PAVBLU aflibercept-ayyh 2 mg/.05mL Injection, Solution, 1 vial
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Vascular Endothelial Growth Factor Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Aflibercept injection is used to treat: wet age-related macular degeneration (AMD; an ongoing disease of the eye that causes loss of the ability to see straight ahead and may make it more difficult to read, drive, or perform other daily activities) diabetic macular edema (an eye disease caused by diabetes that can lead to vision loss) diabetic retinopathy (damage to the eyes caused by diabetes) macular edema after retinal vein occlusion (an eye disease caused by blockage of blood flow from the eye that leads to blurry vision and vision loss) retinopathy of prematurity (ROP; an eye disea...
Read the full MedlinePlus article ↗- Right now, injecting aflibercept directly into the eye is the only way the medication works for these conditions. It needs to reach the retina in high enough concentrations to bloc...
- Why do I need injections in my eye — is there any other way to take this?
- It depends on your specific condition. For wet AMD and diabetic conditions, you'll typically start with monthly injections for a few months, and then your doctor will likely space...
- How often will I need to come in for injections?
Patient education
Supplement & herbal interactions
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Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 6OZP39ZG8H
Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
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UNII C151H8M554
A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.
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UNII 7YIN7J07X4
A natural sugar derived from plants and microorganisms. It acts as a filler to give the medication bulk and stability, and helps preserve the active ingredient during storage and manufacturing.
3 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $22,098.42 | $1,104.92 / 0.05 ml |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · Q5147 | $803.255 / Q5147 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Pavblu 2 mg/.05mLthis 55513-0065-01 | Amgen, | 1 vial | — | — | FDA listed | — |
| Pavblu 2 mg/.05mL 55513-0056-01 | Amgen, | 1 syringe | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & biosimilar status
5 biosimilars and 1 interchangeable are FDA-licensed for this reference biologic — see the list below. (Biologics have no small-molecule generics.)
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Aug 23, 2036 |
Is there a biosimilar for PAVBLU 2 MG/0.05 ML VIAL?
Why do different websites show different biosimilar dates?
Can a biosimilar launch before the last patent expires?
What does “current Purple Book estimate” mean?
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Where does this data come from?
🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 55513-0065-01 You're viewing this | 1 VIAL in 1 CARTON (55513-065-01) / .05 mL in 1 VIAL | 2024-10-28 | Active |
| 55513-0065-96 | 1 VIAL in 1 CARTON (55513-065-96) / .05 mL in 1 VIAL | 2024-10-28 | Active |
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in NDC 55513-0065-01?
What is the difference between NDC 55513-0065-01 and NDC 55513-0065-96?
What NDC number is used to bill for this package of PAVBLU aflibercept-ayyh 2 mg/.05mL Injection, Solution?
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
Questions about this listing
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE PAVBLU is indicated for the treatment of: PAVBLU is a vascular endothelial growth factor (VEGF) inhibitor indicated for the treatment of patients with: Neovascular (Wet) Age-Related Macular Degeneration (AMD) ( 1.1 ) Macular Edema Following Retinal Vein Occlusion (RVO) ( 1.2 ) Diabetic Macular Edema (DME) ( 1.3 ) Diabetic Retinopathy (DR) ( 1.4 )
1.1 Neovascular (Wet) Age-Related Macular Degeneration (AMD)
1.2 Macular Edema Following Retinal Vein Occlusion (RVO)
1.3 Diabetic Macular Edema (DME)
1.4 Diabetic Retinopathy (DR)
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Neovascular (Wet) Age-Related Macular Degeneration (AMD): The recommended dose for PAVBLU is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 3 months, followed by 2 mg (0.05 mL of 40 mg/mL solution) via intravitreal injection once every 8 weeks (2 months). ( 2.2 ) Although PAVBLU may be dosed as frequently as 2 mg every 4 weeks (approximately every 25 days, monthly), additional efficacy was not demonstrated in most patients when aflibercept was dosed every 4 weeks compared to every 8 weeks.
Some patients may need every 4 week (monthly) dosing after the first 12 weeks (3 months). ( 2.2 ) Although not as effective as the recommended every 8 week dosing regimen, patients may also be treated with one dose every 12 weeks after one year of effective therapy. Patients should be assessed regularly.
( 2.2 ) Macular Edema Following Retinal Vein Occlusion (RVO): The recommended dose for PAVBLU is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection once every 4 weeks (approximately every 25 days, monthly). ( 2.3 ) Diabetic Macular Edema (DME) and Diabetic Retinopathy (DR): The recommended dose for PAVBLU is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 5 injections followed by 2 mg (0.05 mL of 40 mg/mL solution) via intravitreal injection once every 8 weeks (2 months).
( 2.4 , 2.5 ) Although PAVBLU may be dosed as frequently as 2 mg every 4 weeks (approximately every 25 days, monthly), additional efficacy was not demonstrated in most patients when aflibercept was dosed every 4 weeks compared to every 8 weeks. Some patients may need every 4 week (monthly) dosing after the first 20 weeks (5 months). ( 2.4 , 2.5 )
2.1Important Injection Instructions For ophthalmic intravitreal injection. PAVBLU must only be administered by a qualified physician. Prefilled Syringe: A 30-gauge × ½-inch sterile injection needle is needed but not provided.
Vial: 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 but not provided. PAVBLU is available packaged as follows: Prefilled Syringe Vial Only [see How Supplied/Storage and Handling (16) ] .
2.2Neovascular (Wet) Age-Related Macular Degeneration (AMD) The recommended dose for PAVBLU is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 12 weeks (3 months), followed by 2 mg (0.05 mL of 40 mg/mL solution) via intravitreal injection once every 8 weeks (2 months). Although PAVBLU may be dosed as frequently as 2 mg every 4 weeks (approximately every 25 days, monthly), additional efficacy was not demonstrated in most patients when aflibercept was dosed every 4 weeks compared to every 8 weeks [see Clinical Studies (14.1) ] .
Some patients may need every 4 week (monthly) dosing after the first 12 weeks (3 months). Although not as effective as the recommended every 8 week dosing regimen, patients may also be treated with one dose every 12 weeks after one year of effective therapy. Patients should be assessed regularly.
2.3Macular Edema Following Retinal Vein Occlusion (RVO) The recommended dose for PAVBLU is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection once every 4 weeks (approximately every 25 days, monthly) [see Clinical Studies (14.2) , (14.3) ] .
2.4Diabetic Macular Edema (DME) The recommended dose for PAVBLU is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 5 injections, followed by 2 mg (0.05 mL of 40 mg/mL solution) via intravitreal injection once every 8 weeks (2 months). Although PAVBLU may be dosed as frequently as 2 mg every 4 weeks (approximately every 25 days, monthl…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS PAVBLU is a clear to opalescent and colorless to slightly yellow solution available as: Injection: 2 mg (0.05 mL of 40 mg/mL solution) in a single-dose prefilled plastic syringe Injection: 2 mg (0.05 mL of 40 mg/mL solution) in a single-dose glass vial Injection: 2 mg (0.05 mL of 40 mg/mL) solution in a single-dose prefilled syringe ( 3 ) Injection: 2 mg (0.05 mL of 40 mg/mL) solution in a single-dose vial ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Ocular or periocular infections ( 4.1 ) Active intraocular inflammation ( 4.2 ) Hypersensitivity ( 4.3 )
4.1Ocular or Periocular Infections PAVBLU is contraindicated in patients with ocular or periocular infections.
4.2Active Intraocular Inflammation PAVBLU is contraindicated in patients with active intraocular inflammation.
4.3Hypersensitivity PAVBLU is contraindicated in patients with known hypersensitivity to aflibercept or any of the excipients in PAVBLU. Hypersensitivity reactions may manifest as rash, pruritus, urticaria, severe anaphylactic/anaphylactoid reactions, or severe intraocular inflammation.
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Endophthalmitis, retinal detachments, and retinal vasculitis with or without occlusion may occur following intravitreal injections. 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. ( 5.1 ) Increases in intraocular pressure have been seen within 60 minutes of an intravitreal injection.
( 5.2 ) There is a potential risk of arterial thromboembolic events following intravitreal use of VEGF inhibitors. ( 5.4 )
5.1Endophthalmitis, Retinal Detachments, and Retinal Vasculitis with or without Occlusion Intravitreal injections, including those with aflibercept products, 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 PAVBLU. 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 (2.8) and Patient Counseling Information (17) ] .
5.2Increase in Intraocular Pressure Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with aflibercept products [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 (2.8) ] .
5.4Thromboembolic Events There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including aflibercept products. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The incidence of reported thromboembolic events in wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined group of patients treated with aflibercept compared with 1.5% (9 out of 595) in patients treated with ranibizumab; through 96 weeks, the incidence was 3.3% (60 out of 1824) in the aflibercept group compared with 3.2% (19 out of 595) in the ranibizumab group.
The incidence in the DME studies from baseline to week 52 was 3.3% (19 out of 578) in the combined group of patients treated with aflibercept compared with 2.8% (8 out of 287) in the control group; from baseline to week 100, the incidence was 6.4% (37 out of 578) in the combined group of patients treated with aflibercept compared with 4.2% (12 out of 287) in the control group. There were no reported thromboembolic events in the patients treated with aflibercept in the first six months of the RVO studies.
🤒 Adverse Reactions ▾
6. ADVERSE REACTIONS The following potentially serious adverse reactions are described elsewhere in the labeling: Hypersensitivity [see Contraindications (4.3) ] Endophthalmitis, Retinal detachments, and Retinal Vasculitis with or without Occlusion [see Warnings and Precautions (5.1) ] Increase in intraocular pressure [see Warnings and Precautions (5.2) ] Thromboembolic events [see Warnings and Precautions (5.4) ] The most common adverse reactions (≥5%) reported in patients receiving aflibercept were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and intraocular pressure increased.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Inc. at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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 2980 adult patients treated with aflibercept constituted the safety population in eight phase 3 studies. Among those, 2379 patients were treated with the recommended dose of 2 mg.
Serious adverse reactions related to the injection procedure have occurred in <0.1% of intravitreal injections with aflibercept including endophthalmitis and retinal detachment. The most common adverse reactions (≥5%) reported in patients receiving aflibercept were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and intraocular pressure increased. Neovascular (Wet) Age-Related Macular Degeneration (AMD) The data described below reflect exposure to aflibercept in 1824 patients with wet AMD, including 1223 patients treated with the 2-mg dose, in 2 double-masked, controlled clinical studies (VIEW1 and VIEW2) for 24 months (with active control in year 1) [see Clinical Studies (14.1) ] .
Safety data observed in the aflibercept group in a 52-week, double-masked, Phase 2 study were consistent with these results. Table 1. Most Common Adverse Reactions (≥1%) in Wet AMD Studies Adverse Reactions Baseline to Week 52 Baseline to Week 96 Aflibercept (N=1824) Active Control (ranibizumab) (N=595) Aflibercept (N=1824) Control (ranibizumab) (N=595) Conjunctival hemorrhage 25% 28% 27% 30% Eye pain 9% 9% 10% 10% Cataract 7% 7% 13% 10% Vitreous detachment 6% 6% 8% 8% Vitreous floaters 6% 7% 8% 10% Intraocular pressure increased 5% 7% 7% 11% Ocular hyperemia 4% 8% 5% 10% Corneal epithelium defect 4% 5% 5% 6% Detachment of the retinal pigment epithelium 3% 3% 5% 5% Injection site pain 3% 3% 3% 4% Foreign body sensation in eyes 3% 4% 4% 4% Lacrimation increased 3% 1% 4% 2% Vision blurred 2% 2% 4% 3% Intraocular inflammation 2% 3% 3% 4% Retinal pigment epithelium tear 2% 1% 2% 2% Injection site hemorrhage 1% 2% 2% 2% Eyelid edema 1% 2% 2% 3% Corneal edema 1% 1% 1% 1% Retinal detachment <1% <1% 1% 1% Less common serious adverse reactions reported in <1% of the patients treated with aflibercept were hypersensitivity, retinal tear, and endophthalmitis.
Macular Edema Following Retinal Vein Occlusion (RVO) The data described below reflect 6 months exposure to aflibercept with a monthly 2 mg dose in 218 patients following central retinal vein occlusion (CRVO) in 2 clinical studies (COPERNICUS and GALILEO) and 91 patients following branch retinal vein occlusion (BRVO) in one clinical study (VIBRANT) [see Clinical Studies (14.2) , (14.3) ] . Table 2. Most Common Adverse Reactions (≥1%) in RVO Studies Adverse Reactions CRVO BRVO Aflibercept (N=218) Control (N=142) Aflibercept (N=91) Control (N=92) Eye pain 13% 5% 4% 5% Conjunctival hemorrhage 12% 11% 20% 4% Intraocular pressure increased 8% 6% 2% 0% Corneal epithelium defect 5% 4% 2% 0% Vitreous floaters 5% 1% 1% 0% Ocular hyperemia 5% 3% 2% 2% Foreign body sensation in eyes 3% 5% 3% 0% Vitreous detachment 3% 4% 2% 0% L…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary Adequate and well-controlled studies with aflibercept 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 exposures (based on AUC for free aflibercept) were approximately 6 times higher than AUC values observed in humans after a single intravitreal treatment at the recommended clinical dose (see Data ) . Animal reproduction studies are not always predictive of human response, and it is not known whether aflibercept 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 aflibercept may pose a risk to human embryofetal development.
PAVBLU 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 6 times higher than systemic exposure (AUC) observed in adult patients after a single intravitreal dose of 2 mg.
8.2Lactation Risk Summary There is no information regarding the presence of aflibercept products 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, PAVBLU is not recommended during breastfeeding. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for PAVBLU and any potential adverse effects on the breastfed child from PAVBLU.
8.3Females 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 3 months after the last intravitreal injection of PAVBLU. Infertility There are no data regarding the effects of aflibercept on human fertility. Aflibercept adversely affected female and male reproductive systems in cynomolgus monkeys when administered by intravenous injection at a dose approximately 1500 times higher than the systemic level observed in adult patients with an intravitreal dose of 2 mg.
A No Observed Adverse Effect Level (NOAEL) was not identified. These findings were reversible within 20 weeks after cessation of treatment [see Nonclinical T…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Adequate and well-controlled studies with aflibercept 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 exposures (based on AUC for free aflibercept) were approximately 6 times higher than AUC values observed in humans after a single intravitreal treatment at the recommended clinical dose (see Data ) . Animal reproduction studies are not always predictive of human response, and it is not known whether aflibercept 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 aflibercept may pose a risk to human embryofetal development.
PAVBLU 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 6 times higher than systemic exposure (AUC) observed in adult patients after a single intravitreal dose of 2 mg.
🧒 Pediatric Use ▾
8.4Pediatric Use A pediatric assessment for PAVBLU demonstrates that PAVBLU is safe and effective for pediatric patients in an indication for which EYLEA (aflibercept) is approved. However, PAVBLU is not approved for such indication due to marketing exclusivity for EYLEA (aflibercept).
🧓 Geriatric Use ▾
8.5Geriatric Use In the clinical studies, approximately 76% (2049/2701) of patients randomized to treatment with aflibercept were ≥65 years of age and approximately 46% (1250/2701) were ≥75 years of age. No significant differences in efficacy or safety were seen with increasing age in these studies.
🆘 Overdosage ▾
10 OVERDOSAGE 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF) are members of the VEGF family of angiogenic factors that can act as mitogenic, chemotactic, and vascular permeability factors for endothelial cells. VEGF acts via two receptor tyrosine kinases, VEGFR-1 and VEGFR-2, present on the surface of endothelial cells. PlGF binds only to VEGFR-1, which is also present on the surface of leucocytes.
Activation of these receptors by VEGF-A can result in neovascularization and vascular permeability. Aflibercept products act as a soluble decoy receptor that binds VEGF - A and PlGF, and thereby can inhibit the binding and activation of these cognate VEGF receptors.
12.2Pharmacodynamics Neovascular (Wet) Age-Related Macular Degeneration (AMD) In the clinical studies anatomic measures of disease activity improved similarly in all treatment groups from baseline to week 52. Anatomic data were not used to influence treatment decisions during the first year. Macular Edema Following Retinal Vein Occlusion (RVO) Reductions in mean retinal thickness were observed in COPERNICUS, GALILEO, and VIBRANT at week 24 compared to baseline.
Anatomic data were not used to influence treatment decisions [see Clinical Studies (14.2) , (14.3) ] . Diabetic Macular Edema (DME) Reductions in mean retinal thickness were observed in VIVID and VISTA at weeks 52 and 100 compared to baseline. Anatomic data were not used to influence aflibercept treatment decisions [see Clinical Studies (14.4) ] .
12.3Pharmacokinetics Aflibercept is administered intravitreally to exert local effects in the eye. In patients with wet AMD, RVO, or DME, following intravitreal administration of aflibercept, a fraction of the administered dose is expected to bind with endogenous VEGF in the eye to form an inactive aflibercept: VEGF complex. Once absorbed into the systemic circulation, aflibercept presents in the plasma as free aflibercept (unbound to VEGF) and a more predominant stable inactive form with circulating endogenous VEGF (i.e., aflibercept: VEGF complex).
Absorption/Distribution Following intravitreal administration of 2 mg per eye of aflibercept to patients with wet AMD, RVO, and DME, the mean C max of free aflibercept in the plasma was 0.02 mcg/mL (range: 0 to 0.054 mcg/mL), 0.05 mcg/mL (range: 0 to 0.081 mcg/mL), and 0.03 mcg/mL (range: 0 to 0.076 mcg/mL), respectively and was attained in 1 to 3 days. The free aflibercept plasma concentrations were undetectable two weeks post - dosing in all patients. Aflibercept did not accumulate in plasma when administered as repeated doses intravitreally every 4 weeks.
It is estimated that after intravitreal administration of 2 mg to patients, the mean maximum plasma concentration of free aflibercept is more than 100 fold lower than the concentration of aflibercept required to half - maximally bind systemic VEGF. The volume of distribution of free aflibercept following intravenous (I.V.) administration of aflibercept has been determined to be approximately 6 L. Metabolism/Elimination Aflibercept is a therapeutic protein and no drug metabolism studies have been conducted.
Aflibercept is expected to undergo elimination through both target - mediated disposition via binding to free endogenous VEGF and metabolism via proteolysis. The terminal elimination half - life (t 1/2 ) of free aflibercept in plasma was approximately 5 to 6 days after I.V. administration of doses of 2 to 4 mg/kg aflibercept. Specific Populations Renal Impairment Pharmacokinetic analysis of a subgroup of patients (n=492) in one wet AMD study, of which 43% had renal impairment (mild n=120, moderate n=74, and severe n=16), revealed no differences with respect to plasma concentrations of free aflibercept after intravitreal administration every 4 or 8 weeks.
Similar results were seen in patients in a RVO study and in patients in a DME study. No dose adjustment based on renal impairment status is needed…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF) are members of the VEGF family of angiogenic factors that can act as mitogenic, chemotactic, and vascular permeability factors for endothelial cells. VEGF acts via two receptor tyrosine kinases, VEGFR-1 and VEGFR-2, present on the surface of endothelial cells. PlGF binds only to VEGFR-1, which is also present on the surface of leucocytes.
Activation of these receptors by VEGF-A can result in neovascularization and vascular permeability. Aflibercept products act as a soluble decoy receptor that binds VEGF - A and PlGF, and thereby can inhibit the binding and activation of these cognate VEGF receptors.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Each prefilled syringe or vial is a clear to opalescent and colorless to slightly yellow solution and is for single eye use only. PAVBLU is supplied in the following presentations [see Dosage and Administration (2.1) , (2.6) , (2.7) and (2.8) ]. Discard unused portion.
NDC NUMBER CARTON TYPE CARTON CONTENTS 55513-056-01 Prefilled Syringe one blister pack containing one PAVBLU 2 mg (0.05 mL of a 40 mg/mL solution) sterile, single-dose prefilled plastic syringe one Prescribing Information 55513-065-01 Vial Only one PAVBLU 2 mg (0.05 mL of a 40 mg/mL solution) single-dose glass vial one Prescribing Information
16.2Storage and Handling Refrigerate PAVBLU at 2°C to 8ºC (36°F to 46ºF). PAVBLU may be kept at room temperature (up to 30° C (86° F)) for a single-period of 3 days. Do not freeze. Do not use beyond the date stamped on the carton and container label. Store in the original carton until time of use to protect from light. Do not open sealed blister tray until time of use.
📦 Storage and Handling ▾
16.2Storage and Handling Refrigerate PAVBLU at 2°C to 8ºC (36°F to 46ºF). PAVBLU may be kept at room temperature (up to 30° C (86° F)) for a single-period of 3 days. Do not freeze. Do not use beyond the date stamped on the carton and container label. Store in the original carton until time of use to protect from light. Do not open sealed blister tray until time of use.
📋 Description ▾
11 DESCRIPTION Aflibercept-ayyh is a recombinant fusion protein consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1 formulated as an iso-osmotic solution for intravitreal administration. Aflibercept-ayyh is a dimeric glycoprotein with a protein molecular weight of 97 kilodaltons (kDa) and contains glycosylation, constituting an additional 15% of the total molecular mass, resulting in a total molecular weight of 115 kDa. Aflibercept-ayyh is produced in recombinant Chinese hamster ovary (CHO) cells.
PAVBLU (aflibercept-ayyh) injection is a sterile, clear to opalescent and colorless to slightly yellow solution. PAVBLU does not contain anti-microbial preservative and is supplied as an aqueous solution for intravitreal injection in a single-dose prefilled plastic syringe or a single-dose glass vial designed to deliver 0.05 mL (50 microliters) of solution containing 2 mg of aflibercept-ayyh in polysorbate 80 (0.005 mg), sucrose (2.5 mg), trehalose (1.58 mg) and water for injection with a pH of 6.2.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION In the days following PAVBLU 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) ] . Patients may experience temporary visual disturbances after an intravitreal injection with PAVBLU and the associated eye examinations [see Adverse Reactions (6) ] .
Advise patients not to drive or use machinery until visual function has recovered sufficiently.