DESCRIPTION
Entecavir is a guanosine nucleoside analogue with selective activity against hepatitis B virus (HBV). The chemical name for entecavir is 2-amino-1,9-dihydro-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl]-6 H-purin-6-one, monohydrate. Its molecular formula is C12H15N5O3•H2O.Its molecular weight is 295.3.

PHARMACOLOGICAL ACTIONS
Pharmacodynamic properties
Entecavir, a guanosine nucleoside analogue with activity against HBV polymerase, is efficiently phosphorylated to the active triphosphate form, which has an intracellular half-life of 15 hours. By competing with the natural substrate deoxyguanosine triphosphate, entecavir triphosphate functionally inhibits all three activities of the HBV polymerase (1) base priming, (2) reverse transcription of the negative strand from the pre genomic messenger RNA, and (3) synthesis of the positive strand of HBV DNA.Entecavir inhibited HBV DNA synthesis. The co administration of HIV nucleoside reverse transcriptase inhibitors (NRTIs) with entecavir is unlikely to reduce the antiviral efficacy of entecavir against HBV or of any of these agents against HIV.

Pharmacokinetic properties
Absorption: Following oral administration, entecavir achieves peak plasma concentrations between 0.5 and 1.5 hours. Steady state was achieved after 6 to 10 days of once-daily administration with approximately 2-fold accumulation.
Distribution: Entecavir is extensively distributed into tissues. Serum protein binding of entecavir is approximately 13%.
Metabolism: Following oral administration the drug remains unchanged in the body.
Excretion: Entecavir is predominantly eliminated by the kidney with urinary recovery of unchanged drug at steady state ranging from 62% to 73% of the administered dose.

INDICATIONS AND USAGE
Entecavir is indicated for the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

DOSAGE AND ADMINISTRATION
The recommended dose of entecavir for chronic hepatitis B virus infection in nucleoside-treatment adults and adolescents 16 years of age and older is 0.5 mg once daily.
The recommended dose of entecavir in adults and adolescents (•16 years of age) with a history of hepatitis B viremia while receiving lamivudine or known lamivudine resistance mutations is 1 mg once daily.

Note: Entecavir should be administered on an empty stomach (at least 2 hours after a meal and 2 hours before the next meal).

CONTRAINDICATIONS
Entecavir is contraindicated in patients with hypersensitivity to the drug or any of the components of the product.

ADVERSE EFFECTS
The common adverse effects include headache, fatigue, dizziness, nausea and insomnia.

WARNINGS AND SPECIAL PRECAUTIONS
Pregnancy:
Pregnancy category C
Entecavir should be used during pregnancy only if clearly needed and after careful consideration of the risks and benefits.
Nursing mothers: It is not known whether this drug is excreted in human milk. Mothers should be instructed not to breast-feed if they are taking entecavir.
Renal impairment: Dosage adjustment is recommended for patients with a creatinine clearance <50 mL/min, including patients on hemodialysis or continuous ambulatory peritoneal dialysis (CAPD)
Hepatic impairment: No dosage adjustment is required for patients with hepatic impairment.

DRUG INTERACTIONS
The pharmacokinetics of entecavir are unlikely to be affected by coadministration with agents that are either metabolized by or induce the CYP450 system. Likewise, the pharmacokinetics of known CYP substrates are unlikely to be affected by coadministration of entecavir.

OVERDOSAGE
If overdose occurs, the patient must be monitored for evidence of toxicity, and necessary supportive treatment should be given.

STORAGE
Store at room temperature.
Protect from light, heat and moisture.
Keep all medicines out of the reach of children.

PRESENTATION
Ecavir 0.5 mg tablets in Alu Alu pack of 3 x 10s.