Oral therapy approved for hepatitis B infection
BaracludeEntecavir tablets and oral solution
BRISTOL-MYERS SQUIBBOral therapy approved for hepatitis B infection
A guanosine nucleoside analog, entecavir functionally inhibits all 3 activities of the hepatitis B virus (HBV) polymerase: base priming, reverse transcription of the negative strand of messenger RNA, and synthesis of the positive strand of HBV DNA. Entecavir was approved on March 29, 2005, for the treatment of chronic HBV infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
Efficacy. The efficacy of entecavir was evaluated in 3 active, controlled trials of 1,633 patients aged 16 years or older with chronic HBV infection. In 2 trials evaluating HbeAg-positive and -negative nucleoside-naïve patients, individuals received either entecavir 0.5 mg or lamivudine 100 mg. In both of these trials, entecavir was superior to lamivudine for the primary efficacy end point of histological improvement, as defined as a ≥2-point reduction in Knodell Necroinflammatory score, with no worsening in Ishak Fibrosis Score at Week 48. HbeAg-positive and -negative patients receiving entecavir achieved histologic improvement rates of 72% and 70%, respectively, compared with rates of 62% and 61%, respectively, for patients receiving lamivudine (P<.05). In a separate study of patients with HBV infection that was refractory to lamivudine, individuals were either switched from lamivudine to entecavir 1 mg or continued on lamivudine 100 mg for 52 weeks. Again, entecavir was superior to lamivudine for the end point of histologic improvement. Patients receiving entecavir achieved a histologic improvement rate of 55% compared with a rate of 28% for patients receiving lamivudine (P<.01).
Safety. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including entecavir. In patients discontinuing anti-hepatitis B therapy, hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months. Coadministration of entecavir with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of entecavir or the coadministered drug. Patients should be monitored closely for adverse events when entecavir is coadministered with such drugs. The most common adverse events associated with the use of entecavir are similar to those typically seen with HBV therapy and include headache, abdominal pain, diarrhea, fatigue, and dizziness.