evolocumab (Rx)

Brand and Other Names:Repatha
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

solution for SC injection

  • 140mg/mL in a single-use prefilled syringe OR single-use SureClick autoinjector
  • 420mg/3.5mL in a single-use Pushtronex system (on-body infusor with prefilled cartridge)

Prevention of Cardiovascular Events

Indicated to reduce the risk of myocardial infarction, stroke, and coronary revascularization

140 mg SC q2weeks OR 420 mg SC once monthly, based on patient preference for dosing frequency and injection volume

When switching dosage regimens, administer first dose of new regimen on the next scheduled date of the prior regimen

Primary Hyperlipidemia

Adjunct to diet, alone or in combination with other lipid-lowering therapies (eg, statins), for treatment of adults with primary hyperlipidemia, including heterozygous familial hyperlipidemia (HeFH), to reduce LDL-C

140 mg SC q2weeks or 420 mg SC once monthly

When switching dosage regimens, administer first dose of new regimen on the next scheduled date of the prior regimen

Homozygous Familial Hypercholesterolemia

Indicated as an adjunct to diet and other LDL-lowering therapies (eg, statins, ezetimibe, LDL apheresis) for the treatment of patients with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDL-C

420 mg SC once monthly

Measure LDL-C levels 4-8 wk after initiating, since response to therapy depends on the degree of LDL-receptor function

Dosage Modifications

Renal impairment

  • Mild or moderate: No dose adjustment required
  • Severe or end-stage renal disease (ESRD): In a clinical trial, reductions in PCSK9 levels in patients with severe renal impairment or ESRD receiving hemodialysis was similar to those with normal renal function

Hepatic impairment

  • Mild or moderate: No dose adjustment required
  • Severe: No data available

Dosage Forms & Strengths

SC injection

  • 140mg/mL

Primary Hyperlipidemia

Safety and efficacy not established in children with heterozygous familial hypercholesterolemia (HeFH)

Homozygous Familial Hypercholesterolemia

Indicated as an adjunct to diet and other LDL-lowering therapies (eg, statins, ezetimibe, LDL apheresis) for the treatment of patients with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDL-C

<13 years: Safety and efficacy not established

13-17 years: 420 mg SC once monthly (see Administration for instructions regarding 1 or 3 injections)

Measure LDL-C levels 4-8 wk after initiating, since response to therapy depends on the degree of LDL-receptor function

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Adverse Effects

>10%

Nasopharyngitis (4-10.5%)

1-10%

Upper respiratory tract infection (2.1-9.3%)

Influenza (1.2-7.5%)

Back pain (2.3-6.2%)

Injection site reactions (3.2-5.7%)

Allergic reaction (5.1%)

Cough (1.2-4.5%)

Urinary tract infection (1.3-4.5%)

Sinusitis (4.2%)

Headache (4%)

Myalgia (4%)

Dizziness (3.7%)

Musculoskeletal pain (3.3%)

Hypertension (3.2%)

Diarrhea (3%)

Gastroenteritis (3%)

Arthralgia (1.8%)

Nausea (1.8%)

Fatigue (1.6%)

Muscle spasms (1.3%)

Contusion (1%)

Postmarketing Reports

Allergic reactions: Angioedema

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Warnings

Contraindications

History of serious hypersensitivity to evolocumab

Cautions

Hypersensitivity reactions (eg, rash, urticaria) reported, including some that led to discontinuation of therapy; if signs or symptoms of serious allergic reactions occur, discontinue treatment, treat accordingly and monitor until signs and symptoms resolve

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Pregnancy

Pregnancy

No available data on use in pregnant women

Monoclonal antibodies in humans indicate that they are unlikely to cross the placenta in the first trimester; however, they are likely to cross the placenta in increasing amounts in the second and third trimesters

Pregnancy outcomes in women exposed to evolocumab during pregnancy are monitored by the pregnancy exposure registry, 1-877-311-8972 or https://mothertobaby.org/ongoing-study/repatha/

Animal studies

  • No effects on pregnancy or neonatal/infant development when monkeys were subcutaneously administered evolocumab from organogenesis through parturition at dose exposures up to 12 times the exposure at the maximum recommended human dosage
  • In a similar study with another drug in the PCSK9 inhibitor antibody class, humoral immune suppression was observed in infant monkeys exposed to that drug in utero at all doses

Lactation

Unknown if distributed in human breast milk

The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant

Human IgG is present in human milk, but published data suggest that breastmilk IgG antibodies do not enter the neonatal and infant circulation in substantial amounts

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

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Pharmacology

Mechanism of Action

Monoclonal antibody that binds to PCSK9 (proprotein convertase subtilisin/kexin type 9)

LDL-C is cleared from the circulation preferentially through the LDL receptor (LDLR) pathway

PCSK9 is a serine protease that destroys LDLR in the liver, resulting in decreased LDL-C clearance and increased plasma LDL-C

PCSK9 inhibitors decrease LDLR degradation by PCSK9, and thereby improve LDL-C clearance and lower plasma LDL-C

Absorption

Bioavailability: 72%

Peak plasma time: 3-4 days

Peak plasma concentration: 18.6 mcg/mL (140 mg); 59 mcg/mL (420 mg)

AUC (last): 188 day·mcg/mL (140 mg); 924 day·mcg/mL (420 mg)

Distribution

Vd: 3.3 L (420 mg)

Metabolism

At low concentrations: Elimination is predominately through saturable binding to target, PCSK9

At higher concentrations: Elimination of evolocumab is largely through a nonsaturable proteolytic pathway

Elimination

Half-life: 11-17 days

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Administration

SC Preparation

Remove prescribed dose from refrigerator at least 30 minutes before administration; this helps administer the entire dose and minimizes injection discomfort

Do not heat syringe, autoinjector, or on-body infuser (eg, microwave or hot water); let them warm to room temperature on their own

Do not leave in direct sunlight; keep in original carton until administered

Do not use autoinjector or on-body infusor if

  • Drug appears cloudy or discolored, or contains particles
  • Device appears cracked or broken
  • The device has been dropped
  • The orange cap is missing or not securely attached

SC Administration

Available as 140-mg/mL prefilled syringe or autoinjector; also available as 420-mg/3.5-mL on-body infusor

420 mg dose: Give three 140-mg SC injections consecutively within 30 minutes OR over 9 minutes using the single-use on-body infusor with refilled cartridge

Clean injection site with alcohol wipe and let dry

Do not inject in areas of skin that are bruised, red, tender, or hard

Avoid injecting in scars or stretch marks

Rotate administration sites

See prescribing information for images depicting injection technique for the various devices

Administration sites

  • Self-injection: Thigh or abdomen (except for a 2-inch area around the naval)
  • Caregiver: Thigh, abdomen, or outer area of upper arm

Missed dose

  • Dose missed within 7 days: Administer dose and start a new schedule based on this date
  • Dose not administered within 7 days
    • 140 SC q2week dose: Wait until the next dose on the original schedule
    • 420 mg SC once monthly: Administer dose and start a new schedule based on this date

Storage

Refrigerate at 2-8°C (36-46°F) in the original carton

Alternatively, may store at room temperature (20-25°C [68-77°F]) in the original carton; however, under these conditions, drug must be used within 30 days; if not used within the 30 days, discard

Protect from direct light

Do not expose to temperatures >25°C (77°F)

Do not shake

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Images

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Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
  • Manage and view all your plans together – even plans in different states.
  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.