Drug Criteria & Outcomes: Telbivudine Formulary Evaluation
Drug Criteria & Outcomes
Telbivudine Formulary Evaluation
By James M. Davis, Pharm. D. candidate Auburn (AL) University, Harrison School of Pharmacy
[Editor's note: This is the conclusion of a two-part formulary evaluation of telbivudine. It is being compared with entecavir, a newer drug for similar use. Please see the first part of this evaluation in the April 2007 issue Drug Criteria & Outcomes]
Warnings and Precautions:
Tyzeka™ (telbivudine):
Black Box Warnings:
- Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases have been reported with the use of nucleoside analogues alone or in combination with antiretrovirals.
- Severe acute exacerbations of hepatitis B have occurred in patients who have discontinued therapy; therefore, liver function tests should be monitored in these patients.
Baraclude™ (entecavir):
Black Box Warnings:
- Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases have been reported with the use of nucleoside analogues alone or in combination with antiretrovirals.
- Severe acute exacerbations of hepatitis B have occurred in patients who have discontinued therapy; therefore, liver function tests should be monitored in these patients.
Tyzeka™ (telbivudine):
Precautions:
- Discontinuation of treatment may result in an acute exacerbation of hepatitis.
- Patients predisposed to or taking concomitant therapy that increases risk for myopathy should be monitored since risk with telbivudine therapy is unknown.
- Co-infection with hepatitis C, D, and HIV or patients with alcohol and drug abuse in the previous two years safety and efficacy of therapy is unknown.
Baraclude™ (entecavir):
Precautions:
- Discontinuation of treatment may result in an acute exacerbation of hepatitis.
- Efficacy and safety in liver transplant patients has not been established.
Tyzeka™ (telbivudine):
Pregnancy Category: B
Baraclude™ (entecavir):
Pregnancy Category:C
Tyzeka™ (telbivudine):
Potential Look-alike/Sound-alike Errors: Taztia XT™, telmisartan, Tiazac®, tenofovir, Terak™, Tarceva™, Tazicef®, Trizvir®
Baraclude™ (entecavir):
Potential Look-alike/Sound-alike Errors: Baricon™, Barobag®, barium, entacapone, Epivir®
Monitoring:
Tyzeka™ (telbivudine):
Renal: Serum creatinine
Hepatic: ALT, AST
Other: Physical exams, CBC, signs and symptoms of hepatotoxicity, lactic acidosis, rhabdomyolysis or myalagias, and Hepatitis antigen and DNA.
Baraclude™ (entecavir):
Renal: Serum creatinine
Hepatic: ALT, AST
Other: Physical exams, CBC, signs and symptoms of hepatotoxicity, lactic acidosis, and Hepatitis antigen and DNA.
Clinical Studies:
(study is not published in final form)
Lai CL, Gane E, Hsu CW, et al. Two year results from the GLOBE trial in patients with hepatitis B: greater clinical and antiviral efficacy for telbivudine (LDT) vs. lamivudine. Hepatology. 2006; 44(4 suppl1):22A. and GLOBE Study NV-02B-007 Data on file with NOVARTIS pharmaceuticals.
Study Design:
Phase III, randomized, double-blind, multi-center, multinational trial to compare efficacy and safety of telbivudine 600 mg daily to lamivudine 100 mg daily.
Methods:
1367 patients with chronic hepatitis B with evidence of compensated hepatic function and nucleoside naïve were randomized to treatment groups noted above, HBeAg (+) and (–) and ALT levels > or < 2.5 x ULN were stratified into different groups. Patients received treatment for a total of 104 weeks with outcomes measured at 52 weeks and 104 weeks.
Inclusion criteria:
- HBsAg (+) (for longer than six months)
- HBV DNA greater than six log copies/mL (COBAS PCR assay)
- ALT = 1.3 to 10 times ULN
- Compensated Liver Disease evidenced on biopsy at baseline and outcomes assessed via a Knodell inflammatory score comparison at 52 weeks.
Exclusion criteria: (not complete with current information available)
Results:
Therapeutic response (HBV DNA suppression (<5 log10), HBeAg loss or ALT normalization): 61% LDT vs. 47% lamivudine for HBeAg (+), 74% LDT vs. 62% lamivudine for HBeAg (-).
These results appear primarily due to mean HBV DNA decreases and HBeAg loss being greater in the LDT group, with LDT providing some advantage in ALT normalization.
Histologic: Data not reported in this preliminary data release.
Resistance: Significantly higher with lamivudine group with resistance and virologic rebound present in both treatment groups for HBeAg (–), no resistance data for HBeAg (+) currently.
Authors Conclusion:
Telbivudine shows superior antiviral activity in comparison to lamivudine throughout a two year treatment period with improved maintenance of clinical efficacy.
Strengths:
- Strong study design
- Large patient population
- Standard assessment for outcomes
- Standard doses, and length of therapy applied
Weaknesses:
- Study currently not complete
- Statistics lack explanation at this point
- Patient population not well defined
Recommendations:
Clinical experience and decreased cost with adefovir should make it first line therapy; entecavir is an attractive alternative, with telbivudine recommended as a third line agent with formulary status. Therapeutic substitution is not suggested in this class of agents; therefore, telbivudine is recommended to be available in limited quantities for use in patients admitted while currently taking this medication.
Clarification
The article on NovoSeven®, which is approved for uncontrolled bleeding episodes in hemophiliacs, in the April 2007 issue of Drug Criteria & Outcomes should have included the following information about drug cost: "The cost of the drug depends on the weight-based dose; generally, for one dose the cost ranges from $2500 - $4000. Due to the high expense of the drug, NovoSeven® use should be limited to specific patients with severe/life threatening bleeding, where other methods of controlling the bleeding have been unsuccessful."
This is the conclusion of a two-part formulary evaluation of telbivudine. It is being compared with entecavir, a newer drug for similar use.Subscribe Now for Access
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