Evolocumab

• If stored in the refrigerator, allow it to warm to room temperature for at least 30 minutes for the single-use prefilled syringe or autoinjector or 45 minutes for the single-use on-body infusor with prefilled cartridge before use. Do not warm by using a heat source or leave in direct sunlight. If the solution has not reached room temperature, it may cause discomfort and may take longer to inject the full dose.
• Do not shake.
• Administer into areas of the abdomen (except for a 2-inch area around the umbilicus), thigh, or upper arm that are not tender, bruised, red, or indurated.
• Rotate the site with each injection.
• Do not administer with other injectable drugs at the same injection site.
• The 420 mg dose can be administered as 3 injections, consecutively within 30 minutes, utilizing the single-use prefilled syringe or autoinjector or as a single injection over 9 minutes using the single-use on-body infusor with the prefilled cartridge.

Single-use prefilled syringe administration

• Carefully remove the syringe from the tray.
• Do not pick up or pull the prefilled syringe by the plunger rod or gray needle cap. Always hold the syringe by the barrel.
• Pull the gray needle cap straight off. It is normal to see a drop of solution at the end of the needle. Do not try to remove any air bubbles in the syringe.
• Pinch the skin injection site to create a firm surface approximately 2 inches wide. Hold the pinch, and insert the needle into the skin using a 45 to 90-degree angle.
• Using slow and constant pressure, push the plunger rod all the way down until the syringe is empty.
• When done, release the plunger, and gently lift the syringe off the skin.
• Storage: Store in the refrigerator at 2 to 8 degrees C (36 to 46 degrees F) in the original carton to protect from light. Do not freeze. If needed, may keep at room temperature at 20 to 25 degrees C (68 to 77 degrees F) in the original carton for 30 days. If not used within 30 days, discard evolocumab.

Single-use SureClick autoinjector administration

• Do not use it if it has been dropped on a hard surface, even if you cannot see a break in the autoinjector.
• Do not remove the orange cap until you are ready to inject. Do not leave the orange cap off for more than 5 minutes; this can dry out the medication.
• When ready for injection, pull the orange cap straight off. Do not twist, bend, or wiggle the orange cap. Do not put fingers into or on the yellow safety guard.
• Stretch (thigh) or pinch (stomach or upper arm) the cleansed injection site skin to create a firm surface approximately 2 inches wide. Hold the stretch or pinch, and place the yellow end of the autoinjector on the skin at 90 degrees.
• Firmly push the autoinjector down onto the skin until it stops moving. When ready to inject, press the gray button. A click should be heard. Keep pushing on the skin and then lift the thumb. The injection could take about 15 seconds. The window on the autoinjector will turn from clear to yellow when the injection is complete. A second click may be heard.
• Remove the autoinjector from the skin; the needle will be automatically covered.
• After removing the autoinjector from the skin, if the window has not turned yellow or if it looks like the medicine is still injecting, this means you have not received a full dose. Do not try to reuse the autoinjector. Call the health care provider immediately. For more information, call 1-844-REPATHA.
• Dispose of the used autoinjector in an appropriate sharps container.
• Storage: Store in the refrigerator at 2 to 8 degrees C (36 to 46 degrees F) in the original carton to protect from light. Do not freeze. If needed, may keep at room temperature at 20 to 25 degrees C (68 to 77 degrees F) in the original carton for 30 days. If not used within 30 days, discard evolocumab.

Single-use on-body infusor with prefilled cartridge (Pushtronex system) administration

• Pediatric patients 10 to 17 years of age should only use the on-body infusor and prefilled cartridge under adult supervision.
• Do not expose the on-body infuser to Magnetic Resonance (MR) Environment (e.g., MRI).
• Open the carton and peel away the white paper cover. Remove the plastic cover from the clear tray.
• Do not use if the white paper cover is missing or damaged or if the cartridge looks cracked, broken, or pieces are missing or not securely attached.
• Open the on-body infusor by swinging the cartridge door to the right and leave the door open. Do not close the cartridge door before the cartridge is loaded. If the cartridge door accidentally closes, press the left side of the door to release the door latch.
• Load the cleaned cartridge straight into the on-body infusor and firmly press the top until it is securely in place.
• Do not touch the start button until the on-body infusor is on the skin and ready for injection.
• Swing the door to the left, and squeeze firmly until it snaps shut. Make sure the cartridge fits securely in the on-body infusor before closing the door.
• Peel away both green pull tabs to show the adhesive. Do not pull the skin adhesive backing off of the on-body infusor. Do not touch the skin adhesive. Do not touch the needle cover area. Do not place on the body if the red status light flashes continuously.
• Choose the injection site. Use a firm and flat skin surface. Avoid injecting into areas with wrinkles, skin folds, scars, stretch marks, moles, and excessive hair. Adjust body posture to avoid skin folds and bulges.
• The on-body infusor is ready when the blue light flashes. If using the stomach, keep the skin stretched. Hold the loaded on-body infusor with the blue light visible and place it on the skin. The beeping may be heard. The loaded on-body infusor will lay flat on the body. Make sure all of the adhesive is attached to the skin. Run a finger around the adhesive edges to secure it. Ensure clothing does not get in the way of the infusor. The blue light should be visible at all times.
• Do not move the infusor once it is attached to the skin.
• Firmly press and release the start button. A flashing green light and a click signals the injection has started.
• An audible pumping sound may be heard, and a pinch may be felt.
• The injection takes about 5 minutes. The status light turns solid green and the device beeps when finished.
• When the injection is finished, grab the skin adhesive to carefully peel the on-body infusor from the skin. After removal, check the medicine window. The green light should be off. The infusor will beep when removed from the skin. A few drops of fluid on the skin after removal of the infusor are normal.
• Storage: Store in the refrigerator at 2 to 8 degrees C (36 to 46 degrees F) in the original carton to protect from light. Do not freeze. If needed, may keep at room temperature at 20 to 25 degrees C (68 to 77 degrees F) in the original carton for 30 days. If not used within 30 days, discard evolocumab.[60127]

The median time to maximum serum evolocumab concentration (Tmax) after administration of single doses of 140 mg or 420 mg is 3 to 4 days. Maximum suppression of free circulating PCSK9 occurs within 4 hours after a single subcutaneous dose of evolocumab 140 mg or 420 mg and returns to baseline once evolocumab concentrations are undetectable. Evolocumab exhibits non-linear pharmacokinetics. An approximate 2- to 3-fold accumulation is observed in trough serum concentrations after 140 mg doses administered every 2 weeks or 420 mg doses administered monthly. Steady state is reached within 12 weeks of dosing. The absolute bioavailability after subcutaneous administration is 72%.[60127]

The mean maximum serum concentration (Cmax) and mean AUC are lower (20 to 30% and 40 to 50%, respectively) in patients with mild and moderate hepatic impairment. Evolocumab has not been studied in patients with severe hepatic impairment.[60127]

Since monoclonal antibodies are not known to be eliminated via renal pathways, renal function is not expected to impact the pharmacokinetics of evolocumab.[60127]

Children and Adolescents 10 to 17 years

Mean trough serum concentrations of evolocumab were 22.4 mcg/mL and 25.8 mcg/mL over Week 12 and Week 24 time points, respectively, during clinical trials in 103 pediatric patients with heterozygous familial hypercholesteremia (HeFH).[60127]

Mean trough serum concentrations of evolocumab were 20.3 mcg/mL and 17.6 mcg/mL over Week 12 and Week 80 time points, respectively, during clinical trials in 12 pediatric patients with homozygous familial hypercholesteremia (HoFH).[60127]

Age was not shown to have an effect on the pharmacokinetics of evolocumab.[60127]

Gender was not shown to have an effect on the pharmacokinetics of evolocumab.[60127]

Race was not shown to have an effect on the pharmacokinetics of evolocumab.[60127]

Evolocumab exposure has been found to decrease with increasing body weight; however, these differences are not clinically meaningful.[60127]