General

Pronunciation:
e-vo-lo-kyoo-mab

Trade Name(s)

• Repatha

Ther. Class.
lipid-lowering agents

Pharm. Class.
proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor antibodies

Indications

• Lowering of low density lipoprotein cholesterol (LDL-C) as an adjunct to diet in patients with primary hyperlipidemia (including heterozygous familial hypercholesterolemia [HeFH] as monotherapy or in combination with other lipid-lowering therapies).
• Additional lowering of LDL-C as an adjunct to diet and other LDL-C-lowering therapies in patients with homozygous familial hypercholesterolemia (HoFH).
• To reduce the risk of myocardial infarction, stroke, and coronary revascularization in patients with cardiovascular disease.

Action

A human monoclonal immunoglobulin (IgG2) 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 from blood.

Therapeutic Effect(s):

• ↓ LDL-C
• Reduction in the risk of myocardial infarction, stroke, and coronary revascularization.

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)

Contraindication/Precautions

Contraindicated in:

• History of serious hypersensitivity to evolocumab.

Use Cautiously in:

• Severe renal/hepatic impairment;
• OB:  Crosses the placenta, consider fetal risks;
• Lactation: Consider benefits of breast feeding against possible risk to infant;
• Pedi:  Children <13 yr (safety and effectiveness not established);
• Geri:  Elderly patients may be more sensitive to drug effects.

Adverse Reactions/Side Effects

Local: injection site reactions

MS: back pain

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANGIOEDEMA, RASH, URTICARIA)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None noted.

Route/Dosage

Established Cardiovascular Disease or Primary Hyperlipidemia (including HeFH)

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

HoFH

SC (Adults): 420 mg once monthly.

Availability

Solution for injection (needle cover contains latex derivative): 420 mg/mL (Pushtronex system), 140 mg/mL (prefilled syringes and autoinjector)

Assessment

• Obtain a diet history, especially with regard to fat consumption.
• Monitor for signs and symptoms of hypersensitivity reactions (rash, urticaria) during therapy. If symptoms occur, discontinue therapy.
• Assess for latex allergy. Needle cover of the glass prefilled syringe and the autoinjector contain dry natural rubber (a derivative of latex); may cause allergic reactions.

Lab Test Considerations:

Assess LDL-C levels within 4–8 wk of initiating; response to therapy depends on degree of LDL-receptor function.

Potential Diagnoses

• Noncompliance, related to diet and medication regimen (Patient/Family/Teaching) 

Implementation

• SC To administer the 140 mg dose using  Single-Use Prefilled SureClick® Autoinjector , give 3 injections, using 3 separate pens/syringes in 3 separate sites, consecutively within 30 min. When switching dose regimens, administer first dose of new regimen on next scheduled date of prior regimen. If stored in refrigerator allow solution to warm to room temperature for at least 30 min before injecting. May also be stored at room temperature, but only stable for 30 days. Solution is clear to opalescent and colorless to pale yellow; do not administer solutions that are cloudy or contain particulate matter. 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.
  • To administer the 420 mg dose using  Pushtronex on-body infusor system:  Remove on-body infusor and prefilled cartridge from refrigerator 45 min prior to use to allow to reach room temperature; do not use other sources of warming. Prepare injection site with little hair (may trim) and firm and flat skin surface by cleaning with alcohol and allowing to dry. May use thigh, abdomen (except 2 inches from umbilicus) or outer area of upper arm if not self-administered. Avoid areas that are tender, bruised, red, or hard, or areas with wrinkles, skin folds, scars, stretch marks, moles and excessive hair. Solution in cartridge should be clear and colorless to slightly yellow; do not administer solutions that are discolored or contain particular matter. Clean bottom of cartridge with alcohol and load into on-body infusor; press firmly on top of unit to secure. Administer injection within 5 min after loading the cartridge; >5 min may dry out medication. Swing door close until it snaps. Peel away both green pull tabs to show adhesive. When blue light flashes, infusor is on. If using abdomen, stretch skin prior to applying; do not stretch skin for thigh placement. Apply infusor to skin making sure blue light is visible and firmly press start button. Flashing green light and click indicates infusion has begun; may beep and patient may feel a pinch. Solution is injected over 9 min. When green light changes to solid, infusion is complete. Remove from skin and check medicine window for green light to be off. Dispose of on-body infusor in a sharps container.

Patient/Family Teaching

• Instruct patient in correct technique for self-injection or on-body infusor, 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 to read  Patient Information  before starting therapy and with each Rx refill in case of changes.
• 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.
• Advise patient to notify health care professional if pregnancy is planned or suspected or if breast feeding. Encourage pregnant patients to enroll in pregnancy exposure registry that monitors pregnancy outcomes in women exposed to evolocumab during pregnancy by contacting 1-877-311-8972 or https://mothertobaby.org/ongoing-study/repatha/

Evaluation/Desired Outcomes

• ↓ LDL-C levels.
• Reduction in the risk of myocardial infarction, stroke, and coronary revascularization.