evolocumab

Therapeutic Classification: lipid-lowering agents

Pharmacologic Classification: proprotein convertase subtilisin kexin type-9 pcsk-9 inhibitors, monoclonal antibodies

Indications ⬆ ⬇

REMS

Primary hyperlipidemia (including heterozygous familial hypercholesterolemia [HeFH]) in adults (as an adjunct to diet as monotherapy or in combination with other low-density lipoprotein cholesterol [LDL-C]-lowering therapies).
Homozygous familial hypercholesterolemia (in combination with other LDL-C lowering therapies).
HeFH in pediatric patients ≥10 yr (as an adjunct to diet in combination with other LDL-C-lowering therapies).
To reduce the risk of cardiovascular death, MI, stroke, unstable angina requiring hospitalization, and coronary revascularization in patients with cardiovascular disease.

Action ⬆ ⬇

A human monoclonal immunoglobulin produced in genetically engineered Chinese hamster ovary cells that binds to PCSK9, inhibiting its binding to the low-density lipoprotein receptor (LDLR), resulting in ↑ number of LDLRs available to clear LDL-C from blood.

Therapeutic effects:

Reduction in LDL-C.
Reduction in the risk of MI, stroke, and coronary revascularization.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed (72%) following SUBQ administration.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Eliminated by binding to PCSK9 and by proteolytic degradation.

Half-Life: 11–17 days.

Time/Action Profile ⬆ ⬇

(effect on circulating unbound PCSK9)

ROUTE	ONSET	PEAK	DURATION
SUBQ	rapid	4 hr	2–4 wk

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity.

Use Cautiously in:

Hypersensitivity to latex (use preparation that does not contain dry natural rubber);
Severe renal impairment;
Severe hepatic impairment;
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Children <10 yr (safety and effectiveness not established);
Geri: Older adults may be more sensitive to drug effects.

Adv. Reactions/Side Effects ⬆ ⬇

Local: injection site reactions

MS: back pain

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

None reported.

Route/Dosage ⬆ ⬇

Established Cardiovascular Disease or Primary Hyperlipidemia

SC (Adults ): 140 mg every 2 wk or 420 mg once monthly.

Heterozygous Familial Hypercholesterolemia

SC (Children ≥10 yr): 140 mg every 2 wk or 420 mg once monthly.

Homozygous Familial Hypercholesterolemia

SC (Adults and Children ≥10 yr): 420 mg once monthly; if inadequate response after 12 wk, may ↑ to 420 mg every 2 wk. Patients on lipid apheresis: 420 mg every 2 wk (administered after apheresis session completed).

Availability ⬆ ⬇

Solution for injection (some needle covers contains latex derivative) (prefilled syringes and autoinjectors): 140 mg/mL

Assessment ⬆ ⬇

Obtain a diet history, especially with regard to saturated fat consumption.
Monitor for signs and symptoms of hypersensitivity reactions (rash, urticaria, dyspnea) during therapy. If symptoms occur, discontinue therapy.

Lab Test Considerations:

Assess LDL-C levels within 4–8 wk of initiating; response to therapy depends on degree of LDLR function. For patients on a monthly regimen, measure LDL-C just prior to next scheduled dose.

Implementation ⬆ ⬇

Some needle cover of glass single-dose prefilled syringe and single-dose prefilled autoinjector contain latex; avoid with latex allergies.
SC: To administer the 140-mg or 420-mg dose, give one injection (140-mg dose) or give three injections (420-mg dose) using three separate pens/syringes in three separate sites, consecutively within 30 min. When switching dose regimens, administer 1st dose of new regimen on next scheduled date of prior regimen. If stored in refrigerator, allow solution to warm to room temperature for ≥30 min before injecting. May also be stored at room temperature for 30 days. Solution is clear to opalescent and colorless to pale yellow; do not administer solutions that are cloudy or contain particulates. Do not shake. Stretch or pinch skin. Inject into thigh, abdomen, or upper arm at a 90° angle. Injection may take 15 sec. Window turns from clear to yellow when the injection is done. Rotate sites with each injection. Do not inject into areas that are tender, bruised, red, or indurated. Do not reuse prefilled pen or syringe. Do not administer other injectable drugs at same site.

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of evolocumab. Instruct patient to take as directed. Advise patient to read the Medication Guide before starting and with each refill in case of changes.
Instruct patient in correct technique for self-injection and care and disposal of equipment. Administer missed doses within 7 days; then resume original schedule. If not administered within 7 days, wait until next dose on original schedule.
Advise patient that this medication should be used in conjunction with diet restrictions (fat, cholesterol, carbohydrates, alcohol), exercise, and cessation of smoking.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products.
Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Inform patients of pregnancy safety study that monitors pregnancy outcomes in women exposed to evolocumab during pregnancy. Enroll patient by contacting Amgen at 1-800-77-AMGEN (1-800-772-6436).

Evaluation/Desired Outcomes ⬆ ⬇

Decreased LDL-C levels.
Reduction in the risk of cardiovascular death, MI, stroke, unstable angina requiring hospitalization and coronary revascularization.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

68225- Patheon Italia S.p.A.
- 68225-080-
  - 68225-080-00- 480 CARTRIDGE in 1 BOX (68225-080-00) / 3.5 mL in 1 CARTRIDGE

72511- Amgen USA Inc.
- 72511-393- REPATHA
  - 72511-393-01- 1 SYRINGE in 1 CARTON (72511-393-01) / 1 mL in 1 SYRINGE

72511- Amgen USA Inc.
- 72511-393- REPATHA
  - 72511-393-02- 2 SYRINGE in 1 CARTON (72511-393-02) / 1 mL in 1 SYRINGE

72511- Amgen USA Inc.
- 72511-393- REPATHA
  - 72511-393-96- 1 SYRINGE in 1 CARTON (72511-393-96) / 1 mL in 1 SYRINGE

72511- Amgen USA Inc.
- 72511-501- REPATHA
  - 72511-501-01- 1 SYRINGE in 1 CARTON (72511-501-01) / 1 mL in 1 SYRINGE

72511- Amgen USA Inc.
- 72511-750- REPATHA
  - 72511-750-01- 1 SYRINGE in 1 CARTON (72511-750-01) / 1 mL in 1 SYRINGE

72511- Amgen USA Inc.
- 72511-760- REPATHA
  - 72511-760-02- 2 SYRINGE in 1 CARTON (72511-760-02) / 1 mL in 1 SYRINGE (72511-760-01)

72511- Amgen USA Inc.
- 72511-760- REPATHA
  - 72511-760-91- 1 SYRINGE in 1 CARTON (72511-760-91) / 1 mL in 1 SYRINGE

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Pronunciation ⬇

Classifications ⬆ ⬇