Because entecavir is eliminated primarily through the kidneys, vigilant clinical monitoring and dosage adjustments should be considered if other renally eliminated agents are being coadmin-istered. The administration of entecavir with nucleoside reverse transcriptase inhibitors (NRTIs) was favorable and did not demonstrate a decrease in antiviral efficacy in either treatment regimen.
In vitro testing was performed with additional agents such as abacavir (Zio-gen, GlaxoSmithKline), didanosine (Videx, Bristol-Myers Squibb), lamivudine, stavudine (Zerit, Bristol-Myers Squibb), tenofovir (Viread, Gilead), and canadian zidovudine (AZT, GlaxoSmith-Kline). No significant antagonistic properties were apparent at wide range concentrations. Studies of specific drug interactions with the use of entecavir are under way.
Entecavir is contraindicated in patients with a known hypersensitivity to any component of the product.
PRECAUTIONS AND WARNINGS
Severe acute exacerbations of hepatitis B flare-ups have been reported upon abrupt discontinuation of entecavir therapy. As a result, when discontinuation of HBV therapy is appropriate, close clinical and laboratory monitoring is essential and should continue for several months.
The administration of nucleoside analogues alone or in combination with anti-retroviral agents has led to the development of lactic acidosis and severe hepatomegaly with steatosis. Although entecavir has been found safe and efficacious in patients with hepatic impairment, liver transplant recipients should be advised that the safety and efficacy of this drug are not confirmed.
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Dosage adjustments are recommended in patients with renal insufficiency (Table 5).
DOSAGE AND ADMINISTRATION
Entecavir is indicated for adults and adolescents 16 years of age or older with chronic HBV infection. The safety and efficacy with entecavir in children have not been established, and the drug is not recommended for children at this time.
Patients with active chronic HBV infection and who are considered new to nucleoside treatment should receive an oral dose of entecavir 0.5 mg once daily. Patients with a history of hepatitis B viremia, if they are receiving lamivudine or if they are known to have lamivudine-resistant mutations, should receive an oral dose of entecavir 1 mg once daily.
Entecavir is available as an oral solution containing 0.05 mg/ml of the drug. Therefore, 10 ml provides a 0.5-mg dose and 20 ml provides a 1-mg dose.
Both the tablets and the solution should be stored at room temperature. The solution should be protected from light. After the product is opened, it is stable until the bottle’s expiration date.
Patients should be advised to take entecavir on an empty stomach before meals. The optimal duration of entecavir therapy is unclear at this point.
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On the basis of present pharmaco-kinetic studies, no specific dosage adjustments have been recommended for geriatric patients, liver transplant recipients who are receiving immunosuppressant therapy, or patients with hepatic impairment.
Given that entecavir decreases creati-nine clearance in patients with renal impairment, the dose should be adjusted for patients whose creatinine clearance is less than 50 ml/minute, patients receiving dialysis, and patients with age-related decreased renal function (see Table 5).
Table 5 Recommended Dosage of Entecavir in Patients with Renal Impairment
|Creatinine Clearance (ml/minute)||
Usual Dose (0.5 mg)
|Lamivudine (Refractory) (1 mg)|
|0.5 mg once daily||
i.0 mg once daily
30 – < 50
|0.25 mg once daily||
0.5 mg once daily
10 – < 30
|0.i5 mg once daily||
0.3 mg once daily
|0.05 mg once daily||
0.i mg once daily
|* For patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis, entecavir should be administered after dialysis and adjusted according to the patient’s renal function.Data from Baraclude (entecavir) prescribing information,Bristol-Myers Squibb,2005.5|
At a daily dosage of 0.5 mg daily, the average wholesale price (AWP) for entecavir is approximately $8,500 annually. The cost appears to be three times that of Epivir-HBV (lamivudine) and slightly more than that of Hepsera (adefovir dipivoxil), at approximately $7,000 per year. A cost-effectiveness analysis encompassing the various treatment options should be conducted in order to determine overall expenses.
PREVENTION AND DETECTION
HBV remains a primary concern today, because chronic HBV infection leads to increased morbidity and mortality. Only a small percentage of patients with chronic HBV infection are believed to be receiving treatment, an unfortunate circumstance that most certainly leads to complications.
Table 6 Indications for Screening of Hepatitis B Virus (HBV) Infection
|•||Persons born in endemic areas|
|•||Intravenous drug abusers|
|•||Patients with a history of sexually|
|•||Family members, close contacts,|
|and sexual contacts of HBV-|
Strategies to prevent HBV infection include avoidance of high-risk behaviors such as alterations in sexual practices, appropriate screening, immunizations, checking blood products used in transfusions, developing needle-exchange programs, and patient education. Routine screening can help to identify high-risk patients who are likely to contract HBV infection (Table 6).
Hepatitis B immune globulin (HBIg), administered after exposure, may benefit patients with passive immunity. More effective measures for protection against HBV infection include active immunization with appropriate vaccination recommendations against HBV before possible exposure. Despite advances with current antiviral therapy, some patients with chronic HBV infection may experience a sustained viral response even with appropriate therapy.
Studies of investigational agents, such as lobucavir (Bristol-Myers Squibb), tenofovir (Viread), emtricitabine (Emtriva, Gilead), telbivudine (LdT, Idenix), and pradefovir (formerly remo-fovir, Valeant), are currently under way for the treatment of chronic HBV infection. Enhanced viral activity has sometimes been demonstrated with these new antiviral drugs over currently approved agents. Combination antiviral agents are also being studied. To date, however, combination antiviral therapy has not been found to be superior to traditional monotherapy. viagra soft
It is hoped that entecavir will provide a better option than standard treatment regimens for patients with chronic HBV infection, given that this agent has been associated with very low rates of drug resistance.
In addition to antiviral therapy, advising patients to maintain a healthy lifestyle of proper diet, exercise, and avoidance of hepatotoxic agents can help prevent the morbidity and mortality associated with chronic forms of hepatitis B viremia.