PCSK9 Inhibitor (Monoclonal Antibody) Pregnancy: Avoid — insufficient data; IgG2 antibody may cross placenta; effective contraception required

Evolocumab

Brand names: Repatha

Adult dose

Dose: 140 mg SC every 2 weeks or 420 mg SC once monthly

Route: Subcutaneous injection (self-administered autoinjector)

Frequency: Every 2 weeks or monthly

Max: 420 mg/month

Primary hypercholesterolaemia or mixed dyslipidaemia; ASCVD risk reduction (FOURIER); homozygous familial hypercholesterolaemia (HoFH) — 420 mg monthly; patient self-injection after training

Paediatric dose

Dose: HoFH ≥10 years: 420 mg SC monthly mg/kg

Route: Subcutaneous

Frequency: Monthly

Max: 420 mg/month

Licensed for HoFH ≥10 years; specialist lipid clinic only

Dose adjustments

Renal

No dose adjustment required

Hepatic

No dose adjustment required

Paediatric weight-based calculator

Patient weight (kg)

Licensed for HoFH ≥10 years; specialist lipid clinic only

Clinical pearls

FOURIER trial (Sabatine et al. NEJM 2017): evolocumab added to statin significantly reduced major cardiovascular events (CV death, MI, stroke, UA hospitalisation, revascularisation) by 15% vs placebo over 2.2 years — LDL-C reduced from 2.4 to 0.78 mmol/L (67%); NICE TA394
PCSK9 mechanism: PCSK9 (proprotein convertase subtilisin/kexin type 9) binds LDL-receptors on hepatocyte surface and targets them for lysosomal degradation — evolocumab neutralises circulating PCSK9, allowing LDL receptors to recycle and take up more LDL-C
Familial hypercholesterolaemia (FH): heterozygous FH patients often cannot reach LDL-C targets on statins ± ezetimibe alone; PCSK9 inhibitors achieve additional 50-60% LDL-C reduction on top of statin therapy; HoFH responds less well (still some LDL receptor function needed)
Cognitive safety: long-term FOURIER extension and EBBINGHAUS trial showed no cognitive adverse effects despite very low achieved LDL-C levels (median 0.78 mmol/L) — addresses patient/prescriber concern about extreme LDL lowering
Alirocumab vs evolocumab: ODYSSEY OUTCOMES (alirocumab, NEJM 2018) and FOURIER (evolocumab, NEJM 2017) show comparable cardiovascular benefit; prescribe based on local formulary, patient preference (device type), and NICE TA approvals

Contraindications

Known hypersensitivity to evolocumab

Side effects

Injection site reactions
Nasopharyngitis
Back pain
Arthralgia
Influenza-like illness
Urinary tract infections

Interactions

No clinically significant drug-drug interactions — monoclonal antibody with no CYP involvement

Monitoring

LDL-C (at 4-8 weeks after starting — confirm response)
Injection site reactions
Annual lipid profile
No routine laboratory monitoring otherwise required

Reference: BNFc; BNF 90; FOURIER trial (Sabatine et al. NEJM 2017); NICE TA394; MHRA SPC Repatha; ESC/EAS Dyslipidaemia Guidelines (2019). Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways