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Toxicity Effects

CAS Registry Number: 134678-17-4

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 2.

Names 1

  • 2'-Deoxy-3'-Thiacytidine
  • 3TC
  • 3TC (AIDS initiative)
  • Epivir
  • Lamivudine

Human Toxicity Excerpts

  • CASE REPORTS: The aim of this report is to describe five patients with lamivudine-induced pure red cell aplasia, an association not previously described. We describe patients with unresponsive anemia in whom a complete study including blood cell counts, reticulocyte counts, hemolysis tests, and bone marrow aspiration was performed. Pure red cell aplasia was considered when anemia was associated with normal leukocyte and platelet counts with a corrected reticulocyte count below 1% and less than 5% bone marrow erythroid progenitors in the absence of positive hemolysis tests. Complete remission was considered when bone marrow erythroid progenitors were at least 16%. Five male patients had pure red cell aplasia with a median age of 32 years (range 29 to 37 years). Before lamivudine, they had hemoglobin >11.8 g/dL without transfusion requirements. After receiving the drug, hemoglobin dropped to 5.2 g/dl (4.3 to 6.1 g/dL) with high transfusion requirements and mean bone marrow erythroid progenitors of 1.84% (0 to 4%). Withdrawal of lamivudine was attempted to confirm the diagnosis. Seven weeks after stopping lamivudine, hemoglobin rose up to 12.8 g/dL (11 .3 to 13.8 g/dL) and bone marrow erythroid progenitors increased up to 25.6% (21 to 40%) without transfusion requirements. Lamivudine-induced pure red cell aplasia may be a cause of anemia unresponsive to conventional treatment in AIDS.[Majluf-Cruz A; Am J Hematol 65 (3): 189-91 (2000)] **PEER REVIEWED** PubMed Abstract
  • HUMAN EXPOSURE STUDIES: In clinical studies in HIV-infected pediatric patients who received lamivudine in conjunction with zidovudine, paresthesia and peripheral neuropathies have been reported in up to 15% of patients. Pancreatitis, including some fatalities, has occurred in 14-18% of HIV-infected pediatric patients receiving lamivudine alone or in conjunction with other nucleoside antiretroviral agents. Other adverse effects reported in pediatric patients receiving lamivudine in conjunction with zidovudine were similar to those reported in adults and include GI effects, hepatic effects, sensitivity reactions, and hematologic effects.[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 670] **PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Lactic acidosis and severe hepatomegaly with steatosis, including some fatalities, have been reported rarely in patients receiving lamivudine and also have been reported in patients receiving other nucleoside reverse transcriptase inhibitors. Most reported cases have involved women; obesity and long-term therapy with nucleoside reverse transcriptase inhibitors also may be risk factors. Lamivudine should be used with caution in patients with known risk factors for liver disease; however, lactic acidosis and severe hepatomegaly with steatosis have been reported in patients with no known risk factors.[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 669] **PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: There are no adequate and controlled studies to date using lamivudine in pregnant women, and the drug should be used during pregnancy only if the potential benefits justify the potential risks to the fetus.[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 670] **PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • GENOTOXICITY: Lamivudine was not mutagenic in a microbial mutagenicity screen or an in vitro cell transformation assay, but showed weak in vitro mutagenic activity ... in the mouse lymphoma assay.[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 670] **PEER REVIEWED**
  • GENOTOXICITY: The carcinogenic potential of lamivudine has been studied in mice and rats. No evidence of carcinogenicity was seen in long-term studies in mice or rats.[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 670] **PEER REVIEWED**
  • GENOTOXICITY: There was no evidence of genotoxic activity in rats given oral dosages up to 2 g/kg.[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 670] **PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Reproduction studies in rats or rabbits using oral lamivudine in dosages up to 4 or 1 g/kg daily, respectively, have not revealed evidence of teratogenicity.[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 670] **PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: there was evidence of early embryolethality in rabbits receiving lamivudine at dosages similar to the recommended dosages in humans, this effect was not seen in rats receiving lamivudine at dosages 60 times the recommended human dosage for /hepatitis B virus/ infection and 35 times the recommended human dosage for HIV infection.[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 670] **PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • None found

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Absorption, Distribution And Excretion

  • Lamivudine crosses the placenta and has been detected in the fetal circulation.[Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1359] **PEER REVIEWED**
  • Lamivudine has high oral bioavailability with or without food and reaches peak plasma levels within approximately 1 hour.[Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1359] **PEER REVIEWED**

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Metabolism/Metabolites

  • None found

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Tsca Test Submissions

  • None found

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Footnotes

1 Source: the NTP's CEBS database.

2 Source: the National Library of Medicine's Hazardous Substance Database, 02/28/2017.

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