Entecavir

Trade Names:
Baraclude
- Tablets 0.5 mg
- Tablets 1 mg
- Oral solution 0.05 mg/mL

Pharmacology

Feedback for Entecavir As a treatment for... Avg User Ratings [?] Hepatitis B - Chronic Be the first to rate it 0 comments   Compare with other drugs.

Inhibits hepatitis B virus (HBV) polymerase (reverse transcriptase) by competing with the natural substrate deoxyguanosine triphosphate.

Pharmacokinetics

Absorption

Bioavailability of tablet is 100% relative to oral solution. T _max is between 0.5 and 1.5 h. Steady state achieved after 6 to 10 days. For 0.5 mg dose, C _max was 4.2 ng/mL and C _trough was 0.3 ng/mL; for 1 mg dose, C _max was 8.2 ng/mL and C _trough was 0.5 ng/mL. Administration with food decreases C _max 44% to 46% and AUC 18% to 20%.

Distribution

Approximately 13% protein bound. Vd in excess of total body water suggesting extensive distribution into tissues.

Metabolism

No oxidative or acetylated metabolites found. Minor amounts of phase 2 metabolites (glucuronide, sulfate conjugates) noted.

Elimination

Terminal elimination t _½ is 128 to 149 h; accumulation t _½ approximately 24 h. Eliminated predominantly by kidney (both glomerular filtration and tubular secretion), with 62% to 73% of dose recovered in the urine.

Special Populations

C _max and AUC increased in patients with moderate to severe renal impairment or with end-stage renal disease. Dose reduction recommended for patients with Ccr less than 50 mL/min.

AUC 29.3% greater in elderly subjects; most likely secondary to decrease in renal function. Base dose adjustment of entecavir on renal function of patient and not on age.

Indications and Usage

Treatment of chronic hepatitis B virus in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

Contraindications

Standard considerations.

Dosage and Administration

PO 0.5 mg daily.

PO 1 mg daily.

PO For Ccr 30 to 49 mL/min, administer 0.25 mg daily if nucleoside-naive, or 0.5 mg daily if lamivudine-refractory; for Ccr 10 to 29 mL/min, administer 0.15 mg daily if nucleoside-naive, or 0.3 mg daily if lamivudine-refractory; hemodialysis, CAPD patients, or Ccr less than 10 mL/min, administer 0.05 mg daily if nucleoside-naive, or 0.1 mg daily if lamivudine-refractory (after hemodialysis on dialysis day).

General Advice

• Administer on an empty stomach, at least 2 h after a meal or 2 h before the next meal.
• Oral solution and tablets may be used interchangeably on a mg-to-mg basis.
• Oral solution contains 0.05 mg entecavir/mL. 10 mL of oral solution provides 0.5 mg dose and 20 mL provides 1 mg dose.
• Oral solution is a ready-to-use product; dilution or mixing with water or any other liquid product is not recommended.
• Oral solution is supplied with dosing spoon calibrated in 1 mL increments up to 10 mL. Hold spoon in vertical position and fill gradually to prescribed dose. Administer dose directly from dosing spoon. Rinse dosing spoon with water after each use.
• If a dose is missed, administer as soon as remembered that day, unless it is nearing time for the next dose, in which case skip the dose and administer the next dose at the scheduled time. Do not administer more than 1 dose in a day. Do not administer 2 doses at the same time to catch up.

Storage/Stability

Store tablets and oral solution at controlled room temperature (59° to 86°F). Protect oral solution from light.

Drug Interactions

Serum concentrations of entecavir or the coadministered drug may be elevated, possibly increasing pharmacologic and adverse effects.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache (4%); fatigue (3%).

GI

Diarrhea, dyspepsia (1%).

Hepatic

Exacerbation of hepatitis after stopping treatment HBeAg-negative patients (8%) and HBeAg-positive patients (1%).

Lab Tests

Elevated ALT (12%); hematuria (9%); increased lipase (8%); elevated AST (5%); glycosuria (4%); increased total bilirubin, increased amylase (3%); increased creatinine, fasting hyperglycemia (2%).

Metabolic-Nutritional

Lactic acidosis.

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy in children younger than 16 yr of age not established.

Elderly

Select dose with caution, reflecting greater frequency of decreased hepatic, renal, or cardiac function and comorbidity.

Liver transplant recipients

Monitor renal function carefully in liver transplant patients who have received or are receiving an immunosuppressant that may affect renal function (eg, cyclosporine, tacrolimus).

Overdosage

Symptoms

No experience reported.

Patient Information

• Advise patient to review the patient information leaflet carefully before starting therapy and to read and check for new information each time the medication is refilled.
• Review dosing schedule with patient.
• Advise patient that each dose must be taken on an empty stomach, 2 h after a meal or 2 h before the next meal.
• Advise patient or caregiver using oral solution to measure prescribed dose using supplied dosing spoon. Instruct patient or caregiver to hold spoon in upright position and gradually fill it to mark corresponding to prescribed dose and then swallow medication directly from the spoon and then rinse the spoon with water and allow it to air dry. Caution patient or caregiver not to dilute or mix oral solution with any other liquid.
• Advise patient that if a dose is missed to take it as soon as remembered on that day unless it is nearing time for the next dose, in which case the dose should be skipped and the next dose taken at the scheduled time. Caution patient not to take more than 1 dose of entecavir in a day nor to take 2 doses at the same time to catch up.
• Caution patient not to change the dose or stop taking unless advised by health care provider. Advise patient that stopping therapy may result in severe exacerbation of the hepatitis.
• Advise patient to get an HIV test before starting therapy and anytime after that when there is a chance of exposure to HIV.
• Advise patient that medication will not cure hepatitis B infection nor any other viral infection (eg, HIV) and to continue to take other antiviral medications as prescribed.
• Advise patient that this therapy will not prevent transmission of hepatitis B to others and to avoid things that could spread hepatitis B to others: do not share needles or injection equipment; do not share personal items that have blood or body fluids on them (eg, toothbrushes, razor blades); do not have any kind of sex without protection (eg, condoms, dental dams).
• Advise patient that it is not known if entecavir can prevent cirrhosis, liver failure, or liver cancer that may develop as a result of hepatitis B infection.
• Instruct patient to immediately report any of the following to health care provider: difficulty breathing, unusual muscle pain, generalized body discomfort, unexplained drowsiness, dizziness, light-headedness, fast or irregular heart beat, stomach pain with nausea and vomiting, cold feeling, especially in arms and legs, yellowing of the skin or eyes, appetite loss, bowel movements turn light in color, or urine turns very dark in color.

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