Drugs for Hepatitis B
Discuss the drugs for hepatitis B?
- Current therapy of chronic hepatitis B has limited long-term efficacy. Thus, careful balance of patient age, severity of liver disease, likelihood of response, and potential adverse events and complications is needed before treatment is initiated.
- The ?rst-line drugs recommended for treatment of hepatitis B are pegIFN, entecavir or tenofovir. In view of the high rate of drug resistance during long-term treatment, lamivudine and telbivudine are not preferred. Since adefovir is less potent than other NA and is associated with increasing rate of antiviral resistance after the ?rst year of therapy, it is best utilized as a second line drug in treatment-naive patients.
- The advantages of IFN- include a finite duration of treatment, more durable response, and the lack of resistant mutants. The disadvantages of IFN- are the costs and side effects.
Lamivudine
- Lamivudine is a nucleoside reverse transcriptase inhibitor antiviral drug. Incorporation of the active triphosphate of lamivudine into growing DNA chains results in premature chain termination thereby inhibiting HBV DNA synthesis.
- Long term lamivudine treatment leads to high rates of resistance (60-70% after 5 years of treatment) and hence is not a preferred treatment for chronic hepatitis B.
- The dose in adults is 100 mg per day. It can be given both as a circumscribed course of treatment or as long-term viral suppressive therapy.
Adefovir
- Adefovir is converted intracellularly to the diphosphate, which inhibits the synthesis of hepatitis B virus DNA through competition for the enzyme reverse transcriptase and incorporation into the viral DNA.
- Adefovir is not well absorbed after oral administration so is given by mouth as the prodrug adefovir dipivoxil.
- The most commonly reported adverse effects for adefovir dipivoxil are gastrointestinal effects including nausea, flatulence, diarrhoea and dyspepsia. Increases in serum creatinine are common but usually mild to moderate. However, cases of renal impairment and acute renal failure have been reported.
Tenofovir
- Tenofovir disoproxil is a nucleotide analogue. It works by blocking the enzyme reverse transcriptase, which is responsible for hepatitis B virus (HBV) replication.
- Adverse events associated with the use of nucleotide analogues include lactic acidosis and progression of hepatomegaly. Additional adverse events reported for tenofovir disoproxil include headache, fatigue and gastrointestinal disorders.
- Tenofovir disoproxil is licensed for use in adults over 18 years. The dosage is a once-daily tablet of 245 mg. The dose should be adjusted for patients with estimated creatinine clearance less than 50 mL/min.
Entecavir
- Entecavir is an oral nucleoside analogue. It works by inhibiting the viral DNA polymerase responsible for hepatitis B virus (HBV) replication.
- Adverse events associated with the use of nucleoside analogues include lactic acidosis and severe hepatomegaly with steatosis. Additional adverse events reported for entecavir include headache, fatigue, dizziness and nausea.
- The optimal treatment duration is currently unknown. For people who have not previously received treatment with antiviral drugs for chronic hepatitis B, the recommended dose is 500 micrograms once daily. For people taking lamivudine who have evidence of viraemia or lamivudine resistance, the recommended dose is 1 mg, once daily. Dose reductions are required for people with renal impairment.
