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Evolocumab

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 mouse (murine) and/or hamster protein, 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 mouse (murine) and/or hamster protein, 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

Peak effect: 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

Hyperlipidemia, primary: Adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (CVD), who require additional lowering of low density lipoprotein cholesterol (LDL-C).

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 (HoFH) who require additional lowering of LDL-C.

Limitation of use: The effect of evolocumab on cardiovascular morbidity and mortality has not been determined.

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

Hyperlipidemia, primary: 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.

Homozygous familial hypercholesterolemia: SubQ:

US labeling: 420 mg once monthly

Canadian labeling: Initial: 420 mg once monthly; if clinical response is not achieved after 12 weeks of treatment, dose frequency may be titrated up to 420 mg once every 2 weeks. Patients on apheresis may initiate treatment with 420 mg every 2 weeks to correspond with their apheresis schedule.

Missed doses: Administer as soon as possible if there are more than 7 days until next scheduled dose, or omit the missed dose and administer next dose according to the original schedule.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Homozygous familial hypercholesterolemia:

US labeling: Adolescents 13 to 17 years: SubQ: Refer to adult dosing

Canadian labeling: Children ≥12 years and Adolescents: SubQ: Refer to adult dosing.

Missed doses: Administer as soon as possible if there are more than 7 days until next scheduled dose, or omit the missed dose and administer next dose according to the original schedule.

Dosing: Renal Impairment

Mild to moderate impairment: No dosage adjustment necessary.

Severe impairment (estimated GFR <30 mL/minute/1.73 m2):

US labeling: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); however, dosage adjustment is unlikely to be required as monoclonal antibodies are not known to be renally eliminated.

Canadian labeling: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use is not recommended.

Dosing: Hepatic Impairment

Mild to moderate impairment (Child Pugh class A and B): No dosage adjustment necessary.

Severe impairment (Child Pugh class C): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Reconstitution

Prior to use, if refrigerated, allow to warm to room temperature for at least 30 minutes. Do not warm in any other way.

Administration

If refrigerated, allow to stand at room temperature for at least 30 minutes prior to use (do not warm with heat or hot water).

SubQ: Using a single-use prefilled syringe or single-use prefilled autoinjector, administer subcutaneously 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.

To administer the once-monthly dose (ie, 420 mg), may either administer subcutaneously over 9 minutes using the single-use infusor with prefilled cartridge or give 3 separate subcutaneous 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 be kept 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. Do not shake.

Drug Interactions

Belimumab: Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab. Avoid combination

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%)

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%), erythema at injection site (3% to ≤6%)

Neuromuscular & Skeletal: Myalgia (4%)

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

<1% (Limited to important or life-threatening): Antibody development, decreased LDL cholesterol (<25 mg/dL), hypersensitivity

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Hypersensitivity reactions (eg, 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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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; in patients with homozygous familial hypercholesterolemia, measure LDL-C levels 4 to 8 weeks after initiation (response to evolocumab will depend on degree of LDL-receptor function); signs/symptoms of hypersensitivity reactions.

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. IgG antibodies are known to cross the placenta in increasing amounts during the second and third trimesters; exposure of the fetus to evolocumab is expected.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience pharyngitis, rhinitis, flu-like symptoms, common cold symptoms, back pain, or injection site irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating, and advising patients.

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