REPATHA Evolocumab 140 mg/mL Injection, Solution, 2 syringes
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the PCSK9 Inhibitor class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Evolocumab injection is used to lower cholesterol (a fat-like substance in the blood) and to lower risk of a stroke or a heart attack in patients with cardiovascular disease (disease of the heart or blood vessels). Evolocumab injection is in a class of medications called proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor monoclonal antibody. It works by stopping the production of cholesterol. Accumulation of cholesterol along the walls of your arteries (a process known as atherosclerosis) decreases blood flow and, therefore, the oxygen supply to your heart, brain, and other parts...
Read the full MedlinePlus article ↗- Repatha is used for two main purposes. First, it lowers LDL ('bad') cholesterol — it's prescribed for adults with high cholesterol and for adults and kids aged 10 and older with an...
- You inject Repatha under the skin — into your abdomen, thigh, or upper arm. The most important things to remember: let it warm up to room temperature for at least 30 minutes before...
- How do I give myself this injection, and does it hurt?
- The most common ones are pretty mild — cold symptoms, upper respiratory infections, flu, back pain, and occasional muscle aches. These usually aren't a reason to stop. What you do...
Patient education
Supplement & herbal interactions
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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1.2 mg / 1 mL
UNII 569DQM74SC
Acetate ion is a salt form derived from acetic acid. It's commonly used in medicines as a buffer to help maintain the correct pH level and stabilize the product.
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0.1 mg / 1 mL
UNII 6OZP39ZG8H
Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
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25 mg / 1 mL
UNII 9DLQ4CIU6V
Proline is an amino acid used in pharmaceutical formulations as a bulking agent and stabilizer. It helps maintain product stability and can improve the texture or consistency of medicines, particularly in powders and freeze-dried products.
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UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
5 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
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Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $281.969 | $563.94 / 2 ml |
| Medicaid paysCMS SDUD · 12 mo | $278.48 | $556.97 / 2 ml |
| Medicare drug plans payPart D · Q2 2026 | $282.33 | $564.65 / 2 ml |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Repatha 140 mg/mL 72511-0501-01 | Amgen | 1 syringe | $281.806 | — | Availability likely | +0% |
| Repatha 140 mg/mL 72511-0750-01 | Amgen | 1 syringe | $281.806 | — | Availability likely | +0% |
| Repatha 140 mg/mLthis 72511-0760-02 | Amgen | 2 syringes | $281.969 | — | Availability likely | — |
| Repatha 140 mg/mL 72511-0393-01 | Amgen | 1 syringe | — | — | FDA listed | — |
| Repatha 140 mg/mL 72511-0143-01 | Amgen | 1 syringe | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Aug 27, 2027 |
Is there a biosimilar for REPATHA 140 MG/ML SURECLICK?
Why do different websites show different biosimilar dates?
Can a biosimilar launch before the last patent expires?
What does “current Purple Book estimate” mean?
What does “FDA listed” mean?
What does a patent or protection date mean here?
Where does this data come from?
🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 72511-0760-02 You're viewing this | 2 SYRINGE in 1 CARTON (72511-760-02) / 1 mL in 1 SYRINGE (72511-760-01) | $281.97 / mL | $563.94 | 2018-10-09 | Active |
| 72511-0760-91 | 1 SYRINGE in 1 CARTON (72511-760-91) / 1 mL in 1 SYRINGE | — | — | 2022-06-01 | Active |
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in NDC 72511-0760-02?
What is the difference between NDC 72511-0760-02 and NDC 72511-0760-91?
What NDC number is used to bill for this package of REPATHA Evolocumab 140 mg/mL Injection, Solution?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE REPATHA is indicated: To reduce the risk of major adverse cardiovascular (CV) events (CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, or coronary revascularization) in adults at increased risk for these events. As an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in: adults with hypercholesterolemia. adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH). adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH).
REPATHA is a PCSK9 (proprotein convertase subtilisin kexin type 9) inhibitor indicated: To reduce the risk of major adverse cardiovascular (CV) events (CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, or coronary revascularization) in adults at increased risk for these events. ( 1 ) As an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in ( 1 ): adults with hypercholesterolemia. adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH). adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH).
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION In adults at increased risk for CV events or with hypercholesterolemia : The recommended dosage of REPATHA is either 140 mg every 2 weeks OR 420 mg once monthly administered subcutaneously. ( 2.1 ) If switching dosage regimens, administer the first dose of the new regimen on the next scheduled date of the prior regimen. ( 2.1 ) In adults and pediatric patients aged 10 years and older with HeFH : The recommended dosage of REPATHA is either 140 mg every 2 weeks OR 420 mg once monthly administered subcutaneously.
( 2.1 ) If switching dosage regimens, administer the first dose of the new regimen on the next scheduled date of the prior regimen. ( 2.1 ) In adults and pediatric patients aged 10 years and older with HoFH : The initial recommended dosage of REPATHA is 420 mg once monthly administered subcutaneously. ( 2.1 ) The dosage can be increased to 420 mg every 2 weeks if a clinically meaningful response is not achieved in 12 weeks.
( 2.1 ) Patients on lipid apheresis may initiate treatment with 420 mg every 2 weeks to correspond with their apheresis schedule. Administer REPATHA after the apheresis session is complete. ( 2.1 ) Assess LDL-C when clinically appropriate.
The LDL-lowering effect of REPATHA may be measured as early as 4 weeks after initiation. ( 2.1 ) REPATHA is available as prefilled single-dose SureClick ® autoinjectors, and prefilled single-dose syringes that either contain dry natural rubber (a derivative of latex) in the needle cover or are not made with natural rubber latex. Consider prescribing a presentation of REPATHA that does not contain dry natural rubber for individuals that are sensitive to latex.
( 2.3 , 16 ) Administer REPATHA subcutaneously into areas of the abdomen, thigh, or upper arm. Rotate injection sites for each administration. ( 2.3 ) See Full Prescribing Information for important administration instructions.
( 2.3 )
2.1Recommended Dosage In adults at increased risk for CV events or with hypercholesterolemia: The recommended dosage of REPATHA is either 140 mg every 2 weeks OR 420 mg once monthly administered subcutaneously [see Dosage and Administration (2.3) ] . If switching dosage regimens, administer the first dose of the new regimen on the next scheduled date of the prior regimen. In adults and pediatric patients aged 10 years and older with HeFH: The recommended dosage of REPATHA is either 140 mg every 2 weeks OR 420 mg once monthly administered subcutaneously [see Dosage and Administration (2.3) ] .
If switching dosage regimens, administer the first dose of the new regimen on the next scheduled date of the prior regimen. In adults and pediatric patients aged 10 years and older with HoFH: The initial recommended dosage of REPATHA is 420 mg once monthly administered subcutaneously [see Dosage and Administration (2.3) ] . The dosage can be increased to 420 mg every 2 weeks if a clinically meaningful response is not achieved in 12 weeks.
Patients on lipid apheresis may initiate treatment with 420 mg every 2 weeks to correspond with their apheresis schedule. Administer REPATHA after the apheresis session is complete. Assess LDL-C when clinically appropriate.
The LDL-lowering effect of REPATHA may be measured as early as 4 weeks after initiation. When monitoring LDL-C for patients receiving REPATHA 420 mg once monthly, note that LDL-C can vary during the dosing interval in some patients; recommend measuring LDL-C just prior to the next scheduled dose [see Clinical Studies (14) ] .
2.2Missed Doses If a dose is missed: Within 7 days from the missed dose, instruct the patient to administer REPATHA and resume the patient's original schedule. More than 7 days after the missed dose: For an every 2-week dose, instruct the patient to wait until the next dose on the original schedule. For a once-monthly dose, instruct the patient to administer the dose and start a new schedule based on this date.
2.3 Important Administration Instructions REPATHA is available as prefilled s…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS REPATHA injection is a clear to opalescent, colorless to pale yellow solution available as follows: 140 mg/mL solution in a prefilled single-dose pen 140 mg/mL solution in a prefilled single-dose SureClick ® autoinjector 140 mg/mL solution in a prefilled single-dose syringe Injection ( 3 ): 140 mg/mL solution prefilled single-dose pen 140 mg/mL solution prefilled single-dose SureClick ® autoinjector 140 mg/mL solution prefilled single-dose syringe
⛔ Contraindications ▾
4 CONTRAINDICATIONS REPATHA is contraindicated in patients with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in REPATHA. Serious hypersensitivity reactions including angioedema have occurred in patients treated with REPATHA [see Warnings and Precautions (5.1) ] . Patients with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in REPATHA. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions : Angioedema has occurred. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with REPATHA, treat according to the standard of care, and monitor until signs and symptoms resolve. ( 5.1 )
5.1Hypersensitivity Reactions Hypersensitivity reactions, including angioedema, have been reported in patients treated with REPATHA. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with REPATHA, treat according to the standard of care, and monitor until signs and symptoms resolve. REPATHA is contraindicated in patients with a history of serious hypersensitivity reactions to evolocumab or any excipient in REPATHA [see Contraindications (4) ] .
The prefilled single-dose SureClick ® autoinjector and prefilled single-dose syringe presentations of REPATHA that contain dry natural rubber (a derivative of latex) in the needle cover may cause an allergic reaction in individuals sensitive to latex. Instruct patients to inform their healthcare provider if they are sensitive to latex. Consider prescribing a presentation of REPATHA that does not contain dry natural rubber for individuals that are sensitive to latex [see How Supplied/Storage and Handling (16) ] .
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are also discussed in other sections of the label: Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Common (> 5% of patients treated with REPATHA and more frequently than placebo) adverse reactions in adults with: Primary hypercholesterolemia: nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions. ( 6 ) Established CV Disease: diabetes mellitus, nasopharyngitis and upper respiratory tract infection. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Medical Information at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adverse Reactions in Adults with Primary Hypercholesterolemia The data described below reflect exposure to REPATHA in 8 placebo-controlled trials that included 2651 patients treated with REPATHA, including 557 exposed for 6 months and 515 exposed for 1 year (median treatment duration of 12 weeks).
The mean age of the population was 57 years, 49% of the population were women, 85% White, 6% Black, 8% Asian, and 2% other races. Adverse Reactions in a 52 - Week Controlled Trial In a 52-week, double-blind, randomized, placebo-controlled trial, 599 patients received 420 mg of REPATHA subcutaneously once monthly [see Clinical Studies (14) ] . The mean age was 56 years (range: 22 to 75 years), 23% were older than 65 years, 52% women, 80% White, 8% Black, 6% Asian; 6% identified as Hispanic ethnicity.
Adverse reactions reported in at least 3% of REPATHA-treated patients, and more frequently than in placebo-treated patients are shown in Table 1. Adverse reactions led to discontinuation of treatment in 2.2% of REPATHA-treated patients and 1% of placebo-treated patients. The most common adverse reaction that led to REPATHA treatment discontinuation and occurred at a rate greater than placebo was myalgia (0.3% versus 0% for REPATHA and placebo, respectively).
Table 1. Adverse Reactions Occurring in ≥ 3% of REPATHA-treated Patients and More Frequently than with Placebo in a 52-Week Trial Placebo (N = 302) % REPATHA (N = 599) % Nasopharyngitis 9.6
10.5Upper respiratory tract infection 6.3
9.3Influenza 6.3
7.5Back pain 5.6
6.2Injection site reactions includes erythema, pain, bruising 5.0
5.7Cough 3.6
4.5Urinary tract infection 3.6
4.5Sinusitis 3.0
4.2Headache 3.6
4.0Myalgia 3.0
4.0Dizziness 2.6
3.7Musculoskeletal pain 3.0
3.3Hypertension 2.3
3.2Diarrhea 2.6
3.0Gastroenteritis 2.0
3.0Adverse Reactions in Seven Pooled 12 - Week Controlled Trials In seven pooled 12-week, double-blind, randomized, placebo-controlled trials, 993 patients received 140 mg of REPATHA subcutaneously every 2 weeks and 1059 patients received 420 mg of REPATHA subcutaneously monthly. The mean age was 57 years (range: 18 to 80 years), 29% were older than 65 years, 49% women, 85% White, 5% Black, 9% Asian; 5% identified as Hispanic ethnicity. Adverse reactions reported in at least 1% of REPATHA-treated patients, and more frequently than in placebo-treated patients, are shown in Table 2.
Table 2. Adverse Reactions Occurring in ≥ 1% of REPATHA-treated Patients and More Frequently than with Placebo in Pooled 12-Week Trials Placebo (N = 1224) % REPATHA 140 mg every 2 weeks and 420 mg once monthly combined (N = 2052) % Nasopharyngitis 3.9
4.0Back pain 2.2
2.3Upper respiratory tract infection 2.0
2.1Arthralgia 1.6
1.8Nausea 1.2
1.8Fatigue 1.0
1.6Muscle spasms 1.2
1.3Urinary tract infection 1.2
1.3Cough 0.7
1.2Influenza 1.1
1.2Contusion 0.5
1.0Adverse Reactions in Eight Pooled Controlled Trials (Seven 12 - Week Trials and One 52 - Week Trial) The adverse reactions described below are…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary Available data from clinical trials and postmarketing reports on REPATHA use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, there were 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 dose of 420 mg every month.
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. The exposures where immune suppression occurred in infant monkeys were greater than those expected clinically. No assessment for immune suppression was conducted with evolocumab in infant monkeys.
Measurable evolocumab serum concentrations were observed in the infant monkeys at birth at comparable levels to maternal serum, indicating that evolocumab, like other IgG antibodies, crosses the placental barrier. Monoclonal antibodies are transported across the placenta in increasing amounts especially near term; therefore, evolocumab has the potential to be transmitted from the mother to the developing fetus. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. There is a pregnancy safety study for REPATHA. If REPATHA is administered during pregnancy, healthcare providers should report REPATHA exposure by contacting Amgen at 1-800-77-AMGEN (1-800-772-6436) or https://wwwext.amgen.com/products/global-patient-safety/adverse-event-reporting.
Data Animal Data In cynomolgus monkeys, no effects on embryo-fetal or postnatal development (up to 6 months of age) were observed when evolocumab was dosed during organogenesis to parturition at 50 mg/kg once every 2 weeks by the subcutaneous route at exposures 30- and 12-fold the recommended human doses of 140 mg every 2 weeks and 420 mg once monthly, respectively, based on plasma AUC. No test of humoral immunity in infant monkeys was conducted with evolocumab.
8.2Lactation Risk Summary There is no information regarding the presence of evolocumab in human milk, the effects on the breastfed infant, or the effects on milk production. Human IgG is present in human milk, but published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for REPATHA and any potential adverse effects on the breastfed infant from REPATHA or from the underlying maternal condition.
8.4Pediatric Use The safety and effectiveness of REPATHA in combination with diet and other LDL-C-lowering therapies for the treatment of HoFH have been established in pediatric patients aged 10 years and older. Use of REPATHA for this indication is supported by evidence from an adequate and well-controlled trial in adults and pediatric patients aged 13 years and older with HoFH (including 7 pediatric patients treated with REPATHA) and from open-label studies which included an additional 19 pediatric patients aged 11 years and older with HoFH not previously treated with REPATHA [see Adverse Reactions (6.1) and Clinical Studies (14) ] .
The safety and effectiveness of REPATHA as an adjunct to diet and other LDL-C-lowering therapies for the treatment of HeFH have been established in pediatric patients aged 10 years and older. Use of REPATHA for this indication is based on data from a 24-week, randomized, placebo-controlled, double-blind trial in pediatric patients with HeFH. In the trial, 104 p…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Available data from clinical trials and postmarketing reports on REPATHA use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, there were 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 dose of 420 mg every month.
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. The exposures where immune suppression occurred in infant monkeys were greater than those expected clinically. No assessment for immune suppression was conducted with evolocumab in infant monkeys.
Measurable evolocumab serum concentrations were observed in the infant monkeys at birth at comparable levels to maternal serum, indicating that evolocumab, like other IgG antibodies, crosses the placental barrier. Monoclonal antibodies are transported across the placenta in increasing amounts especially near term; therefore, evolocumab has the potential to be transmitted from the mother to the developing fetus. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. There is a pregnancy safety study for REPATHA. If REPATHA is administered during pregnancy, healthcare providers should report REPATHA exposure by contacting Amgen at 1-800-77-AMGEN (1-800-772-6436) or https://wwwext.amgen.com/products/global-patient-safety/adverse-event-reporting.
Data Animal Data In cynomolgus monkeys, no effects on embryo-fetal or postnatal development (up to 6 months of age) were observed when evolocumab was dosed during organogenesis to parturition at 50 mg/kg once every 2 weeks by the subcutaneous route at exposures 30- and 12-fold the recommended human doses of 140 mg every 2 weeks and 420 mg once monthly, respectively, based on plasma AUC. No test of humoral immunity in infant monkeys was conducted with evolocumab.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of REPATHA in combination with diet and other LDL-C-lowering therapies for the treatment of HoFH have been established in pediatric patients aged 10 years and older. Use of REPATHA for this indication is supported by evidence from an adequate and well-controlled trial in adults and pediatric patients aged 13 years and older with HoFH (including 7 pediatric patients treated with REPATHA) and from open-label studies which included an additional 19 pediatric patients aged 11 years and older with HoFH not previously treated with REPATHA [see Adverse Reactions (6.1) and Clinical Studies (14) ] .
The safety and effectiveness of REPATHA as an adjunct to diet and other LDL-C-lowering therapies for the treatment of HeFH have been established in pediatric patients aged 10 years and older. Use of REPATHA for this indication is based on data from a 24-week, randomized, placebo-controlled, double-blind trial in pediatric patients with HeFH. In the trial, 104 patients received REPATHA 420 mg subcutaneously once monthly and 53 patients received placebo; 39 patients (25%) were 10 to 11 years of age [see Adverse Reactions (6.1) and Clinical Studies (14) ] .
The safety and effectiveness of REPATHA have not been established in pediatric patients with HeFH or HoFH who are younger than 10 years old or in pediatric patients with other types of hypercholesterolemia.
🧓 Geriatric Use ▾
8.5Geriatric Use In controlled trials, 7656 (41%) patients treated with REPATHA were ≥ 65 years old and 1500 (8%) were ≥ 75 years old. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Evolocumab is a human monoclonal IgG2 directed against human proprotein convertase subtilisin kexin type 9 (PCSK9). PCSK9 binds to the low-density lipoprotein receptor (LDLR) on the surface of hepatocytes to promote LDLR degradation within the liver. 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.
12.2Pharmacodynamics Following single subcutaneous administration of 140 mg or 420 mg of evolocumab, maximum suppression of circulating unbound PCSK9 occurred by 4 hours. Unbound PCSK9 concentrations returned toward baseline when evolocumab concentrations decreased below the limit of quantitation. Maximum LDL-C reduction occurred by 2 weeks after a single-dose of 140 mg of evolocumab and by 3 weeks after a single-dose of 420 mg of evolocumab.
12.3Pharmacokinetics Evolocumab exhibits non-linear kinetics as a result of binding to PCSK9. Administration of the 140 mg dose in healthy volunteers resulted in a C max mean of 18.6 µg/mL and AUC last mean of 188 day∙µg/mL. Administration of the 420 mg dose in healthy volunteers resulted in a C max mean of 59.0 µg/mL and AUC last mean of 924 day∙µg/mL.
Following a single 420 mg intravenous dose, the mean systemic clearance was estimated to be 12 mL/hr. An approximate 2- to 3-fold accumulation was observed in trough serum concentrations (C min 7.21) following 140 mg doses administered subcutaneously every 2 weeks or following 420 mg doses administered subcutaneously monthly (C min 11.2), and serum trough concentrations approached steady-state by 12 weeks of dosing. Absorption Following a single subcutaneous dose of 140 mg or 420 mg evolocumab administered to healthy adults, median peak serum concentrations were attained in 3 to 4 days, and estimated absolute bioavailability was 72%.
Distribution Following a single 420 mg intravenous dose, the mean steady-state volume of distribution was estimated to be
3.3L. Elimination Two elimination phases were observed for REPATHA. At low concentrations, the elimination is predominately through saturable binding to target (PCSK9), while at higher concentrations the elimination of REPATHA is largely through a non-saturable proteolytic pathway.
REPATHA was estimated to have an effective half-life of 11 to 17 days. Specific Populations The pharmacokinetics of evolocumab were not affected by age, gender, race, or creatinine clearance across all approved populations [see Use in Specific Populations (8.5) ] . The exposure of evolocumab decreased with increasing body weight.
These differences are not clinically meaningful. Pediatric Patients The pharmacokinetics of REPATHA were evaluated in 103 pediatric patients aged 10 to 17 years with HeFH (Study 6) [see Use in Specific Populations (8.4 ) and Clinical Studies (14) ] . Following subcutaneous administration of 420 mg REPATHA once monthly, mean trough serum concentrations were 22.4 mcg/mL and 25.8 mcg/mL over the Week 12 and Week 24 time points, respectively.
The pharmacokinetics of REPATHA were evaluated in 12 pediatric patients aged 11 to 17 years with HoFH (Study 9) [see Use in Specific Populations (8.4 ) and Clinical Studies (14) ] . Following subcutaneous administration of 420 mg REPATHA once monthly, mean serum trough concentrations were 20.3 mcg/mL and 17.6 mcg/mL at Week 12 and Week 80, respectively. Renal Impairment Since monoclonal antibodies are not known to be eliminated via renal pathways, renal function is not expected to impact the pharmacokinetics of evolocumab.
In a clinical trial of 18 patients with either normal renal function (estimated glomerular filtration rate [eGFR] ≥ 90 mL/min/1.73 m 2 , n = 6), severe renal impairment (eGFR < 30 mL/min/1.73 m 2 , n = 6), or end-stage renal disease (ESRD) receiving hemodialysis (n = 6), exposure to evolocumab after a single 140 mg subcutaneous dose was decreased in patients with severe renal impairme…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Evolocumab is a human monoclonal IgG2 directed against human proprotein convertase subtilisin kexin type 9 (PCSK9). PCSK9 binds to the low-density lipoprotein receptor (LDLR) on the surface of hepatocytes to promote LDLR degradation within the liver. 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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING REPATHA is a clear to opalescent, colorless to pale yellow solution supplied as follows: Not Made with Natural Rubber Latex – Strength Packaging Unit NDC 140 mg/mL prefilled single-dose pen Carton of 2 72511-143-02 140 mg/mL prefilled single-dose pen Carton of 1 72511-143-01 140 mg/mL prefilled single-dose SureClick ® autoinjector Carton of 2 72511-393-02 140 mg/mL prefilled single-dose SureClick ® autoinjector Carton of 1 72511-393-01 140 mg/mL prefilled single-dose syringe Carton of 1 72511-501-01 Contains Dry Natural Rubber – Strength Packaging Unit NDC 140 mg/mL prefilled single-dose SureClick ® autoinjector The needle cover of the glass prefilled single-dose SureClick ® autoinjector and prefilled single-dose syringe contain dry natural rubber (a derivative of latex) that may cause allergic reactions in individuals sensitive to latex [see Warnings and Precautions (5.1) ] .
Carton of 2 72511-760-02 140 mg/mL prefilled single-dose syringe Carton of 1 72511-750-01 Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake.
REPATHA prefilled single-dose pen, prefilled single-dose SureClick ® autoinjector, or prefilled single-dose syringe may also be kept at room temperature at 68°F to 77°F (20°C to 25°C) in the original carton for 30 days. If not used within the 30 days, discard REPATHA.
📦 Storage and Handling ▾
Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake. REPATHA prefilled single-dose pen, prefilled single-dose SureClick ® autoinjector, or prefilled single-dose syringe may also be kept at room temperature at 68°F to 77°F (20°C to 25°C) in the original carton for 30 days. If not used within the 30 days, discard REPATHA.
📋 Description ▾
11 DESCRIPTION Evolocumab is a human monoclonal immunoglobulin G2 (IgG2) directed against human proprotein convertase subtilisin kexin type 9 (PCSK9). Evolocumab has an approximate molecular weight (MW) of 144 kDa and is produced in genetically engineered mammalian (Chinese hamster ovary) cells. REPATHA is a sterile, preservative-free, clear to opalescent, colorless to pale yellow solution for subcutaneous use.
Each 1 mL prefilled single-dose pen, prefilled single-dose SureClick ® autoinjector and prefilled single-dose syringe contains 140 mg evolocumab, acetate (1.2 mg), polysorbate 80 (0.1 mg), proline (25 mg) in Water for Injection, USP. Sodium hydroxide may be used to adjust to a pH of 5.0.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient and/or caregiver to read the FDA-Approved Patient Labeling (Patient Information and Instructions for Use). Hypersensitivity Inform patients that serious hypersensitivity reactions (e.g., angioedema) have been reported in patients treated with REPATHA. Advise patients on the symptoms of hypersensitivity reactions and instruct them to discontinue REPATHA and seek medical attention promptly, if such symptoms occur.
Latex-Sensitivity Instruct patients to inform their healthcare provider if they are sensitive to latex. Inform patients that REPATHA is available as prefilled single-dose SureClick ® autoinjectors and prefilled single-dose syringes that either contain dry natural rubber (a derivative of latex) in the needle cover or are not made with natural rubber latex, and the carton and Instructions for Use state if the product contains dry natural rubber. Advise latex-sensitive patients that the needle cover of the glass prefilled single-dose SureClick ® autoinjector and prefilled single-dose syringe that contain dry natural rubber (a derivative of latex) may cause allergic reactions in individuals sensitive to latex [see How Supplied/Storage and Handling (16) ] .
Pregnancy Advise women who are exposed to REPATHA during pregnancy that there is a pregnancy safety study that monitors pregnancy outcomes. Encourage these patients to report their pregnancy to Amgen at 1-800-77-AMGEN (1-800-772-6436) or https://wwwext.amgen.com/products/global-patient-safety/adverse-event-reporting [see Use in Specific Populations (8.1) ] . Administration Provide guidance to patients and caregivers on proper subcutaneous administration technique and how to use the prescribed REPATHA device correctly.
Inform patients that it may take up to 15 seconds to administer REPATHA using the prefilled single-dose pen, prefilled single-dose SureClick ® autoinjector, or prefilled single-dose syringe. The prefilled single-dose pen is not made with natural rubber latex.