pegaptanib (Discontinued)

Action and Spectrum

Actions and Spectrum: 

• pegaptanib is a VEGF antagonist. The production of new blood vessels, or angiogenesis, is greatly aided by the protein VEGF. In AMD, abnormal blood vessel growth occurs in the macula, the central part of the retina, leading to vision impairment. VEGF promotes this abnormal blood vessel growth. 
• pegaptanib targets explicitly a particular isoform of VEGF called VEGF-165, which is associated with abnormal blood vessel formation in the eye. pegaptanib helps people with wet AMD preserve or enhance their eyesight by attaching to and neutralising VEGF-165, which slows the angiogenic process. 
• pegaptanib’s spectrum of activity is limited to its specificity for VEGF-165. It does not target all isoforms of VEGF but focuses on the specific isoform associated with the pathogenesis of wet AMD. This targeted approach is designed to minimize side effects that might occur if other isoforms of VEGF were affected. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Blurred vision 

Conjunctival hemorrhage 

Anterior chamber inflammation 

Cataract 

Corneal edema 

Increased IOP 

Punctate keratitis 

Visual disturbance 

Hypertension 

Ocular discomfort 

Reduced visual acuity 

1-10% 

Blepharitis 

Conjunctivitis 

Bone spur 

Carotid artery occlusion 

Allergic conjunctivitis 

Conjunctival edema 

Arthritis 

Bronchitis 

<1% 

Retinal detachment 

Angioedema hypersensitivity 

Iatrogenic traumatic cataract 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

Hypersensitivity 

Ocular infections 

Caution: 

• Ocular Infections: pegaptanib is administered through an injection into the eye. There is a risk of infection associated with any intraocular procedure.  
• Bleeding Disorders: Because pegaptanib targets VEGF, which is involved in blood vessel creation, there is a risk of bleeding problems.  
• Hypersensitivity: Patients with a known hypersensitivity or allergic reaction to pegaptanib or any of its components should not use the medication. 

Pregnancy / Lactation

Pregnancy consideration: There is insufficient human data; in mice, there was no maternal toxicity and no signs of teratogenicity or fetal mortality. 

Pregnancy Category: B 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

• A single-stranded RNA molecule called an aptamer, such as pegaptanib, is made particularly to bind to and neutralise the vascular endothelial growth factor (VEGF). 
• VEGF is a protein which plays a key role in angiogenesis, the process of forming new blood vessels. In neovascular AMD, abnormal blood vessels grow beneath the retina, leading to vision impairment. 
• Pegaptanib selectively binds to the VEGF-165 isoform,  
• inhibiting its activity. VEGF-165 is associated with the abnormal blood vessel growth seen in neovascular AMD. 

Pharmacokinetics: 

Absorption 

pegaptanib is administered directly into the vitreous humor of the eye through intravitreal injection. This route allows for localized delivery of the drug to the target tissues in the eye, bypassing the need for absorption through the gastrointestinal tract. 

Distribution 

After intravitreal injection, pegaptanib is distributed within the vitreous humor of the eye. Due to the localized administration, systemic distribution is minimal, and the drug remains mainly within the ocular tissues. 

Metabolism 

pegaptanib is an aptamer, which is a type of oligonucleotide (RNA) that acts as a molecular scaffold with high specificity for its target (VEGF-165). Unlike small-molecule drugs, aptamers like pegaptanib are not metabolized in the same way. They do not undergo hepatic metabolism or other traditional metabolic processes. 

Elimination and Excretion 

The elimination of pegaptanib from the eye involves processes such as diffusion and clearance from the vitreous humor. The exact mechanisms of excretion are not fully elucidated, but pegaptanib is gradually cleared from the eye over time. 

Adminstartion

Administration: 

Intravitreal administration 

• Pre-injection Assessment: Before administering pegaptanib, the healthcare provider will perform a thorough examination of the eye, assessing the patient’s overall ocular health and determining the need for treatment. 
• Topical Anesthesia: Topical anesthesia (numbing eye drops) is typically applied to the eye to minimize discomfort during the injection. 
• Cleaning and Draping: The eye is cleaned to reduce the risk of infection, and a sterile drape may be placed around the eye. 
• Injection Procedure: The actual injection is performed using a fine needle. The healthcare provider carefully inserts the needle through the sclera (the white part of the eye) and into the vitreous humor, avoiding injury to other structures within the eye. The injection is typically administered into the lower part of the eye. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: pegaptanib 

Why do we use pegaptanib? 

It is primarily used for the treatment of neovascular (wet) age-related macular degeneration (AMD). The macula, or core portion of the retina, is home to aberrant blood vessel growth in neovascular AMD, a degenerative eye disorder. These abnormal vessels can leak fluid and blood, leading to vision impairment. 

Inhibiting VEGF activity is pegaptanib’s principal mode of action. This protein is critical in the development of these aberrant blood vessels. By targeting VEGF, pegaptanib helps to reduce the growth of these vessels, preventing further damage to the retina and preserving or improving vision in individuals with neovascular AMD.