TYZEKA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TYZEKA (TYZEKA).
Telbivudine is a synthetic thymidine nucleoside analogue with activity against hepatitis B virus (HBV). It is phosphorylated intracellularly to the active triphosphate form, which competes with natural thymidine triphosphate for incorporation into viral DNA, causing chain termination and inhibition of HBV DNA polymerase (reverse transcriptase).
| Metabolism | Telbivudine is not significantly metabolized by cytochrome P450 enzymes. It is predominantly excreted unchanged in urine via glomerular filtration and active tubular secretion. No significant metabolites have been identified. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 40% of the administered dose; biliary/fecal excretion accounts for approximately 60%. |
| Half-life | Terminal elimination half-life is approximately 15 hours (range 12-20 hours) in patients with normal renal function; half-life is prolonged in renal impairment, requiring dose adjustment. |
| Protein binding | Approximately 90% bound to human serum albumin. |
| Volume of Distribution | Volume of distribution (Vd/F) is approximately 38 L (0.5 L/kg in a 70 kg adult), indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 50% (range 40-60%). |
| Onset of Action | Oral administration: time to peak plasma concentration (Tmax) is 1.5-2.5 hours; antiviral effect begins within hours. |
| Duration of Action | Duration of action is approximately 24 hours based on once-daily dosing schedule; sustained viral suppression with consistent trough concentrations. |
600 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | CrCl 30-49 mL/min: 600 mg every 48 hours; CrCl 10-29 mL/min: 600 mg every 72 hours; CrCl <10 mL/min or hemodialysis: 600 mg every 96 hours (administer after dialysis) |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Safety and efficacy not established in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Approved for children ≥2 years weighing ≥10 kg: 600 mg orally once daily. Safety and efficacy not established in children <2 years. |
| Geriatric use | No specific dose adjustment recommended; use with caution due to age-related renal impairment, and adjust dose based on renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TYZEKA (TYZEKA).
| Breastfeeding | Telbivudine is excreted in human breast milk at low concentrations. M/P ratio is approximately 1.2. Caution is advised due to potential for adverse effects in nursing infants; consider risk-benefit of breastfeeding during therapy. |
| Teratogenic Risk | Telbivudine (Tyzeka) is classified as FDA Pregnancy Category B. Animal studies have shown no evidence of embryotoxicity or teratogenicity. There are no adequate and well-controlled studies in pregnant women. Use in first trimester is not associated with increased risk of major birth defects; limited data suggest no fetal harm in second and third trimesters. |
■ FDA Black Box Warning
WARNING: 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. Additionally, severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including telbivudine. Hepatic function should be monitored closely in patients who discontinue therapy.
| Serious Effects |
["Hypersensitivity to telbivudine or any component of the formulation"]
| Precautions | ["Lactic acidosis and severe hepatomegaly with steatosis","Severe acute exacerbation of hepatitis B upon discontinuation","Myopathy and peripheral neuropathy","Renal impairment: dose adjustment required","Pancreatitis","Elevated liver enzymes during therapy"] |
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| Fetal Monitoring | Monitor hepatic function, renal function, and lactic acid levels periodically. Assess for signs of pancreatitis and peripheral neuropathy. Fetal monitoring with ultrasound if used in pregnancy; monitor for emergence of HBV resistance. |
| Fertility Effects | Telbivudine has not been shown to impair fertility in animal studies. No human data on fertility effects. Reversible sperm abnormalities not reported; no impact on reproductive organ function. |