Entegard

Entecavir (Entegard) 500 mcg is a white to off-white triangular-shaped film-coated tablet, plain on both sides.
Each film-coated tablet contains: Entecavir, USP 500 mcg.
Entecavir is a white to off-white powder. It is slightly soluble in water (2.4 mg/mL), and the pH of the saturated solution in water is 7.9 at 25°±0.5°C.

Pharmacology: Pharmacodynamics: HBV polymerase (reverse transcriptase, rt): base priming, reverse transcription of the negative strand from the pregenomic messenger rna, and 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.
Pharmacokinetics: Entecavir is absorbed from the gastrointestinal tract after doses. Peak plasma concentrations occur 30 to 90 minutes after a dose and steady state concentration after 6 to 10 days of treatment. Bioavailability of the tablet formulation is equal to that of the oral solution and they may be given interchangeably. Binding of entecavir to plasma proteins is about 13% in vitro. Entecavir is not metabolized by the cytochrome P450 system. It is mainly eliminated by the kidneys by glomerular filtration and active tubular secretion, with a terminal elimination half-life of 128 to 149 hours. Minor amounts of glucuronide and sulfate conjugate metabolites occur. Entecavir is partially removed by hemodialysis.
Microbiology: Antiviral Action: Entecavir is phosphorylated intracellularly to the active triphosphate form which competes with deoxyguanosine triphosphate, the natural substrate of hepatitis B virus reverse transcriptase, thereby inhibiting every stage of the enzyme's activity.

Treatment of chronic hepatitis B in adults with compensated liver disease with evidence of active viral replication, persistently elevated liver enzyme values, and histologically active disease including those resistant to lamivudine.

The usual dose of entecavir in nucleoside treatment-naive patients is 500 micrograms once daily, with or without food. A dose of 1 mg once daily should be used in patients with a history of hepatitis B viraemia during lamivudine therapy or with known resistance to lamivudine. For details of reduced doses to be used in patients with renal impairment, see as follows: Administration in Renal Impairment: Doses of entecavir should be reduced in patients with renal impairment according to creatinine clearance (CC) as follows: CC 30 to 49 mL/minute: 250 micrograms once daily in nucleoside treatment-naïve patients; 500 micrograms once daily in lamivudine-refractory patients or as prescribed by the physician.
CC 10 to 29 mL/minute: 150 micrograms once daily in nucleoside treatment-naïve patients; 300 micrograms once daily in lamivudine-refractory patients or as prescribed by the physician.
CC less than 10 mL/minute: 50 micrograms once daily in nucleoside treatment-naïve patients; 100 micrograms once daily in lamivudine-refractory patients or as prescribed by the physician.
Patients receiving hemodialysis should receive the appropriate dose after each dialysis session.

There is limited experience of entecavir overdose reported in patients. Healthy subjects who received up to 20 mg/day for up to 14 days, and single doses up to 40 mg had no unexpected adverse reactions. If overdose occurs, the patient must be monitored for evidence of toxicity and given standard supportive treatment as necessary.

Hypersensitivity to the active substance or to any of the excipients.

Severe exacerbation of hepatitis B has been reported after stopping treatment with entecavir and hepatic function should be monitored closely, with both clinical and laboratory follow-up for several months after treatment is discontinued. Dosage reduction may be necessary in patients with renal impairment.

Women of childbearing potential: Given that the potential risks to the developing fetus are unknown, women of childbearing potential should use effective contraception.
Pregnancy: There are no adequate data from the use of entecavir in pregnant women. Studies in animals have shown reproductive toxicity at high doses. The potential risk for humans is unknown. Entegard should not be used during pregnancy unless clearly necessary. There are no data on the effect of entecavir on transmission of HBV from mother to newborn infant. Therefore, appropriate interventions should be used to prevent neonatal acquisition of HBV.
Breast-feeding: It is unknown whether entecavir is excreted in human milk. Available toxicological data in animals have shown excretion of entecavir in milk. A risk to the infants cannot be excluded. Breast-feeding should be discontinued during treatment with Entegard.
Fertility: Toxicology studies in animals administered entecavir have shown no evidence of impaired fertility.

The most common adverse drug reactions of entecavir have been headache, fatigue, dizziness, and nausea. Lactic acidosis, usually associated with severe hepatomegaly and steatosis, has been associated with treatment with nucleoside reverse transcriptase inhibitors. Entecavir is carcinogenic in rodents, but a relationship with human cancer has not been established.

Since entecavir is predominantly eliminated by the kidney, coadministration with medicinal products that reduce renal function or compete for active tubular secretion may increase serum concentrations of either medicinal product. Apart from lamivudine, adefovir, dipivoxil and tenofovir disoproxil fumarate, the effects of coadministration of entecavir with medicinal products that are excreted renally or affect renal function have not been evaluated. Patients should be monitored closely for adverse drug reactions when entecavir is coadministered with such medicinal products.
No pharmacokinetic interactions between entecavir and lamivudine, adefovir or tenofovir were observed. Entecavir is not a substrate, an inducer or an inhibitor of cytochrome P450 (CYP450) enzymes. Therefore, CYP450 mediated drug interactions are unlikely to occur with entecavir.
Pediatric Population: Interaction studies have only been performed in adults.

Store at temperatures not exceeding 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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