aflibercept intravitreal (Rx)

>10%

Wet AMD, RVO, or DME

• Conjunctival hemorrhage (12-31%)
• Eye pain (9-13%)
• Cataract (1-13%)

1-10%

Wet AMD, RVO, or DME

• Increased IOP (5-9%)
• Vitreous detachment (1-8%)
• Vitreous floaters (6-8%)
• Corneal epithelium defect (2-7%)
• Retinal pigment epithelium detachment (3-5%)
• Ocular hyperemia (42-5%)
• Foreign body sensation in eyes (3-4%)
• Lacrimation increased (3-4%)
• Blurred vision (1-4%)
• Intraocular inflammation (1-3%)
• Injection site pain (1-3%)
• Retinal pigment epithelium tear (2%)
• Injection site hemorrhage (1-2%)
• Eyelid edema (1-2%)
• Corneal edema (1%)

ROP

• Conjunctival hemorrhage (5-9%)
• Retinal detachment (5-6%)
• Increased IOP (4%)
• Eyelid edema (3%)
• Corneal epithelium defect (1%)
• Corneal edema (1%)
• Lenticular opacities (1%)

Contraindications

Hypersensitivity reactions

Ocular or periocular infection

Active intraocular inflammation

Cautions

Endophthalmitis and retinal detachments reported with intravitreal injections; instruct patients and/or caregivers to report any signs and/or symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately

Acute increases in intraocular pressure (IOP) observed within 60 minutes of intravitreal injection; sustained increases also reported after repeat dosing; monitor and manage IOP and perfusion of optic nerve head

Risk of arterial thromboembolic events (eg, nonfatal stroke, nonfatal myocardial infarction, or vascular death) following intravitreal use of VEGF inhibitors (incidence over 1 yr varies depending on the study ranging from 1.5-6.4%); no thromboembolic events reported within the first 6 months of RVO studies

Hypersensitivity reactions may present as severe intraocular inflammation

Females of reproductive potential should use effective contraception prior to initial dose, during treatment, and for at least 3 months after last intravitreal injection

Extended monitoring and additional treatment in ROP

• Reactivation of abnormal angiogenesis and tortuosity may occur following treatment
• Monitor infants closely after injection until retinal vascularization has completed or until the examiner is assured that reactivation of ROP will not occur
• In infants with ROP, treatment necessitates extended periods of ROP monitoring and additional injections and/or laser treatments may be necessary

Pregnancy

Adequate and well-controlled studies have not been conducted in pregnant women; aflibercept produced adverse embryofetal effects in rabbits, including external, visceral, and skeletal malformations

Animal reproduction studies not always predictive of human response; not known whether product can cause fetal harm when administered to pregnant woman; based on anti-VEGF mechanism of action for aflibercept, treatment may pose a risk to human embryofetal development

Contraception

• Females of reproductive potential are advised to use effective contraception prior to initial dose, during treatment, and for at least 3 months after last intravitreal injection

Infertility

• There are no data regarding effects 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 systemic level observed humans with an intravitreal dose of 2 mg; a No Observed Adverse Effect Level (NOAEL) was not identified; aflibercept produced fetal malformations at all doses assessed in rabbits and the fetal NOAEL was <0.1 mg/kg; findings were reversible within 20 weeks after cessation of treatment

Lactation

There is no information regarding presence of aflibercept in human milk, effects on breastfed infant, or on milk production/excretion; because many drugs are excreted in human milk, and potential for absorption and harm to infant growth and development exists, therapy is not recommended during breastfeeding

Developmental and health benefits of breastfeeding should be considered along with mother's clinical need for therapy and potential adverse effects on breastfed child

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Binds and prevents activation of vascular endothelial growth factors (VEGF-A) and placental growth factor (PIGF)

Activation of VEGF-A and PIGF can result in neovascularization and vascular permeability

Absorption

Peak plasma time: 1-3 days

Peak plasma concentration: 0.02 mcg/mL

Distribution

Vd: 6 L

Elimination

Half-life: 5-6 days

Intravitreal injection preparation

Vial

• Vial contains 2 mg/0.05 mL solution

• Prepare using following medical devices

  • Use provided 5-micron filter needle (19-gauge x 1.5-inch)
  • 1-mL sterile Luer lock syringe with marking to measure 0.05 mL for adults or 0.01 mL for preterm infants with ROP
  • Sterile injection needle (30-gauge x 0.5-inch)

• Preparation

  • Remove 19-gauge x 1.5-inch, 5-micron, filter needle and 1-mL syringe from their packaging; attach filter needle to syringe by twisting it onto the Luer lock syringe tip
  • Withdraw all contents of vial (keep vial in upright position, slightly inclined to ease complete withdrawal)
  • Remove and discard filter needle
  • Replace needle with 30-gauge x 0.5-inch needle (provided in kit) onto Luer lock syringe tip
  • Gently tap syringe to remove bubbles; expel air and set dose (0.05 mL for adults or 0.01 mL for infants)
  • Each vial should only be used for a single eye

Prefilled syringe

• Do not use prefilled syringe for treatment of ROP
• Inspect visually before administration; do not use if particulates, cloudiness, or discoloration are visible, or if package is open or damaged, or syringe cap is detached from the Luer lock
• Twist off (do not snap off) the syringe cap
• Attach 30-gauge x 0.5-inch needle (provided in kit)
• Gently tap syringe to remove bubbles; expel air and set dose
• Each prefilled syringe should only be used for a single eye

Intravitreal administration

See prescribing information for detailed intravitreal injection procedure

Intravitreal injection should be done under aseptic conditions, which include surgical hand disinfection and the use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent).

Prior to injection, adequate anesthesia and a topical broad–spectrum microbicide

Monitor patient immediately following administration 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

If contralateral eye requires treatment, use a new sterile prefilled syringe or vial and change the sterile field, syringe, gloves, drapes, eyelid speculum, filter, and injection needles before administration to the other eye

After injection, discard any unused product

Storage

Refrigerate unopened vials or prefilled syringes at 2-8°C (36-46°F); do not freeze

Protect from light

Store in the original carton until time of use