PEGylation

Mr. Sanju Patel a visitor of this blog asked me to post detail information on pegylation.

According to medical dictionary -
Oeginterferon alfa-2a,
a covalent conjugate of recombinant interferon alfa-2a and polyethylene glycol, used in the treatment of chronic infection by hepatitis C virus. It is administered subcutaneously. - Mosby's Medical Dictionary, 8th edition.

Pegasys
Pharmacologic class: Interferon
Therapeutic class: Biological response modifier
Pregnancy risk category C
FDA Boxed Warning

• Drug may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Monitor patient closely with periodic clinical and laboratory evaluations. Withdraw drug in patients who have persistently severe or worsening signs or symptoms of these conditions. In most cases, these disorders resolve once therapy ends.
• Concurrent use with ribavirin may cause birth defects or fetal death. Use extreme care to avoid pregnancy in female patients and female partners of male patients.
Action

Unclear. Thought to bind to specific cell-surface receptors, suppressing cell proliferation and viral replication. Also increases effector protein levels and reduces white blood cell (WBC) and platelet counts.
Availability

Injection: 180-mcg/ml vial

⊘Indications and dosages

➣ Chronic hepatitis C virus infection

Adults: 180 mcg subcutaneously q week for 48 weeks. If poorly tolerated, reduce to 135 mcg weekly; some patients may need reduction to 90 mcg.
Dosage adjustment

• Neutrophil count less than 750 cells/mm3 or platelet count less than 50,000 cells/mm3
• Hepatic disease
• End-stage renal disease requiring dialysis
• Serious adverse reactions
Off-label uses

• Renal cell carcinoma
Contraindications

• Hypersensitivity to drug
• Autoimmune hepatitis
• Decompensated hepatic disease
• Infants and neonates (due to benzyl alcohol content)
Precautions

Use cautiously in:
• thyroid disorders; bone marrow depression; hepatic, renal, or cardiac disease; pancreatitis; autoimmune disorders; pulmonary disorders; colitis; ophthalmic disorders; depression
• elderly patients
• pregnant or breastfeeding patients
• children younger than age 18.
Administration

• Keep refrigerated. Before giving, roll vial between palms for 1 minute to warm; don't shake. Protect solution from light.
• Don't use if solution is cloudy or contains visible particles.
• Administer undiluted in abdomen or thigh by subcutaneous injection.
• Know that drug may be used alone or with ribavirin.

Adverse reactions

CNS: dizziness, vertigo, insomnia, fatigue, rigors, poor memory and concentration, asthenia, depression, irritability, anxiety, peripheral neuropathy, mood changes, suicidal ideation

CV: hypertension, chest pain, supraventricular arrhythmias, myocardial infarction

EENT: vision loss, blurred vision, retinal artery or vein thrombosis, retinal hemorrhage, optic neuritis, retinopathy, papilledema

GI: nausea, vomiting, diarrhea, abdominal pain, dry mouth, anorexia, GI tract bleeding, ulcerative and hemorrhagic colitis, pancreatitis

Hematologic: anemia, leukopenia, thrombocytopenia, neutropenia

Metabolic: diabetes mellitus, aggravated hypothyroidism or hyperthyroidism

Musculoskeletal: myalgia, back pain, joint pain

Respiratory: pneumonia, interstitial pneumonitis, bronchoconstriction, respiratory failure

Skin: alopecia, pruritus, diaphoresis, rash, dermatitis, dry skin, eczema

Other: weight loss, flulike symptoms, injection-site reaction, pain, autoimmune phenomena, severe and possibly fatal bacterial infections, severe hypersensitivity reactions including angioedema and anaphylaxis
Interactions

Drug-drug. Theophylline: increased theophylline blood level

Drug-diagnostic tests. Absolute neutrophil count, hematocrit, hemoglobin, platelets, WBCs: decreased values

Alanine aminotransferase: transient increase

Glucose, thyroid function tests: decreased or increased levels

Triglycerides: increased levels
Patient monitoring

Assess cardiac and pulmonary status closely. Watch for evidence of infections and hypersensitivity reactions, including anaphylaxis.
• Before therapy begins, assess CBC (including platelet count), blood glucose level, and thyroid, kidney, and liver function tests. Continue to monitor at 1, 2, 4, 6, and 8 weeks and then every 4 weeks during therapy (more often if abnormalities occur). Monitor thyroid function tests every 12 weeks.
Monitor for development of diabetes mellitus, hypothyroidism, and hyperthyroidism.
If serious adverse reaction occurs, discontinue drug or adjust dosage until reaction abates, as prescribed. If reaction persists or recurs despite adequate dosage adjustment, discontinue drug.
Patient teaching

• Teach patient or caregiver how to administer injection subcutaneously in thigh or abdomen and how to dispose of equipment properly, if appropriate.
Advise patient to promptly report rash, bleeding, bloody stools, infection symptoms (such as fever), decreased vision, chest pain, severe stomach or lower back pain, shortness of breath, depression, or suicidal thoughts.
• Instruct patient to administer drug exactly as prescribed. If he misses a dose but remembers it within 2 days, tell him to take missed dose as soon as possible; if more than 2 days have elapsed, tell him to contact prescriber.
• Caution patient not to switch brands without prescriber's approval.
• Instruct patient to have periodic eye exams.
• Advise female patient of childbearing age to avoid pregnancy and use two birth control methods before, during, and up to 6 months after therapy. Instruct male patient to use condoms.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

Nursing Spectrum Drug Handbook 2009. © 2009 by The McGraw-Hill Companies, Inc.

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