Pharmacodynamic (Mechanism of Action):
- Entecavir, a deoxyguanosine nucleoside analogue with activity against HBV reverse
transcriptase (rt), 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 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 peak plasma concentrations occurred between 0.5 and 1.5 hours. Following
multiple daily doses ranging from 0.1 to 1 mg, (Cmax) and area under the concentration-time
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. For a
0.5mg oral dose, Cmax at steady state was 4.2 ng/mL and trough plasma concentration (Ctrough)
was 0.3 ng/mL. For a 1 mg oral dose, Cmax was 8.2 ng/mL and Ctrough was 0.5 ng/mL. The
bioavailability of the tablet was 100% relative to the oral solution. The oral solution and
tablet may be used interchangeably. Effects of food on oral absorption: Oral administration
of 0.5 mg of entecavir with a standard high-fat meal (945 kcal, 54.6 g fat) or a light meal
(379 kcal, 8.2 g fat) resulted in a delay in absorption (1.0–1.5 hours fed vs. 0.75 hours
fasted), a decrease in Cmax of 44%– 46%, and a decrease in AUC of 18%–20%.
The estimated apparent volume of distribution is in excess of total body water, suggesting
that entecavir is extensively distributed into tissues. Binding of entecavir to human serum
proteins in vitro was approximately 13%.
No oxidative or acetylated metabolites were observed. Minor amounts of phase II
metabolites (glucuronide and sulfate conjugates) were observed. Entecavir is not a
substrate, inhibitor, or inducer of the cytochrome P450 (CYP450) enzyme system.
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. Renal clearance
is independent of dose and ranges from 360 to 471 mL/min suggesting that entecavir
undergoes both glomerular filtration and net tubular secretion.
Pharmacodynamic (Mechanism of Action):
Modvir-B® tablets are indicated for the treatment of chronic hepatitis B virus infection in
adults and pediatric patients 2 years of age and older with evidence of active viral
replication and either evidence of persistent elevations in serum aminotransferases (ALT
or AST) or histologically active disease.
Dosage & Administration
Modvir-B® tablets should be administered on an empty stomach (at least 2 hours after a
meal and 2 hours before the next meal).
- Compensated Liver Disease
For Chronic hepatitis B virus infection in nucleoside inhibitor-treatment-naïve adults and
adolescents 16 years of age and older is 0.5 mg once daily.
For Lamivudine-refractory or known lamivudine or telbivudine resistance substitutions
(greater than or equal to 16 years old): 1 mg once daily.
- Decompensated Liver Disease
The recommended dose of Modvir-B® for chronic hepatitis B virus infection in adults
with decompensated liver disease is 1 mg once daily.
* Pediatric Patients (At least 2 years of age and weighing at least 10 kg):
The followed table describes the recommended dose of Modvir-B® for pediatric patients 2
years of age or older and weighing at least 10 kg. The Modvir-B® solution should be used
for patients with body weight up to 30 kg.
* Renal impairment:-
In adult subjects with renal impairment, the apparent oral clearance of entecavir decreased
as creatinine clearance decreased. The followed table describes the recommended dose for
patients with creatinine clearance less than 50 mL/min, including patients on hemodialysis
or continuous ambulatory peritoneal dialysis (CAPD).
Each film coated tablet of Modvir-B® contains:
Entecavir 1 mg ( as Entecavir monohydrate )
- Each 1ml of Modvir-B® oral solution contains:
Entecavir 0.05 mg ( as Entecavir monohydrate )
- Coadministration of Modvir-B® with drugs that reduce renal function or compete for active
tubular secretion may increase serum concentrations of either entecavir or the coadministered
drug. Coadministration of entecavir with lamivudine, adefovir dipivoxil, or tenofovir
disoproxil fumarate did not result in significant drug interactions.
- The effects of coadministration of Modvir-B® with other drugs that are renally eliminated or
are known to affect renal function have not been evaluated, and patients should be monitored
closely for adverse events when Modvir-B® is coadministered with such drugs.
It is not known whether Modvir-B® is present in human breast milk, affects human milk
production, or has effects on the breastfed infant. The developmental and health benefits of
breastfeeding should be considered along with the mother’s clinical need for Modvir-B® and
any potential adverse effects on the breastfed infant from Modvir-B® or from the underlying
- It has not been demonstrated that Modvir-B® is safe to use during pregnancy.
Modvir-B® must not be used during pregnancy unless specifically directed by doctor.
It is important that women of childbearing age receiving treatment with Modvir-B® use an
effective method of contraception to avoid becoming pregnant.
Dizziness, tiredness (fatigue) and sleepiness (somnolence) are common side effects which
may impair your ability to drive and use machines.
Like all medicines, Modvir-B® can cause side effects, although not everybody gets them.
Common (may affect up to 1 in 100 people):
- Headache, insomnia (inability to sleep), fatigue (extreme tiredness), dizziness, somnolence
(sleepiness), vomiting, diarrhoea, nausea, dyspepsia (indigestion), and increased blood levels of liver enzymes.
Uncommon (may affect up to 1 in 1000 people):
- Rash, hair loss.
Rare (may affect up to 1 in 10,000):
- Severe allergic reaction.
- If overdose occurs, the patient must be monitored for evidence of toxicity, and standard
supportive treatment applied as necessary.
Following a single 1 mg dose of entecavir, a 4-hour hemodialysis session removed
approximately 13% of the entecavir dose.
Severe Acute Exacerbations of Hepatitis B:
Severe acute exacerbations of hepatitis B virus infection have been reported in patients who
have discontinued anti-hepatitis B therapy: Monitor hepatic function closely for at least
* Patients Co-infected with HIV and HBV:
Co-infection with HIV: Modvir-B® is not recommended unless the patient is also receiving
* Lactic Acidosis and Severe Hepatomegaly with Steatosis:
Lactic acidosis and severe hepatomegaly with steatosis: If suspected, treatment should be
Use in Specific Populations:-
* Hepatic Impairment
No dosage adjustment is necessary for patients with hepatic impairment.
* Liver Transplant Recipients
If Modvir-B® treatment is determined to be necessary for a liver transplant recipient who
has received or is receiving an immunosuppressant that may affect renal function, such as
cyclosporine or tacrolimus, renal function must be carefully monitored both before and
during treatment with Modvir-B®.
Modvir-B® 1 tablet: ( Blister of 10 tablets, pack of three Blister).
- Modvir-B® 0.05 oral solution: ( Bottle of 100ml solution ).
- Modvir-B® 1 tablet: Store at a dry place at temperature below 25 °C.
- Modvir-B® 0.05 oral solution: Store at temperature below 25 °C.