REPATHA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REPATHA (REPATHA).
PCSK9 inhibitor; binds to proprotein convertase subtilisin/kexin type 9 (PCSK9), preventing PCSK9 from binding to LDL receptors, thereby increasing the number of LDL receptors available to clear LDL cholesterol from the blood.
| Metabolism | Degraded via general protein catabolism into small peptides and amino acids; not metabolized by cytochrome P450 enzymes. |
| Excretion | Renal excretion is minimal (<1% of administered dose); elimination occurs primarily via binding to target PCSK9 and subsequent degradation, with biliary/fecal excretion of degraded fragments (<5% unchanged in feces). |
| Half-life | Terminal elimination half-life is 11-17 days (mean 14 days) following subcutaneous administration; supports dosing every 2 weeks or monthly. The long half-life is due to low systemic clearance (0.04 L/day) and target-mediated drug disposition. |
| Protein binding | 99% bound to serum proteins; primarily to albumin (no specific binding protein identified, but albumin constitutes majority). |
| Volume of Distribution | Vd is 3.0 L (approx 0.04 L/kg assuming 70 kg), indicating distribution primarily within the vascular compartment and minimal extravascular distribution; consistent with a monoclonal antibody. |
| Bioavailability | Subcutaneous: 80% (absolute bioavailability); intravenous administration is not used clinically. |
| Onset of Action | Subcutaneous: Reduction in LDL-C observed within 1 week (21% reduction at day 7); maximal effect achieved by 2-4 weeks. |
| Duration of Action | LDL-C reduction persists for 2-4 weeks after a single dose; with every-2-week dosing, steady-state LDL-C reduction is maintained. The drug remains active for up to 2 months after last dose due to long half-life. |
140 mg subcutaneously every 2 weeks or 420 mg subcutaneously once monthly.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for any degree of renal impairment, including end-stage renal disease. |
| Liver impairment | No dose adjustment required for mild or 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 not established. |
| Geriatric use | No specific dose adjustment necessary. Clinical studies included patients aged 65 years and older, with 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 REPATHA (REPATHA).
| Breastfeeding | It is unknown whether evolocumab is excreted in human milk. However, evolocumab is a monoclonal antibody, and monoclonal antibodies are excreted in breast milk in very low concentrations. The M/P ratio is not available. Caution should be exercised when administered to a nursing woman. |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. In animal reproduction studies, no evidence of fetal harm was observed at exposures up to 12 times the human exposure at the maximum recommended human dose. However, because animal studies are not always predictive of human response, Repatha should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. There is no risk by trimester specified; generally, caution is advised throughout pregnancy. |
■ FDA Black Box Warning
None.
| Serious Effects |
History of serious hypersensitivity reaction to evolocumab or any excipients.
| Precautions | ["Hypersensitivity reactions (e.g., angioedema, urticaria) have been reported; discontinue if severe.","Increases in serum uric acid levels have been observed.","Risk of injection site reactions (e.g., erythema, pain, bruising)."] |
Loading safety data…
| Fetal Monitoring | No specific maternal or fetal monitoring is required beyond standard pregnancy care. However, because Repatha reduces LDL cholesterol, and the effects on the fetus are unknown, monitoring of maternal lipid levels and fetal growth via ultrasound may be considered. |
| Fertility Effects | No clinical data on the effect of Repatha on human fertility. In animal studies, no adverse effects on male or female fertility were observed at exposures up to 12 times the clinical exposure. |