Evolocumab

REPATHA

What it isPCSK9-binding monoclonal antibody that increases LDL-receptor recycling; hyperlipidemia and ASCVD risk reduction.

Why this oneUnlike response-titrated alirocumab, its standard hyperlipidemia regimens use fixed, clinically equivalent dosing options.

What limits itInjection-site reactions are usually mild; cost, access and the need for ongoing injections are the main reasons treatment fails.

FDA-approved for

FDA dosing	Population	Start	Target	Max
Primary hyperlipidemia / CV risk reduction	Adults	140 mg q2wk or 420 mg monthly SC	140 mg q2wk or 420 mg monthly SC
HeFH	Adults & peds ≥10 yr	140 mg q2wk or 420 mg monthly SC	140 mg q2wk or 420 mg monthly SC
HoFH	Adults & peds ≥10 yr	420 mg monthly SC	may ↑ to 420 mg q2wk if inadequate response at 12 wk	420 mg q2wk

Titration HoFH: may increase to 420 mg q2wk only if inadequate response after 12 wk

Renal No adjustment needed

Hepatic No adjustment for mild–moderate (Child-Pugh A/B); no data in severe

Inject SC into abdomen, thigh, or upper arm; rotate sites
Allow to warm to room temperature ≥30 min before use
Give the 420 mg dose as 3 injections consecutively within 30 min
If switching regimens, give first dose of new regimen on next scheduled date of prior regimen
Missed dose: give within 7 days and resume schedule; if >7 days, for q2wk wait for next scheduled dose, for monthly give dose and start new schedule

Hypersensitivity reactions including angioedema — discontinue if serious reaction occurs
Some autoinjector/syringe presentations have dry natural rubber (latex) in needle cover — caution if latex-sensitive

Pregnancy Insufficient data; IgG crosses placenta (increasingly near term) and may transmit to fetus

Lactation No information on presence in human milk; breast-milk antibodies unlikely to enter infant circulation in substantial amounts

NO BOXED WARNINGS

Principal riskInjection-site reactions

Cost, est. cash$300–$5,000/dose or month

Generic entry2037 est. (biosimilar)

Therapeutic safety burden1 / 4

Overdose danger0 / 4

Weight-gain liability0 / 4

Sedation liability0 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Legacy pregnancy categoryNot assigned — PLLR-era drug

Defining liabilityInjection-site and hypersensitivity reactions; systemic acute toxicity is minimal.

no kinetic interactions