Eylea Hd
(aflibercept)Dosage & Administration
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Eylea HD Prescribing Information
EYLEA HD is indicated for the treatment of:
Neovascular (Wet) Age-Related Macular Degeneration (nAMD)
Diabetic Macular Edema (DME)
Diabetic Retinopathy (DR)
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.
EYLEA HD is available packaged as follows:
- Vial Only
- Vial Kit with Injection Components (filter needle, syringe, injection needle)
[see How Supplied/Storage and Handling (16)].
Neovascular (Wet) Age-Related Macular Degeneration (nAMD)
The recommended dose for EYLEA HD is 8 mg (0.07 mL of 114.3 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days +/- 7 days) for the first three doses, followed by 8 mg (0.07 mL of 114.3 mg/mL solution) via intravitreal injection once every 8 to 16 weeks, +/- 1 week.
Diabetic Macular Edema (DME)
The recommended dose for EYLEA HD is 8 mg (0.07 mL of 114.3 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days +/- 7 days) for the first three doses, followed by 8 mg (0.07 mL of 114.3 mg/mL solution) via intravitreal injection once every 8 to 16 weeks, +/- 1 week.
Diabetic Retinopathy (DR)
The recommended dose for EYLEA HD is 8 mg (0.07 mL of 114.3 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days +/- 7 days) for the first three doses, followed by 8 mg (0.07 mL of 114.3 mg/mL solution) via intravitreal injection once every 8 to 12 weeks, +/- 1 week.
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: |
 |  |
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 [see Patient Counseling Information (17)].
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.
EYLEA HD is a clear to slightly opalescent, colorless to pale yellow solution available as:
- Injection: 8 mg (0.07 mL of a 114.3 mg/mL solution) in a single-dose glass vial
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 [see Clinical Pharmacology (12.1)], 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.
Lactation
Risk Summary
There is no information regarding the presence of aflibercept in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production/excretion. Because many drugs are excreted in human milk, and because the potential for absorption and harm to infant growth and development exists, EYLEA HD is not recommended during breastfeeding.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for EYLEA HD and any potential adverse effects on the breastfed child from EYLEA HD.
Females and Males of Reproductive Potential
Contraception
Females of reproductive potential are advised to use effective contraception prior to the initial dose, during treatment, and for at least 4 months after the last intravitreal injection of EYLEA HD.
Infertility
There are no data regarding the effects of EYLEA HD on human fertility. Aflibercept adversely affected female and male reproductive systems in cynomolgus monkeys when administered by intravenous injection at a dose 91 times higher (based on AUC of free aflibercept) than the corresponding systemic level estimated based on population pharmacokinetic analysis in humans following an intravitreal dose of 8 mg. A No Observed Adverse Effect Level (NOAEL) was not identified. These findings were reversible within 20 weeks after cessation of treatment [see Nonclinical Toxicology (13.1)].
Pediatric Use
The safety and effectiveness of EYLEA HD in pediatric patients have not been established.
Geriatric Use
In PULSAR, approximately 90% (604/673) of the patients in the HDq12 and HDq16 groups were 65 years of age or older and approximately 51% (343/673) were 75 years of age or older.
In PHOTON, approximately 44% (214/491) of the patients in the HDq12 and HDq16 groups were 65 years of age or older and approximately 10% (50/491) were 75 years of age or older.
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.
Hypersensitivity
EYLEA HD is contraindicated in patients with known hypersensitivity to aflibercept or any of the excipients in EYLEA HD. Hypersensitivity reactions may manifest as rash, pruritus, urticaria, severe anaphylactic/anaphylactoid reactions, or severe intraocular inflammation.
Endophthalmitis, Retinal Detachments, and Retinal Vasculitis with or without Occlusion
Intravitreal injections including those with aflibercept have been associated with endophthalmitis and retinal detachments [see Adverse Reactions (6.1)] and, more rarely, retinal vasculitis with or without occlusion [see Adverse Reactions (6.2)]. Proper aseptic injection technique must always be used when administering EYLEA HD. Patients and/or caregivers should be instructed to report any signs and/or symptoms suggestive of endophthalmitis, retinal detachment, or retinal vasculitis without delay and should be managed appropriately [see Dosage and Administration (2.6) and Patient Counseling Information (17)].
Increase in Intraocular Pressure
Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with EYLEA HD [see Adverse Reactions (6.1)]. Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with vascular endothelial growth factor (VEGF) inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately [see Dosage and Administration (2.6)].
Thromboembolic Events
There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including EYLEA HD. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The incidence of reported thromboembolic events in the wet AMD study (PULSAR) from baseline through week 48 was 0.4% (3 out of 673) in the combined group of patients treated with EYLEA HD compared with 1.5% (5 out of 336) in patients treated with EYLEA 2 mg. The incidence of reported thromboembolic events in the DME study (PHOTON) from baseline to week 48 was 3.1% (15 out of 491) in the combined group of patients treated with EYLEA HD compared with 3.6% (6 out of 167) in patients treated with EYLEA 2 mg.