peginterferon alfa-2b


peginterferon alfa-2b

 [peg″in″ter-fēr´on] a covalent conjugate of recombinant interferon alfa-2b and polyethylene glycol; a biologic response modifier administered subcutaneously in the treatment of chronic hepatitis C virus infection.

peginterferon alfa-2b

PEG-Intron, Peglntron (UK), Unitron Peg (CA), ViraferonPeg (UK)

Pharmacologic class: Immunomodulator

Therapeutic class: Immunologic agent

Pregnancy risk category C (monotherapy), X (when given with ribavirin)

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 with 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

Binds to specific cell-surface membrane receptors, causing suppression of cell proliferation, enhanced phagocytic macrophage activity, and inhibition of viral replication

Availability

Powder for injection with diluent: 50 mcg/0.5-ml vial, 80 mcg/0.5-ml vial, 120 mcg/0.5-ml vial, 150 mcg/0.5-ml vial (Redipen)

Indications and dosages

➣ Chronic hepatitis C virus (HCV) infection in patients with compensated liver disease

Adults ages 18 and older: For monotherapy, 1 mcg/kg/week subcutaneously for 1 year given on the same day of the week. When given with ribavirin, 1.5 mcg/kg/week subcutaneously. When used in combination with ribavirin, recommended duration in interferon alfa-naïve patients is based on viral genotype. Combination treatment duration for patients who previously failed therapy is 48 weeks, regardless of HCV genotype.

Children ages 3 to 17: 60 mcg/m2/week subcutaneously in combination with ribavirin. Recommended treatment duration is based on viral genotype.

Dosage adjustment

• Serious adverse reactions

• Renal impairment

• Cardiac disease

• Hematologic toxicity

Contraindications

• Hypersensitivity to drug or its components

• Autoimmune hepatitis

• Decompensated hepatic damage

Precautions

Use cautiously in:

• renal insufficiency

• cardiovascular disease, patients with history of psychiatric disorders, patients with debilitating medical conditions, such as those with history of pulmonary disease

• human immunodeficiency virus, hepatitis B infection

• patients who have failed other interferon alfa therapy

• patients who develop neutralizing antibodies

• organ transplant recipients

• elderly patients

• pregnant or breastfeeding patients

• children.

Administration

• Reconstitute by holding dual-chamber glass cartridge upright with dose button down and pressing two halves of pen together until you hear an audible click. Then gently invert (don't shake) pen to mix solution.

• To administer, hold pen upright, attach supplied needle, and select appropriate dosage by pulling back on dosing button until dark bands are visible. Then turn button until dark band aligns with correct dose.

• Use reconstituted solution immediately.

• Know that drug may be used alone or with ribavirin.

• Don't use combination therapy in patients with creatinine clearance less than 50 ml/minute.

Adverse reactions

CNS: fatigue, headache, malaise, asthenia, dizziness, insomnia, depression, anxiety, emotional lability, irritability, poor concentration, agitation, nervousness, rigors, suicidal behavior, suicidal or homicidal ideation

CV: hypotension, tachycardia, chest pain, angina pectoris, arrhythmias, cardiomyopathy, myocardial infarction

EENT: vision decrease or loss, retinal artery or vein thrombosis, retinal hemorrhage, cotton-wool spots in visual field, rhinitis, sinusitis, pharyngitis

GI: nausea; vomiting; diarrhea; constipation; abdominal pain; dyspepsia; right upper abdominal quadrant pain; anorexia; dry mouth; ulcerative, hemorrhagic, or ischemic colitis; pancreatitis

GU: menstrual disorder

Hematologic: neutropenia, thrombocytopenia

Hepatic: hepatomegaly

Metabolic: aggravated hypothyroidism or hyperthyroidism

Musculoskeletal: myalgia, arthralgia, musculoskeletal pain

Respiratory: dyspnea, pneumonia, bronchiolitis obliterans, cough, sarcoidosis, pulmonary infiltrates, interstitial pneumonitis, bronchoconstriction

Skin: rash, dry skin, pruritus, sweating, flushing, alopecia

Other: exacerbation or development of autoimmune disorders, injection-site reaction, fever, viral or fungal infection, systemic lupus erythematosus, severe hypersensitivity reactions including angioedema and anaphylaxis

Interactions

Drug-diagnostic tests. Bilirubin, triglycerides, uric acid: increased levels

Glucose, thyroid function tests: decreased or increased levels

Hemoglobin, neutrophils, platelets, white blood cells: decreased levels

Patient monitoring

• Before therapy begins, assess CBC (including platelet count); blood glucose level, and thyroid, kidney, and liver function tests. Continue to monitor at weeks 2, 4, 8, and 12 and then every 6 weeks during therapy (more often if abnormalities occur). Monitor thyroid function tests every 12 weeks.

See Assess cardiac and pulmonary status closely. Watch for signs and symptoms of infection and hypersensitivity reactions, including anaphylaxis.

See Monitor neurologic status. Stay alert for such behavioral changes as irritability, anxiety, depression, and homicidal or suicidal ideation.

See If serious adverse reaction occurs, know that drug will be discontinued or dosages adjusted accordingly.

• Monitor patient for development of diabetes mellitus, hypothyroidism, or hyperthyroidism.

• Be aware that if HCV level remains high after 6 months, drug should be discontinued.

Patient teaching

• Tell patient to take exactly as prescribed. If he misses a dose but remembers it within 2 days, instruct him to take it as soon as possible. However, if more than 2 days have elapsed, advise him to contact prescriber.

• Teach patient or caregiver how to administer injection subcutaneously into thigh or abdomen, if appropriate, and how to properly dispose of equipment.

See Advise patient to stop drug and promptly report infection symptoms, such as high fever, easy bruising or bleeding, decreased vision, chest pain, shortness of breath, severe stomach or lower back pain, depression, or suicidal or homicidal thoughts.

• Urge patient to have periodic eye exams.

• Instruct female patient of childbearing age to avoid pregnancy and to 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 tests mentioned above.

peginterferon alfa-2B

(peg-in-ter-feer-on al-fa 2b) peginterferonalfa2b,

Pegintron

(trade name),

Sylatron

(trade name)

Classification

Therapeutic: immune modifiers
Pharmacologic: interferons
Pregnancy Category: C

Indications

Pegintron— Combination therapy with ribavirin and approved hepatitis C virus (HCV) NS3/4A protease inhibitor in patients ≥18 yr old with chronic hepatitis C who have compensated liver disease and HCV genotype 1 infection.Pegintron— Combination therapy with ribavirin in patients with chronic hepatitis C and compensated liver disease who have HCV genotypes 2 or 3, are 3–17 years old, or have HCV genotype 1 and are unable to take a HCV NS3/4A protease inhibitor.Pegintron— Monotherapy of chronic hepatitis C in previously untreated patients who have compensated liver disease and contraindications to or significant intolerances to ribavirin.Sylatron: Adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection including complete lymphadenectomy.

Action

Binds to specific receptors on cell surfaces; initiate a chain of events which include suppression of cell proliferation, enhanced phagocytic activity and augmented specific cytoxicity of lymphocytes; also inhibits viral replication in virus-infected cells.Unknown mechanism for melanoma.

Therapeutic effects

Decreased progression of liver damage (for hepatitis C).Improved relapse-free survival (for melanoma).

Pharmacokinetics

Absorption: Well absorbed following subcut administration.Distribution: Unknown.Metabolism and Excretion: 30% renally excreted; remainder of metabolism and excretion. Pegylation of interferon results in decreased elimination and longer duration of action.Half-life: 40 hr.

Time/action profile

ROUTEONSETPEAKDURATION
Subcutunknown6 mo or moreunknown

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Autoimmune hepatitis; Moderate or severe hepatic impairment; Lactation: Pregnancy or lactation.Use Cautiously in: CCr <50 mL/min (dose ↓ may be necessary); Cardiovascular disease; Neuropsychiatric history (condition may be exacerbated); Diabetes mellitus or hypertension (may have ↑ risk of ophthalmic adverse reactions); History of retinopathy; Geriatric: ↑ risk of adverse reactions; age related ; Obstetric: Use only if benefits outweigh risks to fetus; Pediatric: Pegintron: Children <3 yr (safety and effectiveness not established); Sylatron: Children <18 yr (safety and effectiveness not established).

Adverse Reactions/Side Effects

Central nervous system

  • suicidal ideation (life-threatening)
  • anxiety (most frequent)
  • depression (most frequent)
  • dizziness (most frequent)
  • fatigue (most frequent)
  • headache (most frequent)
  • insomnia (most frequent)
  • aggressive behavior
  • homicidal ideation
  • psychoses

Ear, Eye, Nose, Throat

  • cotton wool spots
  • retinal artery/vein obstruction
  • retinal hemorrhage

Cardiovascular

  • myocardial infarction (life-threatening)
  • arrhythmias
  • cardiomyopathy
  • heart block
  • hypotension
  • tachycardia

Respiratory

  • pulmonary infiltrates/pNEumonitis (life-threatening)
  • pharyngitis (most frequent)
  • cough
  • dyspnea
  • sinusitis

Gastrointestinal

  • colitis (life-threatening)
  • pancreatitis (life-threatening)
  • abdominal pain (most frequent)
  • anorexia (most frequent)
  • diarrhea (most frequent)
  • ↑ liver enzymes (most frequent)
  • nausea (most frequent)
  • dyspepsia
  • vomiting

Dermatologic

  • alopecia (most frequent)
  • dry skin
  • flushing
  • ↑ sweating
  • pruritus
  • rash

Endocrinologic

  • hyperglycemia
  • thyroid abnormalities

Hematologic

  • neutropenia (life-threatening)
  • thromboCytopenia (life-threatening)

Local

  • injection site pain/reactions (most frequent)

Metabolic

  • weight loss

Musculoskeletal

  • musculoskeletal pain (most frequent)

Miscellaneous

  • allergic reactions including anaphylaxis
  • fever (most frequent)
  • flu-like syndrome (most frequent)
  • development of antibodies
  • development/exacerbation of autoimmune disorders
  • rigors

Interactions

Drug-Drug interaction

None currently known.

Route/Dosage

Dose modifications are recommended for depression, renal dysfunction, or hematologic toxicity

Hepatitis C

MonotherapySubcutaneous (Adults) 137–160 kg—150 mcg once weekly for 1 yr.107–136 kg—120 mcg once weekly for 1 yr. 89–106 kg—96 mcg once weekly for 1 yr. 73–88 kg—80 mcg once weekly for 1 yr. 57–72 kg—64 mcg once weekly for 1 yr. 46–56 kg—50 mcg once weekly for 1 yr. ≤45 kg—40 mcg once weekly for 1 yr.Combination Therapy (Duration of therapy is 48 wk for viral genotype 1 or if previously failed therapy; 24 wk for viral genotypes 2 and 3)Subcutaneous (Adults) >105kg—1.5 mcg/kg once weekly based on actual body weight.86–105 kg—150 mcg once weekly. 76–85 kg—120 mcg once weekly. 61–75 kg—96 mcg once weekly. 51–60 kg—80 mcg once weekly. 40–50 kg—64 mcg once weekly. <40 kg—50 mcg once weekly.Subcutaneous (Children 3–17 yr) 60 mcg/m2 once weekly.

Melanoma

Subcutaneous (Adults) 6 mcg/kg/week for 8 doses, then 3 mcg/kg/week for up to 5 yr.

Availability

Powder for injection (Redipen system or vials) (Pegintron): 50 mcg/0.5 mL, 80 mcg/0.5 mL, 120 mcg/0.5 mL, 150 mcg/0.5 mL Powder for injection (Sylatron): 296 mcg/vial, 444 mcg/vial, 888 mcg/vial

Nursing implications

Nursing assessment

  • Assess patient for development of flu-like syndrome (fever, chills, myalgia, headache). Symptoms tend to decrease, even with continued therapy. Acetaminophen or administration at bedtime may be used to control these symptoms.
    • Assess mental status throughout therapy. May cause depression and suicidal ideation. May require discontinuation of medication and continued treatment.
    • Monitor cardiac status, especially in patients with underlying cardiac disease. Monitor ECG prior to and periodically during therapy.
    • Assess patient for signs and symptoms of ulcerative colitis (abdominal pain, bloody diarrhea, fever). Discontinue peginterferon alpha 2b immediately if these symptoms occur; may be fatal. Colitis usually resolves within 1-3 wks of discontinuation.
    • Assess patient for signs of pancreatitis (nausea, vomiting, abdominal pain) periodically during therapy. May be fatal. Suspend therapy in patients with symptoms of pancreatitis. Discontinue therapy if pancreatitis is diagnosed.
    • Observe for signs and symptoms of hypersensitivity reactions (urticaria, angioedema, bronchoconstriction, anaphylaxis). Notify health care professional and discontinue treatment immediately if these occur. Transient rashes do not necessitate discontinuation of therapy.
  • Lab Test Considerations: Monitor serum HCV RNA levels after 24 wks of treatment. Discontinuation should be considered in any patient who has detectable levels after 24 wks of therapy.
    • Monitor for CBC and differential prior to and periodically during therapy. May cause neutropenia and thrombocytopenia. Levels usually return to normal within 4 wks of discontinuation of therapy.
    • Monitor liver function tests periodically during therapy. May cause transient elevated ALT not associated with liver dysfunction.
    • May aggravate hypothyroidism or hyperthyroidism. Monitor thyroid-stimulating hormone levels.
    • May cause hyperglycemia.

Potential Nursing Diagnoses

Risk for injury (Side Effects)
Risk for infection (Side Effects)

Implementation

  • If serious adverse reactions occur, dose should be decreased by 50%. If persistent intolerance occurs following dose reduction, discontinue therapy.
  • Subcutaneous: Two syringes are provided by manufacturer, one for reconstitution and one for administration. Syringes are equipped with a plastic safety shield that locks over the needle with an audible click (green stripe on safety shield fits over red stripe on needle).
    • Reconstitute with 0.7 mL of supplied diluent (sterile water for injection). Do not reconstitute with other diluents. Swirl gently. Discard remaining diluent; for single use only. Do not administer solutions that are discolored or contain particulate matter. Administer immediately after reconstitution; stable for 24 hr if refrigerated. Discard unused portion.
    • Administer subcut.

Patient/Family Teaching

  • Instruct patient to take medication as directed at the same time each day, same day each week. Take missed doses as soon as possible the same day or next day. Notify health care professional if dose is missed for several days. Do not double doses or take more than 1 dose/wk without consulting health care professional.
    • Discuss possibility of flu-like reaction 3–6 hr after dose. Acetaminophen may be taken prior to injection and every 3–4 hr afterward as needed to control symptoms.
    • May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
    • Review side effects with patient. Peginterferon alfa 2b may be temporarily discontinued or dose decreased by 50% if serious side effects occur.
    • Instruct patient to notify health care professional promptly if abdominal pain, bloody diarrhea, or fever occur.
    • Inform patient of the potential for depression and advise patient to notify health care professional immediately if depression or suicidal ideation occurs. May require discontinuation of therapy.
    • Discuss with patient the possibility of hair loss. Explore coping strategies.
    • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
    • Advise patient to inform health care professional if pregnancy is planned or suspected, or if breast feeding.
    • Emphasize need for periodic lab tests to monitor for side effects.
  • Home Care Issues: Instruct patient and family on preparation and correct technique for administration of injection and care and disposal of equipment.

Evaluation/Desired Outcomes

  • Decrease in symptoms and improvement in liver function tests in patients with chronic hepatitis C infection.
  • Improved relapse-free survival (for melanoma)