Agafi Injection

Aflibercept Intravitreal Injection

2 mg/0.05 ml

Incepta Pharmaceuticals Ltd.

Pack size	2 mg
Retail Price	32000.00

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Indications

Neovascular (wet) age-related macular degeneration (AMD) Visual impairment due to macular oedema secondary to retinal vein occlusion (branch RVO or central RVO) Visual impairment due to diabetic macular oedema (DME) Visual impairment due to myopic choroidal neovascularisation (myopic CNV)

Adult Dose

Neovascular (Wet) Age-Related Macular Degeneration (AMD)- The recommended dose for Aflibercept is 2 mg (0.05 mL) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 3 months, followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months). Although Aflibercept 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 weeks (monthly) dosing after the first 12 weeks (3 months). Although not as effective as the recommended every 8 weeks dosing regimen, patients may also be treated with one dose every 12 weeks after one year of effective therapy. Patients should be assessed regularly.   Macular Edema Following Retinal Vein Occlusion (RVO)- The recommended dose for Aflibercept is 2 mg (0.05 mL) administered by intravitreal injection once every 4 weeks (approximately every 25 days, monthly)   Diabetic Macular Edema (DME) and Diabetic Retinopathy (DR)- The recommended dose for Aflibercept is 2 mg (0.05 mL) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 5 injections followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months). Although Aflibercept 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 weeks (monthly) dosing after the first 20 weeks (5 months).     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     Intravitreal Injection Preparation 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)

Administration

Intravitreal Injection Preparation 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)   Intravitreal administration 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

Contra Indications

Hypersensitivity reactions Ocular or periocular infection Active intraocular inflammation

Precautions

Endophthalmitis, retinal detachments, and retinal vasculitis Endophthalmitis, retinal detachments, and more rarely retinal vasculitis with or without occlusion reported with intravitreal injections Proper aseptic injection technique must always be used when administering by ophthalmologist specializing in intravitreal injections Instruct patients and/or caregivers to report any signs and/or symptoms suggestive of endophthalmitis, retinal detachment, or retinal vasculitis without delay and should be managed appropriately   Increased intraocular pressure Acute increases in intraocular pressure (IOP) have been observed within 60 minutes of intravitreal injection Sustained increases also reported after repeat dosing Monitor and manage IOP and perfusion of optic nerve head   Thromboembolic events Risk of arterial thromboembolic events (eg, nonfatal stroke, nonfatal myocardial infarction, or vascular death) reported following intravitreal use of VEGF inhibitors Incidence over 1 yr varies depending on the study   Extended monitoring and additional treatment in retinopathy of prematurity (ROP) Reactivation of abnormal angiogenesis and tortuosity may occur following treatment Monitor infants closely after injection until retinal vascularization has completed or until examiner is assured that reactivation of ROP will not occur In infants with ROP, treatment may necessitate extended periods of ROP monitoring and additional injections and/or laser treatments may be necessary

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

Adverse Effects

>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%) Intraocular pressure increased (5-7%) 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%)

Mechanism 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 acts as a soluble decoy receptor that binds VEGF-A and PlGF, and thereby can inhibit the binding and activation of these cognate VEGF receptors

Note

Agafi 2 mg/0.05 ml Injection manufactured by Incepta Pharmaceuticals Ltd.. Its generic name is Aflibercept Intravitreal Injection.