P-gp substrate drugs cannot be ruled out.