Peginterferon alfa-2a [Pegylated Interferon alfa-2a]

Approved Indications:

• Chronic Hepatitis C (CHC):
  Treatment of adults and children (≥5 years) with compensated liver disease due to chronic hepatitis C virus (HCV) infection, including those coinfected with HIV.
• As monotherapy when ribavirin is contraindicated or not tolerated.
• In combination with ribavirin in treatment-naïve or experienced patients.
• Chronic Hepatitis B (CHB):
  Treatment of HBeAg-positive and HBeAg-negative chronic hepatitis B in adults with compensated liver disease and evidence of viral replication and liver inflammation.

Clinically Accepted Off-Label Uses:

• Polycythemia Vera (PV):
  Used to control erythrocytosis in patients intolerant to hydroxyurea or younger patients.
• Essential Thrombocythemia (ET):
  To reduce platelet counts and prevent thrombotic complications in high-risk patients.
• Myelofibrosis (MF):
  Occasionally used in early or low-risk cases to control symptoms and cytoses.
• Malignant Melanoma (adjuvant therapy):
  Previously used post-surgical resection of high-risk stage III melanoma (replaced largely by immunotherapies).

Route: Subcutaneous (SC) injection
Formulation: Prefilled syringe or autoinjector (180 mcg/0.5 mL)

Adults:

• Chronic Hepatitis C:
  180 mcg SC once weekly for up to 48 weeks
• In combination with weight-based ribavirin unless contraindicated
• Chronic Hepatitis B:
  180 mcg SC once weekly for 48 weeks (monotherapy)

Pediatrics (≥5 years):

• Chronic Hepatitis C:
  180 mcg/1.73 m² body surface area SC once weekly (max 180 mcg)
• Combined with ribavirin for 48 weeks

Elderly:

• No specific dose adjustment, but start cautiously due to increased sensitivity. Monitor closely.

Renal Impairment:

• CrCl <30 mL/min or ESRD:
  Reduce dose to 135 mcg SC once weekly
• Use with caution and monitor for accumulation

Hepatic Impairment:

• Compensated liver disease (Child-Pugh A): Use as indicated
• Decompensated liver disease (Child-Pugh B/C): Contraindicated

Administration Notes:

• Inject SC in upper arm, abdomen, or thigh
• Do not shake vial/syringe
• Allow syringe to reach room temperature before injection
• Rotate injection sites weekly
• Do not administer IM or IV

Peginterferon alfa-2a is a covalent conjugate of recombinant interferon alfa-2a and polyethylene glycol (PEG). The pegylation slows absorption, reduces renal clearance, and prolongs serum half-life. Interferon alfa-2a binds to type I interferon receptors on host cells, activating the JAK-STAT signaling pathway, leading to the transcription of interferon-stimulated genes. These proteins enhance antiviral activity by promoting apoptosis in infected cells, inhibiting viral replication, and enhancing phagocytic activity of macrophages and cytotoxic T-cell responses. This immunomodulatory and antiviral mechanism helps control hepatitis B and C virus replication.

• Absorption: ~80% bioavailable after SC injection
• Tmax: ~72–96 hours after injection
• Volume of Distribution (Vd): ~0.99 L/kg
• Protein Binding: ~7%
• Metabolism: Primarily proteolytic degradation in liver and kidneys
• Half-life: ~80–90 hours (much longer than standard interferon)
• Steady-State: Achieved within 5–8 weeks of once-weekly dosing
• Excretion: Eliminated primarily via renal and hepatic pathways; not dialyzable

• Pregnancy:
  FDA Category C (former system)
  Animal studies show embryotoxicity. No well-controlled studies in humans. Use only if potential benefit justifies fetal risk.
  If used with ribavirin, pregnancy is contraindicated (Category X). Reliable contraception is required during treatment and for 6 months after.
• Lactation:
  Unknown if excreted in breast milk. Due to potential serious effects in infants, breastfeeding is not recommended during therapy.

• Primary Class: Antiviral / Immunomodulator
• Subclass: Pegylated Type I Interferon (alfa-2a)
• Formulation: Long-acting cytokine conjugate

• Known hypersensitivity to peginterferon alfa-2a, interferon alfa, or formulation components
• Autoimmune hepatitis
• Decompensated liver disease (Child-Pugh class B or C)
• Severe psychiatric illness (e.g., suicidal ideation, psychosis)
• Severe renal impairment without dose reduction
• Pregnancy (if used with ribavirin)
• Neonates and infants

• Neuropsychiatric Effects: Depression, suicidal ideation, aggression—evaluate history before treatment
• Autoimmune Disorders: May induce or worsen autoimmune diseases (e.g., thyroiditis, SLE)
• Hematologic Toxicity: Monitor for neutropenia, thrombocytopenia, and anemia—may require dose adjustments
• Ocular Effects: Retinopathy, retinal hemorrhage, and vision loss—baseline and periodic eye exams recommended
• Infections: Risk of bacterial, fungal, or viral infections—monitor closely
• Growth Suppression in Children: May impair height and weight growth velocity
• Pancreatitis, Hepatotoxicity, Pulmonary Toxicity: Discontinue if signs or symptoms appear
• Cardiovascular Risks: Use cautiously in patients with cardiovascular disease
• Combination with Ribavirin: Teratogenic and hematotoxic—strict contraception required

Common (≥10%):

• Constitutional: Fatigue, fever, chills, headache
• CNS: Depression, anxiety, irritability, insomnia
• GI: Nausea, anorexia, abdominal pain
• Musculoskeletal: Arthralgia, myalgia, back pain
• Hematologic: Neutropenia, anemia, thrombocytopenia
• Dermatologic: Alopecia, rash, dry skin

Serious or Rare:

• Severe depression or suicidal ideation
• Thyroid dysfunction (hypo- or hyperthyroidism)
• Retinal hemorrhage or loss of vision
• Severe infections (e.g., pneumonia, sepsis)
• Hepatic failure or decompensation
• Pulmonary fibrosis or interstitial pneumonitis
• Pancreatitis
• Anaphylaxis (rare)

Onset: Within first 4–8 weeks of treatment
Dose-dependence: Yes; more common with longer duration and higher doses

• Ribavirin: Combined use increases efficacy but also teratogenicity and risk of anemia
• Theophylline: Peginterferon may increase theophylline serum levels—monitor closely
• Antiretrovirals (e.g., zidovudine): Increased risk of neutropenia and anemia
• Methadone: Peginterferon may increase plasma levels of methadone
• CYP450 System: May alter metabolism of CYP substrates, especially in liver-disease patients

• WHO (2023): Peginterferon remains an alternative for hepatitis B in resource-limited settings where newer antivirals are unavailable
• AASLD (2024): Peginterferon no longer first-line for HCV due to availability of direct-acting antivirals (DAAs); remains an option for HBV
• Labeling Update (FDA): Reaffirmed warnings for depression, autoimmune reactions, and growth suppression in pediatrics
• NICE Guidance (UK): Recommends finite 48-week peginterferon monotherapy for HBeAg-negative HBV when oral therapy is not preferred

• Temperature: Store at 2°C to 8°C (36°F to 46°F)
• Freezing: Do not freeze; discard if frozen
• Light: Protect from light; keep in original carton
• Handling:
• Allow to reach room temperature before injecting
• Do not shake
• Inspect visually for particles or discoloration
• Use immediately after opening
• Shelf Life (unopened): Up to expiration date if refrigerated properly