peginterferon alfa-2a

(redirected from Pegylated interferon-alpha-2a)

peginterferon alfa-2a

Pegasys

Pharmacologic class: Interferon

Therapeutic class: Biological response modifier

Pregnancy risk category C

FDA Box 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. Also, ribavirin causes hemolytic anemia, which may result in worsening of cardiac disease. (See ribavirin package insert for additional information and other warnings.)

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, 180 mcg/0.5-ml prefilled syringe, 180 mcg/0.5-ml autoinjector for single use, 135 mcg/0.5-ml autoinjector for single use

Indications and dosages

Chronic hepatitis C virus infection in patients with compensated liver disease not previously treated with interferon alfa and in patients with histological evidence of cirrhosis and compensated liver disease

Adults: 180 mcg subcutaneously q week for 48 weeks. When used in combination with ribavirin, recommended ribavirin dosage and duration for peginterferon alfa-2a are based on viral genotype.

Children ages 5 and older: 180 mcg/1.73 m2 X body surface area subcutaneously q week, to a maximum dose of 180 mcg in combination with ribavirin. Recommended treatment duration is based on viral genotype.

Chronic HCV infection with HIV coinfection and CD4 count greater than 100 cells/mm3

Adults: 180 mcg subcutaneously q week for 48 weeks. When used in combination with ribavirin, duration for pegin-terferon alfa-2a is 48 weeks regardless of viral genotype.

Chronic hepatitis B virus infection in patients with compensated liver disease and evidence of viral replication and liver inflammation

Adults: 180 meg subcutaneously as monotherapy q week for 48 weeks.

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 or its components
• Autoimmune hepatitis
• Decompensated hepatic disease
• Hemoglobinopathies
• Concurrent use of didanosine (in peginterferon alfa-2a and ribavirin combination therapy)
• Infants and neonates (due to benzyl alcohol content)
• Pregnant patients, men whose female partners are pregnant

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.
• Administer undiluted in abdomen or thigh by subcutaneous injection.
• Use only one vial or prefilled syringe or disposable autoinjector per dose. Discard unused portion of single-use vials or prefilled syringes.
• Know that drug may be used alone or with ribavirin. However, monotherapy isn't recommended for treatment of chronic hepatitis C unless patient has a contraindication or significant intolerance to 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, supra-ventricular 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; delay in weight and height increases (children)

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.

peginterferon alfa-2a

(in-ter-feer-on al-fa) ,

Pegasys

(trade name)

Classification

Therapeutic: immune modifiers
Pharmacologic: interferons
Pregnancy Category: C
Pregnancy Category: X (when used with ribavirin)

Indications

Chronic hepatitis C virus infection with compensated hepatic function not previously treated with interferon alfa therapy (with or without ribavirin).Chronic hepatitis B virus infection with compensated hepatic function, evidence of viral replication, and hepatic inflammation.

Action

Interferons are proteins capable of modifying the immune response.
Interferon alfa-2a is produced by recombinant DNA techniques; pegylation of interferon alfa-2a is formulated to have a longer duration of action.
Interferons also have antiviral activity.

Therapeutic effects

Decreased progression of hepatic damage.

Pharmacokinetics

Absorption: Well absorbed following subcut administration.
Distribution: Unknown.
Metabolism and Excretion: Unknown.
Half-life: 80 hr (range 50–140 hr).

Time/action profile (blood levels*)

ROUTEONSETPEAKDURATION
Subcutunknown72–96 hrapprox 1 wk
*Accumulation to steady state levels occurs over 5–8 wk

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Autoimmune hepatitis; Hepatic decompensation (Child-Pugh classes B or C) before treatment; Pediatric: Infants (contains benzyl alcohol); Since peginterferon alfa-2a is given concurrently with ribavirin, consideration must be given to all aspects of ribavirin therapy.
Use Cautiously in: Baseline neutrophil count <1500 cells/mm3 or platelet count <90,000 cells/mm3; Hemoglobin <10 g/dL; History of suicidal ideation or depression; Obstetric / Lactation / Pediatric: Pregnancy, lactation or children <5 yr (safety not established; ribavirin is contraindicated in pregnancy and lactation).
Exercise Extreme Caution in: History of depression.

Adverse Reactions/Side Effects

Central nervous system

  • neuropsychiatric reactions (life-threatening)

Dermatologic

  • skin reactions (including Stevens-Johnson syndrome and exfoliative dermatitis)

Ear, Eye, Nose, Throat

  • ↓ vision
  • optic neuritis
  • papilledema
  • retinal hemorrhage/cotton wool spots
  • retinal vascular thrombosis
  • retinopathy

Cardiovascular

  • myocardial infarction (life-threatening)
  • chest pain
  • hypertension
  • supraventricular arrhythmias

Respiratory

  • dyspnea
  • interstitial pneumonitis
  • pulmonary infiltrates

Gastrointestinal

  • colitis (life-threatening)
  • pancreatitis (life-threatening)

Endocrinologic

  • ↓ growth (children)
  • hyperglycemia
  • hypoglycemia
  • hyperthyroidism
  • hypothyroidism

Hematologic

  • bone marrow depression

Miscellaneous

  • allergic reactions including anaphylaxis (life-threatening)
  • development/exacerbation of autoimmune disorders
  • infections

Interactions

Drug-Drug interaction

May ↑ serum theophylline levels (adjust dose accordingly).

Route/Dosage

Subcutaneous (Adults) Chronic hepatitis C (Genotype 1 or 4)—180 mcg once weekly (with PO ribavirin 500 mg twice daily in patients <75 kg or 600 mg twice daily for patients >75 kg) for 48 wk (should be used in combination with hepatitis C virus NS3/4A protease inhibitor in patients with genotype 1 infection); Chronic hepatitis C (Genotype 2 or 3)—180 mcg once weekly (with PO ribavirin 400 mg twice daily) for 24 wk; Patients with chronic hepatitis C co-infected with HIV—180 mcg once weekly (with or without PO ribavirin 400 mg twice daily) for 48 wk; Chronic hepatitis B—180 mcg once weekly for 48 wk.
Subcutaneous (Children 5–17 yr) Chronic hepatitis C (Genotype 1 or 4)—180 mcg/1.73 m2 X BSA once weekly (not to exceed 180 mcg) (with PO ribavirin) for 48 wk; Chronic hepatitis C (Genotype 2 or 3)—180 mcg/1.73 m2 X BSA once weekly (not to exceed 180 mcg) (with PO ribavirin) for 24 wk.

Renal Impairment

Subcutaneous (Adults) CCr 30–50 mL/min—180 mcg once weekly (with PO ribavirin 200 mg alternating with 400 mg every other day)CCr <30 mL/min (including hemodialysis)—135 mcg once weekly (with PO ribavirin 200 mg once daily).

Availability

Solution for injection: 180 mcg/mL in single use vials
Prefilled syringes: 180 mcg/0.5 mL
Autoinjector: 135 mcg/0.5 mL, 180 mcg/0.5 mL

Nursing implications

Nursing assessment

  • Assess for signs of neuropsychiatric disorders (irritability, anxiety, depression, suicidal ideation, aggressive behavior). May require discontinuation of peginterferon alfa-2a.
  • Monitor patient for signs of infection (vital signs, WBC) during therapy. Peginterferon alfa-2a should be discontinued in cases of severe infection, and antibiotic therapy instituted.
  • Assess patient for cardiovascular disorders (pulse, BP, chest pain). May cause hypertension, arrhythmias, or myocardial infarction.
  • Assess pulmonary status (lung sounds, respirations) periodically during therapy.
  • Monitor patient for signs of hypersensitivity reactions (urticaria, angioedema, wheezing). Discontinue drug and notify health care professions immediately if these occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in case of an anaphylactic reaction.
  • Assess patients for signs of colitis (abdominal pain, bloody diarrhea, fever) and pancreatitis (nausea, vomiting, abdominal pain) during therapy. Discontinue therapy if these occur; may be fatal. Colitis usually resolves within 1–3 wks of discontinuation.
  • Perform a baseline eye exam prior to initiation of therapy. Monitor patients with pre-existing diabetic or hypertensive retinopathy periodically during therapy. Discontinue therapy if patients develop new or worsening eye disorders.
  • Assess patient for skin reactions. If severe, therapy should be discontinued.
  • Lab Test Considerations: Monitor CBC with platelet count prior to, 2 wks and 4 wks after initiation of therapy. May cause hemolytic anemia. Platelet count should be ≥90,000 cells/mm3, ANC ≥1500 cells/mm3, and hemoglobin ≥12 g/dL for women or 13 g/dL for men with chronic hepatitis C monoinfection or ≥11 g/dL for women and ≥12 g/dL in men infected with both HIV and chronic hepatitis C, prior to initiation of therapy. Commonly causes ↓ hemoglobin, hematocrit, WBC, ANC, lymphocytes and platelet counts within first 2 wks of therapy.
    • Monitor liver function tests, uric acid and triglyceride levels every 4 wks during therapy. May cause transient ↑ ALT and triglycerides.
    • Monitor thyroid stimulating hormone (TSH) every 12 wks during therapy.
    • Monitor renal function periodically during therapy. Serum creatinine should be <1.5 times the upper limit of normal prior to initiation of therapy.
    • Perform monthly pregnancy test in women of childbearing years during therapy with ribavirin.

Potential Nursing Diagnoses

Risk for infection (Indications)

Implementation

  • Inspect solution prior to administration. Solution should be colorless to light yellow. Do not administer solutions that are discolored or contain a participate; notify pharmacist. Warm solution by rolling between hands for 1 minute; do not shake. Refrigerate solution and protect from light. Do not freeze. Discard unused solution.
  • Subcutaneous: Administer into the abdomen or thigh. Rotate sites with each injection.

Patient/Family Teaching

  • Instruct patient on the correct technique for administering peginterferon alfa-2a. Review patient Medication Guide, preparation of dose, administration sites and technique, and disposal of equipment into a puncture-resistant container. If a dose is missed, administer as soon as remembered if within 2 days; if >2 days, notify health care professional.
  • Advise patient to maintain good hydration, especially during initial therapy.
  • Inform patient about teratogenic effects when used with ribavirin. Instruct women with childbearing potential, and men, to use two forms of effective contraception during and for at least 6 mo following conclusion of therapy. Men must use a condom.
  • May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
  • Inform patient that peginterferon alfa-2a may not reduce the risk of transmission of HCV to others or prevent cirrhosis, liver failure, or liver cancer.
  • Instruct patient to contact health care professional immediately if depression, suicidal thoughts, chest pain, difficulty breathing, changes in vision, unusual bleeding or bruising, worsening psoriasis, persistent high fever, severe stomach or lower back pain, bloody diarrhea, or pregnancy occur.

Evaluation/Desired Outcomes

  • Decreased progression of hepatic damage. Consider discontinuation of therapy if at least a 2 log10 reduction from baseline in HCV RNA titer by 12 wk of therapy or undetectable HCV RNA after 24 wk of therapy.

peginterferon 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.