Usual Adult Dose for Chronic Hepatitis B

Compensated Liver Disease:

• Nucleoside-inhibitor-therapy-naive: 0.5 mg orally once a day
• History of hepatitis B viremia while using lamivudine or known lamivudine or telbivudine resistance substitutions rtM204I/V with or without rtL180M, rtL80I/V, or rtV173L: 1 mg orally once a day

Decompensated Liver Disease: 1 mg orally once a day

Use: For the treatment of chronic HBV infection in patients with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease

Usual Pediatric Dose for Chronic Hepatitis B

2 to 15 years:
Therapy-naive:

• Weight 10 to 11 kg: 0.15 mg orally once a day
• Weight greater than 11 to 14 kg: 0.2 mg orally once a day
• Weight greater than 14 to 17 kg: 0.25 mg orally once a day
• Weight greater than 17 to 20 kg: 0.3 mg orally once a day
• Weight greater than 20 to 23 kg: 0.35 mg orally once a day
• Weight greater than 23 to 26 kg: 0.4 mg orally once a day
• Weight greater than 26 to 30 kg: 0.45 mg orally once a day
• Weight greater than 30 kg: 0.5 mg orally once a day

Lamivudine-experienced:

• Weight 10 to 11 kg: 0.3 mg orally once a day
• Weight greater than 11 to 14 kg: 0.4 mg orally once a day
• Weight greater than 14 to 17 kg: 0.5 mg orally once a day
• Weight greater than 17 to 20 kg: 0.6 mg orally once a day
• Weight greater than 20 to 23 kg: 0.7 mg orally once a day
• Weight greater than 23 to 26 kg: 0.8 mg orally once a day
• Weight greater than 26 to 30 kg: 0.9 mg orally once a day
• Weight greater than 30 kg: 1 mg orally once a day

Comments:

• The oral solution is recommended for patients weighing up to 30 kg.

16 years or older:
Compensated Liver Disease:

• Nucleoside-inhibitor-therapy-naive: 0.5 mg orally once a day
• History of hepatitis B viremia while using lamivudine or known lamivudine or telbivudine resistance substitutions rtM204I/V with or without rtL180M, rtL80I/V, or rtV173L: 1 mg orally once a day

Use: For the treatment of chronic HBV infection in patients with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease

Renal Dose Adjustments

Adult Patients:
Nucleoside-inhibitor-therapy-naive:

• CrCl at least 50 mL/min: 0.5 mg orally once a day
• CrCl 30 to less than 50 mL/min: 0.25 mg orally once a day or 0.5 mg orally every 48 hours
• CrCl 10 to less than 30 mL/min: 0.15 mg orally once a day or 0.5 mg orally every 72 hours
• CrCl less than 10 mL/min: 0.05 mg orally once a day or 0.5 mg orally every 7 days

Lamivudine-refractory or decompensated liver disease:

• CrCl at least 50 mL/min: 1 mg orally once a day
• CrCl 30 to less than 50 mL/min: 0.5 mg orally once a day or 1 mg orally every 48 hours
• CrCl 10 to less than 30 mL/min: 0.3 mg orally once a day or 1 mg orally every 72 hours
• CrCl less than 10 mL/min: 0.1 mg orally once a day or 1 mg orally every 7 days

Pediatric Patients:

• CrCl less than 50 mL/min: Data not available

Comments:

• The once-daily dosing regimens are preferred for adult patients.
• Insufficient data available to recommend specific dose adjustments in pediatric patients with renal dysfunction; dose reduction or increased dosing interval similar to adult dose adjustments should be considered.

Liver Dose Adjustments

Liver dysfunction: No adjustment recommended.

Precautions

US BOXED WARNINGS:

• SEVERE ACUTE EXACERBATIONS OF HEPATITIS B: Severe acute exacerbations of hepatitis B reported in patients who have discontinued antihepatitis B therapy. Patients who discontinue this drug should have close monitoring of hepatic function with clinical and laboratory follow-up for at least several months. If appropriate, resumption of antihepatitis B therapy may be necessary.
• PATIENTS COINFECTED WITH HIV AND HBV: This drug is not recommended for HIV/HBV-coinfected patients not also receiving HAART. There is a risk of developing resistance to HIV nucleoside reverse transcriptase inhibitors if this drug is used for chronic HBV in coinfected patients not receiving adequate treatment for their HIV infection.
• LACTIC ACIDOSIS AND HEPATOMEGALY: Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) reported with use of nucleoside analog inhibitors, alone or in combination with antiretrovirals.

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 2 years.

Consult WARNINGS section for additional precautions.

Dialysis

Adult Patients:
Hemodialysis or CAPD:

• Nucleoside-inhibitor-therapy-naive: 0.05 mg orally once a day or 0.5 mg orally every 7 days
• Lamivudine-refractory or decompensated liver disease: 0.1 mg orally once a day or 1 mg orally every 7 days

Pediatric Patients:

• Hemodialysis or CAPD: Data not available

Comments:

• The once-daily dosing regimens are preferred for adult patients; this drug should be administered after hemodialysis sessions if administered on hemodialysis days.
• Insufficient data available to recommend specific dose adjustments in pediatric patients with renal dysfunction; dose reduction or increased dosing interval similar to adult dose adjustments should be considered.

Other Comments

Administration advice:

• Administer at least 2 hours after a meal and 2 hours before the next meal (on an empty stomach).
• May use the tablets and oral solution interchangeably without dose adjustment (bioequivalent)
• Use the oral solution for doses less than 0.5 mg.
• Use the provided dosing spoon for the oral solution.
• Do not dilute the oral solution or mix it with water or any other solvent or liquid product.

Storage requirements:

• Oral solution: Store in outer carton; protect from light.
• Tablets: Store in tightly closed container; store in outer carton to protect from light.

General:

• Optimal duration of therapy and relationship between therapy and long-term outcomes (e.g., cirrhosis, hepatocellular carcinoma) are unknown.

Monitoring:

• Hepatic: Hepatic function (periodically during therapy); hepatic function with clinical and laboratory follow-up (for at least several months after stopping therapy)
• Infections/Infestations: HIV antibody testing (before starting therapy)
• Renal: Renal function in elderly patients

Patient advice:

• Read the US FDA-approved patient labeling (Patient Information).
• Do not stop this drug without first informing your healthcare provider.
• Contact your healthcare provider at once and stop this drug if clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity develop.
• Avoid missing doses by following a regular dosing regimen.
• If using the oral solution, hold the provided dosing spoon vertically and slowly fill it to the mark corresponding to the prescribed dose; rinse the dosing spoon with water after each daily dose.