SCENESSE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SCENESSE (SCENESSE).
SCENESSE (afamelanotide) is a synthetic analog of alpha-melanocyte stimulating hormone (α-MSH) that binds to the melanocortin-1 receptor (MC1R) on melanocytes. Activation of MC1R stimulates eumelanin synthesis, which reduces the generation of free radicals and reactive oxygen species induced by ultraviolet light, thereby protecting against phototoxicity in erythropoietic protoporphyria (EPP) patients.
| Metabolism | Afamelanotide is metabolized primarily via hydrolysis of the peptide bonds to smaller peptides and amino acids; specific CYP enzymes are not involved. |
| Excretion | Primarily hepatic metabolism; less than 1% excreted unchanged in urine; biliary/fecal excretion accounts for ~80% of elimination. |
| Half-life | Terminal elimination half-life is approximately 270 hours (11.25 days) following subcutaneous injection, supporting once-monthly dosing. |
| Protein binding | ~96% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 34 L (0.43 L/kg based on 70 kg), indicating distribution into extracellular fluid and tissues. |
| Bioavailability | Subcutaneous: ~80% (estimated from pharmacokinetic studies). |
| Onset of Action | Subcutaneous: Clinical effect (reduction in phototoxicity) observed within 1-2 weeks after first dose. |
| Duration of Action | Duration of clinical effect is approximately 1 month, consistent with dosing interval; melanin levels remain elevated for several months after discontinuation. |
16 mg subcutaneously once daily. Administer as a single daily injection into the abdomen, thighs, or upper arms. Rotate injection sites.
| Dosage form | IMPLANT |
| Renal impairment | No dose adjustment recommended for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease; use with caution. |
| Liver impairment | Not studied in hepatic impairment. Use with caution; no specific dose adjustment guidelines available. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). No dosing recommendations. |
| Geriatric use | No specific dose adjustment recommended. Clinical studies included limited number of patients aged ≥65 years; no overall differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SCENESSE (SCENESSE).
| Breastfeeding | It is unknown if SCENESSE is excreted in human milk. Afamelanotide is a synthetic α-MSH analog with high molecular weight, suggesting minimal transfer into milk. No M/P ratio available. Breastfeeding is not recommended during treatment due to potential for adverse effects in the infant and lack of safety data. |
| Teratogenic Risk | SCENESSE (afamelanotide) is not recommended during pregnancy. Animal studies have shown developmental toxicity including increased post-implantation loss and reduced fetal weight at maternal exposures similar to clinical doses. No adequate human data in pregnant women. Risk cannot be excluded in first trimester; potential risks in second and third trimesters include effects on fetal melanocyte development. Use only if benefit outweighs risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["History of hypersensitivity to afamelanotide or any component of the formulation"]
| Precautions | ["Risk of skin darkening (hyperpigmentation) that may be reversible upon discontinuation","Risk of new onset or exacerbation of freckles and nevi; periodic skin examination recommended","Gastrointestinal adverse reactions including nausea, abdominal pain, and diarrhea","Injection site reactions such as erythema, swelling, and pain"] |
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| Fetal Monitoring | No specific fetal monitoring required during treatment. Routine pregnancy monitoring and assessment for maternal adverse effects (e.g., nausea, headache, injection site reactions) should be performed. If pregnancy occurs, prenatal care should be optimized. |
| Fertility Effects | In animal studies, afamelanotide did not impair male or female fertility at doses up to 10 times the clinical exposure. No human fertility data available. Effects on human fertility are unknown but expected to be minimal based on mechanism; however, patients should be counseled on potential risk. |