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. |
| 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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BARACLUDE (BARACLUDE).
| Breastfeeding | It is not known whether entecavir is excreted in human milk. In lactating rats, entecavir was detected in milk at concentrations approximately 0.2% of the administered dose. No human M/P ratio is available. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| 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. |
■ 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 formulation"]
| 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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| 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. |