Interferon Alfa-2a [Recombinant]

Approved Indications

• Chronic Hepatitis C Virus (HCV) Infection
• For adults and pediatric patients ≥5 years with compensated liver disease and confirmed HCV infection.
• Often combined with ribavirin to improve sustained virologic response.
• Chronic Hepatitis B Virus (HBV) Infection
• For adults with HBeAg-positive or negative chronic hepatitis B and compensated liver function.
• Hairy Cell Leukemia
• Indicated for active disease in adults to induce remission.
• Kaposi’s Sarcoma (AIDS-related)
• For AIDS-related Kaposi’s sarcoma in patients with minimal systemic symptoms.
• Cutaneous T-Cell Lymphoma (CTCL)
• For advanced or recurrent CTCL after failure of other therapies.
• Renal Cell Carcinoma
• For advanced renal cell carcinoma as monotherapy or in combination.

Off-Label Uses

• Myeloproliferative disorders (e.g., polycythemia vera, essential thrombocythemia).
• Chronic myeloid leukemia (CML) in certain cases.
• Adjuvant therapy for malignant melanoma in select protocols.

Route: Subcutaneous (SC) or Intramuscular (IM) injection.

Adults

• Chronic Hepatitis C:
  3 million IU SC or IM three times weekly for up to 48 weeks (monotherapy or with ribavirin).
• Chronic Hepatitis B:
  2.5–5 million IU SC or IM three times weekly for 16–24 weeks.
• Hairy Cell Leukemia:
  3 million IU SC or IM three times weekly; adjust based on response.
• Kaposi’s Sarcoma (AIDS-related):
  30 million IU SC or IM three times weekly; titrate for tolerance.
• Cutaneous T-Cell Lymphoma:
  3 million IU SC or IM three times weekly; may increase based on response.
• Renal Cell Carcinoma:
  3–10 million IU SC or IM three times weekly.

Pediatric (≥5 years)

• Chronic Hepatitis C:
  3 million IU/m² SC or IM three times weekly for up to 48 weeks.

Special Populations

• Renal Impairment: Use with caution; adjust dose as clinically indicated.
• Hepatic Impairment: Avoid in decompensated liver disease.
• Elderly: Start at lower dose due to increased risk of CNS and cardiac adverse effects.

Administration Tips:

• Rotate injection sites.
• Do not shake vials vigorously; swirl gently.

Interferon alfa-2a binds to specific cell-surface interferon receptors, activating the JAK-STAT signaling pathway. This stimulates transcription of interferon-stimulated genes, producing antiviral proteins such as 2’,5’-oligoadenylate synthetase, which:

• Inhibit viral replication and protein synthesis.
• Enhance macrophage phagocytosis.
• Increase NK cell and cytotoxic T-lymphocyte activity.
  The combined effects result in antiviral, antiproliferative, and immunomodulatory actions.

• Absorption: Peak levels 3–12 hours after SC or IM injection.
• Bioavailability: ~80–90% after SC or IM administration.
• Distribution: Extensive tissue distribution; low CNS penetration.
• Metabolism: Hepatic and renal proteolytic degradation.
• Half-life: 3–8 hours (longer for pegylated forms).
• Excretion: Renal route; metabolites eliminated in urine.
• Onset: Clinical effects take several weeks.

• Pregnancy: Category C — Animal studies show fetal harm; use only if benefits outweigh risks.
• Lactation: Present in breast milk in small amounts; breastfeeding not recommended during therapy.
• Contraception: Effective birth control required during and at least 6 months after therapy.

• Primary Class: Cytokine / Immunomodulator
• Subclass: Recombinant Interferon (Type I)

• Hypersensitivity to interferon alfa or any formulation component.
• Autoimmune hepatitis.
• Decompensated liver disease.
• Severe psychiatric illness (e.g., major depression with suicidal ideation).
• Severe cardiac conditions (e.g., recent myocardial infarction).
• Neonates/infants (due to benzyl alcohol in some products).

• Neuropsychiatric: Depression, suicidal thoughts—monitor closely.
• Hematologic: Risk of neutropenia, anemia, thrombocytopenia—CBC monitoring required.
• Cardiac: May cause arrhythmias; caution in pre-existing heart disease.
• Hepatic: Monitor LFTs; can worsen hepatic dysfunction.
• Autoimmune Disorders: May trigger autoimmune thyroiditis or lupus.
• Ophthalmologic: Risk of retinopathy—baseline and periodic eye exams advised.
• Growth in Children: Monitor height and weight during treatment.
• Seek Immediate Care for: Severe depression, chest pain, sudden vision changes.

Common (≥10%)

• Flu-like symptoms (fever, chills, fatigue, headache, myalgia).
• Gastrointestinal: nausea, anorexia.
• Neuro: insomnia, irritability.

Less Common (1–10%)

• Alopecia.
• Injection site reactions.
• Mild hematologic changes.

Serious/Rare (<1%)

• Severe depression, suicidal ideation.
• Cardiomyopathy, arrhythmias.
• Severe bone marrow suppression.
• Autoimmune thyroiditis.
• Retinopathy and vision loss.

• Antiretrovirals: Zidovudine/didanosine → higher toxicity risk.
• Theophylline: Reduced clearance; monitor plasma levels.
• Methadone: Levels may increase; watch for toxicity.
• CYP450 (esp. CYP1A2): Altered activity; caution with dependent drugs.
• Alcohol: Avoid due to hepatotoxicity risk.

• HCV Management: Interferon largely replaced by DAAs; still used where DAAs unavailable.
• Safety Warnings: Strong emphasis on psychiatric monitoring due to suicide risk.
• Combination Therapy: Ribavirin use continues for certain genotypes in resource-limited settings.

• Store at 2°C–8°C (refrigerated); do not freeze.
• Protect from light.
• Do not shake vigorously.
• Reconstituted solutions should be used immediately or per manufacturer’s guidance.