Repatha (Evolocumab)
PCSK9 inhibitor for cholesterol lowering and cardiovascular risk reduction
Repatha (evolocumab) is a PCSK9 inhibitor — a type of monoclonal antibody that significantly lowers LDL (“bad”) cholesterol levels in the blood. It is used in adults and children aged 10 and older who have high cholesterol that cannot be adequately controlled by diet and statins alone. The landmark FOURIER trial demonstrated that Repatha reduces cardiovascular events including heart attacks and strokes in patients with established atherosclerotic cardiovascular disease.
Quick Facts
Key Takeaways
- Repatha (evolocumab) is a PCSK9 inhibitor that lowers LDL cholesterol by 55–75% when added to statin therapy, and is given as a subcutaneous injection every 2 weeks or once monthly.
- The FOURIER trial showed Repatha reduces heart attack risk by 27% and stroke risk by 21% in patients with established cardiovascular disease on statin therapy.
- Repatha is approved for adults and children aged 10+ with primary hypercholesterolemia (including familial forms), mixed dyslipidemia, and established atherosclerotic cardiovascular disease.
- Common side effects are generally mild and include injection site reactions, nasopharyngitis, flu-like symptoms, back pain, and arthralgia.
- Long-term safety data from the OSLER-1 extension study confirms a favorable safety profile over 5+ years of continuous treatment.
What Is Repatha and What Is It Used For?
Quick Answer: Repatha (evolocumab) is a biologic medication that dramatically lowers LDL cholesterol by blocking a protein called PCSK9. It is used in patients with high cholesterol who need additional LDL lowering beyond what diet and statin therapy can provide, and in patients with established cardiovascular disease to reduce the risk of heart attacks and strokes.
Repatha contains the active substance evolocumab, a fully human monoclonal antibody (IgG2 subclass) that is designed to bind to and inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a naturally occurring protein in the body that plays a crucial role in cholesterol metabolism. Under normal circumstances, PCSK9 binds to LDL receptors on the surface of liver cells (hepatocytes), tagging them for degradation. When these receptors are destroyed, fewer are available to remove LDL cholesterol from the bloodstream, resulting in higher circulating LDL levels.
By attaching to PCSK9 and preventing it from binding to LDL receptors, evolocumab allows more LDL receptors to recycle back to the liver cell surface. This means the liver can capture and clear significantly more LDL cholesterol from the blood. In clinical trials, Repatha has been shown to lower LDL cholesterol by approximately 55–75% from baseline, depending on the patient population and background lipid-lowering therapy. This potent LDL-lowering effect is achieved rapidly, with significant reductions observed within 1–2 weeks of starting treatment.
Approved Indications
Repatha is approved for several cholesterol-related conditions in both adults and selected pediatric populations:
Primary hypercholesterolemia and mixed dyslipidemia in adults: Repatha is indicated for adults with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia. It is prescribed as an adjunct to diet, either in combination with a statin or other lipid-lowering therapy when the maximum tolerated statin dose does not provide sufficient cholesterol reduction, or alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant or for whom statins are contraindicated.
Heterozygous familial hypercholesterolemia (HeFH) in children: Repatha is approved for children aged 10 years and older with HeFH, either alone or in combination with other cholesterol-lowering treatments. HeFH is a genetic condition that causes very high cholesterol levels from birth and significantly increases the lifetime risk of cardiovascular disease.
Homozygous familial hypercholesterolemia (HoFH): Repatha is indicated for adults and children aged 10 years and older with HoFH, in combination with other lipid-lowering therapies. HoFH is a rare but severe genetic condition in which patients inherit two defective copies of genes involved in LDL metabolism, resulting in extremely high LDL cholesterol levels (often exceeding 500 mg/dL or 13 mmol/L). For patients who also undergo LDL apheresis — a procedure similar to dialysis that physically removes cholesterol from the blood — the starting dose may be higher to align with the apheresis schedule.
Established atherosclerotic cardiovascular disease (ASCVD) in adults: Repatha is approved for adults with established ASCVD (history of heart attack, stroke, or peripheral arterial disease) to reduce cardiovascular risk. In this setting, it is given in combination with the maximum tolerated statin dose, or alone or with other lipid-lowering therapies when statins are inadequate or cannot be used. The FOURIER trial demonstrated that Repatha significantly reduces the risk of cardiovascular events in this population.
What Should You Know Before Taking Repatha?
Quick Answer: Do not use Repatha if you are allergic to evolocumab or any of its ingredients. Inform your doctor about liver disease before starting treatment. While no significant drug interactions have been identified, discuss all medications with your healthcare provider. Repatha has not been studied in pregnant or breastfeeding women.
Contraindications
Repatha should not be used if you have a known hypersensitivity (allergy) to evolocumab or to any of the other ingredients in the formulation. The excipients include proline, glacial acetic acid, polysorbate 80, sodium hydroxide, and water for injections. If you have experienced a previous allergic reaction to Repatha, do not use it again without consulting your healthcare provider.
Serious allergic reactions, including angioedema (swelling of the face, lips, tongue, or throat), have been reported in post-marketing surveillance. Although these reactions are rare, they can be potentially serious and require immediate medical attention. If you experience signs of a severe allergic reaction such as difficulty breathing, swelling of the face or throat, or severe rash after using Repatha, seek emergency medical care immediately.
Warnings and Precautions
Before starting Repatha, discuss the following with your healthcare provider:
- Liver disease: If you have liver problems, your doctor may need to monitor your liver function more closely while you are taking Repatha. The liver is the primary organ responsible for clearing LDL cholesterol from the blood, and its function may affect how well Repatha works.
- Traceability: To facilitate traceability of this biological medicinal product, your doctor or pharmacist should record the name and batch number of the product you receive. It may be helpful for you to note this information as well, in case you are asked about it in the future.
- Latex sensitivity: Some Repatha prefilled syringes and autoinjectors contain natural rubber latex in the needle cap, which may cause allergic reactions in individuals sensitive to latex. Check the product labeling and inform your healthcare provider if you have a latex allergy.
Use in Children and Adolescents
The use of Repatha has been studied in children aged 10 years and older for the treatment of heterozygous and homozygous familial hypercholesterolemia. Clinical trials in this age group have demonstrated efficacy and safety comparable to adults. When children aged 10–13 years use the automated minidoser, adult supervision is recommended. Repatha has not been studied in children younger than 10 years of age and is not recommended for this population.
Drug Interactions
No clinically significant drug interactions have been identified in clinical studies with Repatha. As a monoclonal antibody, evolocumab is not metabolized by cytochrome P450 enzymes and is not expected to interact with drugs that are metabolized through these pathways. However, you should always tell your doctor or pharmacist about all medications you are currently taking, have recently taken, or plan to take, including over-the-counter medicines and dietary supplements.
Repatha is frequently used in combination with statins (such as atorvastatin, rosuvastatin, or simvastatin), ezetimibe, and other lipid-lowering therapies. These combinations have been well-studied and are considered safe and effective, providing additive cholesterol-lowering benefits.
Pregnancy and Breastfeeding
If you are pregnant, breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor or pharmacist before using Repatha. The safety of Repatha during pregnancy has not been established in human studies, and it is not known whether evolocumab can harm an unborn child. Because cholesterol and other products of cholesterol biosynthesis are essential for normal fetal development, the potential risk of inhibiting PCSK9 during pregnancy must be carefully weighed against the potential benefit.
It is not known whether evolocumab is excreted in human breast milk. As human IgG antibodies are known to be present in breast milk, a decision should be made whether to discontinue breastfeeding or to discontinue Repatha treatment, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother. Discuss this with your doctor to make the best decision for your situation.
Driving and Using Machines
Repatha has no or negligible influence on the ability to drive and use machines. No special precautions are needed in this regard.
Sodium Content
Repatha contains less than 1 mmol (23 mg) of sodium per dose and is therefore essentially “sodium-free.” This is relevant for patients on a controlled sodium diet.
How Does Repatha Interact with Other Drugs?
Quick Answer: Repatha has no known clinically significant drug interactions. As a monoclonal antibody, it is not metabolized by liver enzymes (CYP450) and does not interfere with the metabolism of other drugs. It is commonly and safely used alongside statins, ezetimibe, and other lipid-lowering medications.
One of the advantages of Repatha compared to some other cholesterol-lowering medications is its favorable drug interaction profile. Unlike small-molecule drugs, monoclonal antibodies like evolocumab are degraded by proteolysis (broken down into amino acids) rather than being metabolized by cytochrome P450 (CYP) enzymes in the liver. This means Repatha does not compete with other medications for liver enzyme metabolism, significantly reducing the risk of drug-drug interactions.
In clinical pharmacology studies, evolocumab showed no effect on the pharmacokinetics of commonly co-administered drugs, and no dose adjustments are required when Repatha is used with other medications. However, it is always prudent to inform your healthcare provider about all medications and supplements you are using.
| Medication | Type | Interaction | Clinical Note |
|---|---|---|---|
| Atorvastatin, Rosuvastatin, Simvastatin | Statins (HMG-CoA reductase inhibitors) | No interaction – Additive LDL lowering | Most commonly used combination. No dose adjustment needed for either drug. |
| Ezetimibe | Cholesterol absorption inhibitor | No interaction – Additive LDL lowering | Can be used in triple combination with a statin and Repatha for maximum LDL reduction. |
| Warfarin, Apixaban, Rivaroxaban | Anticoagulants | No interaction | Safe to use together. Many ASCVD patients are on anticoagulation therapy. |
| Aspirin, Clopidogrel | Antiplatelet agents | No interaction | Commonly co-prescribed in secondary prevention of cardiovascular disease. |
| Fenofibrate, Gemfibrozil | Fibrates | No interaction | May be used together for patients with combined hyperlipidemia (high LDL and triglycerides). |
While no significant interactions have been identified, patients should be aware that very high doses of biotin (vitamin B7, sometimes exceeding 5,000 mcg/day) can potentially interfere with certain laboratory immunoassays used to measure cholesterol levels. This does not affect how Repatha works but could affect the accuracy of blood test results. Inform your doctor if you take high-dose biotin supplements.
What Is the Correct Dosage of Repatha?
Quick Answer: Repatha is given as a subcutaneous injection of either 140 mg every 2 weeks or 420 mg once monthly. The dose depends on your specific condition. The 420 mg monthly dose is delivered using an automated minidoser over approximately 5 minutes. Repatha should always be used exactly as prescribed by your doctor.
Adults
Primary Hypercholesterolemia & Mixed Dyslipidemia
The recommended dose is either 140 mg every 2 weeks or 420 mg once monthly, administered as a subcutaneous injection. Both dosing regimens produce similar reductions in LDL cholesterol.
Established Atherosclerotic Cardiovascular Disease (ASCVD)
The recommended dose is either 140 mg every 2 weeks or 420 mg once monthly, administered as a subcutaneous injection. In the FOURIER trial, the 140 mg biweekly dose was used, demonstrating significant cardiovascular risk reduction.
Children (10 Years and Older)
Heterozygous Familial Hypercholesterolemia (HeFH)
The recommended dose is either 140 mg every 2 weeks or 420 mg once monthly, administered as a subcutaneous injection.
Homozygous Familial Hypercholesterolemia (HoFH)
The recommended starting dose is 420 mg once monthly. After 12 weeks, your doctor may decide to increase the dose to 420 mg every 2 weeks if clinically warranted. For patients also receiving LDL apheresis, the doctor may start with 420 mg every 2 weeks to align the dosing with the apheresis schedule.
| Patient Group | Indication | Dose | Frequency |
|---|---|---|---|
| Adults | Primary hypercholesterolemia / Mixed dyslipidemia | 140 mg or 420 mg | Every 2 weeks or once monthly |
| Adults | Established ASCVD | 140 mg or 420 mg | Every 2 weeks or once monthly |
| Children ≥10 years | Heterozygous FH (HeFH) | 140 mg or 420 mg | Every 2 weeks or once monthly |
| Adults & children ≥10 years | Homozygous FH (HoFH) | 420 mg (start); may increase to 420 mg Q2W | Monthly; may change to every 2 weeks |
How to Administer Repatha
Repatha is given as an injection under the skin (subcutaneous injection). It should not be injected into a vein or muscle. If your doctor decides that you or a caregiver can administer Repatha injections at home, you should receive proper training on how to prepare and inject the medication correctly.
The 420 mg dose is administered using the automated minidoser (on-body infusor) with a prefilled cartridge. The injection takes approximately 5 minutes. Suitable injection sites include the abdomen (at least 5 cm from the navel), the front of the thigh, or the outer upper arm (only if someone else is administering the injection). Rotate injection sites with each dose and avoid injecting into areas that are tender, bruised, red, or hard.
Before use, allow the automated minidoser and cartridge to reach room temperature naturally by leaving them out of the refrigerator for at least 45 minutes. Do not attempt to warm the cartridge using warm water, a microwave, or any other heat source. Do not shake the device or cartridge.
Missed Dose
If you miss a dose of Repatha, administer it as soon as possible. Then contact your doctor, who will advise when you should take the next dose. Follow your doctor’s instructions carefully to get back on schedule.
Overdose
If you use more Repatha than you should, contact your doctor or pharmacist immediately. No specific antidote exists for evolocumab overdose. In clinical trials, doses of up to 420 mg administered subcutaneously and up to 3 mg/kg intravenously were given without dose-limiting adverse effects. In the event of an overdose, symptomatic and supportive treatment should be initiated.
What Are the Side Effects of Repatha?
Quick Answer: Common side effects of Repatha include injection site reactions (bruising, redness, pain), nasopharyngitis, flu-like symptoms, nausea, back pain, joint pain, and headache. Uncommon side effects include urticaria (hives). Rare but serious side effects include angioedema. Most side effects are mild to moderate and do not require discontinuation of treatment.
Like all medicines, Repatha can cause side effects, although not everybody gets them. The overall safety profile of Repatha is well-established through clinical trials involving more than 35,000 patients and extensive post-marketing experience. In the landmark FOURIER trial, which followed 27,564 patients for a median of 2.2 years, the incidence of side effects in the Repatha group was similar to the placebo group, confirming the medication’s favorable safety profile.
Long-term safety data from the OSLER-1 extension study, which followed patients for over 5 years of continuous treatment, showed no new safety signals and confirmed that Repatha maintains a consistent safety profile with prolonged use. Importantly, very low LDL cholesterol levels achieved with Repatha (even below 25 mg/dL or 0.65 mmol/L) were not associated with increased adverse events.
Common
May affect up to 1 in 10 people
- Influenza (high fever, sore throat, runny nose, cough, and chills)
- Common cold symptoms, including runny nose, sore throat, or sinus infections (nasopharyngitis or upper respiratory tract infection)
- Nausea
- Back pain
- Joint pain (arthralgia)
- Muscle pain (myalgia)
- Injection site reactions (bruising, redness, bleeding, pain, or swelling)
- Allergic reactions, including rash
- Headache
Uncommon
May affect up to 1 in 100 people
- Hives (urticaria) – red, itchy bumps on the skin
- Flu-like symptoms (malaise, fever, muscle aches)
Rare
May affect up to 1 in 1,000 people
- Angioedema (swelling of the face, mouth, tongue, or throat) – seek immediate medical attention if this occurs
If you experience signs of a serious allergic reaction such as swelling of the face, lips, tongue, or throat (angioedema), difficulty breathing, severe rash, or dizziness, stop using Repatha and seek emergency medical care immediately. Although these reactions are rare, they can be life-threatening if not treated promptly.
It is important to report suspected side effects after the medicine has been authorized. This allows for continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients are encouraged to report any suspected adverse reactions to their national pharmacovigilance authority (e.g., the FDA MedWatch program in the United States, the Yellow Card Scheme in the United Kingdom, or the EMA EudraVigilance system in Europe).
How Should You Store Repatha?
Quick Answer: Store Repatha in a refrigerator at 2–8°C (36–46°F). Do not freeze. Keep in the original packaging to protect from light and moisture. Repatha may be stored at room temperature (up to 25°C / 77°F) for up to 1 month before use.
Proper storage of Repatha is essential to maintain the medication’s effectiveness and safety. The following storage conditions should be strictly observed:
- Refrigeration: Store Repatha in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze. If the medication has been accidentally frozen, it must not be used.
- Light protection: Keep Repatha in its original packaging to protect it from light.
- Moisture: Protect from humidity. Keep in the original container.
- Room temperature storage: The cartridge and automated minidoser may be removed from the refrigerator and allowed to reach room temperature (up to 25°C / 77°F) before injection. This makes the injection more comfortable. Once removed from refrigeration, Repatha can be stored at room temperature in its original packaging and must be used within 1 month.
- Do not use if the solution appears discolored, cloudy, or contains large lumps, flakes, or colored particles. The solution should be clear to opalescent, colorless to slightly yellow, and essentially free from particles.
- Expiry date: Do not use after the expiry date printed on the label and carton (EXP). The expiry date refers to the last day of that month.
- Keep out of reach of children.
Do not dispose of medications via wastewater or household waste. Ask your pharmacist how to properly dispose of medicines you no longer use. These measures help protect the environment.
What Does Repatha Contain?
Quick Answer: Repatha contains evolocumab as the active substance. Each 3.5 mL cartridge contains 420 mg of evolocumab (120 mg/mL concentration). The other ingredients are proline, glacial acetic acid, polysorbate 80, sodium hydroxide, and water for injections.
Active Ingredient
The active substance is evolocumab. Each cartridge contains 420 mg of evolocumab in 3.5 mL of solution, corresponding to a concentration of 120 mg/mL. Evolocumab is produced in Chinese hamster ovary (CHO) cells using recombinant DNA technology.
Inactive Ingredients (Excipients)
- Proline – an amino acid that serves as a stabilizer to maintain protein structure
- Glacial acetic acid – a buffering agent that maintains the appropriate pH
- Polysorbate 80 – a surfactant that prevents protein aggregation
- Sodium hydroxide – used for pH adjustment
- Water for injections – the solvent vehicle
Appearance and Packaging
Repatha solution for injection is clear to opalescent, colorless to slightly yellowish, and essentially free from particles. Each package contains one cartridge together with a single-use automated minidoser (on-body infusor). The automated minidoser contains electronics, a battery, and a needle, and should be disposed of in a sharps disposal container after use.
Marketing Authorization Holder: Amgen Europe B.V., Minervum 7061, 4817 ZK Breda, Netherlands. Repatha is marketed globally by Amgen and is approved in major regulatory jurisdictions including the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), and numerous other national health authorities worldwide.
Frequently Asked Questions About Repatha
Repatha (evolocumab) is an injectable medication that belongs to a class of drugs called PCSK9 inhibitors. It works by blocking a protein called PCSK9, which normally reduces the liver’s ability to remove LDL (“bad”) cholesterol from the blood. By blocking PCSK9, Repatha increases the number of LDL receptors on liver cells, allowing the liver to clear more LDL cholesterol from the bloodstream. This typically lowers LDL-C levels by 55–75%.
Repatha is given as a subcutaneous injection either every 2 weeks (140 mg dose) or once monthly (420 mg dose). The dosing schedule depends on your specific condition and your doctor’s recommendation. The monthly 420 mg dose is administered using an automated minidoser device and takes approximately 5 minutes to complete.
The most common side effects include injection site reactions (bruising, redness, pain, or swelling), flu-like symptoms, common cold symptoms (nasopharyngitis), nausea, back pain, joint pain (arthralgia), muscle pain, headache, and allergic reactions including rash. Most side effects are mild to moderate and typically resolve on their own without treatment.
Yes, Repatha is commonly used together with statins. In fact, most patients are prescribed Repatha as add-on therapy when the maximum tolerated dose of a statin alone does not sufficiently lower LDL cholesterol. The combination provides additive LDL-C lowering effects. Repatha can also be used alone in patients who cannot tolerate statins or for whom statins are contraindicated.
Yes. The landmark FOURIER trial, which enrolled 27,564 patients with established atherosclerotic cardiovascular disease, demonstrated that Repatha significantly reduces cardiovascular events when added to statin therapy. Specifically, Repatha reduced the risk of heart attack by 27%, the risk of stroke by 21%, and the risk of coronary revascularization by 22% compared to placebo over a median follow-up of 2.2 years.
Repatha is approved for use in children aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH) or homozygous familial hypercholesterolemia (HoFH). Clinical studies have shown that Repatha is effective and well-tolerated in this age group. When children aged 10–13 use the automated minidoser, adult supervision is recommended. Repatha is not currently approved for children under 10 years of age.
References
- Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017;376(18):1713-1722. doi:10.1056/NEJMoa1615664 (FOURIER Trial)
- European Medicines Agency (EMA). Repatha (evolocumab) – Summary of Product Characteristics. Available at: ema.europa.eu/medicines/human/EPAR/repatha.
- U.S. Food and Drug Administration (FDA). Repatha (evolocumab) Prescribing Information. Reference ID: 4922401.
- Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2020;41(1):111-188. doi:10.1093/eurheartj/ehz455
- Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. J Am Coll Cardiol. 2019;73(24):e285-e350. doi:10.1016/j.jacc.2018.11.003
- Koren MJ, Sabatine MS, Giugliano RP, et al. Long-term Safety and Efficacy of Evolocumab in Patients With Hypercholesterolemia. JAMA Cardiol. 2022;7(4):413-421. (OSLER-1 Extension Study)
- Santos RD, Stein EA, Hovingh GK, et al. Long-Term Evolocumab in Patients With Familial Hypercholesterolemia. J Am Coll Cardiol. 2020;75(6):565-574. (TAUSSIG Study)
- World Health Organization (WHO). Cardiovascular diseases (CVDs) – Key facts. Available at: who.int/cardiovascular-diseases.
About Our Medical Editorial Team
This article was written and reviewed by our team of medical professionals specializing in cardiology, clinical pharmacology, and internal medicine. All content follows the iMedic Editorial Standards and is based on current international clinical guidelines and peer-reviewed research.
Licensed specialist physicians in cardiology and clinical pharmacology with extensive experience in cardiovascular disease prevention and lipid management. Members of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS).
Independent panel of medical experts who verify all content according to international guidelines (ESC/EAS 2019, AHA/ACC 2018, EMA SmPC, FDA Label). All clinical claims are graded using the GRADE evidence framework.
Evidence Standard: Level 1A – Based on systematic reviews and meta-analyses of randomized controlled trials, including the FOURIER cardiovascular outcomes trial (N=27,564) and OSLER long-term safety extensions.
Conflict of Interest: None. iMedic receives no funding from pharmaceutical companies and maintains complete editorial independence.