Telbivudine

Unless your doctor tells you otherwise, continue your normal diet.

Tyzeka is the trade name for telbivudine, a synthetic thymidine nucleoside analogue with activity against hepatitis B virus (HBV). The chemical name for telbivudine is 1-((2S,4R,5S)-4-hydroxy-5hydroxymethyltetrahydrofuran-2-y1)-5-methyl-1H-pyrimidine-2,4-dione, or 1-(2-deoxy-β-L-ribofuranosyl)-5methyluracil. Telbivudine is the unmodified β-L enantiomer of the naturally occurring nucleoside, thymidine. Its molecular formula is C10H14N2O5, which corresponds to a molecular weight of 242.23. Telbivudine has the following structural formula:

Telbivudine is a white to slightly yellowish powder. Telbivudine is sparingly soluble in water (greater than 20 mg per mL), and very slightly soluble in absolute ethanol (0.7 mg per mL) and n-octanol (0.1 mg per mL).

Tyzeka Film-Coated Tablets are available for oral administration in 600 mg strength. Tyzeka 600 mg Film-Coated Tablets contain the following inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, povidone, and sodium starch glycolate. The tablet coating contains titanium dioxide, polyethylene glycol, talc, and hypromellose.

Tyzeka Oral Solution is available for oral administration in 100 mg per 5 mL strength. Tyzeka Oral Solution contains the following inactive ingredients: citric acid anhydrous, benzoic acid, passion fruit flavor, sodium saccharin, sodium hydroxide, and purified water. A 600 mg dose (30 mL) of Tyzeka oral solution contains approximately 47 mg of sodium.

Telbivudine may be found in some form under the following brand names:

• Tyzeka

Telbivudine is an antiviral medication. It works by preventing viral cells from multiplying in the body and infecting new liver cells.

Telbivudine is used to treat chronic hepatitis B in adults. This medicine will not cure hepatitis.

Telbivudine may also be used for purposes not listed in this medication guide.

Some people develop lactic acidosis while taking telbivudine. Early symptoms may get worse over time and this condition can be fatal. Get emergency medical help if you have even mild symptoms such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired.

Your liver symptoms may become severe after you stop taking telbivudine, even months after stopping. Your doctor may want to check your liver function for several months after you stop taking telbivudine. Visit your doctor regularly.

Taking this medication will not prevent you from passing hepatitis B to other people. Avoid having unprotected sex or sharing razors or toothbrushes. Talk with your doctor about safe ways to prevent transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

You should not take telbivudine if you are allergic to it, or if you are also using peginterferon alfa-2b (PegIntron, PegIntron Redipen, Sylatron).

To make sure you can safely take telbivudine, tell your doctor if you have any of these other conditions:

• kidney disease;

• other types of hepatitis (C or D);

• HIV or AIDS;

• if you have received a liver transplant; or

• if any hepatitis B medications you received in the past did not work well in treating your condition.

Some people develop a life-threatening condition called lactic acidosis while taking telbivudine. You may be more likely to develop lactic acidosis if you are overweight or have liver disease, if you are a woman, or if you have taken HIV or AIDS medications for a long time. Talk with your doctor about your individual risk.

It is not known whether this medication is safe to use while you are pregnant. Telbivudine may not keep you from passing hepatitis B to your unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while you are taking telbivudine.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of telbivudine on the baby.

It is not known whether telbivudine passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Do not give telbivudine to a child younger than 16 years old without the advice of a doctor.

Contraindications

• Known hypersensitivity to telbivudine or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Clinical and laboratory evidence of severe acute exacerbations of hepatitis may occur following discontinuance of HBV therapy, including telbivudine.1 Data insufficient to date regarding incidence of exacerbation of hepatitis following discontinuance of telbivudine.1

Exacerbations of hepatitis or ALT flare (e.g., ALT elevations >10 times ULN and >2 times baseline) reported during telbivudine treatment in 3% of patients.1

Closely monitor hepatic function clinically and with laboratory studies at repeated intervals for at least several months after telbivudine discontinuance.1 If appropriate, resumption of anti-HBV therapy may be warranted.1

Lactic acidosis and severe hepatomegaly with steatosis (including some fatalities) reported in patients receiving nucleoside analogs alone or in conjunction with antiretrovirals.1

Myopathy (persistent unexplained muscle pain, tenderness, or weakness in conjunction with increased serum CK concentrations) reported.1 Risk factors for myopathy not identified.1 Uncomplicated myalgia also reported.1

Consider myopathy in patients presenting with musculoskeletal symptoms suggestive of this adverse event.1 Temporarily interrupt therapy if myopathy suspected; discontinue if myopathy diagnosed.1

Not known if risk of myopathy is increased by concomitant administration of other drugs associated with myopathy (e.g., corticosteroids, chloroquine, hydroxychloroquine, cyclosporine, niacin, fibric acid derivatives [e.g., gemfibrozil], macrolide antibiotics [i.e., erythromycin], penicillamine, certain azole antifungals [i.e., itraconazole, ketoconazole], certain hydroxymethylglutaryl-CoA [HMG-CoA] reductase inhibitors [statins], zidovudine).1 If such concomitant therapy is considered, weigh potential benefits and risks.1 Carefully monitor patient, especially during dosage titration.1

General Precautions

Telbivudine-resistant HBV detected in patients receiving the drug; diminished treatment response reported.1 2 After 2 years of therapy, viral rebound due to telbivudine resistance was reported in 21.6% of HBeAg-positive patients and 8.6% of HBeAg-negative patients.2

Not systematically evaluated in patients with lamivudine-resistant HBV.1 Lamivudine-resistant HBV with substitutions at rtM204I or rtL180M/rtM204V have high level of cross-resistance to telbivudine.1 Strains with substitutions at rtM204V (a mutation associated with lamivudine resistance) have reduced susceptibility to telbivudine (1.2-fold reduction).1

Not systematically evaluated in patients with adefovir-resistant HBV.1 Telbivudine has in vitro activity against adefovir-resistant strains with substitutions at rtN236T but not against adefovir-resistant strains with substitutions at rtA181V.1

Safety and efficacy in liver transplant recipients not evaluated.1 If telbivudine considered necessary in liver transplant recipients who have received or are receiving an immunosuppressive agent that may affect renal function (e.g., cyclosporine, tacrolimus), monitor renal function prior to and during telbivudine treatment.1 (See Drugs Affecting or Eliminated by Renal Excretion under Interactions.)

Specific Populations

Category B.1 Pregnancy registry at 800-258-4263.1

Data not available regarding the effect of telbivudine therapy during pregnancy on transmission of HBV to the infant; use appropriate interventions to prevent neonatal acquisition of HBV infection (hepatitis B immune globulin [HBIG] and HBV vaccine).1 4 8

Not known whether distributed into human milk.1 Do not breast-feed infants while receiving telbivudine.1

Safety and efficacy not established in children <16 years of age.1

Experience in those ≥65 years of age insufficient to determine whether they respond differently than younger adults.1

Use with caution due to the greater frequency of decreased renal function and of concomitant disease and drug therapy in the elderly.1 Monitor renal function and adjust dosage accordingly.1 (See Renal Impairment under Dosage and Administration.)

Dosage adjustment recommended in patients with Clcr <50 mL/minute, including those undergoing hemodialysis.1 (See Dosage in Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Upper respiratory tract infection, GI symptoms (abdominal pain, nausea, vomiting, diarrhea or loose stools, dyspepsia), fatigue, malaise, nasopharyngitis, headache, influenza or influenza-like symptoms, elevated CK concentrations, cough, pyrexia, arthralgia, rash, back pain, dizziness, myalgia, insomnia.1

Storage

Oral

In original container at 25°C (may be exposed to 15–30°C).1

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Tyzeka: 600 mg [DSC]

Adverse events were not observed in animal reproduction studies.

In hepatitis B-infected women (not coinfected with HIV), the AASLD chronic hepatitis B treatment guidelines suggest antiviral therapy to reduce the risk of perinatal transmission of hepatitis B in HBsAg-positive pregnant women with an HBV DNA >200,000 units/mL. There are limited data on the level of HBV DNA for when antiviral therapy is routinely recommended (>200,000 units/mL is a conservative recommendation); however, the AASLD recommends against antiviral therapy to reduce the risk of perinatal transmission in HBsAg-positive pregnant women with an HBV DNA ≤200,000 units/mL. Telbivudine is one of the antivirals that has been studied in pregnant women, with most studies initiating antiviral therapy at 28 to 32 weeks gestation and discontinuing antiviral therapy between birth to 3 months postpartum (monitor for ALT flares every 3 months for 6 months following discontinuation). There is insufficient long-term safety data in infants born to mothers who took antiviral agents during pregnancy (AASLD [Terrault 2016]).

Health professionals are encouraged to contact the antiretroviral pregnancy registry to monitor outcomes of pregnant women exposed to antiretroviral medications (1-800-258-4263).

Applies to telbivudine: oral solution, oral tablet

Along with its needed effects, telbivudine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking telbivudine:

• Chills
• cough
• diarrhea
• fever
• general feeling of discomfort or illness
• headache
• joint pain
• loss of appetite
• muscle aches and pains
• nausea
• runny nose
• shivering
• sore throat
• stomach pain
• sweating
• trouble with sleeping
• unusual tiredness or weakness
• vomiting

• Back pain
• chest pain
• difficulty with moving
• muscle cramping
• muscle stiffness
• muscle tenderness, wasting, or weakness
• pain
• pain in the extremity
• swollen joints

• Burning feeling in the chest or stomach
• indigestion
• loose stools
• stomach upset
• tenderness in the stomach area

• Burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• dark-colored urine
• decreased appetite
• fast, shallow breathing
• muscle pain or spasms
• shortness of breath
• sleepiness

Some side effects of telbivudine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Body aches or pain
• difficulty with breathing
• ear congestion
• loss of voice
• nasal congestion
• sneezing
• stuffy nose

• Acid or sour stomach
• belching
• dizziness
• heartburn
• rash
• sleeplessness
• stomach discomfort
• unable to sleep

CrCl 30 to 49 mL/min:
Tablets: 600 mg orally every 48 hours
Oral solution: 400 mg orally once a day

CrCl less than 30 mL/min (not requiring dialysis):
Tablets: 600 mg orally every 72 hours
Oral solution: 200 mg orally once a day

There are no data on the excretion of telbivudine into human milk. It is excreted into rat milk. The manufacturer advises against breast-feeding during telbivudine therapy.