Usage
Entecavir is prescribed for the treatment of chronic hepatitis B virus (HBV) infection in adults and children 2 years of age and older with evidence of active viral replication and either persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. It is classified as a nucleoside/nucleotide reverse transcriptase inhibitor (NRTI). Entecavir works by inhibiting HBV polymerase, the enzyme responsible for viral replication. This action reduces the amount of HBV in the body, helping to improve liver function.
Alternate Names
Entecavir is the generic name. A popular brand name is Baraclude®.
How It Works
Pharmacodynamics: Entecavir primarily affects the liver by reducing HBV DNA levels and improving liver histology.
Pharmacokinetics:
- Absorption: Entecavir is readily absorbed orally, with peak plasma concentrations reached in 0.5 to 1.5 hours. Food reduces its absorption, especially high-fat meals. For most patients, entecavir is taken on an empty stomach (at least 2 hours before or after a meal). However, for nucleoside-inhibitor-therapy-naive patients with compensated liver disease, entecavir can be taken with or without food.
- Metabolism: Entecavir is not significantly metabolized by the cytochrome P450 (CYP450) enzyme system, minimizing the risk of drug interactions related to CYP450 metabolism.
- Elimination: Entecavir is primarily eliminated by the kidneys through glomerular filtration and active tubular secretion, with a terminal elimination half-life of approximately 128-149 hours. Dose adjustments are required for patients with renal impairment.
Mode of Action: Entecavir is a guanosine nucleoside analog that competitively inhibits HBV polymerase. It interferes with viral replication by inhibiting three functions of the enzyme:
- Priming of the HBV polymerase.
- Reverse transcription of the negative strand from the pregenomic messenger RNA.
- Synthesis of the positive strand of HBV DNA.
Receptor binding, enzyme inhibition, or neurotransmitter modulation: Entecavir’s primary mechanism involves the inhibition of HBV polymerase. It does not bind to specific receptors or modulate neurotransmitters.
Elimination pathways: Entecavir is predominantly excreted unchanged in the urine.
Dosage
Standard Dosage
Adults:
- Nucleoside-inhibitor-therapy-naive with compensated liver disease: 0.5 mg once daily, taken on an empty stomach.
- Lamivudine-refractory, with known lamivudine or telbivudine resistance substitutions, or with decompensated liver disease: 1 mg once daily, taken on an empty stomach.
Children (2-18 years):
Dosage is weight-based and ranges from 0.15 mg to 0.5 mg once daily. For patients weighing at least 32.6 kg, either the 0.5mg tablet or oral solution can be administered. For patients weighing less than 32.6 kg, oral solution is recommended. Dosage should be determined by the child’s physician. There are no recommendations for children younger than 2 years or weighing less than 10 kg.
Special Cases:
-
Elderly Patients: No specific age-based dose adjustments are necessary, but renal function should be assessed.
-
Patients with Renal Impairment: Dosage adjustment is required based on creatinine clearance (CrCl).
- CrCl ≥ 50 mL/min: No dose adjustment required.
- CrCl 30-49 mL/min: 0.25 mg (0.5 mg every 48 hours) or 0.5 mg (1 mg every 48 hours) depending on the standard dosage.
- CrCl 10-29 mL/min: 0.15 mg (0.5 mg every 72 hours) or 0.3 mg (1 mg every 72 hours) depending on the standard dosage.
- CrCl <10 mL/min (including hemodialysis or CAPD): 0.05 mg (0.5 mg every 5-7 days) or 0.1 mg (1 mg every 5-7 days) depending on the standard dosage. Hemodialysis patients should receive entecavir after dialysis.
-
Patients with Hepatic Dysfunction: No dose adjustment is required.
-
Patients with Comorbid Conditions: Careful monitoring is recommended, especially for patients with HIV/HBV co-infection (they must be receiving highly active antiretroviral therapy (HAART)), diabetes, or cardiovascular disease.
Clinical Use Cases
The use of entecavir in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations is not directly relevant. Entecavir is indicated for chronic hepatitis B treatment and is not used for acute conditions or in these specific medical settings.
Dosage Adjustments
Dosage modifications are necessary for patients with renal impairment as detailed above. Other factors, such as metabolic disorders or genetic polymorphisms, are not known to significantly influence entecavir dosing.
Side Effects
Common Side Effects:
Headache, fatigue, dizziness, nausea, vomiting, diarrhea, and insomnia.
Rare but Serious Side Effects:
Lactic acidosis (buildup of lactic acid in the blood), severe hepatomegaly with steatosis (enlarged fatty liver), and severe allergic reactions.
Long-Term Effects:
The long-term effects of entecavir are still being studied, but potential risks include the development of drug resistance and worsening of liver disease if treatment is stopped prematurely.
Adverse Drug Reactions (ADR):
Lactic acidosis, severe hepatomegaly with steatosis, and serious allergic reactions.
Contraindications
- Hypersensitivity to entecavir or any component of the formulation.
- HIV/HBV co-infection without concurrent HAART.
Drug Interactions
Entecavir has minimal drug interactions due to its limited metabolism by CYP450 enzymes. The most significant interaction is with drugs that are also renally eliminated, as co-administration may reduce the clearance of both drugs. Examples include: aminoglycosides, cyclosporine, and some antiviral drugs. Other potential interactions are noted with adefovir dipivoxil.
Pregnancy and Breastfeeding
- Pregnancy: Entecavir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Effective contraception is essential during treatment and for at least six weeks after stopping treatment.
- Breastfeeding: Entecavir’s excretion in human milk is unknown. Due to potential adverse effects in infants, women should not breastfeed while receiving entecavir.
Drug Profile Summary
- Mechanism of Action: Nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) that inhibits HBV polymerase.
- Side Effects: Common: Headache, fatigue, dizziness, nausea, vomiting, diarrhea, insomnia. Serious: Lactic acidosis, severe hepatomegaly with steatosis, allergic reactions.
- Contraindications: Hypersensitivity to entecavir, HIV/HBV co-infection without HAART.
- Drug Interactions: Primarily with other renally eliminated drugs.
- Pregnancy & Breastfeeding: Use with caution in pregnancy. Breastfeeding contraindicated.
- Dosage: Adults: 0.5 mg – 1 mg once daily. Children (2-18 years): Weight-based dosing. Adjustments required for renal impairment.
- Monitoring Parameters: HBV DNA levels, ALT/AST, renal function, signs of lactic acidosis and hepatic dysfunction.
Popular Combinations
Entecavir is typically used as monotherapy for chronic HBV. Combination therapy with other antiviral agents may be considered in cases of drug resistance or in certain complex situations. However, these combinations should be used judiciously due to the potential for increased toxicity and drug interactions.
Precautions
- General Precautions: Monitor for hepatic and renal function, hypersensitivity reactions, and lactic acidosis.
- Specific Populations: See sections on Pregnancy and Breastfeeding, Children, and Patients with Renal Impairment.
- Lifestyle Considerations: Alcohol should be avoided or consumed in moderation due to the potential for increased liver toxicity.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Entecavir?
A: For adults, 0.5 mg once daily for nucleoside-naive patients with compensated liver disease and 1 mg once daily for lamivudine-refractory, known resistance substitutions, or decompensated liver disease. For children (2-18 years), the dose is weight-based.
Q2: Should Entecavir be taken with food?
A: For most patients, entecavir is taken on an empty stomach. However, for nucleoside-inhibitor-therapy-naive patients with compensated liver disease, entecavir can be taken with or without food.
Q3: How does renal impairment affect Entecavir dosing?
A: Dosage adjustments are necessary for patients with renal impairment. The dose and/or frequency of administration is reduced based on creatinine clearance.
Q4: What are the most serious side effects of Entecavir?
A: Lactic acidosis, severe hepatomegaly with steatosis, and serious allergic reactions.
Q5: Can Entecavir be used during pregnancy?
A: Entecavir should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.
Q6: Can Entecavir be used during breastfeeding?
A: No. Women should not breastfeed while on Entecavir therapy.
Q7: What should be monitored in patients taking Entecavir?
A: HBV DNA levels, liver function tests (ALT/AST), renal function, and signs of lactic acidosis and hepatic dysfunction.
Q8: What is the mechanism of action of Entecavir?
A: Entecavir inhibits HBV polymerase, preventing viral replication.
Q9: Is there a risk of developing resistance to Entecavir?
A: Yes, prolonged use can lead to the emergence of resistant HBV strains, although the rate is relatively low.
Q10: What happens if a patient stops taking Entecavir abruptly?
A: Hepatitis B may worsen or reactivate, potentially leading to serious complications. Patients should not stop taking entecavir without consulting their doctor.
