Drugs Details

Drugs Info of Macugen
Drugs Details
  • Drugs Type  : FDA
  • Date : 9th Mar 2015 04:11 am
  • Brand Name : Macugen
  • Generic Name :  pegaptanib ophthalmic injection (Pronunciation: peg AP ta nib off THAL mik in JEK tion)
Descriptions

Macugen (pegaptanib sodium injection) is a sterile, aqueous solution containing pegaptanib sodium for intravitreous injection. Macugen 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 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.

Pegaptanib sodium is represented by the following structural formula:

 

View Enlarged Table

Where R is

 

MACUGEN® (pegaptanib sodium injection)  Structural Formula Illustration

and n is approximately 450.

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-Am-Am-(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.

The molecular formula for pegaptanib sodium is C294H342F13N107Na28O188P28[C2H4O]n (where n is approximately 900) and the molecular weight is approximately 50 kilodaltons.

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

What are the possible side effects of pegaptanib ophthalmic (Macugen)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • eye pain or redness, swelling around your eyes;
  • sudden vision problems;
  • seeing flashes of light or "floaters" in your vision;
  • eyes being more sensitive to light;
  • sudden numbness or weakness, especially on one side of the body; or
  • sudden severe headache, confusion, problems with speech or...

Read All Potential Side Effects and See Pictures of Macugen »


This monograph has been modified to include the generic and brand name in many instances.

Indications

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

Dosage Administration

General Dosing Information

FOR OPHTHALMIC INTRAVITREAL INJECTION ONLY.

Dosing

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

Preparation for Administration

Macugen 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

Before expelling air bubble and excess drug - Illustration

READY for Injection

Figure 2: After expelling air bubble and excess drug

SLOWLY depress the plunger to eliminate all the bubbles - Illustration

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 REACTIONS].

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 Macugen therapy administered to both eyes concurrently have not been studied.

How Supplied

Dosage Forms And Strengths

Single-use glass syringe pre-filled with 0.3 mg of Macugen® in a nominal 90 μL solution for intravitreal injection.

Storage And Handling

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).

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

Manufactured by: Gilead Sciences, Inc 650 Cliffside Drive San Dimas, CA 91773. For: Eyetech Inc. 11360 Jog Road, Suite 200 Palm Beach Gardens, Florida 33418.
This monograph has been modified to include the generic and brand name in many instances.

Side Effects

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.

Clinical Studies Experience

The most frequently reported adverse events in patients treated with Macugen 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 Macugen 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 Macugen 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.

Postmarketing Experience

Anaphylaxis/anaphylactoid reactions, including angioedema, have been identified during postapproval use of Macugen. 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].

Read the Macugen (pegaptanib sodium) Side Effects Center for a complete guide to possible side effects

Interactions

No information provided.


This monograph has been modified to include the generic and brand name in many instances.

 

Warnings

Included as part of the PRECAUTIONS section.

Precautions

Endophthalmitis

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

Increases in Intraocular Pressure

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

Anaphylaxis

Rare cases of anaphylaxis/anaphylactoid reactions, including angioedema, have been reported in the post-marketing experience following the Macugen intravitreal administration procedure [see ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies with pegaptanib have not been conducted. No data are available to evaluate male or female mating or fertility indices.

Animal Toxicology and/or Pharmacology

Pegaptanib and its monomer component nucleotides (2'-MA, 2'-MG, 2'-FU, 2'-FC) were evaluated for genotoxicity in a battery of in vitro and in vivo assay systems. Pegaptanib, 2'O-methyladenosine (2'-MA), and 2'-O-methylguanosine (2'-MG) were negative in all assay systems evaluated. 2'-fluorouridine (2'-FU) and 2'-fluorocytidine (2'-FC) were nonclastogenic and were negative in all S. typhimurium tester strains, but produced a non-dose related increase in revertant frequency in a single E. coli tester strain. Pegaptanib, 2'FU, and 2'-FC tested negative in cell transformation assays.

Use In Specific Populations

Pregnancy

Teratogenic Effects

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.

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 Macugen is administered to a nursing woman.

Pediatric Use

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

Geriatric Use

Approximately 94% (834/892) of the patients treated with Macugen 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.


This monograph has been modified to include the generic and brand name in many instances.

OverDose

Doses of Macugen 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.

ContrainDications

Ocular or Periocular Infections

Macugen is contraindicated in patients with ocular or periocular infections.

Hypersensitivity

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


This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

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. 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.

Pharmacokinetics

Absorption

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 Macugen alone and in combination with photodynamic therapy (PDT) revealed no apparent difference in the plasma pharmacokinetics of pegaptanib.

Distribution/Metabolism/Excretion

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.

Clinical Studies

Macugen was studied in two controlled, double-masked, and identically designed randomized studies in patients with neovascular AMD. Patients were randomized to receive control (sham treatment) or 0.3 mg, 1 mg or 3 mg Macugen administered as intravitreous injections every 6 weeks for 48 weeks. A total of approximately 1200 patients were enrolled with 892 patients receiving Macugen and 298 receiving a sham injection. The median age of the patients was 77 years. Patients received a mean 8.5 treatments out of a possible 9 total treatments across all treatment arms. Patients were re-randomized between treatment and no treatment during the second year. Patients who continued treatment in year 2 received a mean of 16 treatments out of a possible total 17 overall.

The two trials enrolled patients with neovascular AMD characteristics including classic, occult, and mixed lesions of up to 12 disc areas and baseline visual acuity in the study eye between 20/40 and 20/320. The primary efficacy endpoint was the proportion of patients losing less than 15 letters of visual acuity, from baseline up to 54 week assessment.

Verteporfin PDT usage was permitted at the discretion of the investigators in patients with predominantly classic lesions.

The groups treated with Macugen 0.3 mg exhibited a statistically significant result in both trials for the primary efficacy endpoint at 1 year: Study EOP1003, Macugen 73% vs. Sham 60%; Study EOP1004, Macugen 67% vs. Sham 53%. Concomitant use of PDT overall was low. More sham treated patients (75/296) received PDT than Macugen 0.3 mg treated patients (58/294).

On average, Macugen 0.3 mg treated patients and sham treated patients continued to experience vision loss. However, the rate of vision decline in the Macugen treated group was slower than the rate in the patients who received sham treatment. See Figure 1.

Figure 1 : Mean Visual Acuity: Year 1

View Enlarged Table

At the end of the first year (week 54), approximately 1050 of the original 1200 patients were re-randomized to either continue the same treatment or to discontinue treatment through week 102. See Figure 2.

Macugen was less effective during the second year than during the first year. The percentage of patients losing less than 15 letters from baseline to week 102 was: Study EOP1003, Macugen 38/67 (57%); Sham 30/54 (56%); Study EOP1004, Macugen 40/66 (61%); Sham 18/53 (34%).

Figure 2 : Mean Visual Acuity: Year 2

View Enlarged Table

Dose levels above 0.3 mg did not demonstrate any additional benefit. The safety or efficacy of Macugen beyond 2 years has not been demonstrated.
This monograph has been modified to include the generic and brand name in many instances.

Patient Information

In the days following Macugen administration, patients are at risk for the development of endophthalmitis. If the eye becomes red, sensitive to light, painful or develops a change in vision, the patient should seek the immediate care with their ophthalmologist [see WARNINGS AND PRECAUTIONS].


This monograph has been modified to include the generic and brand name in many instances.

 

Consumer Overview Uses

No Information Available!

Consumer Overview Side Effect

No Information Available!

Consumer Overview Missed Dose

No Information Available!

Patient Detailed Side Effect

Brand Names: Macugen

Generic Name: pegaptanib ophthalmic injection (Pronunciation: peg AP ta nib off THAL mik in JEK tion)

  • What is pegaptanib ophthalmic (Macugen)?
  • What are the possible side effects of pegaptanib ophthalmic (Macugen)?
  • What is the most important information I should know about pegaptanib ophthalmic (Macugen)?
  • What should I discuss with my healthcare provider before taking pegaptanib ophthalmic (Macugen)?
  • How should I take pegaptanib ophthalmic (Macugen)?
  • What happens if I miss a dose (Macugen)?
  • What happens if I overdose (Macugen)?
  • What should I avoid while taking pegaptanib ophthalmic (Macugen)?
  • What other drugs will affect pegaptanib ophthalmic (Macugen)?
  • Where can I get more information?

What is pegaptanib ophthalmic (Macugen)?

Pegaptanib is made from a human antibody fragment. It works by keeping new blood vessels from forming under the retina (a sensory membrane that lines the inside of the eye). In people with a certain type of eye disease, new blood vessels grow under the retina where they leak blood and fluid. This is known as the "wet form" of macular degeneration.

Pegaptanib ophthalmic (for the eyes) is used to treat wet age-related macular degeneration.

Pegaptanib ophthalmic may also be used for purposes not listed in this medication guide.

What are the possible side effects of pegaptanib ophthalmic (Macugen)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • eye pain or redness, swelling around your eyes;
  • sudden vision problems;
  • seeing flashes of light or "floaters" in your vision;
  • eyes being more sensitive to light;
  • sudden numbness or weakness, especially on one side of the body; or
  • sudden severe headache, confusion, problems with speech or balance.

Less serious side effects may include:

  • watery eyes;
  • blurred vision;
  • swelling of the eyelids; or
  • mild eye pain or discomfort after the injection.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Macugen (pegaptanib sodium) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about pegaptanib ophthalmic (Macugen)?

You should not receive pegaptanib if you are allergic to it, or if you have cataracts or glaucoma, or any type of bacterial, fungal, or viral infection in or around your eyes.

Call your doctor at once if you have eye pain or redness, swelling or puffiness around your eyes, or sudden vision problems at any time during treatment.

Side Effects Centers
  • Macugen

Patient Detailed How Take

What should I discuss with my healthcare provider before taking pegaptanib ophthalmic (Macugen)?

You should not receive pegaptanib if you are allergic to it, or if you have any type of bacterial, fungal, or viral infection in or around your eyes.

FDA pregnancy category B. Pegaptanib is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether pegaptanib passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take pegaptanib ophthalmic (Macugen)?

Pegaptanib ophthalmic is given as an injection into your eye. Your doctor will use a medicine to numb your eye before giving you the injection. You will receive this injection in your doctor's office or other clinic setting.

For a short time after your injection, your eyes will be checked periodically to make sure the injection has not caused any side effects.

Pegaptanib is usually given once every 6 weeks. Follow your doctor's dosing instructions very carefully.

Side Effects Centers
  • Macugen

Patient Detailed Avoid Taking

What happens if I miss a dose (Macugen)?

Call your doctor for instructions if you miss an appointment for your pegaptanib injection.

What happens if I overdose (Macugen)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while taking pegaptanib ophthalmic (Macugen)?

This medication may cause blurred vision. Be careful if you drive or do anything that requires you to be able to see clearly.

What other drugs will affect pegaptanib ophthalmic (Macugen)?

It is not likely that other drugs you take orally or inject will have an effect on pegaptanib used in the eyes. But many drugs can interact with each other. Tell your doctor about all medicines you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about pegaptanib ophthalmic.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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