PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Wet AMD Treatment Products

    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.

    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

    The American Diabetes Association (ADA) recommends intravitreous anti-vascular endothelial growth factor (anti-VEGF) agents, such as pegaptanib, as first-line therapies for the management of eyes with central-involved diabetic macular edema (CIDME). Most patients require near-monthly intravitreous injections during the first 12 months, with fewer injections needed in subsequent years. Limited data suggest 0.3 mg of pegaptanib once every 6 weeks by intravitreous injection may be effective. In a double-blind, dose-ranging study, 172 patients with diabetic macular edema involving the center of the macula and a best-corrected visual acuity (BCVA) between 20/50 and 20/320 were randomized to receive intravitreous injections of 0.3 mg, 1 mg, 3 mg, or placebo once every 6 weeks for a minimum of 3 injections. Additional injections were administered every 6 weeks if indicated up to a maximum of 6 injections by week 30. An average of 5 injections was administered to patients in the pegaptanib group vs. 4.5 injections to placebo-treated patients. Laser photocoagulation was allowed if needed after week 13. At week 36, a larger proportion of patients in the pegaptanib 0.3 mg, 1 mg, and 3 mg subgroups experienced a change in mean visual acuity (VA) from baseline vs. placebo (mean change in VA in letters: +4.7, +4.7, +1.1, and -0.4, respectively), a reduced risk of loss of visual acuity (percentage of patients avoiding loss of 3 or more lines VA: 93%, 98%, 93%, and 90%, respectively), and a change in mean retinal thickness (-68 microns, -22.7 microns, -5.3 microns, and +3.7 microns, respectively). In addition, fewer pegaptanib-treated patients required focal photocoagulation compared with placebo (25%, 30%, 40%, and 48%, respectively). Notably, the greatest effect on outcomes (i.e., mean visual acuity, decreased retinal thickness, and need for focal photocoagulation) was seen with the pegaptanib 0.3 mg dose.

    For the treatment of proliferative diabetic retinopathy†.
    Intravitreous injection dosage
    Adults

    According to the American Diabetes Association (ADA), 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. Limited data suggest 0.3 mg pegaptanib once every 6 weeks by intravitreous injection may be effective in slowing progression. In a prospective, open-label study, 20 patients with active PDR were randomized to receive treatment in 1 eye with either intravitreous injections of pegaptanib (IVP) 0.3 mg every 6 weeks for 30 weeks or with panretinal laser photocoagulation (PRP). Two subjects from each arm discontinued because of patient noncompliance prior to study conclusion. At week 36, treatment with IVP resulted in statistically significant improvement in retinal neovascularization (NV) and foveal thickness compared to PRP (p = 0.021 and p = 0.025, respectively), but no statistically significant difference in visual outcome (p = 0.22). All IVP-treated eyes showed complete regression of NV by week 12, which was maintained through week 36. In contrast, among the PRP-treated eyes at week 36, 2 showed complete regression of NV, 2 demonstrated partial regression, and 4 remained active. In the IVP-treated eyes, there was a mean change from baseline in best-corrected visual acuity (BCVA) of +5.8 letters compared to -6 letters in PRP-treated eyes, although this difference was not statistically significant (p = 0.22). In the Macugen Diabetic Retinopathy Study Group, 172 patients with diabetic macular edema involving the center of the macula and a BCVA between 20/50 and 20/320 were randomized to receive IVP 0.3 mg, 1 mg, 3 mg, or placebo once every 6 weeks for a minimum of 3 injections. Additional injections were administered every 6 weeks if indicated up to a maximum of 6 injections by week 30. A subgroup analysis of 16 patients with neovascularization showed that regression of neovascularization occurred in 8 of 13 (62%) IVP-treated eyes; progression of neovascularization was noted in 3 eyes 22 weeks after cessation of therapy. There was no regression of neovascularization in sham (n = 3) or fellow non-study eyes (n = 4). In another uncontrolled study conducted in 14 patients (15 eyes) with recurrent or nonclearing vitreous hemorrhage who had received maximal PRP, an initial 0.3 mg dose of pegaptanib was injected intravitreally into the affected eye followed by additional PRP if possible. No patient had further VH for at least 4 weeks post-injection; improvement in visual acuity was noted in 12 eyes and maintenance of preexisting acuity in 3. Five patients did not need to undergo vitrectomy during the study period; 3 had no recurrence of VH and 2 patients requested further IVP rather than surgery. Four eyes experienced a prolonged period (9 to 22 months) without recurrence of VH before requiring surgery. Vitrectomy was ultimately performed in 10 patients because of recurrent or no-clearing VH (n = 5) or tractional retinal detachment threatening the macula (n = 5).

    †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.