Peginterferon alfa-2a is a recombinant cytokine and fever and flu-like symptoms are very common adverse reactions. Experience seems to be that infection may trigger attacks of acute porphyria. Infections are reported when using peginterferon alfa-2a, but is not very common. There is no evidence to show that inflammation and fever alone are triggering factors. Chronic inflammatory diseases are not associated with higher incidence of porphyric attacks. Infection and inflammation has also shown to down-regulate the activity and expression of cytochrome P450 enzymes involved in hepatic drug clearance. Through inhibition of ALAS1-induction, peginterferon alfa-2a might therefore protect against attacks of acute porphyria. However, very common side effects such as anorexia, diarrhoea, nausea and vomiting are potentially porphyrogenic through reduction in caloric intake. Interaction studies show that peginterferon alpha-2a has no effect on CYP3A4, 2C9, 2D6 or 2C19 activities.

Peginterferon alfa-2a is a polyethylene glycol (PEG)-modified form of human recombinant interferon alfa-2a with a prolonged effect.

Pegnterferon alfa-2a is a cytokine with antiviral, antiproliferative and immunomodulating effects. It binds to human cell surface receptors, initiating a cascade of intracellular events. Peginterferon alfa-2a inhibits virus replication and is used in chronic hepatitis B and chronic hepatitis C. It is administered subcutaneously. In recurrent chronic hepatitis C it is administered in combination with ribavirin. Common adverse reactions of peginterferon that can be confused with an acute porphyric attack are muscle pain, fatigue, anorexia, diarrhoea, nausea and vomiting. Side effects such as anorexia, diarrhoea, nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake. Also potentially porphyrinogenic side effects such as viral and bacterial infections is reported.

Systemic clearance of peginterferon alfa-2a is about 100 times longer than for the unconjugated interferon. Peginterferon alfa-2a is partly eliminated by the kidneys. Interaction studies show that peginterferon alpha-2a has no effect on CYP3A4, 2C9, 2D6 or 2C19 activities, but inhibits CYP1A2 activity (SPC, pegasys) Inflammation suppresses the expression of several hepatic transporters and detoxifying CYPs including CYP3A4 (Aitken, 2005; Moreau, 2008).