BARACLUDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BARACLUDE (BARACLUDE).
Entecavir is a guanosine nucleoside analogue with activity against hepatitis B virus (HBV) polymerase. It inhibits HBV replication by competing with the natural substrate deoxyguanosine triphosphate, blocking the priming and reverse transcriptase steps of HBV DNA synthesis.
| Metabolism | Entecavir is primarily eliminated by the kidneys via glomerular filtration and tubular secretion. Metabolism is minimal, with CYP enzymes not significantly involved. |
| Excretion | Renal elimination of unchanged drug via glomerular filtration and tubular secretion; ~62-73% of dose recovered in urine as unchanged drug, <3% as metabolites; <1% fecal. |
| Half-life | Terminal elimination half-life ~128-149 hours in healthy subjects; clinically, steady-state achieved in ~10-18 days with once-daily dosing. |
| Protein binding | ~13% bound to human serum albumin in vitro; binding independent of drug concentration. |
| Volume of Distribution | Steady-state Vd ~0.74 L/kg (range 0.3-1.2 L/kg), indicating distribution into tissues including extravascular spaces. |
| Bioavailability | Oral bioavailability is not extensively reported due to lack of IV formulation; absorption is rapid with peak concentrations at 0.5-1.5 h; food delays absorption and reduces Cmax by 29-38%. |
| Onset of Action | Oral: Onset of antiviral effect detectable within days; maximal HBV DNA reduction observed over 24-48 weeks. |
| Duration of Action | Duration of antiviral effect persists throughout dosing interval; once-daily dosing maintains continuous suppression; rebound occurs if therapy interrupted. |
| Molecular Weight | 277.34 |
| Action Class | Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) |
| Brand Substitutes | Entarica 1mg Tablet, Entaliv 1mg Tablet, Entavir 1mg Tablet, Entarica 1 Tablet, Austavir 1mg Tablet |
0.5 mg orally once daily; for lamivudine-refractory or decompensated liver disease, 1 mg orally once daily.
| Dosage form | SOLUTION |
| Renal impairment | CrCl ≥50 mL/min: 0.5 mg once daily (or 1 mg once daily for refractory cases). CrCl 30–49 mL/min: 0.25 mg once daily (or 0.5 mg once daily for refractory). CrCl 10–29 mL/min: 0.15 mg once daily (or 0.3 mg once daily for refractory). CrCl <10 mL/min (including hemodialysis): 0.05 mg once daily (or 0.1 mg once daily for refractory). |
| Liver impairment | No adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Safety and efficacy in severe hepatic impairment (Child-Pugh C) not established. |
| Pediatric use | ≥2 years and ≥10 kg: 0.015 mg/kg (max 0.5 mg) once daily; for lamivudine-refractory: 0.03 mg/kg (max 1 mg) once daily. Dose rounded to nearest tablet strength. |
| Geriatric use | Dose selection based on renal function; monitor renal function closely due to age-related decline. |
| 1st trimester | No adequate studies in pregnant women; use only if clearly needed. Antiretroviral Pregnancy Registry data do not show increased risk of major birth defects. |
| 2nd trimester | Crosses placenta; no increased risk of fetal abnormalities reported in registry. Use if benefit outweighs risk. |
| 3rd trimester | Crosses placenta; no evidence of teratogenicity. Monitor for HBV flare postpartum. |
Clinical note
Comprehensive clinical and safety monograph for BARACLUDE (BARACLUDE).
| Placental transfer | Crosses placenta in animal studies and humans; estimated fetal exposure ~50% of maternal plasma concentration. |
| Breastfeeding | Entecavir is excreted in human milk at low levels. Consider risk of potential serious adverse reactions in nursing infants. Decision to discontinue breastfeeding or drug should be based on importance of drug to mother. |
■ FDA Black Box Warning
Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including entecavir. Hepatic function should be monitored closely for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, resumption of anti-hepatitis B therapy may be warranted.
| Serious Effects |
Hypersensitivity to entecavir or any component of the formulationCoinfection with HIV without concomitant antiretroviral therapy (risk of HIV resistance)
| Precautions | Severe acute exacerbations of hepatitis B upon discontinuation of therapy, Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with use of nucleoside analogues alone or in combination with antiretrovirals, Monitor renal function; dosage adjustment required for patients with creatinine clearance < 50 mL/min, HIV coinfection: entecavir may select for HIV resistance; HIV serology should be performed prior to therapy, Emergence of resistance: monitor virologic response and for entecavir resistance; consider alternative therapy if inadequate response or resistance develops |
| Food/Dietary |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, entecavir was not teratogenic at doses up to 1 mg/kg (28 times the human exposure at the recommended dose) in rats and rabbits. However, at maternally toxic doses (3 mg/kg), embryotoxicity (resorptions, reduced fetal body weights) was observed in rats. Use only if potential benefit justifies potential risk to the fetus. During first trimester, risks are highest for structural abnormalities; second and third trimester risks may include low birth weight and preterm delivery. |
| Fetal Monitoring | Monitor hepatic function (ALT, AST, bilirubin), HBV DNA levels, and serum creatinine in pregnant women receiving entecavir. In infants born to mothers treated with entecavir, monitor for hepatitis B infection and adverse effects, including lactic acidosis and hepatomegaly with steatosis. Consider periodic liver ultrasound if elevated transaminases persist. |
| Fertility Effects | In animal studies, entecavir had no significant effects on fertility or reproductive performance in rats at doses up to 30 mg/kg (1000 times the human exposure). There are no human data on the effects of entecavir on fertility. |
| Food delays and reduces absorption of entecavir. Take on an empty stomach at least 2 hours before or after any meal. Avoid high-fat meals as they may further reduce absorption. No specific food restrictions beyond timing. |
| Clinical Pearls | BARACLUDE (entecavir) is a first-line nucleoside analogue for chronic hepatitis B. It has a high genetic barrier to resistance, but resistance can emerge in lamivudine-refractory patients. Monitor renal function; dose adjustment required for CrCl <50 mL/min. Do not use in HIV co-infection without antiretroviral therapy due to risk of HIV resistance. Lactic acidosis and severe hepatomegaly with steatosis have been reported; discontinue if symptoms occur. |
| Patient Advice | Take BARACLUDE exactly as prescribed, once daily on an empty stomach (at least 2 hours before or after a meal). · Do not stop taking this medication without consulting your doctor, as sudden stopping may worsen hepatitis. · Report any symptoms of lactic acidosis (unusual muscle pain, trouble breathing, severe tiredness) or liver problems (yellowing of skin/eyes, dark urine, abdominal pain). · BARACLUDE does not prevent transmission of hepatitis B; practice safe sex and avoid sharing needles. · Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · Regular blood tests are required to monitor liver function and viral load. |