What is the recommended treatment and dosage of Entacavir (entecavir) for chronic hepatitis B?

Entecavir for Chronic Hepatitis B

For treatment-naïve adults with chronic hepatitis B, entecavir 0.5 mg once daily is the recommended first-line dose, while lamivudine-experienced patients or those with decompensated cirrhosis require 1 mg once daily. 1, 2

Dosing by Patient Population

Treatment-Naïve Adults with Compensated Liver Disease

• Standard dose: 0.5 mg once daily on an empty stomach (at least 2 hours after a meal and 2 hours before the next meal) 1, 2
• This applies to both HBeAg-positive and HBeAg-negative chronic hepatitis B 1

Lamivudine-Experienced or Resistant Patients

• Dose: 1 mg once daily for adults and adolescents ≥16 years with history of hepatitis B viremia while receiving lamivudine or known lamivudine/telbivudine resistance mutations (rtM204I/V with or without rtL180M, rtL80I/V, or rtV173L) 1, 2

Decompensated Cirrhosis

• Dose: 1 mg once daily regardless of prior treatment history 1, 2

Pediatric Patients (≥2 years)

• Dose: 0.015 mg/kg daily (up to maximum 0.5 mg) 1
• Entecavir is considered first-line therapy in children older than 2 years 1
• At 48 weeks, entecavir achieved HBeAg seroconversion in 24.2% versus 3.3% with placebo in children aged 2-17 years 1
• Cumulative resistance probability: 0.6% at 1 year and 2.6% at 2 years 1

Renal Dose Adjustments

Dosage adjustment is mandatory for creatinine clearance <50 mL/min: 1, 2

• CrCl ≥50 mL/min: No adjustment needed (0.5 mg once daily for standard dose; 1 mg once daily for lamivudine-refractory/decompensated)
• CrCl 30 to <50 mL/min: 0.5 mg every 48 hours (or 0.5 mg once daily for 1 mg dose; alternatively 1 mg every 48 hours)
• CrCl 10 to <30 mL/min: 0.5 mg every 72 hours (or 1 mg every 72 hours for higher dose)
• CrCl <10 mL/min or hemodialysis/CAPD: 0.5 mg every 7 days (or 1 mg every 7 days); administer after hemodialysis on dialysis days 1, 2

Treatment Duration

HBeAg-Positive Patients

• Continue treatment for at least 1 year after HBeAg seroconversion, then at least 6 additional months of consolidation therapy 1
• In children: at least 1 year from treatment initiation and more than 1 year after HBeAg seroconversion 1

HBeAg-Negative Patients

• Continue until HBsAg clearance is achieved 1
• In children: follow adult recommendations as optimal duration is unclear 1

Compensated Cirrhosis

• Long-term treatment is recommended, but may stop in HBeAg-positive patients after confirmed HBeAg seroconversion plus 6 months consolidation, or in HBeAg-negative patients after HBsAg clearance 1
• Close monitoring for viral relapse and hepatitis flare is mandatory if treatment is stopped 1

Decompensated Cirrhosis and Post-Liver Transplant

• Life-long treatment is recommended 1

Efficacy Data

HBeAg-Positive Disease (at 48 weeks)

• HBV DNA suppression (<50-60 IU/mL): 67-76% 1
• HBeAg seroconversion: 21-22% 1
• ALT normalization: 68-81% 1
• Histologic improvement: 72% versus 62% with lamivudine 1

HBeAg-Negative Disease (at 48 weeks)

• HBV DNA suppression (<50-60 IU/mL): 90-91% 1
• ALT normalization: 78-88% 1
• Histologic improvement: 70% versus 61% with lamivudine 1

Safety Monitoring

Required Baseline and Ongoing Assessments

• Test for HIV prior to treatment initiation (entecavir can select for HIV resistance if used as monotherapy in undiagnosed HIV/HBV coinfection) 1
• Monitor for lactic acidosis if clinical concern arises 1
• No routine laboratory monitoring is required for hepatic function, but assess creatinine clearance at baseline and monitor if renal impairment risk exists 1

Common Adverse Events

• Headache (17-23%), upper respiratory tract infection (18-20%), cough (12-15%), nasopharyngitis (9-14%), fatigue (10-13%), dizziness (9%), upper abdominal pain (9-10%), nausea (6-8%) 3
• Adverse event profile is similar to lamivudine and placebo 1, 3

Critical Warnings and Pitfalls

Severe Hepatitis Flare After Discontinuation

• Severe acute exacerbations of hepatitis can occur after stopping entecavir 1
• Monitor hepatic function closely with clinical and laboratory follow-up for at least several months after discontinuation 1

Resistance Considerations

• Low resistance rate in treatment-naïve patients: 1.2% genotypic resistance through 5 years 1
• High resistance in lamivudine-experienced patients: 51% at 5 years 1
• For lamivudine-resistant patients, combination therapy is preferred over entecavir monotherapy 4

Hepatic Impairment

• No dosage adjustment necessary for hepatic impairment alone 2

Pregnancy

• Pregnancy category C 1
• Insufficient human data on use during pregnancy to inform drug-associated risk 1

Administration Details

• Must be taken on an empty stomach: at least 2 hours after a meal and 2 hours before the next meal 2
• Oral tablet and solution can be used interchangeably 3