Peginterferon Alfa-2b

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Kit, Subcutaneous [preservative free]:

Peg-Intron Redipen: 50 mcg/0.5 mL [DSC], 80 mcg/0.5 mL [DSC], 120 mcg/0.5 mL [DSC], 150 mcg/0.5 mL [DSC]

Peg-Intron Redipen Pak 4: 120 mcg/0.5 mL [DSC]

PegIntron: 50 mcg/0.5 mL, 80 mcg/0.5 mL [DSC], 120 mcg/0.5 mL [DSC], 150 mcg/0.5 mL [DSC] [contains polysorbate 80]

Sylatron: 200 mcg, 300 mcg, 600 mcg [contains polysorbate 80]

Pharmacology

Mechanism of Action

Alpha interferons are a family of proteins, produced by nucleated cells, that have antiviral, antiproliferative, and immune-regulating activity. There are 16 known subtypes of alpha interferons. Interferons interact with cells through high affinity cell surface receptors. Following activation, multiple effects can be detected including induction of gene transcription. Inhibits cellular growth, alters the state of cellular differentiation, interferes with oncogene expression, alters cell surface antigen expression, increases phagocytic activity of macrophages, and augments cytotoxicity of lymphocytes for target cells.

Pharmacokinetics/Pharmacodynamics

Excretion

Urine (~30%); clearance reduced in renal impairment by 17% in moderate dysfunction, 44% in severe dysfunction

Time to Peak

CHC: 15 to 44 hours

Half-Life Elimination

CHC: ~40 hours (range: 22 to 60 hours); Melanoma: ~43 to 51 hours

Use in Specific Populations

Special Populations: Renal Function Impairment

Mean exposure is increased 1.4-fold in patients with moderate impairment and by 2.1-fold in patients with severe renal impairment (including ESRD on dialysis) following a single 4.5 mcg/kg dose. Reduce dose in patients with moderate or severe renal impairment.

Special Populations: Children

In children receiving PegIntron 60 mcg/m²/week, exposure may be ~50% higher than that observed in adults receiving 1.5 mcg/kg/week.

Use: Labeled Indications

Melanoma (adjuvant therapy): Sylatron: Adjuvant treatment of melanoma (with microscopic or gross nodal involvement within 84 days of definitive surgical resection, including complete lymphadenectomy). Note: Indications in the manufacturer's labeling may not reflect current clinical practices.

Contraindications

Hypersensitivity (including urticaria, angioedema, bronchoconstriction, anaphylaxis, Stevens Johnson syndrome, and toxic epidermal necrolysis) to peginterferon alfa-2b, interferon alfa-2b, other alfa interferons, or any component of the formulation; autoimmune hepatitis; decompensated liver disease (Child-Pugh score >6, classes B and C)

Documentation of allergenic cross-reactivity for interferons is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty

Combination therapy with peginterferon alfa-2b and ribavirin is also contraindicated in pregnancy, females who may become pregnant, males with pregnant partners; hemoglobinopathies (eg, thalassemia major, sickle-cell anemia); renal dysfunction (CrCl <50 mL/minute)

Dosage and Administration

Dosing: Adult

Note: PegIntron Redipen and PegIntron 80 mcg, 120 mcg, and 150 mcg vials have been discontinued in the US for more than 1 year.

Melanoma (adjuvant therapy): SubQ: Initial: 6 mcg/kg/week for 8 doses; Maintenance: 3 mcg/kg/week for up to 5 years. Note: Premedicate with acetaminophen (500 to 1,000 mg orally) 30 minutes prior to the first dose and as needed for subsequent doses thereafter.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Due to differences in dosage, patients should not change brands of interferon alfa therapy.

Chronic hepatitis B virus (HBV) infection (HIV-exposed/-positive): Adolescents: PegIntron: SubQ: 1.5 mcg/kg once weekly for 48 weeks (DHHS [adult], 2013)

Chronic hepatitis C virus (HCV) infection:

Non-HIV-exposed/-infected:

Manufacturer's labeling: Children ≥3 years and Adolescents: PegIntron: SubQ: 60 mcg/m² once weekly (in combination with ribavirin). Treatment duration: 48 weeks (genotype 1); 24 weeks (genotypes 2 and 3). Consider discontinuation of combination therapy in patients with HCV (genotype 1) at 12 weeks if a 2 log decrease in HCV-RNA has not been achieved or if HCV-RNA is still detectable at 24 weeks. Note: Adolescents who reach their 18th birthday during treatment should remain on the pediatric regimen.

Alternate dosing: American Association for the Study of Liver Diseases (AASLD) recommendations: Children ≥2 years and Adolescents: PegIntron: SubQ: 60 mcg/m² once weekly (in combination with oral ribavirin) for 48 weeks (all genotypes) (Ghany, 2009)

HIV-exposed/-positive (coinfection):

Children ≥3 years: PegIntron: SubQ: 60 mcg/m² once weekly (in combination with ribavirin). Treatment duration: 48 weeks, regardless of genotype (DHHS [pediatric], 2013)

Adolescents: PegIntron: SubQ: 1.5 mcg/kg once weekly (in combination with ribavirin). Treatment duration: 48 weeks, regardless of genotype (DHHS [adult], 2013)

Dosing adjustment for toxicity:

Chronic hepatitis C: Dosage adjustment for depression (severity based upon DSM-IV criteria):

Mild depression: Children and Adolescents: No dosage adjustment required; evaluate once weekly by visit/phone call. If depression remains stable, continue weekly visits. If depression improves, resume normal visit schedule. For worsening depression, see “Moderate depression” below.

Moderate depression: Evaluate once weekly with an office visit at least every other week. If depression remains stable, consider psychiatric evaluation and continue with reduced dosing. If symptoms improve and remain stable for 4 weeks, resume normal visit schedule; continue reduced dosing or return to normal dose. For worsening depression or development of severe depression, discontinue therapy permanently and obtain immediate psychiatric consultation. Utilize followup psychiatric therapy as needed.

Children and Adolescents: Decrease to 40 mcg/m² once weekly, may further decrease to 20 mcg/m² once weekly if needed

Severe depression: Children and Adolescents: Discontinue peginterferon alfa-2b and ribavirin permanently. Obtain immediate psychiatric consultation.

Chronic hepatitis C: Dosage adjustment in hematologic toxicity:

Children and Adolescents:

Hemoglobin decrease >2 g/dL in any 4-week period in patients with stable cardiac disease: Reduce peginterferon alfa-2b dose by 50%; monitor and evaluate weekly. If after 4 weeks of dose reduction the hemoglobin remains <12 g/dL: Permanently discontinue both peginterferon alfa-2b and ribavirin.

Hemoglobin 8.5 to <10 g/dL in patients without history of cardiac disease: No dosage adjustment for peginterferon alfa-2b. Decrease ribavirin dose.

WBC 1000 to <1500/mm³, neutrophils 500 to <750/mm³, or platelets 50,000 to <70,000/mm³: Reduce peginterferon alfa-2b dose to 40 mcg/m² once weekly; may further reduce to 20 mcg/m² once weekly

Hemoglobin <8.5 g/dL, WBC <1000/mm³, neutrophils <500/mm³, or platelets <50,000/mm³: Permanently discontinue peginterferon alfa-2b and ribavirin

Dosing: Adjustment for Toxicity

Melanoma:

Discontinue for any of the following: Persistent or worsening severe neuropsychiatric disorders, grade 4 nonhematologic toxicity, new or worsening retinopathy, new-onset ventricular arrhythmia or cardiovascular decompensation, evidence of hepatic injury (severe; grade 3) or hepatic decompensation (Child-Pugh score >6 [class B or C]), development of hyper- or hypothyroidism or diabetes mellitus that cannot be effectively managed with medication, or inability to tolerate a dose of 1 mcg/kg/week.

Temporarily withhold for any of the following: ANC <500/mm³, platelets <50,000/mm³, Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, nonhematologic toxicity ≥ grade 3.

May reinitiate at a reduced dose once ANC ≥500/mm³, platelets ≥50,000/mm³, ECOG PS 0 to 1, and nonhematologic toxicity completely resolved or improved to grade 1.

Reduced dose schedule, weeks 1 to 8:

First dose reduction (if prior dose 6 mcg/kg/week): 3 mcg/kg/week.

Second dose reduction (if prior dose 3 mcg/kg/week): 2 mcg/kg/week.

Third dose reduction (if prior dose 2 mcg/kg/week): 1 mcg/kg/week.

Discontinue permanently if unable to tolerate 1 mcg/kg/week.

Reduced dose schedule, weeks 9 to 260:

First dose reduction (if prior dose 3 mcg/kg/week): 2 mcg/kg/week.

Second dose reduction (if prior dose 2 mcg/kg/week): 1 mcg/kg/week.

Discontinue permanently if unable to tolerate 1 mcg/kg/week.

Reconstitution

Redipen: Hold cartridge upright and press the two halves together until there is a “click”. Gently invert to mix; do not shake; do not reuse (single use).

Peg-Intron (vial): Add 0.7 mL sterile water for injection, USP (supplied single-use diluent; discard unused portion) to the vial. Gently swirl. Do not re-enter vial after dose removed.

Sylatron (vial): Add 0.7 mL sterile water for injection and swirl gently (do not shake), resulting in the following concentrations (do not withdraw more than 0.5 mL from each vial):

296 mcg vial: 40 mcg/0.1 mL

444 mcg vial: 60 mcg/0.1 mL

888 mcg vial: 120 mcg/0.1 mL

Administration

For SubQ administration; rotate injection site. The weekly dose may be administered at bedtime to reduce flu-like symptoms.

Storage

Prior to reconstitution, store Redipen at 2°C to 8°C (36°F to 46°F). Store intact vials at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not freeze. Once reconstituted each product should be used immediately or may be stored for ≤24 hours at 2°C to 8°C (36°F to 46°F); do not freeze. Do not shake. Keep away from heat. Products do not contain preservative (single use; do not reuse).

Drug Interactions

Aldesleukin: Interferons (Alfa) may enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination. Consider therapy modification

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

CYP2D6 Substrates (High risk with Inhibitors): Peginterferon Alfa-2b may decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

FLUoxetine: Peginterferon Alfa-2b may decrease the serum concentration of FLUoxetine. Monitor therapy

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Methadone: Interferons (Alfa) may increase the serum concentration of Methadone. Monitor therapy

Pegloticase: May diminish the therapeutic effect of PEGylated Drug Products. Monitor therapy

Pegvaliase: PEGylated Drug Products may enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Monitor therapy

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Ribavirin (Oral Inhalation): Interferons (Alfa) may enhance the adverse/toxic effect of Ribavirin (Oral Inhalation). Hemolytic anemia has been observed. Monitor therapy

Ribavirin (Systemic): Interferons (Alfa) may enhance the adverse/toxic effect of Ribavirin (Systemic). Hemolytic anemia has been observed. Monitor therapy

Telbivudine: Peginterferon Alfa-2b may enhance the adverse/toxic effect of Telbivudine. Specifically, the risk for peripheral neuropathy may be increased. Avoid combination

Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Interferons (Alfa) may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Zidovudine: Interferons may enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine. Monitor therapy

Adverse Reactions

Antiviral:

>10%:

Central nervous system: Headache (56%), fatigue (including asthenia; ≤52%), depression (29%), anxiety (≤28%), emotional lability (≤28%), irritability (≤28%), insomnia (23%), rigors (23%), dizziness (12%)

Dermatologic: Alopecia (22%), pruritus (12%)

Endocrine & metabolic: Weight loss (11%)

Gastrointestinal: Nausea (26%), anorexia (20%), diarrhea (18%), abdominal pain (15%)

Infection: Viral infection (11%)

Local: Inflammation at injection site (47%), injection site reaction (47%)

Neuromuscular & skeletal: Myalgia (54%), weakness (52%), musculoskeletal pain (28%), arthralgia (23%)

Miscellaneous: Fever (22%)

1% to 10%:

Cardiovascular: Chest pain (6%), flushing (6%)

Central nervous system: Lack of concentration (10%), right upper quadrant pain (8%), malaise (7%), nervousness (4%), agitation (2%), suicidal ideation (≤2%)

Dermatologic: Diaphoresis (6%), skin rash (6%)

Endocrine & metabolic: Hypothyroidism (5%), menstrual disease (4%), hyperthyroidism (3%)

Gastrointestinal: Vomiting (7%), dyspepsia (6%), xerostomia (6%), constipation (1%)

Hematologic & oncologic: Thrombocytopenia (7%), neutropenia (6%)

Hepatic: Increased serum alanine aminotransferase (10%), hepatomegaly (6%)

Immunologic: Antibody development (neutralizing: 2%)

Local: Pain at injection site (2% to 3%)

Ophthalmic: Conjunctivitis (4%), blurred vision (2%)

Respiratory: Pharyngitis (10%), cough (8%), sinusitis (7%), dyspnea (4%), rhinitis (2%)

Antineoplastic:

>10%:

Central nervous system: Fatigue (94%), headache (70%), chills (63%), depression (59%), dizziness (35%), neuropathy (olfactory) (23%), paresthesia (21%)

Dermatologic: Exfoliative dermatitis (36%), alopecia (34%)

Endocrine & metabolic: Weight loss (11%)

Gastrointestinal: Anorexia (69%), nausea (64%), dysgeusia (38%), diarrhea (37%), vomiting (26%)

Hepatic: Increased serum alanine aminotransferase (≤77%), increased serum aspartate aminotransferase (≤77%), increased serum alkaline phosphatase (23%)

Immunologic: Antibody development (binding antibodies: 35%)

Local: Injection site reaction (62%)

Neuromuscular & skeletal: Myalgia (68%), arthralgia (51%)

Miscellaneous: Fever (75%)

1% to 10%:

Cardiovascular: Bundle branch block (≤4%), myocardial infarction (≤4%), supraventricular cardiac arrhythmia (≤4%), ventricular tachycardia (≤4%)

Endocrine & metabolic: Increased gamma-glutamyl transferase (8%)

Genitourinary: Proteinuria (7%)

Hematologic & oncologic: Anemia (6%)

Respiratory: Dyspnea (6%), cough (5%)

<1%, postmarketing, and/or case reports: Aggressive behavior, amnesia, anaphylaxis, angina pectoris, angioedema, aphthous stomatitis, aplastic anemia, auditory impairment, bacterial infection, bipolar mood disorder, brain disease (including exacerbations), bronchiolitis obliterans, bronchoconstriction, cardiac arrest, cardiac arrhythmia, cardiomyopathy, cerebrovascular accident, colitis, cytopenia, dehydration, diabetes mellitus, diabetic ketoacidosis, drug dependence (including relapse), drug overdose, dysgeusia, erythema multiforme, exacerbation of autoimmune disease, fungal infection, hallucination, hearing loss, hemorrhagic colitis, homicidal ideation, hyperglycemia, hypersensitivity reaction, hypertension, hypertriglyceridemia, hypotension, immune thrombocytopenia, interstitial nephritis, interstitial pneumonitis, ischemic colitis, leukopenia, lupus-like syndrome, macular edema, mania, migraine, myositis, optic neuritis, palpitations, pancreatitis, papilledema, paresthesia, pericarditis, peripheral neuropathy, pneumonia, psoriasis, pulmonary fibrosis, pulmonary hypertension, pulmonary infiltrates, pure red cell aplasia, reactivation of HBV, renal failure syndrome, renal insufficiency (includes increases in serum creatinine), retinal cotton-wool spot, retinal detachment, retinal hemorrhage, retinal thrombosis, retinopathy, rhabdomyolysis, rheumatoid arthritis, sarcoidosis, seizure, sepsis, Stevens-Johnson syndrome, systemic lupus erythematosus, tachycardia, thrombotic thrombocytopenic purpura, thyroiditis, tongue discoloration, toxic epidermal necrolysis, ulcerative colitis, urticaria, vertigo, vision loss, visual disturbance, Vogt-Koyanagi-Harada syndrome

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Causes bone marrow suppression, including potentially severe cytopenias; alfa interferons may (rarely) cause aplastic anemia. Use with caution in patients who are chronically immunosuppressed, with low peripheral blood counts or myelosuppression, including concurrent use of myelosuppressive therapy. Dosage modification may be necessary for hematologic toxicity. Combination therapy with ribavirin may potentiate the neutropenic effects of alfa interferons. When used in combination with ribavirin, an increased incidence of anemia was observed when using ribavirin weight-based dosing, as compared to flat-dose ribavirin.
• Colitis: Ulcerative or hemorrhagic/ischemic colitis has been observed with alfa interferons (within 12 weeks of initiation); discontinue therapy if signs of colitis (abdominal pain, bloody diarrhea, fever) develop; symptoms typically resolve within 1 to 3 weeks.
• Dental/periodontal disorders: Have been reported with combination therapy; dry mouth may affect teeth and mucous membranes. Instruct patients to brush teeth twice daily; encourage regular dental exams. Rinse mouth thoroughly after vomiting.
• Flu-like symptoms: Interferons are commonly associated with flu-like symptoms. Use with caution in patients with debilitating conditions.
• Hypersensitivity: Acute hypersensitivity reactions (eg, urticaria, angioedema, bronchoconstriction, anaphylaxis) and cutaneous reactions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported (rarely) with alfa interferons; prompt discontinuation and management is recommended. Transient rashes do not require interruption of therapy.
• Hypertriglyceridemia: Has been reported (may result in pancreatitis); periodically monitor and manage with appropriate treatment; consider discontinuing peginterferon if persistent and severe (triglycerides >1000 mg/dL), particularly if combined with symptoms of pancreatitis.
• Neuropsychiatric disorders: [US Boxed Warning]: May cause or aggravate severe depression or other neuropsychiatric adverse events (including suicide and suicidal ideation) in patients with and without a history of psychiatric disorder; monitor closely with clinical evaluations (periodic). Discontinue treatment with worsening or persistently severe signs/symptoms of neuropsychiatric disorders (eg, depression, encephalopathy, psychosis). Many cases resolve upon discontinuation, although some cases may persist. Addiction relapse, aggression, depression, homicidal ideation and suicidal behavior/ideation have been observed with peginterferon alfa-2b; bipolar disorder, encephalopathy, hallucinations, mania, and psychosis have been observed with other alfa interferons. Onset may be delayed (up to 6 months after discontinuation). Higher doses may be associated with the development of encephalopathy (higher risk in elderly patients). Use with caution in patients with a history of psychiatric disorders, including depression or substance abuse history. New or exacerbated neuropsychiatric or substance abuse disorders are best managed with early intervention. Drug screening and periodic health evaluation (including monitoring of psychiatric symptoms) is recommended if initiating treatment in patients with coexisting psychiatric condition or substance abuse disorders. Monitor all patients for evidence of depression and other psychiatric symptoms; patients being treated for melanoma should be monitored for depression and psychiatric symptoms every 3 weeks during the first 8 weeks of treatment and every 6 months thereafter and permanently discontinue treatment if psychiatric symptoms persist, worsen or if suicidal behavior develops. Patients should continue to be monitored for 6 months after completion of therapy.
• Ophthalmic effects: Ophthalmologic disorders (including decreased visual acuity, blindness, macular edema, retinal hemorrhages, optic neuritis, papilledema, cotton wool spots, retinal detachment [serous], and retinal artery or vein thrombosis) have occurred with peginterferon alfa-2b and/or with other alfa interferons. Prior to start of therapy, ophthalmic exams are recommended for all patients; patients with diabetic or hypertensive retinopathy should have periodic ophthalmic exams during treatment; a complete eye exam should be done promptly in patients who develop ocular symptoms. Permanently discontinue treatment with new or worsening ophthalmic disorder.
• Pancreatitis: Pancreatitis, including fatal cases, has been observed with alfa interferon therapy; withhold treatment for suspected pancreatitis; discontinue therapy for known pancreatitis.
• Pulmonary effects: May cause or aggravate dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis which may result in respiratory failure; may recur upon rechallenge with treatment; monitor closely. Use with caution in patients with existing pulmonary disease (eg, chronic obstructive pulmonary disease). Withhold combination therapy with ribavirin for development of pulmonary infiltrate or pulmonary function impairment.

Disease-related concerns:

• Autoimmune disease: [US Boxed Warning]: May cause or exacerbate autoimmune disorders; monitor closely with clinical and lab evaluations (periodic); discontinue treatment in patients with worsening or persistently severe signs/symptoms of autoimmune disease; may resolve with discontinuation. Thyroiditis, thrombotic microangiopathy, immune thrombocytopenia, rheumatoid arthritis, interstitial nephritis, systemic lupus erythematosus, and psoriasis have been reported with therapy; use with caution in patients with autoimmune disorders.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease or a history of cardiovascular disease; hypotension, arrhythmia, bundle branch block, tachycardia, cardiomyopathy, angina pectoris and MI have been observed with treatment. Patients with pre-existing cardiac abnormalities should have baseline ECGs prior to combination treatment with ribavirin; closely monitor patients with a history of MI or arrhythmia. Patients with a history of significant or unstable cardiac disease should not receive combination treatment with ribavirin. Discontinue treatment (permanently) for new-onset ventricular arrhythmia or cardiovascular decompensation.
• Diabetes: Diabetes mellitus (including new-onset type I diabetes) and hyperglycemia have been reported; discontinue if diabetes cannot be effectively managed with medication. Use with caution in patients with a history of diabetes mellitus, particularly if prone to DKA.
• Hepatic impairment: Use is contraindicated in patients with hepatic decompensation or autoimmune hepatitis. Discontinue treatment immediately with hepatic decompensation (Child Pugh score >6) or evidence of severe hepatic injury. Patients with chronic hepatitis C (CHC) with cirrhosis and patients coinfected with human immunodeficiency virus (HIV) receiving antiretroviral therapy are at increased risk for hepatic decompensation; monitor closely. A transient increase in ALT (2 to 5 times above baseline) which is not associated with liver dysfunction may occur with peginterferon alfa-2b use (for the treatment of chronic hepatitis C); may continue treatment with close monitoring. Instruct patients to avoid alcohol; may increase hepatic effects.
• Infectious disorders: [US Boxed Warning]: May cause or aggravate infectious disorders; monitor closely with clinical and lab evaluations (periodic); discontinue treatment in patients with worsening or persistently severe signs/symptoms of infectious disorders; may resolve with discontinuation. Interferon therapy is commonly associated with flu-like symptoms, including fever; rule out other causes/infection with persistent or high fever.
• Ischemic disorders: [US Boxed Warning]: May cause or aggravate ischemic and hemorrhagic cerebrovascular events; monitor closely with clinical and lab evaluations (periodic); discontinue treatment in patients with worsening or persistent ischemia; may resolve with discontinuation. Have been reported in patients without risk factors for stroke.
• Renal impairment: Use with caution in patients with renal impairment (CrCl <50 mL/minute); monitor closely for signs of interferon toxicity. For the treatment of chronic hepatitis C, dosage adjustments are recommended with monotherapy in patients with moderate to severe impairment; do not use combination therapy with ribavirin in adults with renal dysfunction (CrCl <50 mL/minute); discontinue if serum creatinine >2 mg/dL in children. Dosage adjustment is also recommended when used for the treatment of melanoma. Serum creatinine increases have been reported in patients with renal insufficiency.
• Thyroid disorders: Use with caution in patients with thyroid disorders; may cause or aggravate hyper- or hypothyroidism. Discontinue use in patients with thyroid disease who cannot be controlled with medication.

Concurrent drug therapy issues:

• Combination therapy with ribavirin: Ribavirin causes hemolytic anemia; the anemia associated with ribavirin therapy may result in a worsening of cardiac disease. Additional risks are associated with combination therapy; if used in combination with ribavirin, all warnings and precautions related to the use of ribavirin should be followed.
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Telbivudine: Peripheral neuropathy has been reported with alpha interferons when used in combination with telbivudine.

Special populations:

• Elderly: Use with caution in elderly patients; the potential adverse effects (eg, neuropsychiatric events, cardiac events, systemic effects) may be more pronounced. Encephalopathy has also been observed in primarily elderly patients treated with higher doses of peginterferon alfa-2b. For the treatment of hepatitis, elderly patients generally do not respond to interferon treatment as well as younger patients. When used in combination with ribavirin, closely monitor adults >50 years of age for the development of anemia.
• Pediatric: Growth velocity (height and weight) was decreased in children on combination treatment with ribavirin, during the length of treatment. In clinical studies, decreases were noted in weight and height for age z-scores and normative growth curve percentiles. Severely inhibited growth velocity has been noted. Following treatment, rebound growth and weight gain occurred in most patients; however, a small percentage did not. Long-term follow-up data indicate that combination therapy may inhibit growth, resulting in reduced adult height in some patients. Growth should be closely monitored in pediatric patients during therapy and posttreatment until growth catch-up has occurred.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
• Product variability: Due to differences in dosage, patients should not change brands of interferon.

Other warnings/precautions:

• Appropriate use: Combination therapy with ribavirin or monotherapy for the treatment of chronic hepatitis C is not a recommended treatment regimen (AASLD/IDSA 2017). Safety and efficacy have not been established in patients who have received organ transplants or are coinfected with HIV or hepatitis B. Patients with significant bridging fibrosis or cirrhosis, genotype 1 infection or who have not responded to prior therapy, including previous pegylated interferon treatment are less likely to benefit from combination therapy with peginterferon alfa-2b and ribavirin.

Monitoring Parameters

Manufacturer’s labeling:

Baseline and periodic TSH (for patients being treated for melanoma, obtain baseline within 4 weeks prior to treatment initiation, and then at 3 and 6 months, and every 6 months thereafter during treatment); CBC with differential and platelets; serum chemistries, liver function tests (for patients with melanoma, monitor serum bilirubin, ALT, AST, alkaline phosphatase, and LDH at 2 and 8 weeks, and 2 and 3 months following initiation, then every 6 months during therapy), renal function, triglycerides; serum glucose or HbA_1c (for patients with diabetes mellitus). Evaluate pregnancy status prior to use (in females of reproductive potential) regardless of indication.

Evaluate for depression and other psychiatric symptoms before and after initiation of therapy; patients being treated for melanoma should be monitored for depression and psychiatric symptoms every 3 weeks during the first eight weeks of treatment and every 6 months thereafter, and continued monitoring for 6 months after the last dose; baseline ophthalmic eye examination; periodic ophthalmic exam in patients with diabetic or hypertensive retinopathy; baseline ECG in patients with cardiac disease; serum glucose or HbA_1c (for patients with diabetes mellitus).

Pregnancy

Pregnancy Considerations

Alfa interferon is endogenous to normal amniotic fluid (Lebon 1982); however, placenta perfusion studies note exogenous interferon alfa does not cross the placenta (Waysbort 1993). The Health and Human Services (HHS) perinatal HIV guidelines recommend against the use of peginterferon-alfa during pregnancy because of its antigrowth and antiproliferative effects (HHS [perinatal] 2019). Animal reproduction studies have demonstrated abortifacient effects.

Treatment of hepatitis C is not currently recommended to treat maternal infection or to decrease the risk of mother-to-child transmission during pregnancy (Tran 2016). HCV-infected females of childbearing potential should consider postponing pregnancy until therapy is complete to reduce the risk of HCV transmission (AASLD/IDSA 2017).

Verify pregnancy status prior to administration in females of reproductive potential. Disruption of the normal menstrual cycle was observed in animal studies. Female patients of reproductive potential should use effective contraception during treatment and for ≥10 days after the last peginterferon alfa-2b dose.

Peginterferon Alfa-2b in combination with ribavirin is contraindicated in pregnant females and males whose female partners are pregnant. Combination therapy with ribavirin may cause birth defects and death in an unborn child. If used in combination with ribavirin, all warnings related to the use of ribavirin and pregnancy and/or contraception should be followed. Refer to the ribavirin monograph for additional information.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience flu-like symptoms, nausea, vomiting, diarrhea, lack of appetite, hair loss, trouble sleeping, weight loss, headache, flushing, muscle pain, joint pain, change in taste, dry mouth, or injection site irritation. Have patient report immediately to prescriber signs of thyroid problems (change in weight without trying, anxiety, agitation, feeling very weak, hair thinning, depression, neck swelling, difficulty focusing, inability handling heat or cold, menstrual changes, tremors, or sweating), signs of depression (thoughts of suicide, anxiety, emotional instability, confusion), sensing things that seem real but are not, psychosis, signs of infection, signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), chest pain, fast heartbeat, abnormal heartbeat, severe dizziness, passing out, shortness of breath, bruising, bleeding, loss of strength and energy, vision changes, eye pain, severe eye irritation, blindness, teeth or gingival changes, burning or numbness feeling, signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin), signs of bowel problems (black, tarry, or bloody stools; fever; mucus in stools; vomiting; vomiting blood; severe abdominal pain; constipation; diarrhea), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.