evolocumab (e-vo-lo-kyoo-mab) Repatha

 Indications

Lowering of low density lipoprotein cholesterol (LDLC)

as an adjunct to diet and maximally tolerated statin

(HMG CoA reductase inhibitor) therapy in patients with

heterozygous familial hypercholesterolemia (HeFH) or

cardiovascular disease who require supplemental

agents. Additional lowering of low density lipoprotein

cholesterol (LDL-C) as an adjunct to diet and maximally

tolerated statin and other drug therapies in patients

with homozygous familial hypercholesterolemia

(HoFH).

Action

A human monoclonal immunoglobulin (IgG2) produced

in genetically engineered Chinese hamster ovary

cells that binds to PSCSK9 inhibiting its binding to the

low density lipoprotein receptor (LDLR) resulting inq

number of LDLRs available to clear LDL from blood.

Therapeutic Effects:pLDL-C.

Pharmacokinetics

Absorption: Well absorbed (72%) following subcut

administration.

Distribution: Crosses the placenta.

Metabolism and Excretion: Eliminated by binding

to PCSK9 and by proteolytic degradation.

Half-life: 11–17 days.

TIME/ACTION PROFILE (effect circulating

unbound PCSK9)

ROUTE ONSET PEAK DURATION

subcut rapid 4 hr 2–4 wk

Contraindications/Precautions

Contraindicated in: History of serious hypersensitivity

to evolocumab.

Use Cautiously in: Severe renal/hepatic impairment;

Geri: Elderly patients may be more sensitive to

drug effects; OB: Crosses the placenta, consider fetal

risks; Lactation: Consider benefits of breast feeding

against possible risk to infant; Pedi: Safe and effective

use in children 13 yr has not been established.

Adverse Reactions/Side Effects

Local: injection site reactions. MS: back pain. Misc:

allergic reactions (including urticaria and rash), flulike

symptoms.

Interactions

Drug-Drug: None noted.

Route/Dosage

Subcut (Adults): Primary hyperlipidemia with established

CVD/HeFH—140 mg every two wk or 420

mg monthly; HoFH—420 mg monthly.

Availability

Solution for subcutaneous injection (needle

cover contains latex derivative): 120 mg/mL (in

Pushtronex system), 140 mg/mL (in prefilled syringes

and autoinjector).