Entavir 0.50 Tablets

Indications

• Chronic hepatitis B infection in patients with compensated liver disease
• Chronic hepatitis B infection with evidence of viral replication
• Chronic hepatitis B infection with histologically documented active liver inflammation or fibrosis

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing guidelines.

Adults: 500 micrograms once daily, with adjustments required for patients with renal impairment.

Mechanism of action

Entecavir inhibits the hepatitis B virus polymerase by competing with the natural substrate deoxyguanosine triphosphate. It accomplishes this by interfering with three key activities of the polymerase: base priming, reverse transcription of the negative strand from the pregenomic messenger RNA, and synthesis of the positive strand of HBV DNA. Upon being activated by cellular kinases, entecavir is converted into its triphosphate form, which further inhibits HBV polymerase activity. Although it also weakly inhibits some cellular DNA polymerases, its primary action remains focused on HBV.

Pharmacodynamics

As a guanosine nucleoside analogue, entecavir exhibits selective antiviral activity against hepatitis B virus. Its mechanism allows it to effectively block all stages of HBV replication, which contributes to its efficacy in managing chronic hepatitis B. Entecavir is noted for its improved efficiency compared to lamivudine, making it a preferred option for patients.

Pharmacokinetics

Entecavir is absorbed orally, with a bioavailability that is not significantly affected by food. It is primarily eliminated via renal excretion, necessitating dosage adjustments in patients with renal impairment. The half-life of entecavir is approximately 128 to 149 hours, allowing for once-daily dosing. The drug is phosphorylated to its active form within cells, enabling its action on HBV.

Adverse effects

• Lactic acidosis
• Hepatomegaly
• Fatigue
• Headache
• Dizziness
• Nausea
• Diarrhea

Precautions

• Monitor renal function, especially in patients with creatinine clearance less than 50 mL/minute
• Assess for lactic acidosis symptoms
• Consider potential resistance in previously treated patients

Pregnancy

Manufacturer advises use only if potential benefit outweighs risk due to toxicity in animal studies.

Breast-feeding

Manufacturer advises avoiding use as entecavir is present in milk in animal studies.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Entecavir (as Entecavir monohydrate) 0.05 mg/ml oral solution, sugar-free, 210 ml
• Entecavir (as Entecavir monohydrate) 500 microgram tablets, 30 tablets
• Entecavir (as Entecavir monohydrate) 1 mg tablets, 30 tablets

Mechanism of action

By competing with the natural substrate deoxyguanosine triphosphate, entecavir functionally inhibits all three activities of the HBV polymerase (reverse transcriptase, rt): (1) base priming, (2) reverse transcription of the negative strand from the pregenomic messenger RNA, and (3) synthesis of the positive strand of HBV DNA. Upon activation by kinases, the drug can be incorporated into the DNA which has the ultimate effect of inhibiting the HBV polymerase activity. Entecavir is a nucleoside analogue with activity against HBV polymerase. It is efficiently phosphorylated to the active triphosphate form, which competes with the natural substrate deoxyguanosine triphosphate and inhibits all three activities of the HBV polymerase (reverse transcriptase): 1) base priming, 2) reverse transcription of the negative strand from the pregenomic messenger RNA and 3) synthesis of the positive strand of HBV DNA. Entecavir triphosphate is a weak inhibitor of cellular DNA polymerases alpha, beta, and delta and mitochondrial DNA polymerase gamma with Ki values ranging from 18 to > 160 microM.

Pharmacodynamics

Entecavir is a guanosine nucleoside analogue with selective activity against hepatitis B virus (HBV). It is designed to selectively inhibit the Hepatitis B virus, blocking all three steps in the replication process. Entecavir is more efficient than an older Hepatitis B drug, lamivudine.