Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

EYLEA HD (BLA-761355)

(AFLIBERCEPT)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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04/02/2026 (SUPPL-5)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Thromboembolic Events

Additions and/or revisions underlined:

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 96 was 1.8% (12 out of 673) in the combined group of patients treated with EYLEA HD compared with 3.3% (11 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 96 was 6.7% (33 out of 491) in the combined group of patients treated with EYLEA HD compared with 7.2% (12 out of 167) in patients treated with EYLEA 2 mg.

…

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

Extensive changes to Table 1; please refer to label for complete information

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 (PULSAR and PHOTON), each for 96 weeks [see Clinical Studies (14.1, 14.2

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11/19/2025 (SUPPL-10)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Thromboembolic Events

Additions and/or revisions underlined:

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. The incidence of reported thromboembolic events in the RVO study (QUASAR) from baseline to week 36 was 0.5% (3 out of 591) in the combined group of patients treated with EYLEA HD compared with 1.7% (5 out of 301) in patients treated with EYLEA 2 mg.

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

. . .

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 greater than or equal to 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)

. . .

Macular Edema Following Retinal Vein Occlusion (RVO)

The data described below reflects 36 weeks exposure to EYLEA HD administered every 8 weeks (HDq8) after 3 or 5 initial monthly doses (HDq4), or EYLEA 2 mg administered every 4 weeks (2q4) in a controlled clinical study (QUASAR). [see Clinical Studies (14.4)].

Table 2: Most Common Adverse Reactions (greater than or equal to 1%) in at least one group in the QUASAR study

Newly added table; please refer to label for complete information

Adverse reactions reported in <1% 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.

8 Use in Specific Populations

8.5 Geriatric Use

Additions and/or revisions underlined:

In the clinical studies, approximately 66% (1156/1755) of the patients in the HD groups were 65 years of age or older and approximately 31% (543/1755) of the patients were 75 years of age or older.

No overall differences in safety or effectiveness of EYLEA HD have been observed.

10/10/2024 (SUPPL-6)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

Additions and/or revisions underlined:

…

Scleritis.

12/14/2023 (SUPPL-1)

Approved Drug Label (PDF)

5 Warnings and Precautions

Additions and/or revisions underlined:

5.1 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)].

6 Adverse Reactions

Additions and/or revisions underlined:

…

Endophthalmitis, Retinal Detachments, and Retinal Vasculitis with or without Occlusion [see Warnings and Precautions (5.1)]

…

6.2 Postmarketing Experience

New subsection added:

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.

Eye disorders: retinal vasculitis and occlusive retinal vasculitis related to intravitreal injection with aflibercept (reported at a rate of 0.6 and 0.2 per 1 million injections, respectively, based on postmarketing experience from November 2011 until November 2023).

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

In the days following EYLEA HD administration, patients are at risk of developing endophthalmitis, retinal detachment, or retinal vasculitis with or without occlusion. If the eye becomes red, sensitive to light, painful, or develops a change in vision, advise patients and/or caregivers to seek immediate care from an ophthalmologist [see Warnings and Precautions (5.1)].

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