Version May 2024
Atherosclerotic cardiovascular disease, primary or secondary prevention:
Note: May use as an additional agent in patients who do not meet cholesterol treatment goals with dietary modification plus maximally tolerated lipid-lowering therapies (eg, a high-intensity statin and ezetimibe) or as an alternative agent in patients intolerant of such therapies (Ref).
SUBQ: 140 mg once every 2 weeks or 420 mg once monthly.
Familial hypercholesterolemia, heterozygous:
Note: May use as an additional agent in patients who do not meet cholesterol treatment goals with dietary modification plus maximally tolerated lipid-lowering therapies (eg, a high-intensity statin and ezetimibe) or as an alternative agent in patients intolerant of such therapies (Ref).
SUBQ: 140 mg once every 2 weeks or 420 mg once monthly.
Familial hypercholesterolemia, homozygous:
Note: May use as an additional agent in patients who do not meet cholesterol treatment goals with dietary modification plus maximally tolerated lipid-lowering therapies (eg, a high-intensity statin and ezetimibe) or as an alternative agent in patients intolerant of such therapies. Treatment should be guided by a lipid specialist (Ref).
SUBQ: Initial: 420 mg once monthly; may increase to 420 mg once every 2 weeks if clinically meaningful response is not achieved in 12 weeks. Note: For patients receiving lipid apheresis, may begin 420 mg once every 2 weeks administered on the day of apheresis after the session is complete.
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.
No dosage adjustment necessary.
Mild to moderate impairment (Child-Pugh classes 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).
Refer to adult dosing.
(For additional information see "Evolocumab: Pediatric drug information")
Heterozygous familial hypercholesterolemia (HeFH): Note: Should be used as adjunct to diet and other LDL-C lowering therapy.
Children ≥10 years and Adolescents: SUBQ: 140 mg every 2 weeks or 420 mg once a month. If converting between regimens, the first dose of new regimen should be administered on the day of the next scheduled dose of previous regimen (Ref).
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 (Ref).
Children ≥10 years and Adolescents:
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 (Ref).
Patients receiving LDL apheresis: SUBQ: 420 mg every 2 or 4 weeks; dose should be administered immediately after apheresis (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥10 years and Adolescents: No dosage adjustment necessary.
Children ≥10 years and Adolescents:
Mild to moderate impairment (Child Pugh classes 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).
Hypersensitivity reactions (eg, angioedema, urticaria) have been reported. Additionally, delayed rashes have been documented, including a rash mimicking atopic dermatitis (Ref) and maculopapular exanthema (Ref). In the FOURIER study, allergic reactions with evolocumab did not differ significantly from placebo (3.1% versus 2.9%) (Ref). A pooled safety analysis of over 6,000 patients in double-blind and open-label studies identified hypersensitivity reactions in 3.2% and 5.7% of patients receiving evolocumab, respectively, versus 2.4% and 4.3% of patients receiving control or standard of care, respectively. Most of these reactions were mild in severity (Ref).
The most common reactions are delayed injection-site reactions, accompanied by bruising, erythema of the skin, swelling at the site, nasopharyngitis, and flu-like symptoms (Ref). One postmarketing study reported the overall cumulative 5-year risk of injection-site reactions as 7.6%; however, this incidence decreased over years on therapy and infrequently resulted in discontinuation (Ref).
Mechanism: Immediate hypersensitivity reactions (eg, angioedema, urticaria) are either IgE-mediated (non–dose-related) or related to another non–IgE-mediated mechanism (eg, polysorbate 80 excipient may activate complement). Delayed hypersensitivity reactions, including rashes (eg, maculopapular) are typically T-cell-mediated (Ref). Injection-site reactions have been postulated to occur due to degradation of the polysorbate excipient and local neoantigen formation (Ref).
Onset: Immediate hypersensitivity reactions: Rapid; occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref). Delayed hypersensitivity reactions: Varied; maculopapular rashes generally occur 1 to several days after initiation of therapy and have been reported following the second dose of evolocumab (Ref).
Risk factors:
• Cross-reactivity between PCSK9 inhibitors is unknown. Evolocumab contains polysorbate 80 as the excipient and alirocumab contains polysorbate 20. In addition to cross-reactivity between the parent drugs, cross-reactivity may occur between the drugs and other monoclonal antibodies and products (eg, vaccines) based on shared polysorbate excipients. Anti-drug antibodies that cross-react with other PCSK9 inhibitors and may also be implicated in injection-site reactions and loss of efficacy are infrequent (Ref). One patient has been described who developed a rash following alirocumab but was subsequently able to tolerate evolocumab (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults unless otherwise specified.
>10%:
Nervous system: Headache (children, adolescents: 11%)
Respiratory: Nasopharyngitis (children, adolescents, adults: 4% to 12%) (table 1)
|
Drug (Evolocumab) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Evolocumab) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
12% |
11% |
Children and adolescents |
420 mg once monthly |
Heterozygous familial hypercholesterolemia |
104 |
53 |
|
6% |
0% |
Adolescents and adults |
420 mg once monthly |
Homozygous familial hypercholesterolemia |
33 |
16 |
|
8% |
7% |
Adults |
140 mg every 2 weeks or 420 mg once monthly |
Cardiovascular outcomes |
N/A |
N/A |
|
11% |
10% |
Adults |
420 mg once monthly |
Primary hyperlipidemia |
599 |
302 |
|
4% |
4% |
Adults |
140 mg every 2 weeks or 420 mg once monthly |
Primary hyperlipidemia |
2,052 |
1,224 |
1% to 10%:
Cardiovascular: Hypertension (3%)
Dermatologic: Skin rash (1%) (table 2)
|
Drug (Evolocumab) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Evolocumab) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
1% |
0.5% |
Adults |
140 mg every 2 weeks or 420 mg once monthly |
Primary hyperlipidemia |
2,651 |
1,526 |
Endocrine & metabolic: Diabetes mellitus (9%)
Gastrointestinal: Gastroenteritis (children, adolescents, adults: 3% to 6%), nausea (2%)
Genitourinary: Urinary tract infection (5%)
Hematologic & oncologic: Bruise (1%) (table 3)
|
Drug (Evolocumab) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Evolocumab) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
1% |
0.5% |
Adults |
140 mg every 2 weeks or 420 mg once monthly |
Primary hyperlipidemia |
2,052 |
1,224 |
Infection: Influenza (children, adolescents, adults: 6% to 9%)
Local: Injection-site reaction (3% to 6%) (table 4)
|
Drug (Evolocumab) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Evolocumab) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
6% |
5% |
Adults |
420 mg once monthly |
Primary hyperlipidemia |
599 |
302 |
|
3% |
3% |
Adults |
140 mg every 2 weeks or 420 mg once monthly |
Primary hyperlipidemia |
2,651 |
1,526 |
Nervous system: Dizziness (4%), fatigue (2%)
Neuromuscular & skeletal: Myalgia (4%)
Respiratory: Cough (1% to 5%), oropharyngeal pain (children, adolescents: 7%), sinusitis (4%), upper respiratory tract infection (children, adolescents, adults: 6% to 9%)
<1%:
Dermatologic: Eczema, erythema of skin (table 5), urticaria (table 6)
|
Drug (Evolocumab) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Evolocumab) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
0.4% |
0.2% |
Adults |
140 mg every 2 weeks or 420 mg once monthly |
Primary hyperlipidemia |
2,651 |
1,526 |
|
Drug (Evolocumab) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Evolocumab) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
0.4% |
0.1% |
Adults |
140 mg every 2 weeks or 420 mg once monthly |
Primary hyperlipidemia |
2,651 |
1,526 |
Immunologic: Antibody development
Postmarketing:
Hypersensitivity: Angioedema
Respiratory: Flu-like symptoms
Serious hypersensitivity (eg, angioedema) to evolocumab or any component of the formulation.
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.
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]
No
Solution Auto-injector (Repatha SureClick Subcutaneous)
140 mg/mL (per mL): $336.89
Solution Cartridge (Repatha Pushtronex System Subcutaneous)
420MG/3.5ML (per mL): $208.55
Solution Prefilled Syringe (Repatha Subcutaneous)
140 mg/mL (per mL): $336.89
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous:
Repatha: 140 mg/mL (1 mL) [contains mouse (murine) and/or hamster protein, polysorbate 80]
Solution Cartridge, Subcutaneous:
Repatha: 420 mg/3.5 mL (3.5 mL) [contains polysorbate 80]
SUBQ: 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. Avoid administration in areas where skin is tender, bruised, red, indurated, or has scars or stretch marks. 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.
420 mg dose: Administer SUBQ over 5 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.
Parenteral: SUBQ: 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 SUBQ 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; avoid areas with scars or stretch marks. Rotate the injection site with each injection.
Single-use infusor with prefilled cartridge: Administer SUBQ over 5 minutes. Administer medication within 5 minutes of inserting cartridge. Do not use if infusor gets wet (contains electronics that should remain dry), or if dropped onto a hard surface (parts that are not visible may be broken). Use in pediatric patients should be under adult supervision.
Single-use prefilled autoinjector or single-use prefilled syringe: For autoinjector, administer medication within 5 minutes of removing orange cap; injection should take ~15 seconds. For 420 mg (once-monthly) dose, administer 3 separate SUBQ 140 mg injections consecutively within a 30-minute period.
Missed doses: 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.
Atherosclerotic cardiovascular disease, primary prevention: Adjunct to diet, alone or in combination with other lipid-lowering therapies (eg, maximally tolerated statin), for the treatment of adults with primary hyperlipidemia to reduce low-density lipoprotein-cholesterol (LDL-C).
Atherosclerotic cardiovascular disease, secondary prevention: To reduce the risk of myocardial infarction, 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).
Familial hypercholesterolemia, heterozygous: Adjunct to diet, alone or in combination with other lipid-lowering therapies (eg, maximally tolerated statin) for the treatment of adults to reduce LDL-C; adjunct to diet and other lipid-lowering therapies for the treatment of pediatric patients ≥10 years of age to reduce LDL-C.
Familial hypercholesterolemia, homozygous: Adjunct to other lipid-lowering therapies in pediatric patients ≥10 years of age and adults for the treatment of patients with homozygous familial hypercholesterolemia who require additional lowering of LDL-C.
Evolocumab may be confused with elotuzumab
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
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).
A pregnancy safety study is underway. If evolocumab is administered during pregnancy, health care providers should report exposure to Amgen’s pregnancy safety study (1-800-772-6436).
It is not known if evolocumab is present in breast milk.
However, IgG antibodies are present in human milk; available data suggest that concentrations do not reach the neonatal circulation in substantial amounts. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
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.
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.
Onset: Proprotein convertase subtilisin kexin type 9 (PCSK9) suppression: 4 hours.
Distribution: IV: Vd: ~3.3 L.
Metabolism: Nonsaturable proteolysis.
Bioavailability: SUBQ: 72%.
Half-life elimination: 11 to 17 days.
Time to peak: SUBQ: 3 to 4 days.
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.
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