Evolocumab

Evolocumab is used to reduce the risk of major adverse cardiovascular events (MACE) (such as a stroke or heart attack) in adults at increased risk for these events, and to reduce low-density lipoprotein cholesterol (LDL-C) levels in adults and children aged 10 years and older with certain types of high cholesterol in addition to diet and exercise. Evolocumab is self-administered by subcutaneous injection 1 time every 2 to 4 weeks. The brand name is Repatha.

Evolocumab works by targeting a protein in the body called PCSK9 that binds to LDL receptors on the surface of liver cells, degrading them and reducing the liver's ability to clear LDL-C from the bloodstream. By blocking PCSK9, evolocumab increases the number of available LDL-C receptors, allowing more LDL-C to be removed from the blood. The Fourier clinical trial (NCT01764633) reported that evolocumab reduces major cardiovascular events by about 15% in those with cardiovascular disease. This benefit appears directly related to the degree of LDL lowering achieved. Evolocumab belongs to the drug class called PCSK9 inhibitors. It may also be called a monoclonal antibody.

Evolocumab received FDA approval on August 27, 2015, under the brand name Repatha. There is no generic or biosimilar.

Evolocumab is an injectable prescription medicine that is FDA-approved:

• to reduce the risk of major adverse cardiovascular events (MACE), such as death from cardiovascular disease, heart attack, stroke, certain types of chest pain conditions (unstable angina) requiring hospitalization, or certain types of surgery or procedures to restore arterial blood flow to the heart and other parts of the body, in adults at increased risk for these events
• to reduce LDL-C in adults with hypercholesterolemia as an adjunct to diet and exercise
• to reduce LDL-C in adults and children aged 10 years and older with HeFH as an adjunct to diet and exercise
• to reduce LDL-C in adults and children aged 10 years and older with homozygous familial hypercholesterolemia (HoFH) as an adjunct to diet and exercise.

It is not known if evolocumab is safe and effective in children with HeFH or HoFH who are younger than 10 years of age or in children with other types of hyperlipidemia.

You should only give yourself or someone else the injection if you have received full training from your healthcare provider on how to administer it.

Evolocumab can be given as a subcutaneous injection (injection under the skin, SC) using:

• a single-dose prefilled SureClick® autoinjector
• a single-dose prefilled syringe
• or a single-dose prefilled pen.

It takes up to 15 seconds to administer evolocumab using the single-dose prefilled pen, single-dose prefilled autoinjector, or single-dose prefilled syringe.

If your healthcare provider prescribes you or your child the 420 mg dose, you or your child may use:

• 3 separate injections in a row, using a different single-dose prefilled pen, single-dose prefilled syringe, or single-dose prefilled autoinjector for each injection. Give all of these injections within 30 minutes.

Ask your healthcare provider about training on the right way to prepare and inject evolocumab. Do not try to inject evolocumab until you or your child has been shown the right way to do so by your healthcare provider or nurse.

• Put the yellow safety guard of the SureClick® autoinjector on the skin before injecting.

You or your child can inject into the thigh, upper arm, or stomach (abdomen), except for a two-inch area around the belly button.

• Do not choose an area where the skin is tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks.

Always check the label of your single-dose prefilled pen, single-dose prefilled autoinjector, or single-dose prefilled syringe to make sure you have the correct medicine and the correct dose of evolocumab before each injection.

• If your healthcare provider has prescribed evolocumab along with other cholesterol-lowering medicines for you or your child, follow instructions from your healthcare provider. Read the patient information for those medicines.
• If you or your child uses more evolocumab than you should, talk to your healthcare provider or pharmacist.
• Do not stop using evolocumab without talking with your healthcare provider. If you or your child stops using evolocumab, the cholesterol levels can increase.

Full patient instructions with diagrams are available on the Repatha Package Insert.

Do not use evolocumab if you or your child is allergic to it or any of the ingredients in evolocumab. See the end of this page for a complete list of ingredients in evolocumab.

Before you or your child start using evolocumab, tell your healthcare provider about all your medical conditions, including if you or your child:

• Are allergic to rubber or latex. The prefilled single-dose SureClick® autoinjectors and prefilled single-dose syringes either contain dry natural rubber (a derivative of latex) in the needle cover or are not made with natural rubber latex. The carton and "Instructions for Use" will state if your product contains dry natural rubber. The prefilled single-dose pen is not made with natural rubber latex
• Are pregnant, or planning to become pregnant. It is not known if evolocumab will harm your unborn baby. Tell your healthcare provider if you become pregnant while taking evolocumab. If you or your child are pregnant during treatment, you are encouraged to call Amgen at 1-800-772-6436 to share information about the health of you and your baby
• Are breastfeeding, or planning to breastfeed. You and your healthcare provider should decide if you will take evolocumab or breastfeed. If you or your child breastfeed during treatment, you are encouraged to call Amgen at 1-800-772-6436 to share information about the health of you and your baby.

The most common side effects of evolocumab are:

• cold symptoms like a runny nose and a sore throat
• flu or flu-like symptoms
• back pain
• high blood sugar levels or diabetes
• injection site reactions such as redness, pain, or bruising.

Serious side effects and warnings

Evolocumab can cause the following serious side effects:

Serious allergic reactions. Some people taking evolocumab have had serious allergic reactions. Stop taking evolocumab and call your healthcare provider or seek emergency medical help right away if you or your child have any of these symptoms:

• trouble breathing or swallowing
• raised bumps (hives)
• rash, or itching
• swelling of the face, lips, tongue, throat, or arms.

Evolocumab is available as prefilled single-dose Repatha 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. Ask your healthcare provider for the evolocumab injection or autoinjector that does not contain dry natural rubber if you are sensitive to latex.

Tell your healthcare provider if you or your child has any side effect that bothers you or that do not go away. This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects or see the Repatha Package Insert. You may report side effects to the FDA at 1-800-FDA-1088.

Evolocumab is usually given once every 2 weeks or 1 time a month.

• Depending on your dose, you may need to use up to 3 separate injections at one time.
• Follow your doctor's dosing instructions very carefully.

Dose of Evolocumab for Adults at Increased Risk of MACE or with Hypercholesterolemia

• 140 mg SC every 2 weeks or 420 mg SC once a month.

Dose of Evolocumab for HeFH (Adults and Children 10 years and older)

• 140 mg SC every 2 weeks or 420 mg SC once a month.

Dose of Evolocumab for HoFH (Adults and Children 10 years and older)

• 420 mg SC 1 time a month. May increase 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 SC every 2 weeks to correspond with their apheresis schedule. Administer evolocumab after the apheresis session is complete.

If you or your child forget to use evolocumab or are not able to take the dose at the regular time, inject your or your child’s missed dose as soon as you remember, as long as it is within 7 days of the missed dose.

More than 7 days from the missed dose

If it is more than 7 days from the missed dose and you or your child are using the every-2-week dose, inject the next dose based on the original schedule. This will put you or your child back on the original schedule.

If it is more than 7 days from the missed dose and you or your child are using the 1-time each-month dose, inject the dose and start a new schedule using this date.

If you or your child is not sure when to take evolocumab after a missed dose, ask your healthcare provider or pharmacist. Do not use extra medicine to make up a missed dose.

Do not inject evolocumab into skin that is bruised, sore, scarred, or hardened.

Other drugs may interact with evolocumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.

For convenience, evolocumab may 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 30 days, discard evolocumab.

Do not freeze or shake.

Active Ingredient: evolocumab

Inactive Ingredients (Repatha): proline, acetate, polysorbate 80, water for injection USP, and sodium hydroxide.

Evolocumab is made by Amgen under the brand name Repatha. Amgen is based in Thousand Oaks, California.