Lamivudine And Zidovudine

Brand Names: Lamivudine And Zidovudine

Drug Class: Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor

Overview

11 DESCRIPTION Lamivudine and Zidovudine tablets, USP are combination tablets containing lamivudine and zidovudine. Lamivudine (EPIVIR) and zidovudine (RETROVIR, azidothymidine, AZT, or ZDV) are synthetic nucleoside analogues with activity against HIV-1. Lamivudine and Zidovudine tablets, USP are for oral administration.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Lamivudine and zidovudine tablet is an antiretroviral agent [see Microbiology (12.4)]. 12.3 Pharmacokinetics Pharmacokinetics in Adults One lamivudine and zidovudine tablet was bioequivalent to 1 EPIVIR tablet (150 mg) plus 1 RETROVIR tablet (300 mg) following single-dose administration to fasting healthy subjects (n = 24). Lamivudine : Following oral administration, lamivudine is rapidly absorbed and extensively distributed. Binding to plasma protein is low. Approximately 70% of an intravenous dose of lamivudine is recovered as unchanged drug in the urine. Metabolism of lamivudine is a minor route of elimination (approximately 5% of an oral dose after 12 hours).

Indications

  • 1 INDICATIONS & USAGE Lamivudine and zidovudine tablets a combination of 2 nucleoside analogues, are indicated in combination with other antiretrovirals for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Lamivudine and zidovudine tablets, a combination of 2 nucleoside analogue reverse transcriptase inibitors, are indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. (1)

Common Doses

  • 150 mg
  • 300 mg
  • 50 mL

Dosage

2 DOSAGE & ADMINISTRATION • Adults and Adolescents weighing greater than or equal to 30 kg: 1 tablet orally twice daily. (2.1) • Pediatrics weighing greater than or equal to 30 kg: 1 tablet orally twice daily. (2.2) • Because lamivudine and zidovudine tablet is a fixed-dose tablet and cannot be dose adjusted, lamivudine and zidovudine tablet is not recommended in patients requiring dosage adjustment or with hepatic impairment or experiencing dose-limiting adverse reactions. (2.3, 4) 2.

Black Box Warning

BOXED WARNING WARNING: HEMATOLOGIC TOXICITY, MYOPATHY, LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, and EXACERBATIONS OF HEPATITIS B Zidovudine, a component of lamivudine and zidovudine tablets, has been associated with hematologic toxicity including neutropenia and severe anemia, particularly in patients with advanced Human Immunodeficiency Virus (HIV-1) disease [see Warnings and Precautions (5.1)]. Prolonged use of zidovudine has been associated with symptomatic myopathy [see Warnings and Precautions (5.2)].

Contraindications

  • 4 CONTRAINDICATIONS Lamivudine and zidovudine tablets are contraindicated in patients with a previous hypersensitivity reaction to lamivudine or zidovudine. Lamivudine and zidovudine tablets are contraindicated in patients with a previous hypersensitivity reaction to lamivudine or zidovudine. (4)

Side Effects

  • 6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: • Hematologic toxicity, including neutropenia and anemia [see Boxed Warning, Warnings and Precautions (5.1)]. • Symptomatic myopathy [see Boxed Warning, Warnings and Precautions (5.2)]. • Lactic acidosis and severe hepatomegaly with steatosis [see Boxed Warning, Warnings and Precautions (5.3)]. • Exacerbations of hepatitis B [see Boxed Warning, Warnings and Precautions (5.4)]. • Hepatic decompensation in patients co-infected with HIV-1 and hepatitis C [see Warnings and Precautions (5.5)].

Interactions

  • 7 DRUG INTERACTIONS • Agents antagonistic with zidovudine: Concomitant use should be avoided. (7.1) • Hematologic/bone marrow suppressive/cytotoxic agents: May increase the hematologic toxicity of zidovudine. (7.1) • Sorbitol: Coadministration of lamivudine and sorbitol may decrease lamivudine concentrations; when possible, avoid chronic coadministration. (7.2) • Agents antagonistic with zidovudine: Concomitant use should be avoided. (7.1) • Hematologic/bone marrow suppressive/cytotoxic agents: May increase the hematologic toxicity of zidovudine. (7.