Interferons (IFN)
Discuss interferons?
- Interferons are natural proteins that activate the immune system in response to viral infection. IFNs have antiviral, antiproliferative, and immunomodulatory effects.
- IFN-alpha has been shown to be effective in suppressing HBV replication.
- Three recombinant interferon products have UK marketing authorisation for the treatment of chronic hepatitis B: IntronA (interferon alfa-2b, Schering-Plough), Roferon-A (interferon alfa-2a, Roche) and Viraferon (interferon alfa-2b, Schering-Plough)
Discuss pharmacokinetics?
- Interferon alfa is eliminated from the body rapidly, having a plasma half-life of only about 4 hours.
- Peginterferons are formed by attaching strands of polyethylene glycol (PEG) to the interferon molecules. The pegylated form of interferon alfa contains an essentially inert ‘tail’, the function of which is to slow down the rate at which the body eliminates the molecule, enabling dosing to be less frequent.
- Peg interferon alfa has a much longer plasma half-life (50–130 hours for peginterferon alfa-2a and about 40 hours for peginterferon alfa-2b) than interferon alfa.
- It therefore needs to be injected only once per week (vs. three times a week for the unmodified form), and the aggregate dose per month can be lower than for interferon, reducing most side effects.
Discuss the indications?
- Chronic hepatitis B
- Chronic hepatitis C
Discuss the dose?
PegIFN- alpha 2a- fixed dose 180 mcg weekly
Peg IFN-apha 2b- does- consult product literature
Discuss the contraindications?
- Decompensated liver disease
- Pregnant or breast feeding women
Discuss the side effects?
- Flu-like symptoms (fever, chills, myalgias, arthralgias and headache)
- Marrow suppression (especially leucopenia and thrombocytopenia)
- Emotional effects (irritability, memory disturbances, depression)
- Autoimmune disorders-Both hyper or hypo thyroidism can occur
- Cardiovascular- hypertension or hypotension, arrhythmias, oedema, myocardial infarction or stroke
- Hair loss, Rash, Diarrhea, Sleep disorders
- Visual disorders (rarely retinal hemorrhages, especially in diabetic patients and hypertensive patients)
- Weight loss, Seizures, Hearing loss, Pancreatitis, Interstitial pneumonitis, Injection site reactions
- There are significant problems of dropout and non-adherence with treatment as a result. Dropout rates of 7–14% have occurred.
