Each mL contains: Entecavir Monohydrate equivalent entecavir 0.05 mg.
Pharmacology: Pharmacodynamics: Entecavir, a guanosine nucleoside analog, is an antiviral agent that is active against human hepatitis B virus (HBV). The drug undergoes phosphorylation by cellular enzymes to form its active metabolite, entecavir triphosphate. By competing with the natural substrate deoxyguanosine triphosphate, entecavir triphosphate inhibits activities of HBV DNA polymerase (reverse transcriptase) including base priming, reverse transcription of the negative strand from the pregenomic messenger RNA, and synthesis of the positive strand of HBV DNA.
Pharmacokinetics: Absorption: Following multiple daily doses ranging from 0.1 to 1 mg, Cmax and area under the curve (AUC) at steady state increased in proportion to dose. Steady state was achieved after 6 to 10 days of once-daily administration, with approximately 2-fold accumulation.
Oral administration of entecavir with meal resulted in delay in absorption and a decrease in AUC.
Distribution: Binding of entecavir to human serum proteins in vitro was approximately 13%. Based on the pharmacokinetic profile of entecavir after oral dosing, the estimated apparent volume of distribution is in excess of total body water, suggesting that entecavir is extensively distributed into tissues.
Metabolism/Excretion: Entecavir is excreted principally in urine via glomerular filtration and tubular secretion. Entecavir is not a substrate for and does not inhibit or induce cytochrome P-450 (CYP) isoenzymes.
ENCAVIR is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults with evidence of active liver inflammation.
Compensated liver disease: Nucleoside-naive patients: Usual dosage: 0.5 mg once daily.
Lamivudine-refractory patients (history of hepatitis B viremia while receiving lamivudine or with known lamivudine resitance mutations): Usual dosage: 1 mg once daily.
Decompensated liver disease: 1 mg once daily.
Renal impairment: Dosage of entecavir should be adjusted in patients with pre-existing renal impairment (i.e. baseline creatinine clearance less than 50 mL/minute), including patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis (CAPD). (See Table.)
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Mode of Administration:
ENCAVIR is administered orally. Because presence of food in the GI tract may decrease the rate and extent of absorption, ENCAVIR should be administered on an empty stomach at least 2 hours before or 2 hours after meals.
ENCAVIR oral solution contains 0.05 mg of entecavir per milliliter. Therefore, 10 mL of the oral solution provide a 0.5 mg dose and 20 mL provide a 1 mg dose of entecavir.
Patients undergoing hemodialysis should receive the entecavir dose after the dialysis session.
There is limited experience of entecavir overdose reported in patients. If overdose occurs, the patient must be monitored for evidence of toxicity and given standard supportive treatment as necessary.
ENCAVIR is contraindicated in patients with previously demonstrated hypersensitivity to entacavir or any component of the product.
Exacerbations of Hepatitis: Severe acute exacerbations of hepatitis have occurred following discontinuance of HBV therapy, including entecavir therapy. Exacerbations of hepatitis also have been reported during entecavir treatment of HBV, but generally resolved with continued therapy.
Hepatic function should be monitored during ENCAVIR therapy and should be monitored closely both clinical and laboratory follow-up at repeated intervals for at least several months after ENCAVIR is discontinued. If appropriate, resumption of anti-HBV therapy may be warranted.
Individuals Coinfected with HBV and HIV: Use of entecavir for treatment of chronic HBV infections in patients with unrecognized or untreated HIV infection may result in emergence of HIV isolates with resistance to nucleoside reverse transcriptase inhibitors (NRTIs). Prior to initiation of entecavir therapy, all patients should be offered HIV testing. ENCAVIR should not be used for the treatment of HBV in HIV-infected patients who are not receiving antiretroviral therapy.
Entecavir has not been systematically evaluated for the treatment of HIV infection and such use is not recommended.
Lactic Acidosis and Severe Hepatomegaly with Steatosis: Lactic acidosis and severe hepatomegaly with steatosis, including some fatalities, have been reported in patients receiving nucleoside analogs alone or in conjunction with antiretrovirals. ENCAVIR should be discontinued in any patient with clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.
Pregnancy: Category C.
There are no adequate and well-controlled studies in pregnant women. ENCAVIR should be used during pregnancy only if clearly needed and after careful consideration of the risks and benefits.
Lactation: Entecavir is excreted into the milk of rats. It is not known whether this drug is excreted in human milk. Discontinue nursing or ENCAVIR, taking into account the importance of ENCAVIR to the mother.
Most common adverse effects are headache, fatigue, dizziness and nausea. Diarrhea, dyspepsia, vomiting, somnolence and insomnia also have been reported.
The most common laboratory abnormalities are ALT elevations, hematuria, lipase elevations, glycosuria, hyperbilirubinemia, fasting hyperglycemia, and creatinine increases.
Since ENCAVIR is primarily eliminated by the kidneys, co-administration of ENCAVIR with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of ENCAVIR or the co-administered drug. Monitor patients closely for adverse reactions when ENCAVIR is co-administered with such drugs.
Store at a temperature not above 30°C in the original carton.
J05AF10 - entecavir ; Belongs to the class of nucleoside and nucleotide reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.
Oral liqd 0.05 mg/mL (orange-flavored, clear, colorless to pale yellow aqueous solution) x 210 mL x 1's.