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Pegaptanib Sodium Injection





Pegaptanib sodium injection is a sterile, aqueous solution containing pegaptanib sodium for intravitreous injection. Pegaptanib sodium is a covalent conjugate of an oligonucleotide of twenty-eight nucleotides in length that terminates in a pentylamino linker, to which two 20-kilodalton monomethoxy polyethylene glycol (PEG) units are covalently attached via the two amino groups on a lysine residue. Its structural formula is:

where R is

Empirical formula: C294H342F13N107Na28O188P28[C2H4O]n
(where n is approximately 900)
Molecular weight: approximately 50 kilodaltons

The chemical name for pegaptanib sodium is as follows: RNA, ((2'-deoxy-2'-fluoro)C-Gm-Gm-A-A-(2'-deoxy-2'-fluoro)U-(2'-deoxy-2'-fluoro)C-Am-Gm-(2'-deoxy-2'-fluoro)U-Gm-AmAm-(2'-deoxy-2'-fluoro)U-Gm-(2'-deoxy-2'-fluoro)C-(2'-deoxy-2'-fluoro)U-(2'-deoxy-2'fluoro)U-Am-(2'-deoxy-2'-fluoro)U-Am-(2'-deoxy-2'-fluoro)C-Am-(2'-deoxy-2'-fluoro)U-(2'deoxy-2'-fluoro)C-(2'-deoxy-2'-fluoro)C-Gm-(3'→3')-dT), 5'-ester with α,α'-[4,12-dioxo-6[[[5-(phosphoonoxy)pentyl]amino] carbonyl]-3,13-dioxa-5,11-diaza-1,15pentadecanediyl]bis[ω-methoxypoly(oxy-1,2-ethanediyl)], sodium salt.

Pegaptanib sodium is supplied in a single-dose, pre-filled syringe and is formulated as a 3.47 mg/mL solution, measured as the free acid form of the oligonucleotide. The active ingredient is 0.3 mg of the free acid form of the oligonucleotide without polyethylene glycol, in a nominal volume of 90 μL. This dose is equivalent to 1.6 mg of pegaptanib sodium (pegylated oligonucleotide) or 0.32 mg when expressed as the sodium salt form of the oligonucleotide moiety. The product is a sterile, clear, preservative-free solution containing sodium chloride, monobasic sodium phosphate monohydrate, dibasic sodium phosphate heptahydrate, hydrochloric acid, and/or sodium hydroxide to adjust the pH and water for injection.

Pegaptanib sodium is formulated to have an osmolality of 280-360 mOsm/Kg, and a pH of 6–7.


Pegaptanib sodium is indicated for the treatment of neovascular (wet) age-related macular degeneration.


3.1 General Dosing Information


3.2 Dosing

Pegaptanib sodium 0.3 mg should be administered once every six weeks by intravitreous injection into the eye to be treated.

3.3 Preparation for Administration

Pegaptanib sodium should be inspected visually for particulate matter and discoloration prior to administration. If visible particulates are observed and/or the liquid in the syringe is discolored, the syringe must not be used.

Administration of the syringe contents involves assembly of the syringe with the administration needle. The injection procedure should be carried out under controlled aseptic conditions, which includes the use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent). When ready to assemble syringe and administer injection, carefully peel open pouches, remove contents, and place on sterile field. If upon opening the pouch, the plastic clip is missing or not attached to the syringe, the syringe should not be used.

To avoid compromising the sterility of the product, do not pull back on the plunger.

1. Remove the syringe from the plastic clip.

2. Twist off cap.

3. Attach the sterile BD® 30G ½” Precision Glide® administration needle (included) to the syringe by screwing it into the syringe tip.

--Another sterile BD® 30G ½” Precision Glide® administration needle may be used in lieu of the one included. Remove the plastic needle shield from the needle.

4. Holding the syringe with the needle pointing up, check the syringe for bubbles. If there are bubbles, gently tap the syringe with your finger until the bubbles rise to the top of the syringe. SLOWLY depress the plunger to eliminate all the bubbles and to expel the excess drug so that the top edge of the 3rd rib on the plunger stopper aligns with the preprinted black dosing line (See Figure 2, below).

5. Inject the entire contents of the syringe.

PRIOR to Injection

Figure1. Before expelling air bubble and excess drug

READY for Injection

Figure 2. After expelling air bubble and excess drug

3.4 Administration

The injection procedure should be carried out under controlled aseptic conditions, which includes the use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide should be given prior to the injection.

The patient’s medical history for hypersensitivity reactions should be evaluated prior to performing the intravitreal procedure [see Warnings and Precautions and Adverse Events].

Following the injection, patients should be monitored for elevation in intraocular pressure and for endophthalmitis. Monitoring may consist of a check for perfusion of the optic nerve head immediately after the injection, tonometry within 30 minutes following the injection, and monitoring during the week following the injection. Patients should be instructed to report any symptoms suggestive of endophthalmitis without delay.

No special dosage modification is required for any of the populations that have been studied (i.e. gender, elderly).

The safety and efficacy of pegaptanib sodium therapy administered to both eyes concurrently have not been studied.


4.1 Ocular or Periocular Infections

Pegaptanib sodium is contraindicated in patients with ocular or periocular infections.

4.2 Hypersensitivity

Pegaptanib sodium is contraindicated in patients with known hypersensitivity to pegaptanib sodium or any other excipient in this product.


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. VEGF induces angiogenesis, and increases 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), a leading cause of blindness. VEGF has been implicated in blood retinal barrier breakdown and pathological ocular neovascularization.

Pegaptanib is an aptamer, a pegylated modified oligonucleotide, which adopts a three-dimensional conformation that enables it to bind to extracellular VEGF. Under in vitro testing conditions, pegaptanib binds to the major pathological VEGF isoform, 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.


6.1 Usage in Pregnancy

Pregnancy Category B

Pegaptanib produced no maternal toxicity and no evidence of teratogenicity or fetal mortality in mice at intravenous doses of up to 40 mg/kg/day (about 7,000 times the recommended human monocular ophthalmic dose of 0.3 mg/eye). Pegaptanib crosses the placenta in mice.

There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

6.2 Nursing Mothers

It is not known whether pegaptanib is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when pegaptanib sodium is administered to a nursing woman.

6.3 Pediatric Use

Safety and effectiveness of pegaptanib sodium in pediatric patients have not been established.

6.4 Geriatric Use

Approximately 94% (834/892) of the patients treated with pegaptanib sodium were ≥ 65 years of age and approximately 62% (553/892) were ≥ 75 years of age. No difference in treatment effect or systemic exposure was seen with increasing age.


7.1 Endophthalmitis

Intravitreous injections, including those with pegaptanib sodium, have been associated with endophthalmitis. Proper aseptic injection technique should always be utilized when administering pegaptanib sodium. In addition, patients should be monitored during the week following the injection to permit early treatment, should an infection occur [see Dosage and Administration].

7.2 Increases in Intraocular Pressure

Increases in intraocular pressure have been seen within 30 minutes of injection with pegaptanib sodium. Therefore, intraocular pressure as well as the perfusion of the optic nerve head should be monitored and managed appropriately [see Dosage and Administration].

7.3 Anaphylaxis

Rare cases of anaphylaxis/anaphylactoid reactions, including angioedema, have been reported in the post-marketing experience following the pegaptanib sodium intravitreal administration procedure [see Adverse Events and Dosage and Administration].


8.1 Injection Procedure

Serious adverse events related to the injection procedure occurring in < 1% of intravitreous injections included endophthalmitis [see Warnings and Precautions], retinal detachment, and iatrogenic traumatic cataract.

8.2 Clinical Studies Experience

The most frequently reported adverse events in patients treated with pegaptanib sodium 0.3 mg for up to two years were anterior chamber inflammation, blurred vision, cataract, conjunctival hemorrhage, corneal edema, eye discharge, eye irritation, eye pain, hypertension, increased intraocular pressure (IOP), ocular discomfort, punctate keratitis, reduced visual acuity, visual disturbance, vitreous floaters, and vitreous opacities. These events occurred in approximately 10-40% of patients.

The following events were reported in 6-10% of patients receiving pegaptanib sodium 0.3 mg therapy:

Ocular: blepharitis, conjunctivitis, photopsia, vitreous disorder.

Non-Ocular: bronchitis, diarrhea, dizziness, headache, nausea, urinary tract infection.

The following events were reported in 1-5% of patients receiving pegaptanib sodium 0.3 mg therapy:

Ocular: allergic conjunctivitis, conjunctival edema, corneal abrasion, corneal deposits, corneal epithelium disorder, endophthalmitis, eye inflammation, eye swelling, eyelid irritation, meibomianitis, mydriasis, periorbital hematoma, retinal edema, vitreous hemorrhage.

Non-Ocular: arthritis, bone spur, carotid artery occlusion, cerebrovascular accident, chest pain, contact dermatitis, contusion, diabetes mellitus, dyspepsia, hearing loss, pleural effusion, transient ischemic attack, urinary retention, vertigo, vomiting.

8.3 Postmarketing Experience

Anaphylaxis/anaphylactoid reactions, including angioedema, have been identified during postapproval use of pegaptanib sodium. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure [see Warnings and Precautions and Dosage and Administration].


Doses of pegaptanib sodium up to 10 times the recommended dosage of 0.3 mg have been studied. No additional adverse events have been noted but there is decreased efficacy with doses above 1 mg.


No drug interaction information is reported.



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 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 to 4 days after a 3 mg monocular dose (10 times the recommended dose). The mean area under the plasma concentration-time curve (AUC) is about 25 μg·hr/mL at this dose.

Pegaptanib is metabolized by nucleases and is generally not affected by the cytochrome P450 system.

Two early clinical studies conducted in patients who received pegaptanib sodium alone and in combination with photodynamic therapy (PDT) revealed no apparent difference in the plasma pharmacokinetics of pegaptanib.


Twenty-four hours after intravitreous administration of a radiolabeled dose of pegaptanib to both eyes of rabbits, radioactivity was mainly distributed in vitreous fluid, retina, and aqueous fluid. After intravitreous and intravenous administrations of radiolabeled pegaptanib to rabbits, the highest concentrations of radioactivity (excluding the eye for the intravitreous dose) were obtained in the kidney. In rabbits, the component nucleotide, 2’-fluorouridine is found in plasma and urine after single radiolabeled pegaptanib intravenous and intravitreous doses. In rabbits, pegaptanib is eliminated as parent drug and metabolites primarily in the urine.

Based on preclinical data, pegaptanib is metabolized by endo- and exonucleases.

In humans, after a 3 mg monocular dose (10 times the recommended dose), the average (± standard deviation) apparent plasma half-life of pegaptanib is 10 (±4) days.

Special Populations

Plasma concentrations do not appear to be affected by age or gender, but have not been studied in patients under the age of 50.


1) How Available:

a) Brand name: MACUGEN, by Gilead Sciences.

b) Generic drugs: None.

2) How Supplied:

Macugen (pegaptanib sodium injection) is supplied in a sterile foil pouch as a single-use glass syringe pre-filled with 0.3 mg of Macugen® in a nominal 90 μL deliverable volume pack. A sterile packaged BD® single use 30G x ½” Precision Glide® Luer Lok® needle is supplied in a separate pouch. The foil pouch and needle are packaged together in a carton (NDC 68782-001-02).

3) Storage and Handling:

Store in the refrigerator at 2° to 8°C (36° to 46°F). Do not freeze or shake vigorously.

Rx only

Rev 07/11