Peginterferon alfa-2a: a review of approved and investigational uses

In October 2002, the US Food and Drug Administration approved peginterferon alfa-2a for the management of chronic hepatitis C virus (HCV) infection. The addition of polyethylene glycol (PEG) moiety to the interferon (IFN) molecule results in a product with altered pharmacokinetic properties.

The aim of this article is to review the pharmacology, medications interactions, adverse events (AEs), and approved or investigational uses of PEG-IFN alfa-2a for viral hepatitis and oncologic conditions.

Relevant articles were identified through searches of MEDLINE (1980-July 2003) and EMBASE (1980-July 2003). Search terms included, but were not limited to, peginterferon alfa-2a, pharmacokinetics, pharmacology, pharmacodynamics, and therapeutic use, as well as terms for specific disease states and AEs. Further publications were identified from citations of resulting papers.

Pegylation of IFN alfa-2a results in major changes in the pharmacokinetics of the product. Absorption is prolonged and serum concentrations are sustained over the dosing regimen. PEG-IFN alfa-2a has been shown to be more effective with or without ribavirin (RBV), in the management of treatment-naive patients with chronic HCV infection, than unmodified IFN alfa-2a with or without RBV. Results in other disease states are still preliminary. AEs are similar, in incidence and severity, to those occurring with unmodified IFN. They include earlier hematologic symptoms and fewer influenza-like symptoms. Drug-drug interactions are the same as those occurring with the unmodified IFN product.

The pharmacokinetic profile of IFN alfa-2a is improved by pegylation, which enables less frequent administration and results in improved efficacy with a similar side-effect profile. Combination of PEG-IFN alfa-2a with RBV is associated with a greater chance of achieving a sustained virologic response in treatment-naive patients with chronic HCV, compared with unmodified IFN alfa-2a/RBV combinations. Documentation of efficacy in other conditions awaits results of controlled clinical trials.