Eylea Hd Drug Information

Neovascular (Wet) Age-Related Macular

Degeneration (nAMD)

Diabetic Macular Edema (DME)

Diabetic Retinopathy (DR)

Macular Edema Following Retinal Vein Occlusion (RVO)

Important Injection Instructions

For ophthalmic intravitreal injection. EYLEA HD must only be administered by a qualified physician. A 5-micron sterile filter needle (18-gauge × 1½-inch), a 1-mL Luer lock syringe and a 30-gauge × ½-inch sterile injection needle are needed.

These patients may benefit from resuming every 4-week dosing (approximately every 28 days +/- 7 days). Some patients did not maintain a response with extended dosing intervals after successful response to the first three to five initial monthly doses.

Preparation for Administration The EYLEA

HD glass vial is for one-time use in one eye only. Discard unused portion. EYLEA HD does not contain an anti-microbial preservative.

Extraction of multiple doses from a single vial may increase the risk of contamination and subsequent infection. Do not use if the package or its components are expired, damaged, or have been tampered with. Check the label on the vial to make sure you have the correct aflibercept strength.

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 0.07 mL) a sterile injection needle (30-gauge × ½-inch) 1. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use the vial if particulates, cloudiness, or discoloration are visible. 2.

Remove the protective plastic cap from the vial (see Figure 1 ). Figure 1: 3. Clean the top of the vial with an alcohol wipe (see Figure 2 ).

Figure 2: 4. Use aseptic technique to carry out steps 4 – 11. 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 3 ). Figure 3: 5. 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. 6.

Withdraw all of the EYLEA HD 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 4a and Figure 4b ).

Figure 4a: Figure 4b: 7. Ensure that the plunger rod is drawn sufficiently back when emptying the vial in order to completely empty the filter needle. 8. 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. 9. 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 5 ). Figure 5: 10.

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 6 ). Figure 6: 11.

To eliminate all of the bubbles and to expel excess drug, SLOWLY depress the plunger so that the plunger tip aligns with the line that marks 0.07 mL on the syringe (see Figure 7a and Figure 7b ). Figure 7a: Figure 7b: Figure 1 Figure 2 Figure 3 Figure 4a Figure 4b Figure 5 Figure 6 Figure 7a Figure 7b

Injection Procedure

The intravitreal injection procedure should be carried out under controlled aseptic conditions, which include surgical hand disinfection and the use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a topical broad–spectrum microbicide should be given prior to the injection. Immediately following the intravitreal injection, patients should be monitored for elevation in intraocular pressure.

Appropriate monitoring may consist of a check for perfusion of the optic nerve head or tonometry. If required, a sterile paracentesis needle should be available. Following intravitreal injection, patients and/or caregivers should be instructed to report any signs and/or symptoms suggestive of endophthalmitis or retinal detachment (e.g., eye pain, redness of the eye, photophobia, blurring of vision) without delay.

Each vial should only be used for the treatment of a single eye. If the contralateral eye requires treatment, a new vial should be used and the sterile field (including a new syringe, gloves, drapes, eyelid speculum, filter and injection needles) should be changed before EYLEA HD is administered to the other eye. After injection, discard any unused product or waste material in accordance with local regulations.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in other clinical trials of the same or another drug and may not reflect the rates observed in practice. A total of 1755 patients were treated with EYLEA HD and 804 patients were treated with EYLEA 2 mg in three clinical studies. The most common adverse reactions reported in ≥3% of patients treated with EYLEA HD were cataract, conjunctival hemorrhage, corneal epithelium defect, intraocular pressure increased, ocular discomfort/eye pain/eye irritation, retinal hemorrhage, vision blurred, vitreous detachment and vitreous floaters.

Neovascular (Wet) Age-Related Macular Degeneration (AMD) and Diabetic Macular Edema (DME) The data described below reflect exposure to EYLEA HD administered every 12 weeks (HDq12), EYLEA HD administered every 16 weeks (HDq16), or EYLEA 2 mg administered every 8 weeks (2q8) in controlled clinical studies 0 0 0 Adverse drug reactions (ADRs) reported in <1% of participants treated with EYLEA HD were lacrimation increased, eyelid edema, hypersensitivity (includes adverse events of rash, urticaria, pruritus), and injection site hemorrhage. Table 2: Most Common Adverse Reactions (≥1%) in at least one group in the QUASAR study of the patients treated with EYLEA HD in the RVO study were foreign body sensation in eyes (includes foreign body sensation in eyes and sensation of foreign body), ocular hyperaemia (includes conjunctival hyperemia, conjunctival irritation, ocular hyperemia), retinal hemorrhage, retinal pigment epithelial detachment (includes detachment of retinal pigment epithelium), retinal pigment epithelial tear/epitheliopathy (includes retinal pigment epitheliopathy), and retinal tear.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of aflibercept. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Scleritis.

Pregnancy Risk Summary Adequate and well-controlled studies with EYLEA HD have not been conducted in pregnant women. Aflibercept produced adverse embryofetal effects in rabbits, including external, visceral, and skeletal malformations. A fetal No Observed Adverse Effect Level (NOAEL) was not identified.

At the lowest dose shown to produce adverse embryofetal effects, systemic exposure (based on AUC for free aflibercept) was approximately 0.9 -fold of the population pharmacokinetic estimated exposure in humans after an intravitreal dose of 8 mg (see Data ). Animal reproduction studies are not always predictive of human response, and it is not known whether EYLEA HD can cause fetal harm when administered to a pregnant woman. Based on the anti-VEGF mechanism of action for aflibercept, treatment with EYLEA HD may pose a risk to human embryofetal development.

EYLEA HD should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In two embryofetal development studies, aflibercept produced adverse embryofetal effects when administered every three days during organogenesis to pregnant rabbits at intravenous doses ≥3 mg per kg, or every six days during organogenesis at subcutaneous doses ≥0.1 mg per kg. Adverse embryofetal effects included increased incidences of postimplantation loss and fetal malformations, including anasarca, umbilical hernia, diaphragmatic hernia, gastroschisis, cleft palate, ectrodactyly, intestinal atresia, spina bifida, encephalomeningocele, heart and major vessel defects, and skeletal malformations (fused vertebrae, sternebrae, and ribs; supernumerary vertebral arches and ribs; and incomplete ossification).

The maternal No Observed Adverse Effect Level (NOAEL) in these studies was 3 mg per kg. Aflibercept produced fetal malformations at all doses assessed in rabbits and the fetal NOAEL was not identified. At the lowest dose shown to produce adverse embryofetal effects in rabbits (0.1 mg per kg), systemic exposure (AUC) of free aflibercept was approximately 0.9-fold of the population pharmacokinetic estimated systemic exposure (AUC) in humans after an intravitreal dose of 8 mg.

Pediatric Use The safety and effectiveness of EYLEA HD in pediatric patients have not been established.

Ocular or Periocular Infections EYLEA HD is contraindicated in patients with ocular or periocular infections.

Active Intraocular Inflammation EYLEA HD is contraindicated in patients with active intraocular inflammation.

Overdosing with increased injection volume may increase intraocular pressure. Therefore, in case of overdosage, intraocular pressure should be monitored and if deemed necessary by the treating physician, adequate treatment should be initiated.