Interferon alfa-2a

Summary

Interferon alfa-2a (brand name Roferon-A) is a recombinant human type I interferon produced in E. coli. It was approved for treatment of hairy cell leukemia, chronic myelogenous leukemia, AIDS-related Kaposi's sarcoma, and chronic hepatitis C. It has largely been superseded by pegylated interferons and direct-acting antivirals in hepatitis C treatment. Roferon-A was withdrawn from US and EU markets but biosimilars and other alfa-2a formulations remain in use globally.

Mechanism of Action

Binds to cell surface interferon-alpha/beta receptors (IFNAR1/IFNAR2), activating the JAK-STAT signaling pathway (JAK1, TYK2), leading to transcription of interferon-stimulated genes (ISGs). This results in antiviral, antiproliferative, and immunomodulatory effects including enhanced NK cell activity, upregulation of MHC class I expression, and inhibition of viral replication.

Routes of Administration

Goals & Uses

• AIDS-Related Kaposi's SarcomaOncology / Infectious DiseaseModerate
• Chronic Hepatitis C Antiviral TreatmentInfectious Disease / AntiviralHigh
• Antiviral ImmunomodulationImmunologyModerate
• Chronic myelogenous leukemia (CML)OncologyHigh
• Hairy cell leukemia treatmentOncologyHigh
• Follicular LymphomaOncologyModerate

Contraindications

• Severe Psychiatric Disorders (e.g., severe depression, suicidality)PsychiatricHigh
• Hypersensitivity to interferon alfa or formulation componentsImmunologicHigh
• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Neonates and Infants (benzyl alcohol-containing formulations)PediatricHigh
• Autoimmune hepatitisHepatic / AutoimmuneHigh
• Decompensated liver diseaseHepatic ImpairmentHigh

Adverse Effects

• Injection site reactionsLocalCommon
• Hepatotoxicity / Transaminase ElevationHepaticCommon
• Myelosuppression (neutropenia, thrombocytopenia, anemia)HematologicCommon
• Flu-like SyndromeSystemic / ConstitutionalCommon
• Thyroid dysfunction (hypo- or hyperthyroidism)EndocrineUncommon
• Neuropsychiatric Effects (depression, irritability, suicidality)Psychiatric / NeurologicalCommon

Drug Interactions

• Zidovudine (AZT)High
• Immunosuppressants (e.g., cyclosporine)Moderate
• RibavirinModerate
• ClozapineHigh
• TheophyllineModerate
• MethadoneModerate

Population Constraints

• PregnancyReproductive SafetyRelative
• Cardiac DiseaseCardiovascularRelative
• Renal impairmentOrgan ImpairmentRelative
• Pediatric patientsAgeRelative
• Pre-existing Psychiatric ConditionsPsychiatricRelative
• Elderly patientsAgeRelative

Regulatory Status

• European UnionWithdrawnApproved: Hairy cell leukemia, Chronic myelogenous leukemia, Follicular lymphoma, Chronic hepatitis B and C, AIDS-related Kaposi's sarcomaRoferon-A marketing authorization withdrawn in EU. Pegasys (peginterferon alfa-2a) remains EMA-approved for hepatitis B and C.
• United StatesWithdrawnApproved: Hairy cell leukemia, AIDS-related Kaposi's sarcoma, Chronic myelogenous leukemia, Follicular non-Hodgkin's lymphoma, Chronic hepatitis CRoferon-A (non-pegylated interferon alfa-2a) voluntarily withdrawn by Roche in 2007. Pegylated form (Pegasys) remains FDA-approved.
• United KingdomWithdrawnApproved: Hairy cell leukemia, Chronic hepatitis B and C, Follicular lymphomaNon-pegylated Roferon-A no longer authorized in UK. Pegylated alfa-2a (Pegasys) is licensed via MHRA for chronic hepatitis B and C.

Roferon-A (Roche) was voluntarily withdrawn from the US market in 2007 and from the EU market. Pegylated interferon alfa-2a (Pegasys) remains approved. Various biosimilar formulations are approved in some countries. Not interchangeable with interferon alfa-2b.

Evidence & Sources

No sources recorded yet.