Enteca

Approved Indications:

• Chronic Hepatitis B Virus (HBV) Infection in Adults:
• Treatment of HBeAg-positive and HBeAg-negative chronic HBV infection with evidence of active viral replication and elevated liver enzymes.
• Pediatric Use (≥2 years):
• For children with chronic HBV infection showing active viral replication and liver inflammation.

Off-Label / Clinically Accepted Uses:

• Occasionally used in post-liver transplant HBV prophylaxis to prevent reinfection.
• May be considered in combination therapy for lamivudine-resistant HBV (with caution and specialist supervision).

Adults:

• Nucleoside-Naïve Patients: 0.5 mg orally once daily on an empty stomach (at least 2 hours before or after food).
• Lamivudine-Resistant Patients: 1 mg orally once daily.
• Renal Impairment: Dose adjustment required based on creatinine clearance.

Pediatrics:

• 2–16 years (weight-based): 0.015 mg/kg orally once daily, up to a maximum of 0.5 mg daily.
• Adjust in cases of renal impairment as per adult dosing adjustment guidelines.

Administration Notes:

• Swallow tablets whole with water; do not crush or chew.
• Administer on an empty stomach for optimal absorption.
• Duration: Long-term therapy is often required; treatment may continue until sustained viral suppression is achieved, with monitoring.

Entecavir is a guanosine nucleoside analog that inhibits HBV DNA polymerase through multiple mechanisms:

1.        Reverse transcriptase inhibition – blocks conversion of viral RNA to DNA.

2.        Priming inhibition – prevents initiation of HBV DNA synthesis.

3.        DNA chain elongation inhibition – terminates viral DNA elongation.

These combined effects suppress viral replication, reduce viral load, and allow hepatic inflammation to subside, thereby slowing progression to cirrhosis and hepatocellular carcinoma.

• Absorption: Oral bioavailability ~100% in fasting state; peak plasma concentration in ~0.5–1.5 hours.
• Distribution: Volume of distribution ~1.3–1.7 L/kg; ~13% plasma protein binding.
• Metabolism: Minimal hepatic metabolism; primarily excreted unchanged.
• Elimination: Renal excretion is predominant (~70% unchanged).
• Half-Life: Plasma half-life ~128–149 hours; intracellular triphosphate half-life ~15 hours.
• Onset of Action: Virologic response generally observed within 2–4 weeks of therapy.

• Pregnancy: Category C. Animal studies indicate potential fetal risk at high doses; human data are limited. Use only if benefits justify risk.
• Lactation: Excreted in human milk in low concentrations; breastfeeding is not recommended during therapy.
• Caution: Insufficient data for routine use in pregnant or nursing women; monitor closely if use is unavoidable.

• Primary Class: Antiviral agent
• Subclass: Nucleoside analog, Reverse transcriptase inhibitor (HBV-specific)

• Known hypersensitivity to Entecavir or any formulation excipients.
• Severe renal impairment without proper dose adjustment.
• Co-administration with other potent nucleoside analogs without specialist supervision (risk of additive toxicity).

• Lactic Acidosis and Severe Hepatomegaly: Rare but life-threatening; monitor liver function, especially in patients with advanced liver disease.
• HBV Exacerbation on Discontinuation: Abrupt therapy cessation may trigger HBV flare; taper or monitor closely.
• Renal Impairment: Dose adjustment essential to prevent toxicity.
• HIV Coinfection: Risk of selecting HIV-resistant strains; use in combination therapy as indicated.
• Monitoring: Regular assessment of liver enzymes, HBV DNA levels, and renal function.

Common Adverse Effects:

• Headache
• Fatigue
• Dizziness
• Nausea
• Abdominal pain

Serious or Rare Adverse Effects:

• Lactic acidosis
• Severe hepatomegaly with steatosis
• Pancreatitis (rare)
• Exacerbation of HBV on treatment withdrawal

Timing and Severity:

• Most adverse effects are mild and occur early in therapy. Serious events are rare but require immediate discontinuation and medical evaluation.

• Other Nucleoside Analogs (e.g., Lamivudine, Tenofovir): May have additive antiviral effects or renal toxicity.
• Nephrotoxic Agents: Concomitant use may increase risk of renal impairment; monitor renal function.
• No significant CYP450 interactions reported; minimal potential for major drug-drug interactions.
• Antacids: May reduce absorption if taken simultaneously; separate dosing by 2 hours.

• FDA Updates (2022–2023): Reinforced monitoring for renal impairment and lactic acidosis; no new dosing changes.
• Clinical Guidelines: AASLD and EASL recommend Entecavir as first-line therapy for treatment-naïve adult patients with chronic HBV due to high potency and low resistance risk.
• Pediatric Guidance: Expanded approval for children ≥2 years with evidence of active viral replication.

• Temperature: Store at 20°C–25°C (68°F–77°F); short excursions permitted to 15°C–30°C.
• Humidity & Light: Protect from moisture and light; keep in original container.
• Handling: Do not crush or chew tablets; keep out of reach of children.
• Reconstitution: Not applicable; oral tablets ready for use.