Tecavir1 mg

Tecavir is a nucleoside analog antiviral indicated for the treatment of chronic hepatitis B virus (HBV) infection.

Established / FDA-approved uses

• Chronic hepatitis B infection in adults with evidence of active viral replication and either persistently elevated serum aminotransferases (ALT or AST) or histologically active disease, including patients with compensated and decompensated liver disease.
• Chronic hepatitis B infection in pediatric patients 2 years of age and older with evidence of active viral replication and either persistently elevated ALT or histologically active disease.
• Lamivudine-refractory chronic hepatitis B (known lamivudine- or telbivudine-resistant HBV) - a higher dose of Tecavir is used in this setting.

Important limitation

Tecavir is not indicated for, and is not effective against, HIV infection. It is not a treatment for hepatitis C or hepatitis D. Patients being started on Tecavir should be tested for HIV infection before treatment begins, because Tecavir monotherapy in a patient with unrecognised or untreated HIV/HBV co-infection may lead to the development of HIV resistance.

Each film-coated tablet contains Entecavir (INN) 0.5 mg or 1 mg. Entecavir is also available as an oral solution containing Entecavir 0.05 mg/mL for patients unable to swallow tablets, including younger pediatric patients. Inactive ingredients vary by manufacturer.

Tecavir is a guanosine nucleoside analogue with selective activity against the hepatitis B virus (HBV) polymerase (reverse transcriptase). Chemically, it is a cyclopentyl guanosine analogue that, after intracellular phosphorylation to its active triphosphate form, interferes with the HBV life cycle.

Tecavir is used long-term to suppress HBV viral replication in patients with chronic hepatitis B, reducing liver inflammation and slowing progression of liver disease. It is administered orally, once daily, and is available as tablets and as an oral solution.

Antiviral agent - nucleoside analogue (HBV polymerase/reverse transcriptase inhibitor) used specifically for chronic hepatitis B; Tecavir belongs to this class of hepatitis B antivirals.

Entecavir is a guanosine nucleoside analogue that is phosphorylated intracellularly to the active triphosphate form, entecavir triphosphate (ETV-TP). ETV-TP competes with the natural substrate deoxyguanosine triphosphate for incorporation into viral DNA and functionally inhibits all three activities of the HBV polymerase enzyme:

• Priming of the HBV polymerase;
• Reverse transcription of the negative strand from the pregenomic messenger RNA; and
• Synthesis of the positive strand of HBV DNA.

ETV-TP is a weak inhibitor of cellular DNA polymerases alpha, beta, and delta, and of mitochondrial DNA polymerase gamma, at clinically relevant concentrations. Entecavir has intracellular half-life allowing once-daily dosing. It is predominantly eliminated unchanged by the kidneys (glomerular filtration and net tubular secretion), which is why renal function determines dosing interval.

• Take Tecavir by mouth exactly as prescribed, once daily.
• Take on an empty stomach - at least 2 hours after a meal and at least 2 hours before the next meal - for optimal absorption.
• Swallow tablets whole; the oral solution should be measured with the calibrated dosing device provided and can be taken directly or diluted just before use.
• Take at approximately the same time each day to maintain a steady drug level.
• If a dose is missed, take it as soon as remembered the same day; do not double the dose. Contact your physician if unsure.
• Do not stop Tecavir on your own even if you feel well - stopping suddenly can cause a serious hepatitis B flare.

Tecavir is not significantly metabolised by the cytochrome P450 (CYP450) enzyme system, so it is unlikely to interact with drugs that are CYP450 substrates, inhibitors, or inducers.

Tecavir is eliminated primarily by the kidneys through a combination of glomerular filtration and active tubular secretion.

• Drugs that reduce renal function or compete for active renal secretion (e.g. certain nephrotoxic agents) - co-administration may increase serum concentrations of Tecavir or the co-administered drug; renal function should be monitored, particularly in patients with pre-existing renal impairment.
• Other anti-hepatitis B or antiretroviral nucleoside/nucleotide analogues - no clinically significant pharmacokinetic interactions have been established with most agents used together for HBV, but combination use should be guided by a physician.

Always inform your physician or pharmacist of all other medicines, including over-the-counter drugs, herbal products, and supplements, before starting Tecavir.

Most patients tolerate Tecavir well. The following adverse effects have been reported:

Seek prompt medical attention for unusual muscle pain, difficulty breathing, unexplained fatigue with abdominal discomfort, or signs of an allergic reaction while taking Tecavir.

Pregnancy: Data on the use of Tecavir in pregnant women are limited. Animal reproduction studies have not shown adverse fetal effects at clinically relevant exposures, but this does not guarantee safety in humans. Tecavir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, and only under the direct supervision of a physician. Do not stop Tecavir during pregnancy without first consulting your doctor, as abrupt discontinuation can precipitate a severe hepatitis B flare (see Precautions and Warnings). Women who become pregnant while taking Tecavir should discuss options for hepatitis B management with their physician.

Breastfeeding: It is not known whether Tecavir passes into human breast milk. Because of the potential for adverse effects in a nursing infant, breastfeeding is generally not recommended while taking Tecavir unless a physician determines the benefit outweighs the risk.

Boxed warnings

• Lactic acidosis and severe hepatomegaly with steatosis: Rare but potentially fatal cases have been reported with nucleoside analogues, including Tecavir, usually with prolonged use. Risk factors include obesity, female sex, and prolonged nucleoside analogue exposure. Tecavir should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.
• Severe acute exacerbation of hepatitis B after discontinuation: Stopping Tecavir can cause a severe flare of hepatitis B, which may be life-threatening in some patients, especially those with advanced liver disease or cirrhosis. Hepatic function must be monitored clinically and with laboratory tests for at least several months after stopping Tecavir. Do not stop Tecavir without your physician's guidance.
• Risk of HIV resistance in HIV/HBV co-infection: Tecavir is not approved for treatment of HIV infection and has not been shown to reliably suppress HIV replication. Using Tecavir in a patient with unrecognised or untreated HIV infection may lead to the development of HIV resistance to certain antiretroviral drug classes. All patients should be tested for HIV infection before starting Tecavir; if HIV/HBV co-infection is present, effective antiretroviral therapy should be given alongside Tecavir.

Other precautions

• Use with caution in patients with decompensated liver disease or advanced cirrhosis - close monitoring is required.
• Dose must be adjusted in renal impairment (see Dosage and Administration).
• Tecavir does not eliminate the risk of transmitting HBV to others; appropriate precautions should still be taken.
• Resistance can emerge, particularly in patients with prior lamivudine resistance; virologic response should be monitored periodically by a physician.

There is limited clinical experience with Tecavir overdose. In case of suspected overdose, seek immediate medical attention or contact emergency services / a poison control centre. There is no specific antidote for Tecavir overdose; treatment is supportive, with monitoring of clinical status and vital signs as needed. Haemodialysis can remove a portion of circulating Tecavir, but this should only be undertaken under medical supervision.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children. Do not use after the expiry date printed on the pack.

Renal impairment

Dose and/or dosing interval of Tecavir must be adjusted according to creatinine clearance - see the renal dosing table under Dosage and Administration. This applies to both adult dose levels (0.5 mg and 1 mg).

Hepatic impairment

No dose adjustment is needed for compensated hepatic impairment in nucleoside-naive patients. Patients with decompensated liver disease require the higher (1 mg once-daily) dose of Tecavir and closer monitoring.

Elderly patients

Limited data are available in patients over 65 years of age. Because Tecavir is renally eliminated and older patients more often have reduced renal function, dose selection should take renal function into account, with periodic monitoring.

HIV/HBV co-infection

Patients should be tested for HIV before starting Tecavir. In unrecognised or untreated HIV infection, Tecavir may lead to HIV resistance (see boxed warning); co-infected patients require effective combination antiretroviral therapy alongside Tecavir.

Pediatric patients

See Pediatric Uses for weight-based dosing details in patients 2 years of age and older; safety and efficacy have not been established in children younger than 2 years.

The optimal duration of Tecavir therapy for chronic hepatitis B has not been definitively established and is individualised by the treating physician, guided by markers such as HBeAg seroconversion, sustained HBV DNA suppression, and HBsAg loss. Many patients require long-term or indefinite therapy. Tecavir must never be stopped abruptly or without medical advice, because discontinuation carries a risk of severe hepatitis B flare; treatment cessation should only occur under physician supervision with planned post-treatment monitoring.

Nucleoside analogue; HBV polymerase (reverse transcriptase) inhibitor; Antiviral agent for chronic hepatitis B - Entecavir is classified within this antiviral drug class.

Entecavir is phosphorylated intracellularly to its active triphosphate form, which inhibits the hepatitis B virus polymerase by competing with the natural nucleotide substrate. This blocks base priming, reverse transcription of the HBV pregenome, and synthesis of the positive DNA strand, thereby suppressing HBV replication.

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Tecavir is approved for chronic hepatitis B in pediatric patients 2 years of age and older with evidence of active viral replication and either persistently elevated ALT or histologically active disease. Safety and efficacy have not been established in children younger than 2 years of age.

Weight-based dosing (nucleoside-treatment-naive, using 0.05 mg/mL oral solution)

Lamivudine-experienced pediatric patients require a higher weight-based dose of Tecavir, as determined by the treating physician. As in adults, pediatric patients must be monitored for hepatitis B flare if Tecavir is discontinued, and should be tested for HIV before starting therapy.