Tyzeka

Tyzeka

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Lactic Acidosis

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. Female gender, obesity, and prolonged nucleoside exposure may be risk factors. Particular caution should be exercised when administering HBV nucleoside analogue reverse transcriptase inhibitors to patients with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with Tyzeka should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).

Exacerbations of Hepatitis B after Discontinuation of Treatment

Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including Tyzeka. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, resumption of anti-hepatitis B therapy may be warranted [see ADVERSE REACTIONS].

Myopathy

Cases of myopathy/myositis have been reported with Tyzeka use several weeks to months after starting therapy. Myopathy has also been reported with some other drugs in this class. Rhabdomyolysis has been reported during postmarketing use of Tyzeka [see ADVERSE REACTIONS].

Uncomplicated myalgia has been reported in Tyzeka-treated patients [see ADVERSE REACTIONS]. Myopathy, defined as persistent unexplained muscle aches and/or muscle weakness in conjunction with increases in creatine kinase (CK) values, should be considered in any patient with diffuse myalgias, muscle tenderness, or muscle weakness. Among patients with Tyzeka-associated myopathy, no pattern with regard to the degree or timing of CK elevations has been observed. In addition, the predisposing factors for the development of myopathy among Tyzeka recipients are unknown. Patients should be advised to report promptly unexplained muscle aches, pain, tenderness, or weakness. Tyzeka therapy should be interrupted if myopathy is suspected, and discontinued if myopathy is confirmed. It is unknown whether the risk of myopathy during treatment with drugs in this class is increased with concurrent administration of other drugs associated with myopathy, including but not limited to: corticosteroids, chloroquine, hydroxychloroquine, certain HMGCoA reductase inhibitors, fibric acid derivatives, penicillamine, zidovudine, cyclosporine, erythromycin, niacin, and certain azole antifungals. Physicians initiating concomitant treatment with any drug associated with myopathy should monitor patients closely for any signs or symptoms of unexplained muscle pain, tenderness, or weakness.

Peripheral Neuropathy

Peripheral neuropathy has been reported with Tyzeka alone or in combination with pegylated interferon alfa-2a and other interferons. In one clinical trial, an increased risk and severity of peripheral neuropathy was observed with the combination use of Tyzeka 600mg daily and pegylated interferon alfa-2a 180 micrograms once weekly compared to Tyzeka or pegylated interferon alfa-2a alone [see CONTRAINDICATIONS and DRUG INTERACTIONS]. Such risk cannot be excluded for other dose regimens of pegylated interferon alfa-2a, or other alfa interferons (pegylated or standard). The safety and efficacy of Tyzeka in combination with pegylated interferons or other interferons for the treatment of chronic hepatitis B have not been demonstrated. Patients should be advised to report any numbness, tingling, and/or burning sensations in the arms and/or legs, with or without gait disturbance. Tyzeka therapy should be interrupted if peripheral neuropathy is suspected, and discontinued if peripheral neuropathy is confirmed [see ADVERSE REACTIONS].

Patient Counseling Information

Patients should remain under the care of a physician while taking Tyzeka. They should discuss any new symptoms or concurrent medications with their physician.

Patients should be advised to report promptly unexplained muscle weakness, tenderness, or pain.

Patients should be advised to report promptly any numbness, tingling, and/or burning sensations in the arms and/or legs, with or without difficulty walking.

Patients should be advised that Tyzeka is not a cure for hepatitis B, that the long-term treatment benefits of Tyzeka are unknown at this time. In particular, the relationship of initial treatment response to outcomes such as hepatocellular carcinoma and decompensated cirrhosis is unknown.

Patients should be informed that deterioration of liver disease may occur in some cases if treatment is discontinued, and that they should discuss any change in regimen with their physician.

Patients should be advised that treatment with Tyzeka has not been shown to reduce the risk of transmission of HBV to others through sexual contact or blood contamination. HBV prevention strategies should be discussed with patients, including safe sexual practices, and avoidance of needle sharing or sharing any personal items which may contain residual blood or body fluids, such as razor blades or toothbrushes. Additionally, a vaccine is available for prevention of hepatitis B infection in susceptible individuals.

Patients on a low sodium diet should be advised that Tyzeka oral solution contains approximately 47 mg of sodium per 600 mg dose (30 mL).

Patients should be advised to dispose of unused or expired Tyzeka by using a community pharmaceutical take-back disposal program, or by placing unused Tyzeka in a closed container, such as a sealed bag, into household trash. All identifying information should be removed from the original Tyzeka container prior to disposal.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Telbivudine has shown no carcinogenic potential. Long term oral carcinogenicity studies with telbivudine were negative in mice and rats at exposures up to 14 times those observed in humans at the therapeutic dose of 600 mg per day.

There was no evidence of genotoxicity based on in vitro or in vivo tests. Telbivudine was not mutagenic in the Ames bacterial reverse mutation assay using S. typhimurium and E. coli strains with or without metabolic activation. Telbivudine was not clastogenic in mammalian-cell gene mutation assays, including human lymphocyte cultures and an assay with Chinese hamster ovary cells with or without metabolic activation. Furthermore, telbivudine showed no effect in an in vivo micronucleus study in mice.

Effects on fertility were studied in rats administered telbivudine as juveniles or adults. Juvenile rats were treated with telbivudine at doses of 0, 250, 1000, and 2000 mg per kg per day from post natal days 14 to 70. These rats were mated following a 5 week drug-free recovery period. Up to 50% reduction of fertility was associated with doses 1000 mg per kg per day and higher, which was equivalent to a systemic exposure approximately 7.5 times that achieved in humans at the therapeutic dose. The no observed adverse effect level (NOAEL) for effects on fertility or mating parameters was 250 mg per kg per day, which was equivalent to systemic exposure levels 2.5 to 2.8 times that achieved in humans at the therapeutic dose. In contrast, such reduction of fertility was absent in adult rats treated with telbivudine at doses up to 2000 mg per kg per day, equivalent to a systemic exposure approximately 14 times that achieved in humans at the therapeutic dose.

Use In Specific Populations

Pregnancy

Category B

Telbivudine is not teratogenic and has shown no adverse effects in developing embryos and fetuses in preclinical studies. Studies in pregnant rats and rabbits showed that telbivudine crosses the placenta. Developmental toxicity studies revealed no evidence of harm to the fetus in rats and rabbits at doses up to 1000 mg per kg per day, providing exposure levels 6- and 37-times higher, respectively, than those observed with the 600 mg per day dose in humans.

There are no adequate and well-controlled trials of Tyzeka in pregnant women. Because animal reproductive toxicity studies are not always predictive of human response, Tyzeka should be used during pregnancy only if potential benefits outweigh the risks.

Pregnancy Registry

To monitor fetal outcomes of pregnant women exposed to Tyzeka, healthcare providers are encouraged to register such patients in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263.

Labor and Delivery

There are no trials in pregnant women and no data on the effect of Tyzeka on transmission of HBV from mother to infant. Therefore, appropriate interventions should be used to prevent neonatal acquisition of HBV infection.

Nursing Mothers

Telbivudine is excreted in the milk of rats. It is not known whether Tyzeka is excreted in human milk. Mothers should be instructed not to breast-feed if they are receiving Tyzeka.

Pediatric Use

Safety and effectiveness of Tyzeka in pediatric patients have not been established.

Geriatric Use

Clinical trials of Tyzeka did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. In general, caution should be exercised when prescribing Tyzeka to elderly patients, considering the greater frequency of decreased renal function due to concomitant disease or other drug therapy. Renal function should be monitored in elderly patients, and dosage adjustments should be made accordingly [see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION].

Renal Impairment

Tyzeka is eliminated primarily by renal excretion, therefore dose regimen adjustment is recommended in patients with creatinine clearance less than 50 mL per min, including patients with ESRD requiring hemodialysis [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].

Liver Transplant Recipients

The safety and efficacy of Tyzeka in liver transplant recipients have not been evaluated. The steady-state pharmacokinetics of Tyzeka was not altered following multiple dose administration in combination with cyclosporine. If Tyzeka treatment is determined to be necessary for a liver transplant recipient who has received or is receiving an immunosuppressant that may affect renal function, such as cyclosporine or tacrolimus, renal function should be monitored both before and during treatment with Tyzeka [see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION].

Co-infected Patients

Tyzeka has not been investigated in co-infected hepatitis B patients (e.g., patients co-infected with HIV, HCV, or HDV).

Racial/Ethnic Minorities

The safety and efficacy of Tyzeka have not been evaluated in Black/African American or Hispanic patients. It is not known if safety and efficacy can be extrapolated from studied populations.

Last reviewed on RxList: 2/19/2013
This monograph has been modified to include the generic and brand name in many instances.

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