Dosing & Uses
Dosage Forms & Strengths
injectable solution for intravitreal use
- 2mg/0.05mL (40mg/mL single-dose vial)
Macular Degeneration
Indicated for treatment of neovascular (wet) age-related macular degeneration (AMD)
2 mg (0.05 mL) by intravitreal injection q4Week for the first 3 injections, followed by 2 mg q8Week (~ every 2 months)
Some patients may need to be dosed as frequently as 2 mg q4Weeks (~ every 25 days, monthly), additional efficacy was not demonstrated in most patients when dosed q4Weeks compared to q8Weeks
Although not as effective as the recommended q8Week dosing regimen, after 1 year of effective therapy, may treat with 1 dose q12Weeks
Macular Edema
Indicated for treatment of macular edema following retinal vein occlusion (RVO) (branched or central retinal vein occlusion)
2 mg (0.05 mL) by intravitreal injection q4Week (~ every 25 days, monthly)
Diabetic Macular Edema (DME)
2 mg (0.05 mL) administered by intravitreal injection q4Week for the first 5 injections, followed by 2 mg q8Week
May be dosed as frequently as 2 mg q4Week; however, additional efficacy was not demonstrated when dosed q4Week compared to q8Week
Some patients may need q4Week (monthly) dosing after first 20 weeks (5 months)
Diabetic Retinopathy
2 mg (0.05 mL) administered by intravitreal injection q4Week for the first 5 injections, followed by 2 mg q8Week
May be dosed as frequently as 2 mg q4Week; however, additional efficacy was not demonstrated when dosed q4Week compared to q8Week
Some patients may need q4Week (monthly) dosing after first 20 weeks (5 months)
Safety and efficacy not established
Adverse Effects
>10%
Conjunctival hemorrhage (25%)
Eye pain (9-13%)
1-10%
Cataract (7%)
Vitreous floaters (6%)
Increased IOP (5%)
Conjunctival hyperemia (4%)
Corneal erosion (4%)
Retinal pigment epithelium detachment (3%)
Injection site pain (3%)
Foreign body sensation in eyes (3%)
Lacrimation increased (3%)
Blurred vision (2%)
Retinal pigment epithelium tear (2%)
Injection site hemorrhage (1%)
Eyelid edema (1%)
Corneal edema (1%)
Postmarketing Reports
Hypersensitivity
Endophthalmitis and retinal detachments
Increase in intraocular pressure
Thromboembolic events
Warnings
Contraindications
Hypersensitivity reactions that may manifest as rash, pruritus, urticaria, severe anaphylactic/anaphylactoid reactions, or severe intraocular inflammation
Ocular or periocular infection
Active intraocular inflammation
Cautions
Endophthalmitis and retinal detachments reported with intravitreal injections
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
Potential 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
Pregnancy & Lactation
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.
Pharmacology
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
Administration
Intravitreal Injection Preparation
Vial contains 0.278 mL of 40 mg/mL solution
Use provided 5-micron filter needle
Using aseptic technique, 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)
Gently tap syringe to remove bubbles
To eliminate all of the bubbles and to expel excess drug, slowly depress the plunger to the plunger tip aligns with the 0.05 mL measurement line
Each vial should only be used for a single eye
Storage
Refrigerate unopened vials at 2-8°C (36-46°F); do not freeze
Protect from light
Store in the original carton until time of use
Images
Patient Handout
Formulary
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Adding plans allows you to:
- View the formulary and any restrictions for each plan.
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- Compare formulary status to other drugs in the same class.
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