ENTECAVIR
Clinical safety rating: safe
Animal studies have demonstrated safety
Entecavir is a guanosine nucleoside analogue with activity against hepatitis B virus (HBV) polymerase. It is phosphorylated intracellularly to the active triphosphate form, which competes with the natural substrate deoxyguanosine triphosphate and inhibits HBV polymerase (reverse transcriptase) activity, resulting in inhibition of viral DNA synthesis.
| Metabolism | Entecavir is primarily eliminated by the kidneys via glomerular filtration and net tubular secretion. It is not a substrate for cytochrome P450 enzymes; metabolism is minimal with oxidation and glucuronidation forming minor metabolites. |
| Excretion | Renal excretion of unchanged drug accounts for 60-73% of the dose; biliary/fecal elimination accounts for 27-40% via active tubular secretion and glomerular filtration. |
| Half-life | Terminal elimination half-life is approximately 128-149 hours (5-6 days) in patients with normal renal function; prolonged in renal impairment (up to 40 hours in severe impairment), necessitating dose adjustment based on creatinine clearance. |
| Protein binding | Approximately 13% bound to human serum albumin (low binding). |
| Volume of Distribution | Volume of distribution is 0.7-1.0 L/kg (total body water), indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is 100% (high); absorption not affected by food (administer on empty stomach or with food). |
| Onset of Action | Oral administration: Reduction of HBV DNA levels detectable within 1 week; maximal antiviral effect observed at 4-6 weeks. |
| Duration of Action | Sustained viral suppression for the duration of therapy; rebound occurs upon discontinuation. Clinical duration is dose-dependent with once-daily dosing maintaining therapeutic levels over 24 hours. |
0.5 mg orally once daily; for lamivudine-refractory or decompensated liver disease: 1 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | Creatinine clearance (CrCl) ≥50 mL/min: 0.5 mg every 24h (or 1 mg every 24h for refractory); CrCl 30-49: 0.5 mg every 48h (or 1 mg every 48h); CrCl 10-29: 0.5 mg every 72h (or 1 mg every 72h); CrCl <10 (including hemodialysis): 0.5 mg every 96-120h (or 1 mg every 96-120h), administered after dialysis. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). For severe hepatic impairment (Child-Pugh C), limited data; use with caution and monitor. If decompensated liver disease, use 1 mg daily regardless of Child-Pugh score. |
| Pediatric use | For patients ≥2 years and ≥10 kg: weight-based dosing. 10-11 kg: 0.15 mg; >11-14 kg: 0.2 mg; >14-17 kg: 0.25 mg; >17-20 kg: 0.3 mg; >20-25 kg: 0.35 mg; >25-30 kg: 0.4 mg; >30-40 kg: 0.45 mg; >40 kg: 0.5 mg. For lamivudine-experienced or decompensated: 1 mg daily for those >40 kg. |
| Geriatric use | No specific geriatric dose adjustments; select dose based on renal function (creatinine clearance) due to age-related decline in renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Drugs that reduce renal function may increase levels Severe acute exacerbations of hepatitis B have been reported upon discontinuation.
| Breastfeeding | Entecavir is excreted into breast milk in rats; human data unavailable. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended. M/P ratio not established in humans. |
| Teratogenic Risk | Insufficient human data; animal studies show no evidence of teratogenicity at clinically relevant doses. First trimester: risk unknown; second and third trimesters: no increased malformation risk reported. However, untreated hepatitis B infection poses maternal-fetal risks. |
■ FDA Black Box Warning
WARNING: SEVERE ACUTE EXACERBATION OF HEPATITIS B IN PATIENTS CO-INFECTED WITH HIV AND HBV; LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS; POST-TREATMENT SEVERE ACUTE EXACERBATION OF HEPATITIS B. Entecavir is not recommended for use in HIV/HBV co-infected patients not receiving highly active antiretroviral therapy (HAART) due to risk of development of HIV resistance. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with nucleoside analogues. Severe acute exacerbation of hepatitis B may occur upon discontinuation of entecavir.
| Common Effects | Headache |
| Serious Effects |
["Hypersensitivity to entecavir or any component of the formulation"]
| Precautions | ["Lactic acidosis and severe hepatomegaly with steatosis (including fatalities)","Severe acute exacerbation of hepatitis B after discontinuation","Risk of HIV resistance in HIV/HBV co-infected patients not on HAART","Renal impairment: dose adjustment required","Liver transplant recipients: monitor renal function and immunosuppressant levels","Pregnancy: use only if potential benefit justifies risk"] |
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| Fetal Monitoring |
| Monitor liver function tests (ALT, AST), hepatitis B serology, HBV DNA levels, and renal function (creatinine, BUN) throughout pregnancy. Assess fetal growth via ultrasound if prolonged therapy. |
| Fertility Effects | No adverse effects on fertility observed in animal studies. Human data lacking; theoretical risk of hormonal disturbance remains unconfirmed. |