Lamivudine

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Lamivudine
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Stefano Giannoni [2]

Disclaimer

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Black Box Warning

WARNING: RISK OF LACTIC ACIDOSIS, EXACERBATIONS OF HEPATITIS B IN CO-INFECTED PATIENTS UPON DISCONTINUATION OF LAMIVUDINE, DIFFERENT FORMULATIONS OF LAMIVUDINE.
See full prescribing information for complete Boxed Warning.
Lactic Acidosis and Severe Hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including lamivudine and other antiretrovirals. Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.

Exacerbations of Hepatitis B: Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) and have discontinued lamivudine. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue lamivudine and are co-infected with HIV-1 and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Important Differences Among Lamivudine-Containing Products: Lamivudine tablets (used to treat HIV-1 infection) contain a higher dose of the active ingredient (lamivudine) than EPIVIR-HBV® tablets and oral solution (used to treat chronic HBV infection). Patients with HIV-1 infection should receive only dosage forms appropriate for treatment of HIV-1.

Overview

Lamivudine is a nucleoside analogue reverse transcriptase inhibitor that is FDA approved for the treatment of HIV-1 infection. There is a Black Box Warning for this drug as shown here. Common adverse reactions include headache, nausea, malaise and fatigue, nasal signs and symptoms, diarrhea, and cough..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Human immunodeficiency virus (HIV-1) infection

Chronic Hepatitis B (HBV) infection

  • Dosage: 100 mg daily

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Lamivudine in adult patients.

Non–Guideline-Supported Use

Posttransplant Prophylaxis for Hepatitis B

  • Dosage: 100mg daily [1]
  • In combination with HBIG.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Human immunodeficiency virus (HIV-1) infection

Chronic Hepatitis B (HBV) infection

  • Dosage: patients aged 2 to 17 years is 3 mg per kg once daily up to a maximum daily dosage of 100 mg.
  • The oral solution formulation should be prescribed for patients requiring a dosage less than 100 mg or if unable to swallow tablets.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Lamivudine in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Lamivudine in pediatric patients.

Contraindications

  • Hypersensitivity to lamivudine or to any component of the tablets or oral solution.

Warnings

WARNING: RISK OF LACTIC ACIDOSIS, EXACERBATIONS OF HEPATITIS B IN CO-INFECTED PATIENTS UPON DISCONTINUATION OF LAMIVUDINE, DIFFERENT FORMULATIONS OF LAMIVUDINE.
See full prescribing information for complete Boxed Warning.
Lactic Acidosis and Severe Hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including lamivudine and other antiretrovirals. Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.

Exacerbations of Hepatitis B: Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) and have discontinued lamivudine. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue lamivudine and are co-infected with HIV-1 and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Important Differences Among Lamivudine-Containing Products: Lamivudine tablets (used to treat HIV-1 infection) contain a higher dose of the active ingredient (lamivudine) than EPIVIR-HBV® tablets and oral solution (used to treat chronic HBV infection). Patients with HIV-1 infection should receive only dosage forms appropriate for treatment of HIV-1.

Lactic Acidosis and Severe Hepatomegaly With Steatosis

  • Obesity and prolonged nucleoside exposure may be risk factors.
  • Particular caution should be exercised when administering EPIVIR to any patient with known risk factors for liver disease; however, cases also have been reported in patients with no known risk factors. Treatment with EPIVIR 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).

Patients With HIV-1 and Hepatitis B Virus Co-infection

Posttreatment Exacerbations of Hepatitis

  • In clinical trials in non-HIV-1-infected patients treated with lamivudine for chronic hepatitis B, clinical and laboratory evidence of exacerbations of hepatitis have occurred after discontinuation of lamivudine.
  • These exacerbations have been detected primarily by serum ALT elevations in addition to re-emergence of HBV DNA. Although most events appear to have been self-limited, fatalities have been reported in some cases.
  • Similar events have been reported from postmarketing experience after changes from lamivudine-containing HIV-1 treatment regimens to non-lamivudine-containing regimens in patients infected with both HIV-1 and HBV.
  • The causal relationship to discontinuation of lamivudine treatment is unknown.
  • Patients should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment.
  • There is insufficient evidence to determine whether re-initiation of lamivudine alters the course of posttreatment exacerbations of hepatitis.

Important Differences Among Lamivudine-Containing Products

  • EPIVIR Tablets and Oral Solution contain a higher dose of the same active ingredient (lamivudine) than EPIVIR-HBV Tablets and EPIVIR-HBV Oral Solution.
  • EPIVIR-HBV was developed for patients with chronic hepatitis B.
  • The formulation and dosage of lamivudine in EPIVIR-HBV are not appropriate for patients co-infected with HIV-1 and HBV. Safety and efficacy of lamivudine have not been established for treatment of chronic hepatitis B in patients co-infected with HIV-1 and HBV.
  • If treatment with EPIVIR-HBV is prescribed for chronic hepatitis B for a patient with unrecognized or untreated HIV-1 infection, rapid emergence of HIV-1 resistance is likely to result because of the subtherapeutic dose and the inappropriateness of monotherapy HIV-1 treatment.
  • If a decision is made to administer lamivudine to patients co-infected with HIV-1 and HBV, EPIVIR Tablets, EPIVIR Oral Solution, COMBIVIR® (lamivudine/zidovudine) Tablets, EPZICOM® (abacavir sulfate and lamivudine) Tablets, or TRIZIVIR® (abacavir sulfate, lamivudine, and zidovudine) Tablets should be used as part of an appropriate combination regimen.

Emergence of Lamivudine-Resistant HBV

  • In non–HIV-1-infected patients treated with lamivudine for chronic hepatitis B, emergence of lamivudine-resistant HBV has been detected and has been associated with diminished treatment response.
  • Emergence of hepatitis B virus variants associated with resistance to lamivudine has also been reported in HIV-1-infected patients who have received lamivudine-containing antiretroviral regimens in the presence of concurrent infection with hepatitis B virus.

Use With Other Lamivudine- and Emtricitabine-Containing Products

Use With Interferon- and Ribavirin-Based Regimens

Pancreatitis

  • In pediatric patients with a history of prior antiretroviral nucleoside exposure, a history of pancreatitis, or other significant risk factors for the development of pancreatitis, EPIVIR should be used with caution.
  • Treatment with EPIVIR should be stopped immediately if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur.

Immune Reconstitution Syndrome

Fat Redistribution

Adverse Reactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adults Population

Clinical Trials in HIV-1

The safety profile of EPIVIR in adults is primarily based on 3,568 HIV-1-infected subjects in 7 clinical trials.

The most common adverse reactions are headache, nausea, malaise, fatigue, nasal signs and symptoms, diarrhea and cough.

Selected clinical adverse reactions in ≥5% of subjects during therapy with EPIVIR 150 mg twice daily plus RETROVIR® 200 mg 3 times daily for up to 24 weeks are listed in Table 3.

Pancreatitis

  • Pancreatitis was observed in 9 out of 2,613 adult subjects (0.3%) who received EPIVIR in controlled clinical trials EPV20001, NUCA3001, NUCB3001, NUCA3002, NUCB3002, and NUCB3007.

EPIVIR 300 mg Once Daily: The types and frequencies of clinical adverse reactions reported in subjects receiving EPIVIR 300 mg once daily or EPIVIR 150 mg twice daily (in 3-drug combination regimens in EPV20001 and EPV40001) for 48 weeks were similar.

Selected laboratory abnormalities observed during therapy are summarized in Table 4.

Pediatric Population

Postmarketing Experience

Because these reactions are reported voluntarily from a population of unknown size, estimates of frequency cannot be made.

Body as a Whole

General

Endocrine and Metabolic

Hemic and Lymphatic

Hepatic and Pancreatic

Hypersensitivity

Musculoskeletal

Skin

Drug Interactions

There is limited information regarding Lamivudine Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Lamivudine in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Lamivudine in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Lamivudine during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Lamivudine in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Lamivudine in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Lamivudine in geriatric settings.

Gender

There is no FDA guidance on the use of Lamivudine with respect to specific gender populations.

Race

There is no FDA guidance on the use of Lamivudine with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Lamivudine in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Lamivudine in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Lamivudine in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Lamivudine in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Lamivudine Administration in the drug label.

Monitoring

There is limited information regarding Lamivudine Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Lamivudine and IV administrations.

Overdosage

There is limited information regarding Lamivudine overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Lamivudine Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Lamivudine Mechanism of Action in the drug label.

Structure

There is limited information regarding Lamivudine Structure in the drug label.

Pharmacodynamics

There is limited information regarding Lamivudine Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Lamivudine Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Lamivudine Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Lamivudine Clinical Studies in the drug label.

How Supplied

There is limited information regarding Lamivudine How Supplied in the drug label.

Storage

There is limited information regarding Lamivudine Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Lamivudine Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Lamivudine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Lamivudine Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Lamivudine Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ Jiang L, Yan L, Li B, Wen T, Zhao J, Jiang L; et al. (2010). "Prophylaxis against hepatitis B recurrence posttransplantation using lamivudine and individualized low-dose hepatitis B immunoglobulin". Am J Transplant. 10 (8): 1861–9. doi:10.1111/j.1600-6143.2010.03208.x. PMID 20659092.


Lamivudine
EPIVIR® FDA Package Insert
Description
Clinical Pharmacology
Microbiology
Indications and Usage
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Overdosage
Dosage and Administration
How Supplied
Labels and Packages

For patient information, click here.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]

Overview

Lamivudine (2',3'-dideoxy-3'-thiacytidine, commonly called 3TC) is a potent nucleoside analog reverse transcriptase inhibitor (nRTI).

It is marketed by GlaxoSmithKline with the brand names Epivir and Epivir-HBV.

Lamivudine has been used for treatment of chronic hepatitis B at a lower dose than for treatment of HIV. It improves the seroconversion of e-antigen positive hepatitis B and also improves histology staging of the liver. Long term use of lamivudine unfortunately leads to emergence of a resistant hepatitis B virus (YMDD) mutant. Despite this, lamivudine is still used widely as it is well tolerated.

Category

Antiretroviral

US Brand Names

EPIVIR®

FDA Package Insert

Description | Clinical Pharmacology | Microbiology | Indications and Usage | Contraindications | Warnings and Precautions | Adverse Reactions | Drug Interactions | Overdosage | Clinical Studies | Dosage and Administration | How Supplied | Labels and Packages

Mechanism of Action

Intracellularly, lamivudine is phosphorylated to its active 5′-triphosphate metabolite, lamivudine triphosphate (3TC-TP). The principal mode of action of 3TC-TP is the inhibition of HIV-1 reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue into viral DNA. 3TC-TP is a weak inhibitor of mammalian DNA polymerases α, β, and γ.

References

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