EVKEEZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EVKEEZA (EVKEEZA).
EVKEEZA (evinacumab) is a recombinant human monoclonal antibody that binds to and inhibits angiopoietin-like 3 (ANGPTL3), a key regulator of lipoprotein metabolism. Inhibition of ANGPTL3 reduces levels of low-density lipoprotein cholesterol (LDL-C), triglycerides, and other lipoproteins by enhancing the activity of lipoprotein lipase and endothelial lipase, leading to increased clearance of very low-density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL). It also decreases hepatic very low-density lipoprotein production.
| Metabolism | Metabolized via general protein degradation pathways; no involvement of cytochrome P450 enzymes or other drug-metabolizing enzymes. |
| Excretion | Eliminated primarily via reticuloendothelial system metabolism; renal excretion is minimal (<1% unchanged drug); fecal excretion of metabolites accounts for ~99%. |
| Half-life | Terminal elimination half-life of 16.8 days (range 10–24 days) in patients with homozygous familial hypercholesterolemia, supporting monthly subcutaneous dosing. |
| Protein binding | Not extensively bound to plasma proteins; evinacumab binds to ANGPTL3 with high affinity; no specific protein binding data available. |
| Volume of Distribution | Approximately 0.04 L/kg (3.1 L for a 70 kg patient), consistent with limited extravascular distribution due to large monoclonal antibody size. |
| Bioavailability | Subcutaneous: absolute bioavailability is approximately 70% (range 60–80%). Intravenous administration yields 100% bioavailability. |
| Onset of Action | Subcutaneous: Reduction in LDL-C observed within 7 days; maximal effect achieved by 4–6 weeks after first dose. |
| Duration of Action | LDL-C reduction persists for approximately 8–10 weeks after a single subcutaneous dose, allowing every 2-week or monthly maintenance dosing. |
Subcutaneous injection of 135 mg once every 2 weeks (every 14 days).
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required based on glomerular filtration rate (GFR). |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not approved for use in pediatric patients. Safety and efficacy have not been established in children or adolescents. |
| Geriatric use | No specific dose adjustment recommended for elderly patients. Dosing is the same as for younger adults. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EVKEEZA (EVKEEZA).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Consider risks versus benefits; avoid breastfeeding if possible. |
| Teratogenic Risk | No adequate human data. In animal studies, no evidence of embryotoxicity or teratogenicity at exposures up to 3 times the human therapeutic exposure. Risk cannot be excluded; use only if benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["History of severe hypersensitivity to evinacumab or any of its excipients (e.g., anaphylaxis)","Pregnant women and women of childbearing potential not using effective contraception due to potential fetal harm (based on animal studies)."]
| Precautions | ["Hypersensitivity reactions (including anaphylaxis, angioedema, urticaria, and rash) have been reported. Discontinue if signs of severe hypersensitivity occur.","Serious allergic reactions may require treatment and monitoring.","Risk of infusion-related reactions (e.g., fever, chills, nausea, headache). Monitor during and after infusion."] |
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| Monitor lipid profile (LDL-C, non-HDL-C, ApoB) every 4 weeks until target achieved, then periodically. No specific fetal monitoring required beyond standard prenatal care. |
| Fertility Effects | No data on impact on fertility in humans. Animal studies show no adverse effects on mating or fertility at exposures up to 3 times human exposure. |