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Evolocumab

Medically reviewed by Drugs.com. Last updated on Aug 27, 2020.

Pronunciation

(e voe LOK ue mab)

Index Terms

  • AMG145

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Auto-injector, Subcutaneous [preservative free]:

Repatha SureClick: 140 mg/mL (1 mL) [contains polysorbate 80]

Solution Cartridge, Subcutaneous [preservative free]:

Repatha Pushtronex System: 420 mg/3.5 mL (3.5 mL) [contains polysorbate 80]

Solution Prefilled Syringe, Subcutaneous [preservative free]:

Repatha: 140 mg/mL (1 mL) [contains polysorbate 80]

Brand Names: U.S.

  • Repatha
  • Repatha Pushtronex System
  • Repatha SureClick

Pharmacologic Category

  • Antilipemic Agent, PCSK9 Inhibitor
  • Monoclonal Antibody

Pharmacology

Evolocumab is a human monoclonal antibody (IgG2 isotype) that binds to proprotein convertase subtilisin kexin type 9 (PCSK9). PCSK9 binds to the low-density lipoprotein receptors (LDLR) on hepatocyte surfaces to promote LDLR degradation within the liver. LDLR is the primary receptor that clears circulating LDL; therefore, the decrease in LDLR levels by PCSK9 results in higher blood levels of LDL-cholesterol (LDL-C). By inhibiting the binding of PCSK9 to LDLR, evolocumab increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.

Distribution

IV: Vd: ~3.3 L.

Metabolism

Nonsaturable proteolysis.

Onset of Action

Proprotein convertase subtilisin kexin type 9 (PCSK9) suppression: 4 hours.

Time to Peak

SubQ: 3 to 4 days.

Half-Life Elimination

11 to 17 days.

Special Populations: Hepatic Function Impairment

In patients with mild or moderate hepatic impairment, a 20% to 30% lower mean Cmax and 40% to 50% lower mean AUC occurs.

Use: Labeled Indications

Homozygous familial hypercholesterolemia: Adjunct to diet and other LDL-lowering therapies (eg, statins, ezetimibe, LDL apheresis) for the treatment of patients with homozygous familial hypercholesterolemia who require additional lowering of LDL-C

Hyperlipidemia, primary: Adjunct to diet, alone or in combination with other lipid-lowering therapies (eg, maximum tolerated dose of statins), for the treatment of adults with primary hyperlipidemia, including heterozygous familial hyperlipidemia, to reduce LDL-C (Sabatine 2015)

Prevention of cardiovascular events in patients with established cardiovascular disease: To reduce the risk of MI, stroke, and coronary revascularization in adults with established cardiovascular disease. Note: Use in combination with an optimized regimen of lipid-lowering therapy (eg, high-intensity statin) (Sabatine 2017).

Contraindications

Serious hypersensitivity to evolocumab or any component of the formulation.

Documentation of allergenic cross-reactivity for PCSK9 inhibitors is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Note: Use may be considered in patients who do not meet cholesterol treatment goals with dietary modification and other lipid-lowering therapies (eg, maximally tolerated statin with or without ezetimibe) (AHA/ACC [Grundy 2018]).

Homozygous familial hypercholesterolemia: SubQ: 420 mg once monthly.

Off-label dosing: 420 mg once every 2 weeks (after 12 weeks, may decrease to 420 mg once a month) in conjunction with lipid apheresis has been studied in a limited number of patients (Bruckert 2014). The European Atherosclerosis Society recommends administration directly after lipid apheresis (EAS [France 2016]).

Hyperlipidemia, primary: SubQ: 140 mg every 2 weeks or 420 mg once monthly.

Prevention of cardiovascular events in patients with established cardiovascular disease: SubQ: 140 mg every 2 weeks or 420 mg once monthly.

Switching regimens: Administer the first dose of the new regimen on the next scheduled day of the prior regimen.

Missed dose: Administer within 7 days from the missed dose and resume original schedule. If an every-2-week dose is not administered within 7 days, wait until the next dose on the original schedule. If a once-monthly dose is not administered within 7 days, administer the dose and start a new schedule based on this date.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Homozygous familial hypercholesterolemia (HoFH):

Note: Should be used in combination with other lipid-lowering therapy (eg, statin therapy, LDL apheresis); overall effectiveness determined by LDLR genotype (LDL receptor function) and variable; evolocumab generally lacks efficacy in patients without any LDLR allele defects (EAS [France 2016]; Raal 2017; Thedrez 2018).

Children ≥12 years weighing ≥40 kg and Adolescents: Limited data available in <13 years of age (Raal 2015a; Raal 2017):

Patients not receiving apheresis: SubQ: Initial: 420 mg once a month; after 12 weeks of therapy, if further optimization of clinical response is warranted (eg, further LDL reduction), dosing interval may be increased to every 2 weeks (Raal 2015a; Raal 2017; Repatha European Medicines Agency 2020).

Patients receiving LDL apheresis: SubQ: 420 mg every 2 or 4 weeks; dose should be administered immediately after apheresis (Raal 2017).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Administration

For SubQ administration. Do not shake. If refrigerated, allow to stand at room temperature for at least 30 minutes (single-use prefilled autoinjector or single-use prefilled syringe) or at least 45 minutes (single-use on-body infusor with prefilled cartridge) prior to use (do not warm with heat or hot water). Administer into areas of the abdomen (except for the 2-inch area around the navel), thigh, or upper arm; only use areas that are not tender, bruised, red, or indurated. Do not coadminister with other injectable drugs at the same injection site. Rotate the injection site with each injection. When using single-use on-body infusor, administer medication within 5 minutes of inserting cartridge; do not use if infusor gets wet.

Once-monthly dose (ie, 420 mg): Administer SubQ over 5 minutes (Note: Prior to May 2020, the manufacturer's labeling stated to administer over 9 minutes) using the single-use infusor with prefilled cartridge or give 3 separate SubQ 140 mg injections consecutively within a 30-minute period using the single-use prefilled autoinjector or single-use prefilled syringe.

Storage

Store between 2°C to 8°C (36°F to 46°F) in the original carton. May also store at room temperature (at 20°C to 25°C [68°F to 77°F]) in the original carton; however, under these conditions, must use within 30 days (discard if not used within 30 days). Protect from direct light and do not expose to temperatures above 25°C (77°F). Do not freeze.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

>10%: Respiratory: Nasopharyngitis (6% to 11%)

1% to 10%:

Cardiovascular: Hypertension (3%)

Central nervous system: Dizziness (4%), fatigue (2%)

Dermatologic: Skin rash (1%)

Endocrine & metabolic: Diabetes mellitus (9%)

Gastrointestinal: Gastroenteritis (3% to 6%), nausea (2%)

Genitourinary: Urinary tract infection (5%)

Hematologic & oncologic: Bruise (1%)

Infection: Influenza (8% to 9%)

Local: Injection site reaction (6%)

Neuromuscular & skeletal: Myalgia (4%)

Respiratory: Upper respiratory tract infection (9%), cough (1% to 5%), sinusitis (4%)

<1%, postmarketing, and/or case reports: Angioedema, antibody development, flu-like symptoms, hypersensitivity reaction

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Hypersensitivity reactions (eg, angioedema, rash, urticaria) have been reported, some requiring discontinuation. Discontinue treatment and initiate supportive treatment in patients who develop signs/symptoms of serious allergic reaction; monitor until symptoms resolve.

Dosage form specific issues:

• Latex: The packaging (needle cap of prefilled syringe and autoinjector) may contain dry natural rubber, which is a derivative of latex.

Monitoring Parameters

Lipid profile (fasting or nonfasting) before initiating treatment; fasting lipid profile should be rechecked 4 to 12 weeks after starting therapy and every 3 to 12 months thereafter (AHA/ACC [Grundy 2018]); signs/symptoms of hypersensitivity reactions.

Pregnancy Considerations

Evolocumab is a humanized monoclonal antibody (IgG2). Potential placental transfer of human IgG is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Data collection to monitor pregnancy and infant outcomes following exposure to evolocumab is ongoing. Health care providers are encouraged to enroll females exposed to evolocumab during pregnancy in the Pregnancy Registry (1-877-311-8972 or https://mothertobaby.org/ongoing-study/repatha).

Patient Education

What is this drug used for?

• It is used to lower cholesterol.

• It is used in some people to lower the chance of heart attack, stroke, and certain heart procedures.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Sore throat

• Stuffy nose

• Flu-like symptoms

• Common cold

• Back pain

• Injection site irritation

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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