Entecavir
Entecavir
Generic Name
Entecavir
Brand Names
Baraclude®) is a potent, low‑genetic‑barrier nucleoside analog used primarily for chronic hepatitis B (HBV) infection.
Mechanism
- Synthetic guanine nucleoside analog that requires intracellular phosphorylation to the active triphosphate form.
- The triphosphate competes with natural deoxyguanosine triphosphate for binding to the viral DNA polymerase enzyme.
- It inhibits chain elongation and leads to termination of viral DNA synthesis.
- High potency, modest selectivity for viral polymerase over host polymerases → minimal mitochondrial toxicity.
- Exhibits a high genetic barrier to resistance; in treatment‑naïve patients, < 1 % develop resistance after 48 weeks.
Pharmacokinetics
| Parameter | Result |
| Absorption | Oral bioavailability ~ 95 %; peak plasma concentration (Tmax) 5–6 h; food does not influence absorption. |
| Distribution | Low protein binding (~2 %); volume of distribution ≈ 30 L. |
| Metabolism | Minimal: mostly unchanged; slight glucuronidation (moderate). |
| Elimination | Renal excretion unchanged: CL ~ 35 mL min⁻¹; half‑life 9–15 h. |
| Special Populations | Dose adjustment required for CrCl < 50 mL min⁻¹; contraindicated when CrCl < 10 mL min⁻¹ (no data). |
| Drug interactions | No clinically significant CYP interactions; avoid co‑administration with drugs that markedly alter renal function. |
Indications
- Chronic hepatitis B (HBV) infection in patients who are HBeAg‑positive or HBeAg‑negative.
- First‑line therapy when patients have not previously received antiviral therapy or when other agents are contraindicated or poorly tolerated.
- Prevention of HBV reactivation in patients undergoing immunosuppressive or chemotherapy regimens (initiated at least 1 month before therapy, continued for 6 months after).
Contraindications
- Contraindicated: Severe renal impairment (CrCl < 10 mL min⁻¹) – no data on safety.
- Warnings:
- Renal dysfunction: Accumulates when CrCl between 10–50 mL min⁻¹; monitor renal function.
- Pregnancy: Category C; potential risk to fetus—use only if benefits outweigh risks.
- Liver toxicity: Rare but monitor liver enzymes.
- Precautions:
- May interfere with other antivirals that are renally cleared.
- No significant drug‑drug interactions with CYP system.
Dosing
| Form | Typical Adult Doses | Renal Adjustment |
| Oral tablet (250 mg) | 0.5 mg once daily |
• CrCl 10–50 mL min⁻¹: 0.25 mg daily. • CrCl > 50 mL min⁻¹: 0.5 mg daily. |
| Long‑acting 30‑day clinic | For maintenance therapy; same dose as above. | - |
Administration Tips
• Take with food or water to improve tolerability; not necessary to take on an empty stomach.
• If taken 4–6 h from a strong chelating agent (e.g., magnesium or calcium supplements), consider staggering doses.
Adverse Effects
- Common (≤ 10 %)
- Fatigue, headache, dizziness
- Nausea, vomiting, abdominal pain
- Arthralgia, myalgia
- Diarrhea, constipation
- Serious (rare)
- Lactic acidosis (very rare; not attributed to mitochondrial toxicity).
- Cytopenias (e.g., neutropenia) – monitor CBC if unexplained cytopenia.
- Hepatotoxicity: ALT/AST elevations > 5× ULN – discontinue and evaluate.
Monitoring
| Parameter | Frequency | Rationale |
| HBV DNA | Baseline, every 3–4 months until undetectable, then every 6–12 months | Detect virologic response, suppress resistance |
| ALT/AST, bilirubin | Every 12 weeks | Liver injury, dose‑adjustment |
| Serum creatinine & CrCl | Baseline, every 12 weeks and if clinically indicated | Dose adjustment, prevent accumulation |
| CBC | Every 12 weeks in patients with risk factors | Identify bone‑marrow suppression |
| Adverse Symptom Log | Patient‑reported daily | Early detection of toxicity |
Clinical Pearls
- High genetic barrier: Entecavir is resistant to most HBV variants; only about 1 % of naïve patients develop resistance after 48 months.
- Renal safety: Because it is renally excreted, the drug is not suitable for patients with severe kidney disease. Use the dose‑reduction algorithm or switch to a different agent in patients with CrCl < 50 mL min⁻¹.
- Combination therapy: In patients with patterns of resistance or suboptimal response, add tenofovir disoproxil fumarate or alafenamide (TDF/TAF) to maintain suppression.
- Pre‑emptive use: Initiate entecavir 1 month before immunosuppression for HBV‑seropositive patients; maintain for at least 6 months post‑therapy.
- Weight loss monitoring: Some patients on long‑term entecavir experience mild weight loss; advise a balanced diet, especially in the first year.
- No mitochondrial toxicity: Unlike lamivudine, entecavir does not cause lactic acidosis or bone‑mineral loss, making long‑term use safe.
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• Key Take‑away: Entecavir is the frontline antiviral for chronic HBV because of its potency, safety profile, and minimal propensity for resistance. Pay close attention to renal function and HBV DNA monitoring to ensure durable viral suppression.