• Repatha is a brand (trade) name for evolocumab which may be used to treat high cholesterol.
• Repatha (evolocumab) works by binding to a protein in the liver called proprotein convertase subtilisin kexin 9 (PCSK9) inhibiting its binding to low-density lipoprotein receptors (LDLR) on the surface of liver cells. LDLR is the primary receptor that clears circulating LDL. By inhibiting the binding of PCSK9 to LDLR, Repatha increases the number of LDLRs available to clear LDL, thereby lowering LDL-C levels.
• Repatha belongs to the class of medications known as PCSK9 inhibitors. It may also be called a human monoclonal antibody.

• May be used alone or in combination with other cholesterol-lowering treatments to reduce LDL-C levels in adults with primary hyperlipidemia (high cholesterol). This includes heterozygous familial hypercholesterolemia (HeFH)(high cholesterol that occurs because of genetic reasons). The recommended dosage is either 140mg every 2 weeks or 420mg once a month.
• May be used in children aged 10 years and older with HeFH in addition to diet and other LDL-C-lowering therapies.
• May be used to reduce the risk of a heart attack (myocardial infarction) stroke, or unstable angina requiring hospitalization, in adults with established cardiovascular disease. The recommended dosage is either 140mg every 2 weeks or 420mg once a month.
• May be used in addition to other medications to lower LDL-C levels in patients with homozygous familial hypercholesterolemia (HoFH). The initial recommended dosage is 420mg once a month, which may be increased to 420mg once every two weeks if a clinically meaningful response has not been achieved after 12 weeks. May be used in adolescents aged 13 years or older.
• Patients with HoFH on lipid apheresis may initiate treatment with 420mg every two weeks to correspond to their apheresis schedule. Administer Repatha after the apheresis session is complete.
• The 420mg dose can be administered over 5 minutes by using the Pushtronex system or by giving three injections of the 140mg prefilled syringe or autoinjector consecutively within 30 minutes.
• Effective at reducing low-density lipoprotein cholesterol (LDL-C) levels when taken on its own, without an additional statin. The lipid-lowering effect of Repatha can be determined as early as 4 weeks after initiation.
• May be used alone or in combination with other medications such as statins or ezetimibe.
• Three dosage forms are available: a single-dose pre-filled syringe, a single-dose prefilled SureClick autoinjector, and a single-dose Pushtronex system on-body infusor with a pre-filled cartridge. Repatha is administered subcutaneously (under the skin).
• Weight gain or weight loss has not been reported as a side effect of Repatha in clinical trials.
• Monoclonal antibodies, such as Repatha, tend to have few drug interactions and are unlikely to cause liver or kidney damage.
• No overall differences in safety or efficacy were observed in elderly patients.
• No dosage adjustment is needed for mild-to-moderately impaired liver or kidney disease.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Nasopharyngitis, upper respiratory tract infections, influenza, back pain, injection site reactions (such as pain, redness, or swelling), urinary tract infections, sinusitis, headache, muscle pain, dizziness, pain, high blood pressure, diarrhea, and gastroenteritis are the most commonly reported side effects.
• The dosage varies depending on its use.
• All formulations of Repatha are injected subcutaneously (under the skin).
• LDL-C can vary during the dosing interval in some patients and LDL-C levels may be more accurate if measured just before the next scheduled dose.
• LDL-C is only one of the major lipids and apolipoproteins that are relevant in cardiovascular disease. Other lipids and apolipoproteins levels may also be elevated and require treatment with other agents. Repatha has little effect on triglyceride levels which is why it is often prescribed with statins which do lower triglyceride levels.
• LDL-C levels should be measured within 4 to 12 weeks of the initial dose. If after 12 weeks the response is inadequate for HoFH, then increase it to 420mg once every two weeks. Measure LDL-C just before the next dose, because LDL-C levels can vary significantly during the dosing interval.
• There have been reports of serious hypersensitivity reactions occurring with other PCSK9 inhibitors. Monitor for any signs of a rash or anaphylaxis and discontinue Repatha if they occur.
• Must be stored in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until time of use. Repatha can be kept at room temperature (20°C to 25°C [68°F to 77°F]) in the original carton and must be used within 30 days. Throw away Repatha which has been left at room temperature for more than 30 days. Do not freeze. Do not shake.
• There is a potential for immunogenicity (antibody formation) with Repatha, with 0.3% of patients testing positive for the development of binding antibodies after one dose of Repatha; none of whom tested positive for neutralizing antibodies. There was no evidence that the presence of these antibodies impacted the efficacy or safety of Repatha.
• The safety of using Repatha in children younger than 13 years has not been established.
• The needle cover of the glass prefilled syringe and the autoinjector contain dry natural rubber which is a derivative of latex and may cause allergic reactions.
• The risk of new-onset diabetes may be slightly increased in the Repatha group compared to the placebo group (8.1% vs 7.7%; a difference of 0.4%).
• There is no data regarding the safety of Repatha during pregnancy; however, generally, cholesterol-lowering medications should not be used during pregnancy. If a woman inadvertently becomes pregnant while taking Repatha, report the exposure to 1-800-77-AMGEN. There is no information regarding the presence of Repatha in breast milk.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

• As with all other cholesterol-lowering medication, Repatha should be administered in conjunction with lifestyle changes including a cholesterol-lowering diet and a weight management plan.
• Regular exercise is also important as well as avoiding smoking.
• Repatha is injected under the skin every two to four weeks (but some people may prefer once a month) into your stomach area (abdomen), thigh, or upper arm and you can learn to give yourself injections at home.
• Repatha is available as a pre-filled syringe, Sureclick auto-injector, or as the Pushtronex system ( a hands-free device that has been designed to adhere to the body and provide 420 mg of Repatha subcutaneously in a single dose). The prefilled syringe and Sureclick autoinjector contain one prefilled dose of medicine in a spring-loaded syringe. You, or your caregiver, can learn to give this medicine at home. Many patients prefer autoinjectors over single-use syringes as they are easier to use and may cause less worry.
• If you have been shown how to self-inject Repatha, administer a dose once every two weeks or monthly depending on what your doctor has prescribed, otherwise see your healthcare provider for a dose every month. If you forget a dose, schedule it as soon as you can, then continue with your regular dosing schedule.
• Immediately before administration take one or Repatha injection out of the refrigerator and leave it on a flat surface, away from children and pets, to warm up to room temperature for around 30 minutes (prefilled autoinjector/syringe) or 45 minutes (on-body infusor). Do not warm it in any other way (such as by putting it in hot water). Repatha at room temperature reduces the risk of stinging. Inspect the injection for any discoloration or particulate matter and do not use it if the liquid is cloudy, contains particles, or is discolored. The liquid in Repatha should be clear, colorless, or have a slightly yellow tinge. Check the expiry date on the side of the injection and do not use Repatha if it has expired. Do not shake Repatha.
• Repatha is best administered into the front of your thighs or the lower part of your abdomen, avoiding the area around your belly button (stay an inch away from your belly button). If somebody else is giving you your injection they can also administer it into the outer area of your upper arm. Change your injection site every time you give yourself a dose so that you are not injecting into the same spot each time.
• Only inject into clear, healthy skin. Do not inject into any areas that are bruised, tender, red, scaly, or hard. You should also not inject into any scars, stretch marks, or areas of psoriasis.
• If you feel pain when you inject Repatha, placing an ice pack on the area of skin where you inject Repatha for a few minutes before and after the injection can help reduce this pain.
• For the Repatha prefilled syringe, carefully remove the grey needle cap of the syringe and discard. Pinch the skin at the clean injection between your thumb and finger to form a firm surface that is about 2 inches wide.
• Insert the needle into the firm skin at an angle between 45 and 90 degrees. Push the plunger down using slow and constant pressure, so that the syringe is empty. Once the injection is completed, release your thumb from the plunger and gently remove the syringe from the skin. Discard the used syringe into your sharps container.
• To inject the Repatha SureClick Autoinjector, remove the orange cap. The cap should only be off the device for a maximum of 5 minutes as the medicine can dry out. At the selected skin injection site, pinch the skin with your thumb and fingers to form a firm surface. Holding the Autoinjector in a fist grip with your thumb towards the top end, press the yellow safety guard end of the device firmly against the skin 90 degrees to the skin surface (straight up and down). Press the grey button down and you will hear a click. Continue holding the injector firmly against the skin until the window goes from clear to yellow, this could be at least 15 seconds. When the injection is complete, lift the autoinjector straight up, and discard the autoinjector into your sharps container.
• To use the Repatha Pushtronex (Repatha on-body infusor), open the carton and first remove the white paper cover, then the plastic cover from the clear tray. Leave the on-body infusor in the clear tray until you are ready to inject. Clean the injection site with an alcohol wipe. The injection site needs to be firm, flat, and relatively hair-free. Take the on-body infusor out of the carton and open the cartridge compartment by swinging the cartridge door to the right. Pick up the cartridge and check the expiration date and check the solution is clear and colorless to slightly yellow. Holding the cartridge barrel, clean the cartridge bottom with an alcohol wipe. Place the cartridge into the cartridge compartment of the on-body infusor and press it downwards until it is secure. Once the cartridge is in place it should be administered within 5 minutes or the medicine can dry out. Swing the cartridge door to the left until it snaps closed. Peel and remove both green tabs. This will expose the skin adhesive and will turn the on-body infusor on. It will start beeping and a blue light should be flashing when it is ready to be applied. Apply the on-body infusor to the selected cleaned skin area avoiding any skin folds or bulges. Make sure it is firmly attached. Once it is firmly attached you can push the start button which will cause the green light to flash, and a click will indicate the injection has started. It will take approximately 5 minutes to complete the infusion and then the green light will stop flashing and become a solid green light. You will hear several beeps and the plunger will fill the medicine window all the way. When the infusion is complete you can grab the edge of the skin adhesive and gently peel the on-body infusor away from the skin. If the plunger does not fill the window it is important to contact your healthcare provider. Discard the used Repatha on-body infusor into your sharps container.
• If you miss a dose of Repatha and it is within 7 days of your scheduled dose, administer it as soon as possible. If it is longer than 7 days since the missed dose, either wait until the next scheduled dose if you are administering it every two weeks, or administer the dose and start a new schedule. Do not double the dose. If you have questions about your dose or when to administer it, call your doctor
• Repatha lowers LDL cholesterol in the blood which slows down the formation of the fatty deposits in the arteries which reduces your risk of a heart attack (myocardial infarction), stroke, or unstable angina requiring hospitalization. Because the accumulation of fatty deposits in the arteries is a process that happens over time. If you want to prevent the slow, consistent future build-up of fatty deposits then you need to take Repatha regularly and long-term.
• There is no interaction between drinking alcohol and Repatha so an occasional drink with Repatha is acceptable; however, binge drinking of alcohol is known to cause an increase in lipid levels.
• Repatha should be stored in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until the time of use. If removed from the refrigerator, Repatha can be kept at room temperature (up to 25°C [77°F]) in the original carton and must be used within 30 days. Throw away Repatha that has been left at room temperature for more than 30 days. Do not freeze. Do not shake. Do not put the prefilled pen or syringe back in the refrigerator after it has reached room temperature.
• If you are pregnant or intend to become pregnant, tell your doctor as it is not known if Repatha will harm an unborn baby. Also, talk to your doctor about breastfeeding your baby while you are self-administering Repatha.

• In the DESCARTES trial, after 52 weeks Repatha by itself reduced LDL-C cholesterol by 63.8% compared to placebo, Repatha + atorvastatin 10mg/d reduced LDL-C by 64.4% compared to placebo, Repatha + atorvastatin 80mg/d reduced LDL-C by 57.9% compared to placebo.
• Needs to be taken long-term to reduce the risk of cardiovascular disease. Once discontinued, LDL-C levels will return to pre-Repatha levels. In the FOURIER clinical trial the median length of time patients were on Repatha was 24.8 months and 5% of the participants were on it for 36 months.
• Half-life ranges between 11 and 17 days, depending on the personal variation.

There are currently no documented interactions with Repatha, according to the product information.

Repatha is not metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.

Although approximately a 20% decrease in the Cmax and AUC of Repatha was seen when it was administered with a high-intensity statin regimen, this difference is not considered clinically meaningful and does not impact dosing recommendations.

You should refer to the prescribing information for Repatha for any updates or newly noted interactions.