Pegaptanib

Usage

Pegaptanib is prescribed for the treatment of neovascular (wet) age-related macular degeneration (AMD). It is classified as an anti-angiogenic ophthalmic agent. Specifically, it is an aptamer, a type of oligonucleotide that binds to and inhibits vascular endothelial growth factor (VEGF). This action suppresses neovascularization and slows vision loss associated with wet AMD.

Alternate Names

The International Nonproprietary Name (INN) is pegaptanib sodium. A popular brand name for pegaptanib is Macugen.

How It Works

Pharmacodynamics: Pegaptanib binds selectively to a specific isoform of VEGF, VEGF₁₆₅, which is primarily responsible for pathological ocular neovascularization in wet AMD. This binding prevents VEGF₁₆₅ from interacting with its receptors, thus inhibiting the formation of new blood vessels in the retina and reducing vascular leakage.

Pharmacokinetics: Pegaptanib is administered via intravitreal injection. After injection, it is slowly absorbed into the systemic circulation. It is primarily metabolized by endo- and exonucleases. The metabolites and parent drug are eliminated primarily in the urine. The apparent plasma half-life is approximately 10 days after a 3 mg dose (10 times the recommended dose). Age and gender do not appear to affect plasma concentrations significantly. Information regarding effects on patients younger than 50 years old is not available.

Mode of Action: Pegaptanib acts by specifically binding to and inactivating the extravascular isoform of vascular endothelial growth factor (VEGF₁₆₅), inhibiting its activity.

Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Pegaptanib is a selective VEGF₁₆₅ inhibitor. It acts by binding to and blocking this isoform, thereby inhibiting its biological activity. No direct enzyme inhibition or neurotransmitter modulation is involved.

Elimination Pathways: Pegaptanib is metabolized by nucleases, and it is eliminated as parent drug and metabolites in the urine. Cytochrome P450 interactions are considered unlikely.

Dosage

Standard Dosage

Adults:

The standard dose is 0.3 mg (90 microliters) administered as an intravitreal injection into the affected eye every six weeks (9 injections per year).

Children:

The safety and efficacy of Pegaptanib have not been established in pediatric patients.

Special Cases:

• Elderly Patients: No dose adjustment is necessary for elderly patients.

• Patients with Renal Impairment: Dose adjustment is not recommended for mild or moderate renal impairment. Data for patients with severe renal impairment are limited.

• Patients with Hepatic Dysfunction: Pegaptanib has not been studied in patients with hepatic impairment, but dose adjustment is not expected to be needed.

• Patients with Comorbid Conditions: Use with caution in patients with a history of stroke or transient ischemic attacks.

Clinical Use Cases

The clinical use of pegaptanib is specifically for the treatment of wet AMD. It is not indicated for use in other clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.

Dosage Adjustments

No specific dosage modifications are required based on patient-specific factors, except for those noted above (renal/hepatic impairment).

Side Effects

Common Side Effects:

Eye irritation, blurred vision, increased intraocular pressure, eye pain, vitreous floaters, conjunctival hemorrhage, eye inflammation/swelling, and eyelid irritation.

Rare but Serious Side Effects:

Endophthalmitis, retinal detachment, anaphylaxis/anaphylactoid reactions (including angioedema), and serious increase in intraocular pressure.

Long-Term Effects:

Cataract formation has been reported.

Adverse Drug Reactions (ADR):

Clinically significant ADRs include endophthalmitis and anaphylaxis, both requiring immediate medical attention.

Contraindications

• Ocular or periocular infection (active or suspected).
• Hypersensitivity to pegaptanib sodium or any of the excipients.

Drug Interactions

Formal drug interaction studies have not been conducted. Due to metabolism by nucleases, cytochrome P450-mediated drug interactions are unlikely. No clinically significant drug interactions have been identified. However, concurrent use of other intravitreal injections may increase the risk of endophthalmitis.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Category B. Animal studies have not shown evidence of teratogenicity or fetal mortality. However, there are no adequate and well-controlled studies in pregnant women. Pegaptanib should be used during pregnancy only if clearly needed.

• Breastfeeding: It is unknown whether pegaptanib is excreted in human milk. Exercise caution if administering Pegaptanib to nursing women.

Drug Profile Summary

• Mechanism of Action: Aptamer that binds to and inhibits VEGF₁₆₅, suppressing neovascularization and slowing vision loss.
• Side Effects: Common: eye irritation, blurred vision, increased intraocular pressure. Serious: Endophthalmitis, retinal detachment, anaphylaxis.
• Contraindications: Active or suspected ocular/periocular infection; hypersensitivity to the drug or excipients.
• Drug Interactions: No significant drug interactions identified.
• Pregnancy & Breastfeeding: Category B; caution advised.
• Dosage: 0.3 mg intravitreal injection every 6 weeks.
• Monitoring Parameters: Intraocular pressure, visual acuity, signs of infection/inflammation.

Popular Combinations

Pegaptanib is typically used as monotherapy for wet AMD. Combination therapy with other anti-VEGF agents or photodynamic therapy may be considered in certain cases, but there are limited data on efficacy and safety.

Precautions

• General Precautions: Strict aseptic technique for injection is crucial to minimize the risk of endophthalmitis. Monitor intraocular pressure after administration.
• Specific Populations: As per pregnancy and breastfeeding guidelines above. Use with caution in patients with a history of stroke or transient ischemic attack.
• Lifestyle Considerations: Patients may experience transient blurred vision after injection and should avoid driving or operating machinery until it resolves.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Pegaptanib?

A: The standard dose is 0.3 mg via intravitreal injection every six weeks.

Q2: How does Pegaptanib work?

A: It binds to and inhibits VEGF₁₆₅, reducing neovascularization in wet AMD.

Q3: What are the common side effects of Pegaptanib?

A: Common side effects include eye irritation, blurred vision, increased intraocular pressure, eye pain, and vitreous floaters.

Q4: What are the serious side effects of Pegaptanib?

A: Serious but rare side effects include endophthalmitis, retinal detachment, and anaphylaxis.

Q5: Is Pegaptanib safe during pregnancy?

A: Pregnancy Category B; Use only if clearly needed and after careful assessment of risks and benefits.

Q6: Can I use Pegaptanib while breastfeeding?

A: It’s unknown if it’s excreted in breast milk; caution advised.

Q7: How is Pegaptanib administered?

A: By intravitreal injection, performed by a qualified ophthalmologist.

Q8: What should patients be monitored for after injection?

A: Monitor for increased intraocular pressure, signs of endophthalmitis (eye pain, redness, decreased vision), and any changes in vision.

Q9: How often should Pegaptanib be administered?

A: Every six weeks.

Q10: What is Pegaptanib used to treat?

A: Neovascular (wet) age-related macular degeneration.