evolocumab
Brand: Repatha
Prototype Drug
Drug Class: PCSK9 inhibitor
Drug Family: antilipemic
Subclass: fully human monoclonal antibody (IgG2)
Organ Systems: cardiovascular
Mechanism of Action
Inhibits PCSK9, preventing its binding to and degradation of LDL receptors; LDL receptors remain on hepatocyte surface for continued LDL clearance; up to 60% additional LDL reduction on top of maximal statin therapy.
PCSK9 (proprotein convertase subtilisin/kexin type 9)
Indications
- ASCVD (secondary prevention)
- heterozygous or homozygous familial hypercholesterolemia
- primary hyperlipidemia uncontrolled on statins
Contraindications
- latex allergy (prefilled autoinjector)
Adverse Effects
Common
- injection site reactions
- nasopharyngitis
- back pain
- flu-like symptoms
Serious
- neurocognitive events (rare, causality uncertain)
- antibody development (rare)
Pharmacokinetics (ADME)
| Absorption | 72% SC bioavailability |
| Distribution | moderate |
| Metabolism | proteolytic degradation/target-mediated |
| Excretion | degradation |
| Half-life | ~11-17 days (SC injection) |
| Onset | 7 days (SC) |
| Peak | 3-4 days |
| Duration | 2-4 weeks |
| Protein Binding | <0% |
| Vd | SC distribution |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| statins | additive LDL reduction (beneficial) | beneficial |
Nursing Considerations
- SC injection q2 weeks or monthly (1 ml) — teach auto-injector technique
- FOURIER trial: 15% reduction in CV events (MI, stroke) vs placebo on background statin therapy
- Store in refrigerator (2-8°C); may be kept at room temp up to 30 days
- Common cold symptoms in first weeks — usually self-limited
- Insurance prior authorization often required due to cost (~$14,000/year)
Clinical Pearls
- FOURIER: evolocumab 140 mg q2w reduced MI 27% and stroke 21% over 2.2 years on background statin
- LDL reduction of 59% — most potent LDL-lowering agent available
- Biologic mechanism: PCSK9 naturally promotes LDL receptor degradation; inhibition prevents this
Safety Profile
Pregnancy avoid
Lactation insufficient-data
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.