Aflibercept (ophthalmic)

Preparation for Administration – Pre-filled Syringe The EYLEA pre-filled glass syringe is sterile and for one-time use in one eye only. Do not use the EYLEA pre-filled syringe for the treatment of ROP. The pre-filled syringe should be inspected visually prior to administration. Do not use if particulates, cloudiness, or discoloration are visible, or if the package is open or damaged.

The appearance of the syringe cap on the pre-filled syringe may vary (for example, color and design). Do not use if any part of the pre-filled syringe is damaged or if the syringe cap is detached from the Luer lock. The intravitreal injection should be performed with a 30-gauge × ½-inch injection needle (not provided). The pre-filled syringe contains more than the recommended dose of 2 mg aflibercept (equivalent to 50 microliters).

The excess volume must be discarded prior to the administration. PRE-FILLED SYRINGE DESCRIPTION – Figure 1: Use aseptic technique to carry out the following steps: 1. PREPARE When ready to administer EYLEA, open the carton and remove sterilized blister pack. Carefully peel open the sterilized blister pack ensuring the sterility of its contents.

Keep the syringe in the sterile tray until you are ready for assembly. 2. REMOVE SYRINGE Using aseptic technique, remove the syringe from the sterilized blister pack. 3. TWIST OFF SYRINGE CAP Twist off (do not snap off) the syringe cap by holding the syringe in one hand and the syringe cap with the thumb and forefinger of the other hand (see Figure 2 ).

Note: To avoid compromising the sterility of the product, do not pull back on the plunger. Figure 2: 4. ATTACH NEEDLE Using aseptic technique, firmly twist a 30-gauge × ½-inch injection needle onto the Luer lock syringe tip (see Figure 3 ). Figure 3: Note: When ready to administer EYLEA, remove the plastic needle shield from the needle. 5.

DISLODGE AIR BUBBLES Holding the syringe with the needle pointing up, check the syringe for bubbles. If there are bubbles, gently tap the syringe with your finger until the bubbles rise to the top (see Figure 4 ). Figure 4: 6. EXPEL AIR AND SET THE DOSE To eliminate all bubbles and to expel excess drug, slowly depress the plunger rod to align the plunger dome edge (see Figure 5a ) with the black dosing line on the syringe (equivalent to 50 microliters) (see Figure 5b ).

Figure 5a: Figure 5b: 7. The pre-filled syringe is for one-time use in one eye only. After injection any unused product must be discarded. Figure 1 Figure 2 Figure 3 Figure 4 Figure 5a Figure 5b

Preparation for Administration - Vial EYLEA should be inspected visually prior to administration. If particulates, cloudiness, or discoloration are visible, the vial must not be used. The glass vial is for one-time use in one eye only. Use aseptic technique to carry out the following preparation steps: Prepare for intravitreal injection with the following medical devices for single use: a 5-micron sterile filter needle (18-gauge × 1½-inch) a 1-mL sterile Luer lock syringe with marking to measure 0.05 mL for adults or 0.01 mL for pre-term infants with ROP a sterile injection needle (30-gauge × ½-inch) Remove the protective plastic cap from the vial (see Figure 6 ).

Figure 6: Clean the top of the vial with an alcohol wipe (see Figure 7 ). Figure 7: Remove the 18-gauge × 1½-inch, 5-micron, filter needle and the 1-mL syringe from their packaging. Attach the filter needle to the syringe by twisting it onto the Luer lock syringe tip (see Figure 8 ). Figure 8: Push the filter needle into the center of the vial stopper until the needle is completely inserted into the vial and the tip touches the bottom or bottom edge of the vial.

Using aseptic technique withdraw all of the EYLEA vial contents into the syringe, keeping the vial in an upright position, slightly inclined to ease complete withdrawal. To deter the introduction of air, ensure the bevel of the filter needle is submerged into the liquid. Continue to tilt the vial during withdrawal keeping the bevel of the filter needle submerged in the liquid (see Figure 9a and Figure 9b ).

Figure 9a: Figure 9b: Ensure that the plunger rod is drawn sufficiently back when emptying the vial in order to completely empty the filter needle. Remove the filter needle from the syringe and properly dispose of the filter needle. Note : Filter needle is not to be used for intravitreal injection. Remove the 30-gauge × ½-inch injection needle from its packaging and attach the injection needle to the syringe by firmly twisting the injection needle onto the Luer lock syringe tip (see Figure 10 ).

Figure 10: When ready to administer EYLEA, remove the plastic needle shield from the needle. Holding the syringe with the needle pointing up, check the syringe for bubbles. If there are bubbles, gently tap the syringe with your finger until the bubbles rise to the top (see Figure 11 ). Figure 11: Administration in Adults: To eliminate all of the bubbles and to expel excess drug, SLOWLY depress the plunger rod so that the plunger edge aligns with the line that marks 0.05 mL on the syringe (see Figure 12a and Figure 12b ).

Figure 6 Figure 7 Figure 8 Figure 9a Figure 9b Figure 10 Figure 11 Figure 12a and b

Preparation for Administration – Vial. 11 . To eliminate all of the bubbles and to expel excess drug, SLOWLY depress the plunger rod so that the plunger edge aligns with the line that marks 0.01 mL on the syringe (see Figure 13a and Figure 13b ). For the treatment of ROP, the injection needle should be inserted into the eye 1 mm from the limbus with the needle angled to avoid the lens and to avoid the retina.

After injection, any unused product must be discarded. Figure 13a and b