Orata

White, triangular-shaped, biconvex film coated tablet with engraved 0.5 on one side and plain on the other side.
Each film coated tablet contains Entecavir 0.5 mg.

Pharmacology: Pharmacodynamics: Entecavir is intracellularly phosphorylated to guanosine triphosphate which competes with natural substrates to effectively inhibit hepatitis B viral polymerase and enzyme inhibition blocks reverse transcriptase activity thereby reducing viral DNA synthesis.
Pharmacokinetics: Absorption: Delayed with food; C_max decreased 44-46% AUC decreased 18-20%.
Distribution: Extensive.
Protein binding: ~13%.
Metabolism: Minor hepatic glucoronide/sulfate conjugation.
Half-life elimination Terminal: ~5-6 days, accumulation ~24 hours.
Time to peak, plasma: 0.5-1.5 hours.
Excretion: Urine (60-73% as unchanged drug).

Orata is indicated for the treatment of chronic HBV infection in adults with evidence of active liver inflammation.

Administer on an empty stomach once daily.
Nucleoside treatment naive: initial 0.5 mg once daily.
Lamivudine refractory (eg. Evidence of viraemia while on lamivudine or the presence of lamivudine resistance mutations that known as YMDD gene): initial 1 mg once daily. Taken on an empty stomach (more than 2 hours before or more than 2 hours after a meal).
Renal impairment: Entecavir is predominantly eliminated by the kidney. The clearance of entecavir decreases with impaired creatinine clearance. Dose adjustment is recommended for patients who have creatinine clearance <50 mL/min including those on hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) as shown in table. (See table.)

Click on icon to see table/diagram/image

Hepatic impairment: No dosage adjustment necessary.
Pediatric and adolescent: The safety and efficacy in patients <16 years of age have not been established.
Geriatric: No dosage adjustment based on age is required.
Treatment duration: The optimal duration of treatment for patients with chronic hepatitis B infection and the relationship between treatment and long-term outcomes eg, cirrhosis and hepatocellular carcinoma are unknown.

There are limited experience of entecavir overdose reported in patients. Healthy subjects who received single entecavir dose up to 40 mg or multiple doses up to 20 mg/day for up to 14 days did not experience any unexpected adverse events. If overdose occurs, the patients must be monitored for evidence of toxicity and given standard supportive treatment as necessary.

Patients with previously demonstrated hypersensitivity to entecavir or any component.

Lactic acidosis and hepatomegaly with steatosis: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases has been reported with the use of nucleoside analogue alone or in combination with antiretroviral.
Exacerbations of hepatitis after discontinuation of treatment: Acute exacerbation of hepatitis has been reported in patients who have discontinued HBV therapy, including therapy with entecavir. The majority of post treatment exacerbations appear to be self-limited. However severe exacerbation including fatalities, may occur. The causal relationship of these event to discontinuation of the therapy is unknown. If appropriate, resumption of HBV therapy may be warranted.
Co-infection with HIV: Entecavir may cause the development of HIV resistance in chronic hepatitis B patients with unrecognized or untreated HIV infection. Not recommend for HIV/HBV coinfected patients unless also receiving highly active antiretroviral therapy regimen (HAART regimen).
Renal Impairment: Dosage adjustment of entecavir is recommended for patient renal impairment. (See Renal Impairment under Dosage & Administration.)
Liver Transplant Recipients: The safety and efficacy of entecavir in liver transplant recipients are unknown. If entecavir treatment is determined to be necessary for a liver transplant recipient who has received or is receiving an immunosuppressant that may affect renal function eg, cyclosporine or tacrolimus, renal function must be carefully monitored both before and during treatment with entecavir.
Information for Patients: Should advice patients that entecavir inhibits virus replication but cannot cure a disease. No evidence supports that entecavir can reduce a risk of transmission of hepatitis B virus. Therefore, should advice patients to more adherence because in some case, stopping entecavir may cause more severe hepatitis B or serious liver problem.

Pregnancy risk factor C.
There are no adequate and well controlled studies in pregnant women. Entecavir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
There are no data on the effect of entecavir on transmission of HBV from mother to infant. Therefore, appropriate interventions should be used to prevent neonatal acquisition of HBV.
Entecavir is excreted in the milk of rats. It is not known whether this drug is excreted in human milk. Mothers should be instructed not to breastfeed if they are taking entecavir.

Cardiovascular: Peripheral edema (with decompensated liver disease).
Central nervous system: Headache, fatigue, dizziness.
Dermatologic: Skin rash.
Endocrine & metabolic: Decreased serum bicarbonate, glycosuria, hyperglycemia.
Gastrointestinal: Abdominal pain, diarrhea, dyspepsia, increased serum amylase, increased serum lipase, unpleasant taste, nausea, vomiting.
Hepatic: Ascites, increased ALT, increased serum bilirubin, hepatic encephalopathy, hepatic carcinoma.
Renal: Increased serum creatinine.
Respiratory: Upper respiratory tract infection.
Miscellaneous: Fever.
Rare but important or life-threatening: Alopecia, anaphylactoid reaction, hepatomegaly, insomnia, lactic acidosis, macular edema, renal failure, thrombocytopenia.

There are no known significant interaction.
Entecavir is primarily eliminated by the kidneys, co-administration with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either entecavir or the co-administered drug. Co-administration of entecavir with lamivudine, adefovir dipivoxil, or tenofovir disoproxil fumarate did not result in significant drug interactions. The effects of co-administration 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 entecavir co-administered with such drugs.
Food delays absorption and reduces AUC by 18%-20%.

Store below 30°C.

Antivirals

J05AF10 - entecavir ; Belongs to the class of nucleoside and nucleotide reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.

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