CLASSES
Wet AMD Treatment Agents
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.
COMMON BRAND NAMES
Macugen
HOW SUPPLIED
Macugen Intravitreal Inj Sol: 0.09mL, 0.3mg
DOSAGE & INDICATIONS
For the treatment of neovascular (wet) age-related macular degeneration (AMD).
Intravitreous injection dosage
Adults and Geriatric
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.
For the treatment of diabetic macular edema†.
Intravitreous injection dosage
Adults
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).
For the treatment of proliferative diabetic retinopathy†.
Intravitreous injection dosage
Adults
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
MAXIMUM DOSAGE
Adults
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.
Elderly
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.
Adolescents
Use not recommended.
Children
Use not recommended.
DOSING CONSIDERATIONS
Hepatic Impairment
Pegaptanib has not been studied in patients with hepatic impairment. No data are available.
Renal Impairment
Patients with renal impairment do not require dosage adjustment when a 0.3 mg monocular intravitreal dose is used.
ADMINISTRATION
For storage information, see the specific product within the How Supplied section.
Injectable Administration
Visually 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.
Other Administration Route(s)
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).
STORAGE
Macugen:
- Do not freeze
- Refrigerate (between 36 and 46 degrees F)
CONTRAINDICATIONS / PRECAUTIONS
General Information
Pegaptanib is contraindicated in patients with hypersensitivity to pegaptanib or any of the components of the product.
Vascular Endothelial Growth Factor (VEGF) has been shown to be an important component in the development of collateral vessels in ischemic heart disease. Inhibition of VEGF in the systemic circulation could present a theoretical increased risk of symptomatic cardiovascular disease in the target patient population of elderly patients. Additional monitoring may be needed.
Ocular infection
Pegaptanib, as with other intravitreal injections, is contraindicated in patients with ocular infection or periocular infection. A broad-spectrum ocular 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).
Glaucoma, ocular surgery
Intravitreous injections have been associated with endophthalmitis. Use proper aseptic injection technique. Any ocular surgery that disrupts the integrity of the globe can lead to exogenous endophthalmitis (e.g., cataract, glaucoma, or retinal surgeries, radial keratotomy). Patients who have received or will receive pegaptanib and have recently undergone or will undergo an ocular surgical procedure should be monitored for signs and symptoms of endophthalmitis (pain, redness, lid swelling, decreased visual acuity) and be counseled on when to seek medical attention. Monitor patients during the week following injection to permit early treatment should an infection occur.
Increased intraocular pressure
Increased intraocular pressure (IOP) has been seen within 30 minutes of pegaptanib injection. Therefore, monitor IOP and the perfusion of the optic nerve head. Instruct patients to seek immediate care with their ophthalmologist if the eye becomes red, sensitive to light, painful or develops a change in vision. Use with caution in patients with a history of glaucoma.
Cataracts
Cataracts or other media opacities may interfere with visual acuity, assessment of toxicity, or fundus photography. Use caution when administering pegaptanib to patients with these ocular abnormalities.
Pregnancy
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.
Breast-feeding
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.
Children
Safe and effective use of pegaptanib is not established in children.
ADVERSE REACTIONS
Severe
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
Moderate
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
Mild
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
DRUG INTERACTIONS
There are no drug interactions associated with Pegaptanib products.
PREGNANCY AND LACTATION
Pregnancy
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.
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.