Lamivudine Interferon alfa

Flink HJ, Hansen BE, Heathcote EJ, Feinman SV, Simsek H, Karayalcin S, Mach T, Leemans WF, de Man RA, Verhey E, Schalm SW, Janssen HL (2006a) Successful treatment with pegjnter-feron alfa-2b of HBeAg-positive HBV non-responders to standard interferon or lamivudine. 

Interferon alfa should typically be used in combination with antiviral agents such as lamivudine or adefovir dipivoxil (refer to BNF), the first-line treatment... 

Lamivudine is used orally to treat chronic hepatitis B in adults and children (9). It increases the rate of loss of hepatitis B e antigen and seroconversion in compensated chronic carriers, with improvement of histology at a similar rate to interferon alfa. However, the tyrosine-methionine-aspartate-aspartate (YMDD) mutation prevents efficacy and can cause flares of hepatitis. The indications for treatment must therefore be established with care and only by those who have expert knowledge of the disease, the drug, and the YMDD mutation. 

Zeuzum S, Akarca US, Cakaloglu Y, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HbeAg positive chronic hepatitis B ... 

Interferon alfa does not alter the pharmacokinetics of didanosine or lamivudine to a clinically relevant extent. Interferon alfa and, particularly, interferon beta can cause an increase in the serum levels of zidovudine. HIV-positive patients infected with hepatitis C and treated with interferon alfa and ribavirin may be at special risk of NRTI-associated lactic acidosis. Interleukin-2 appears not to interact significantly with zidovudine. 

In vitro, ribavirin reduced the intracellular activation and antiretroviral activity of lamivudine. However, in a study in 22 HIV-positive patients with hepatitis C, ribavirin 800 mg daily had no statistically significant effect on the pharmacokinetics of lamivudine (a 27% increase in AUC), and no effect on the intracellular activation of lamivudine, when compared with 24 similar patients who received placebo. As with all NRTIs, lamivudine has, rarely, been associated with lactic acidosis, and the UK manufacturers of all NRTIs state that patients co-infected with hepatitis C and treated with interferon alfa and ribavirin may be at increased risk of lactic acidosis. Patients at increased risk should be monitored closely. ... 

Peginterferon alfa-2a treatment results in more sustained responses than simple interferon alpha, although relapse is not uncommon. Such treatment should generally be avoided in those receiving immunosuppressants and those with decompensated liver disease. Lamivudine, a reverse transscriptase inhibitor is often used in initial treatment and in decompensated liver disease. 

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