L-deoxythymidine

L-deoxythymidine Uses, Dosage, Side Effects, Food Interaction and all others data.

L-deoxythymidine is a synthetic thymidine nucleoside analogue with activity against hepatitis B virus (HBV). L-deoxythymidine is the unmodified β–L enantiomer of the naturally occurring nucleoside, thymidine. It undergoes phosphorylation via interaction with cellular kinases to form the active metabolite, telbivudine 5'-triphosphate.

L-deoxythymidine 5'–triphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate, thymidine 5'–triphosphate. This leads to the chain termination of DNA synthesis, thereby inhibiting viral replication. Incorporation of telbivudine 5'–triphosphate into viral DNA also causes DNA chain termination, resulting in inhibition of HBV replication. L-deoxythymidine inhibits anticompliment or second-strand DNA.

Trade Name L-deoxythymidine
Availability Discontinued
Generic Telbivudine
Telbivudine Other Names Beta-l-thymidine, Epavudine, L-deoxythymidine, L-DT, L-thymidine, Telbivudin, Telbivudina, Telbivudine
Related Drugs tenofovir, entecavir, lamivudine, Vemlidy, Viread, interferon alfa-2b
Type
Formula C10H14N2O5
Weight Average: 242.2286
Monoisotopic: 242.090271568
Protein binding

In vitro binding of telbivudine to human plasma proteins is low (3.3%).

Groups Approved, Investigational
Therapeutic Class Hepatic viral infections (Hepatitis B)
Manufacturer
Available Country
Last Updated: September 19, 2023 at 7:00 am
L-deoxythymidine
L-deoxythymidine

Uses

Chronic Hepatitis B: L-deoxythymidine is used for the treatment of chronic hepatitis B in adult patients with evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. The following points should be considered when initiating therapy with L-deoxythymidine:

  • This indication is based on virologic, serologic, biochemical and histologic responses in nucleoside treatment naïve adult patients with HBeAg positive and HBeAg negative chronic hepatitis B with compensated liver disease
  • For HBeAg-positive patients, L-deoxythymidine should only be initiated in patients with HBV DNA less than 9 log10 copies per mL and ALT greater than or equal to 2x Upper Limit of Normal (ULN) prior to treatment.
  • For HBeAg-negative patients, L-deoxythymidine should only be initiated in patients with HBV DNA less than 7 log10 copies per mL prior to treatment.
  • On-treatment response should guide continued therapy
  • L-deoxythymidine has not been evaluated in patients co-infected with HIV, HCV or HDV.
  • L-deoxythymidine has not been evaluated in liver transplant recipients or in patients with decompensated liver disease.
  • L-deoxythymidine has not been studied in well-controlled trials for the treatment of patients with established nucleoside analog reverse transcriptase inhibitor-resistant hepatitis B virus infection, but is expected to be cross-resistant to lamivudine.
  • The safety and efficacy of L-deoxythymidine have not been evaluated in Black/African American or Hispanic patients

L-deoxythymidine is also used to associated treatment for these conditions: Hepatitis B Chronic Infection

How L-deoxythymidine works

L-deoxythymidine 5'–triphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate, thymidine 5'–triphosphate. This leads to the chain termination of DNA synthesis, thereby inhibiting viral replication. Incorporation of telbivudine 5'–triphosphate into viral DNA also causes DNA chain termination, resulting in inhibition of HBV replication. L-deoxythymidine inhibits anticompliment or second-strand DNA.

Dosage

L-deoxythymidine dosage

Adults and Adolescents (16 years of age and older): Due to higher rates of resistance that may develop with longer term treatment among patients with incomplete viral suppression, treatment should only be initiated, if pre-treatment HBV DNA and ALT measurements are known, in the following patient populations-

For HBeAg-positive patients, HBV DNA should be less than 9 log10copies per mL and ALT should be greater than or equal to 2x ULN prior to treatment with L-deoxythymidine.

For HBeAg-negative patients, HBV DNA should be less than 7 log10copies per mL prior to treatment with L-deoxythymidine.

HBV DNA levels should be monitored at 24 weeks of treatment to assure complete viral suppression (HBV DNA less than 300 copies per mL). Alternate therapy should be initiated for patients who have detectable HBV DNA after 24 weeks of treatment. Optimal therapy should be guided by further resistance testing.

The recommended dose of L-deoxythymidine for the treatment of chronic hepatitis B:600 mg once daily, taken orally, with or without food. L-deoxythymidine Oral Solution (30 mL) may be considered for patients who have difficulty with swallowing tablets.

Side Effects

Cough, dizziness, fatigue, GI effects (e.g. abdominal pain, diarrhoea, nausea, vomiting, dyspepsia), rash, arthralgia, myalgia, myopathy, malaise, back pain, nasopharyngitis, headache, flu or flu-like symptoms, insomnia; increased serum amylase, lipase, creatine phosphokinase, alanine aminotransferase levels; peripheral neuropathy, rhabdomyolysis.

Toxicity

There is no information on intentional overdose of telbivudine, but one subject experienced an unintentional and asymptomatic overdose. Healthy subjects who received telbivudine doses up to 1800 mg/day for 4 days had no increase in or unexpected adverse events. A maximum tolerated dose for telbivudine has not been determined.

Precaution

Severe acute exacerbations of hepatitis B. Monitor hepatic function in discontinued therapy. Lactic acidosis, severe hepatomegaly with steatosis, myopathy, rhabdomyolysis, uncomplicated myalgia. Discontinue if myopathy is diagnosed. Increased risk of peripheral neuropathy when combined with pegylated interferon α-2a. Decompensated cirrhosis, renal impairment or on hemodialysis; liver transplant recipients or under immunosuppressant therapy. May impair the ability to drive or operate machinery. Pregnancy. Childn <16 yr. Elderly.

Interaction

Altered plasma concentration with drugs that affect renal function (e.g. aminoglycosides, loop diuretics, platinum compounds, vancomycin, amphotericin B). May increase risk of myopathy with other drugs associated with myopathy (e.g. azole antifungals, ciclosporin, corticosteroids, erythromycin, fibrates, HMG-CoA reductase inhibitors, penicillamine, zidovudine).

Food Interaction

  • Take with or without food. The absorption is unaffected by food.

L-deoxythymidine Disease Interaction

Major: myopathyModerate: hemodialysis, renal dysfunction

Elimination Route

Absorbed following oral administration. L-deoxythymidine absorption and exposure were unaffected when a single 600–mg dose was administered with a high–fat (~55 g), high–calorie (~950 kcal) meal.

Half Life

Approximately 15 hours.

Clearance

  • 7.6 +/- 2.9 L/h [Normal renal function (Clcr>80 mL/min)]
  • 5.0 +/- 1.2 L/h [Mild renal function impairement (Clcr=50-80 mL/min)]
  • 2.6 +/- 1.2 L/h [Moderate renal function impairement (Clcr=30-49 mL/min)]
  • 0.7 +/- 0.4 L/h [Severe renal function impairement (Clcr<30 mL/min)]

Elimination Route

L-deoxythymidine is eliminated primarily by urinary excretion of unchanged drug.

Pregnancy & Breastfeeding use

Pregnancy Category B. L-deoxythymidine 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.

Contraindication

Hypersensitivity. Combination of L-deoxythymidine with pegylated interferon alfa-2a is contraindicated because of increased risk of peripheral neuropathy

Storage Condition

Store L-deoxythymidine Tablets and Oral Solution in the original bottle at room temperature (15° to 30°C)

Innovators Monograph

You find simplified version here L-deoxythymidine

L-deoxythymidine contains Telbivudine see full prescribing information from innovator L-deoxythymidine Monograph, L-deoxythymidine MSDS, L-deoxythymidine FDA label

FAQ

What is L-deoxythymidine use for?

L-deoxythymidine is used for chronic hepatitis B infection (swelling of the liver caused by a virus) in people who may also show signs of liver damage.L-deoxythymidine is in a class of medications called nucleoside analogues. It works by decreasing the amount of hepatitis B virus  in the body.

How to use L-deoxythymidine?

Take this medication by mouth with or without food, usually once daily or as directed by your doctor.

What are the common side effects of L-deoxythymidine?

Common side effects of L-deoxythymidine include:

  • tiredness
  • headache
  • cough
  • diarrhea
  • stomach area (abdominal) pain
  • nausea
  • sore throat
  • joint pain
  • fever
  • skin rash
  • back pain
  • dizziness
  • muscle aches
  • upset stomach
  • trouble sleeping
  • stomach area (abdominal) swelling
  • certain abnormal blood tests


Is L-deoxythymidine safe during pregnancy?

L-deoxythymidine treatment during pregnancy presents a favorable safety profile without increased rates of live birth defects, spontaneous abortion or elective termination, or fetal/neonatal toxicity.

Is L-deoxythymidine safe during breastfeeding?

Tell your healthcare provider if you are breastfeeding. It is not known if telbivudine can pass into your breast milk or if it can harm your baby. Do not breastfeed if you are taking L-deoxythymidine.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Can I take L-deoxythymidine long time ?

Do not take more of this medicine and do not take it more often than your doctor ordered.

What happens if I take overdose?

If you take too much telbivudine, call your healthcare provider .If L-deoxythymidine is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

L-deoxythymidine can causes liver problems?

Serious liver problems have occurred in some people who take medicines like L-deoxythymidine.

L-deoxythymidine can causes muscle problems?

L-deoxythymidine can cause muscle problems, including unexplained muscle pain, muscle weakness or muscle tenderness.

L-deoxythymidine can causes nerve problems?

People who take telbivudine alone or with any type of injectable interferon product can have nerve problems such as continuing numbness, tingling, burning sensations in the arms or legs , or problems walking.

*** Taking medicines without doctor's advice can cause long-term problems.
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