Peginterferon Alfa | Encyclopeptide

Chemical Identity

Property	Value
Molecular Weight	~31 kDa (40 kDa PEG) or ~60 kDa (12 kDa PEG)
PEG Size	12 kDa (Pegasys) or 40 kDa (Peg-Intron)
CAS Number	198153-51-4 (Pegasys), 215647-85-1 (Peg-Intron)
Route	SC

Structure

Peginterferon alfa is interferon alfa conjugated to polyethylene glycol (PEG). Two forms exist: peginterferon alfa-2a (Pegasys, 40 kDa branched PEG) and peginterferon alfa-2b (Peg-Intron, 12 kDa linear PEG). PEGylation reduces renal clearance and immunogenicity while extending half-life.

Mechanism of Action

Like native IFN-alpha, peginterferon activates IFNAR1/IFNAR2, inducing ISGs with antiviral, antiproliferative, and immunomodulatory effects. The extended half-life maintains sustained interferon signaling with once-weekly dosing, improving efficacy and adherence.

Clinical Applications

Hepatitis B: Peginterferon alfa-2a (first-line option)
Hepatitis C: With ribavirin (historical standard, now replaced by DAAs)
Hairy cell leukemia: Peginterferon alfa-2a
Essential thrombocythemia: Off-label
Melanoma: Adjuvant therapy (high-dose)

Pharmacokinetics

Half-life: 77 hours (Pegasys), 54 hours (Peg-Intron)
Tmax: 72-96 hours (Pegasys), 15-44 hours (Peg-Intron)
Bioavailability: 61-84% (SC)
Dosing: Weekly SC injection
Route: SC

Safety and Side Effects

Flu-like symptoms (50-80%), fatigue (60%), depression (20-30%), neutropenia, thrombocytopenia, hepatotoxicity, autoimmune thyroiditis, and retinopathy. Similar to interferon alfa but with more sustained exposure.

References

Manns, M.P., et al. (2001). Peginterferon alfa-2b plus ribavirin for hepatitis C. New England Journal of Medicine, 345, 222-228.
Hadziyannis, S.J., et al. (2004). Peginterferon alfa-2a for hepatitis C. Annals of Internal Medicine, 140, 346-355.