Generic Name: Pegaptanib Sodium
Class: EENT Drugs, Miscellaneous
VA Class: OP900
Molecular Formula: C294H342F13N107Na28O188P28[C2H4O]n where n is approximately 900.
CAS Number: CAS-222716-86-1
Introduction
Polyethylene glycol (PEG)-conjugated, modified synthetic RNA oligonucleotide and aptamer; selective vascular endothelial growth factor (VEGF) antagonist.1 3 13 14 15 16
Uses for Macugen
Neovascular Age-related Macular Degeneration
Treatment of neovascular (wet) age-related macular degeneration.1 2 6 9 13 14 15 16 17
Macugen Dosage and Administration
General
Manufacturer’s prescribing information should be consulted for details on assembly and proper use of the syringes.1
Administration
Ophthalmic Administration
Evaluate patient's medical history for hypersensitivity reactions to prior intravitreal administration of the drug.1 19 (See Contraindications and also see Hypersensitivity Reactions under Cautions.)
Administer by intravitreal injection only into a single affected eye.1 2 9 14 16 Safety and efficacy of treating both eyes concurrently not determined.1 14
Pegaptanib injection does not need to reach room temperature prior to administration.14
Inject following adequate anesthesia and administration of broad-spectrum anti-infective agents.1 2 4 9 14 15 18
Inject under controlled aseptic conditions (including use of sterile gloves, sterile drape, a sterile eyelid speculum [or equivalent]).1 2 4 9 14 15 18
Monitor patients for elevation of intraocular pressure (IOP) and for development of endophthalmitis following intravitreal injection.1 18
Monitoring for IOP may include evaluation of optic nerve head perfusion immediately after the injection, tonometry within 30 minutes following the injection, and biomicroscopy between 2 and 7 days following injection.1 2 18
Dosage
Available as pegaptanib sodium; dosage expressed in terms of the free acid of the oligonucleotide without polyethylene glycol.1 13 14
Adults
Neovascular Age-related Macular Degeneration
Ophthalmic Administration
Intravitreal injection: 0.3 mg into the affected eye every 6 weeks.1 2
Doses exceeding 0.3 mg do not appear to provide additional therapeutic benefit;1 2 14 15 doses exceeding 1 mg have been associated with decreased efficacy.1
Safety and efficacy of pegaptanib beyond 2 years of therapy have not been established.1
Special Populations
Renal Impairment
No dosage adjustment required.1
Cautions for Macugen
Contraindications
Ocular or periocular infections.1 18
Known hypersensitivity to pegaptanib or any ingredient in the formulation.1 19
Warnings/Precautions
Warnings
Endophthalmitis and Other Serious Ocular Effects
Intravitreal injections of pegaptanib associated with endophthalmitis.1 2 13 15 18
Monitor patients closely for signs of endophthalmitis (e.g., redness, sensitivity to light, pain, changes in vision) during the week following injection to permit early treatment.1 2 18
The most common isolate cultured in patients with endophthalmitis after receiving pegaptanib was coagulase-negative Staphylococcus epidermiditis.2
Proper aseptic injection technique should be used to decrease potential for infection.1 2 15 18 (See Ophthalmic Administration under Dosage and Administration.)
Risk of retinal detachment and iatrogenic traumatic cataract.1
Increased IOP
Risk of increased IOP within 30 minutes of intravitreal injection.1
Monitor and manage appropriately IOP and optic nerve head perfusion.1 19 (See Ophthalmic Administration under Dosage and Administration.)
Sensitivity Reactions
Hypersensitivity Reactions
Rare cases of anaphylaxis/anaphylactoid reactions, including angioedema, reported following intravitreal administration procedure with pegaptanib.1 19
Evaluate patient's medical history for hypersensitivity reactions prior to intravitreal administration of the drug.1 19
Specific Populations
Pregnancy
Category B.1
Lactation
Not known whether pegaptanib is distributed into milk.1 Caution advised if intravitreal injection is used.1
Pediatric Use
Safety and efficacy not established in children.1 14
Adult Use
Safety and efficacy not established in adults <50 years of age.14
Geriatric Use
No substantial differences in efficacy or systemic exposure relative to younger adults.1
Hepatic Impairment
Pharmacokinetics not studied in patients with hepatic impairment.1
Renal Impairment
No dosage adjustment required in patients with renal impairment.1 Not evaluated in patients undergoing hemodialysis.1
Common Adverse Effects
Anterior chamber inflammation,1 2 blurred vision,1 cataract,1 conjunctival hemorrhage,1 corneal edema,1 2 eye discharge,1 2 eye irritation,1 eye pain,1 2 hypertension,1 increased IOP,1 ocular discomfort,1 punctuate keratitis,1 2 vitreous floaters or opacities,1 2 reduced visual acuity,1 visual disturbance.1
Interactions for Macugen
No formal drug interaction studies to date.1
Metabolized by nucleases; generally not affected by CYP isoenzymes.1
Photodynamic Therapy with Verteporfin
No apparent difference in the pharmacokinetic profile of pegaptanib involving patients treated with pegaptanib alone or in combination with photodynamic therapy and verteporfin.1 9 14 No adverse effects attributed directly to concomitant use of pegaptanib with verteporfin.2 4
Macugen Pharmacokinetics
Absorption
Bioavailability
Slowly absorbed into systemic circulation from the eye with mean peak plasma concentration usually attained within 1–4 days.1
Distribution
Extent
Distributed into vitreous fluid, retina, aqueous fluid, and kidneys.1
Crosses the placenta in mice; not known whether crosses the placenta in humans.1
Not known whether distributed into human milk.1
Elimination
Metabolism
Appears to be metabolized by endo- and exonucleases.1
Elimination Route
In animals, excreted principally in urine as unchanged drug and metabolites.1
Half-life
Average: 10 days.1
Special Populations
No dosage adjustment required in those with renal impairment.1
Stability
Storage
Ophthalmic
2–8°C; do not freeze or shake vigorously.1
May be kept at room temperature for up to 8 hours.14
ActionsActions
Binds to extracellular VEGF165, the major VEGF isoform involved in the pathogenesis of the neovascular (wet) form of age-related macular degeneration and inhibits VEGF165 from binding to VEGF receptors.1 2 3 7 8 9 10 11 12 13 14 15 16
VEGF induces angiogenesis and increases vascular permeability and inflammation, all of which appear to play a role in the pathogenesis of neovascular age-related macular degeneration, a leading cause of blindness in adults >55 years of age in developed countries.1 2 3 5 6 7 8 9 10 11 12 13 15 The neovascular form of the disease represents about 10% of overall disease prevalence, but it is responsible for 90% of severe vision loss.2
Advice to Patients
Necessity of advising patients about the risk of developing endophthalmitis.1 Importance of informing their ophthalmologist immediately if changes in vision occur or the treated eye becomes red, sensitive to light, or painful.1
Patients should be instructed to immediately report any symptoms suggestive of endophthalmitis.1 2 18 (See Endophthalmitis and Other Serious Ocular Effects under Cautions.)
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Ophthalmic | Injection, for intravitreal use only | 0.3 mg/0.09 mL (of the free acid of the oligonucleotide without polyethylene glycol) | Macugen (preservative-free; available as single-dose prefilled syringe with needle) | Eyetech (also promoted by Pfizer) |
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions June 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
References
1. Eyetech. Macugen (pegaptanib sodium) injection prescribing information. New York, NY; 2006 Apr.
2. Gragoudas ES, Adamis AP, Cunningham ET Jr et al. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med. 2004; 351:2805-16. [IDIS 525948] [PubMed 15625332]
3. Vinores SA. Technology evaluation: pegaptanib, Eyetech/Pfizer. Curr Opin Mol Ther. 2003; 5:673-9. [PubMed 14755895]
4. Supplementary appendix to: Gragoudas ES, Adamis AP, Cunningham ET Jr et al. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med. 2004; 351:2805-16. From the New England Journal of Medicine website (). Accessed 2005 Mar 21. [IDIS 525948] [PubMed 15625332]
5. Congdon N, O'Colmain B, Klaver CC et al. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol. 2004 Apr; 122:477-85.
6. Ferris FL 3rd. A new treatment for ocular neovascularization. N Engl J Med. 2004; 351:2863-5. [IDIS 525951] [PubMed 15625339]
7. Nimjee SM, Rusconi CP, Sullenger BA. Aptamers: an emerging class of therapeutics. Annu Rev Med. 2005; 56:555-83. [PubMed 15660527]
8. The Eyetech Study Group. Preclinical and phase 1A clinical evaluation of an anti-VEGF pegylated aptamer (EYE001) for the treatment of exudative age-related macular degeneration. Retina. 2002; 22:143-52. [PubMed 11927845]
9. The Eyetech Study Group. Anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration: phase II study results. Ophthalmology. 2003; 110:979-86. [PubMed 12750101]
10. Csaky K. Anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration: promises and pitfalls. Ophthalmology. 2003; 110:879-81. Guest Editorial. [PubMed 12750083]
11. Frank RN. Diabetic retinopathy. N Engl J Med. 2004; 350:48-58. [PubMed 14702427]
12. Aiello LP, Avery RL, Arrigg PG et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994; 331:1480-7. [PubMed 7526212]
13. Siddiqui MAA, Keating GM. Pegaptanib: in exudative age-related macular degeneration. Drugs. 2005; 65:1571-7. [PubMed 16033295]
14. Pfizer, Morris Plains, NJ: Personal communication.
15. van Wijngaarden P, Coster DJ, Williams KA. Inhibitors of ocular neovascularization: promises and potential problems. JAMA. 2005; 293:1509-13. [PubMed 15784876]
16. Anon. Pegaptanib sodium (Macugen) for macular degeneration. Med Lett Drugs Ther. 2005; 47:55-6.
17. D'Amico DJ for the VEGF Inhibition Study in Ocular Neovascularization (VISION) Clinical Trial Group. VEGF inhibition study in ocular neovascularization (VISION): second year efficacy data. Invest Ophthalmol Vis Sci. 2005; 46: E-Abstract 2309.
18. Aiello LP, Brucker AJ, Chang S et al. Evolving guidelines for intravitreous injections. Retina. 2004; 24:S3-19. [PubMed 15483476]
19. Dear health care provider letter regarding rare reports of anaphylaxis/anaphylactoid reactions, including angioedema following administration of Macugen with other drugs as part of the injection preparation procedure. New York, NY: Eyetech and Pfizer; 2006 March 6.
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