Macugen
Classes
Wet AMD Treatment Agents
Administration
For storage information, see the specific product within the How Supplied section.
Injectable AdministrationVisually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Do not use the syringe if the contents are discolored, visible particulates are observed, or if the plastic clip is missing or not attached to the syringe.
Intravitreous administration
Only for use by ophthalmologists trained in this specialized administration technique.
Adequate anesthesia (e.g., 2% lidocaine subconjunctival or 2—4% lidocaine topically) and a broad-spectrum microbicide should be given prior to the injection.
Use controlled aseptic conditions, which include the use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent).
When ready to administer the injection, remove the syringe from the plastic pouch and place on sterile field; to preserve sterility of the product, do not pull back on the plunger.
Remove syringe from plastic clip, twist off cap and attach included needle. If there are any bubbles in the syringe, gently tap the syringe with finger until bubbles rise to the top and slowly push in the plunger to eliminate all bubbles and expel the excess drug so that the top edge of the 3rd rib on the plunger stopper aligns with the preprinted black dosing line then inject the entire contents of the syringe.
Following the injection, monitor patient for elevation in intraocular pressure (IOP) and for endophthalmitis (see Adverse Reactions).
Adverse Reactions
ocular hypertension / Delayed / 10.0-40.0
keratitis / Delayed / 10.0-40.0
ocular hemorrhage / Delayed / 10.0-40.0
visual impairment / Early / 10.0-40.0
retinal edema / Delayed / 1.0-5.0
stroke / Early / 1.0-5.0
myocardial infarction / Delayed / 1.0-5.0
pleural effusion / Delayed / 1.0-5.0
hearing loss / Delayed / 1.0-5.0
endophthalmitis / Delayed / 0-1.0
retinal detachment / Delayed / 0-1.0
anaphylactic shock / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
blurred vision / Early / 10.0-40.0
cataracts / Delayed / 10.0-40.0
corneal edema / Early / 10.0-40.0
ocular inflammation / Early / 10.0-40.0
hypertension / Early / 10.0-40.0
photopsia / Delayed / 6.0-10.0
conjunctivitis / Delayed / 6.0-10.0
ocular infection / Delayed / 6.0-10.0
blepharitis / Early / 6.0-10.0
corneal deposits / Delayed / 1.0-5.0
chest pain (unspecified) / Early / 1.0-5.0
diabetes mellitus / Delayed / 1.0-5.0
urinary retention / Early / 1.0-5.0
contact dermatitis / Delayed / 1.0-5.0
ocular discharge / Delayed / 10.0-40.0
ocular irritation / Rapid / 10.0-40.0
ocular pain / Early / 10.0-40.0
nausea / Early / 6.0-10.0
diarrhea / Early / 6.0-10.0
dizziness / Early / 6.0-10.0
headache / Early / 6.0-10.0
infection / Delayed / 6.0-10.0
mydriasis / Early / 1.0-5.0
dyspepsia / Early / 1.0-5.0
vomiting / Early / 1.0-5.0
vertigo / Early / 1.0-5.0
Common Brand Names
Macugen
Dea Class
Rx
Description
Novel vascular endothelial growth factor (VEGF) antagonist selective for a very specific VEGF isoform (VEGF-165) involved in neovascular (wet) age-related macular degeneration (AMD); used as an intravitreal injection.
Dosage And Indications
0.3 mg once every 6 weeks by intravitreous injection into the eye to be treated. The safety and efficacy of therapy administered to both eyes concurrently have not been studied. Studies beyond a 2-year period of treatment have not been performed.
Safety and efficacy not established, but has been studied. 0.3 mg injected intravitreally per eye given every 6 weeks is suggested by clinical trials during the first 12 months, with fewer injections needed in subsequent years. The American Diabetes Association (ADA) recommends intravitreous anti-vascular endothelial growth factor (anti-VEGF) agents, such as pegaptinib, as first-line therapies for the management of central-involved diabetic macular edema (CIDME).
Limited data suggest 0.3 mg pegaptanib once every 6 weeks by intravitreous injection may be effective in slowing progression. The American Diabetes Association (ADA) recommends that intravitreous anti-vascular endothelial growth factor (anti-VEGF) agents, such as pegaptanib, may be considered for management of proliferative diabetic retinopathy (PDR), especially if high-risk characteristics are present. Intravitreous anti-VEGF agents can reduce the risk of vision loss in patients with PDR.
†Indicates off-label use
Dosing Considerations
Pegaptanib has not been studied in patients with hepatic impairment. No data are available.
Renal ImpairmentPatients with renal impairment do not require dosage adjustment when a 0.3 mg monocular intravitreal dose is used.
Drug Interactions
There are no drug interactions associated with Pegaptanib products.
How Supplied
Macugen Intravitreal Inj Sol: 0.09mL, 0.3mg
Maximum Dosage
0.3 mg single dose monocular. Doses up to 10 times the recommended dosage of 0.3 mg (i.e., 3 mg single dose monocular) have been studied clinically. No additional ADRs were noted, but decreased efficacy occurred with doses > 1 mg.
Elderly0.3 mg single dose monocular. Doses up to 10 times the recommended dosage of 0.3 mg (i.e., 3 mg single dose monocular) have been studied clinically. No additional ADRs were noted, but decreased efficacy occurred with doses > 1 mg.
AdolescentsUse not recommended.
ChildrenUse not recommended.
Mechanism Of Action
Mechanism of Action: Pegaptanib is a selective vascular endothelial growth factor (VEGF) antagonist. VEGF is a secreted protein that selectively binds and activates its receptors located primarily on the surface of vascular endothelial cells. VEGFs induce angiogenesis and increase vascular permeability and inflammation, all of which are thought to contribute to the progression of the neovascular (wet) form of age-related macular degeneration (AMD). Specific VEGFs have been implicated in blood retinal barrier breakdown and pathological ocular neovascularization. Pegaptanib adopts a 3-dimensional configuration that allows it to bind to extracellular VEGF. In vitro, pegaptanib very specifically binds to the major pathological VEGF isoform for wet AMD, extracellular VEGF165, thereby inhibiting VEGF165 binding to its VEGF receptors. The inhibition of VEGF164, the rodent counterpart of human VEGF165, was effective at suppressing pathological neovascularization.
Pharmacokinetics
Pegaptanib is administered via intravitreous route. Any systemically absorbed drug appears in the kidney. Animal data indicates that pegaptanib is eliminated as parent drug and metabolites primarily in the urine. In humans, after a 3 mg monocular dose, the average apparent plasma half-life of pegaptanib is 10 days.
Other Route(s)Intravitreous route
In animals, pegaptanib is slowly absorbed into the systemic circulation from the eye after intravitreous administration. The rate of absorption from the eye is the rate limiting step in the disposition of pegaptanib systemically in animals and is likely to be the rate limiting step in humans. In humans, a mean maximum plasma concentration of about 80 ng/ml occurs within 1—4 days after a 3 mg monocular dose (10 times the recommended prescribed dose, see Dosage). The mean area AUC is roughly 25 mg•hr/ml at this dose. In rabbits, the drug is distributed primarily in vitreous fluid, retina, and aqueous fluid.
Pregnancy And Lactation
Pegaptanib is classified as FDA pregnancy risk category B. There are no adequate and well-controlled studies in pregnant women. According to the manufacturer, pegaptanib should only be used in pregnant women if clearly needed.
According to the manufacturer, pegaptanib should be used with caution during breast-feeding. It is not known whether pegaptanib is excreted into breast milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.