WARNING: RISK OF LACTIC ACIDOSIS, EXACERBATIONS OF HEPATITIS B IN CO-INFECTED PATIENTS UPON DISCONTINUATION OF EPIVIR , DIFFERENT FORMULATIONS OF EPIVIR.
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 [see Warnings and Precautions].
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 EPIVIR. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue EPIVIR and are co-infected with HIV-1 and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted [see Warnings and Precautions].
EPIVIR Tablets and Oral Solution (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 [see Warnings and Precautions] .
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EPIVIR SUMMARY
EPIVIR (also known as 3TC) is a brand name for lamivudine, a synthetic nucleoside analogue with activity against human immunodeficiency virus-1 (HIV-1) and hepatitis B virus (HBV). The chemical name of lamivudine is (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one. Lamivudine is the (-)enantiomer of a dideoxy analogue of cytidine. Lamivudine has also been referred to as (-)2',3'-dideoxy, 3'-thiacytidine.
EPIVIR in combination with other antiretroviral agents is indicated for the treatment of HIV infection.
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NEWS HIGHLIGHTS
Published Studies Related to Epivir (Lamivudine)
A Randomized-Controlled Study investigating Viral Suppression and Serological Response following PreS1/PreS2/S Vaccine Therapy Combined with Lamivudine in HBeAg-positive Chronic Hepatitis B Patients. [2009.09.21]
The aim of the current study was to evaluate viral suppression following combined S/preS1/preS2 vaccine and lamivudine treatment in patients with chronic hepatitis B. We established a randomized, controlled clinical trial to compare the response between three different treatment groups including vaccine monotherapy, lamivudine monotherapy and combination treatment...
A randomized comparative trial of continued zidovudine/lamivudine or replacement with tenofovir disoproxil fumarate/emtricitabine in efavirenz-treated HIV-1-infected individuals. [2009.08.15]
BACKGROUND: Long-term antiretroviral therapy dramatically reduces HIV-related morbidity and mortality but is also associated with metabolic and morphological changes and requires high levels of adherence... CONCLUSIONS: Switching from zidovudine/lamivudine to tenofovir disoproxil fumarate/emtricitabine in persons on efavirenz therapy maintains virological control, establishes a once-daily regimen, results in improvements in hemoglobin and key lipid parameters, and preserves and restores limb fat relative to continuation of zidovudine/lamivudine.
Randomized, double-blind, placebo-matched, multicenter trial of abacavir/lamivudine or tenofovir/emtricitabine with lopinavir/ritonavir for initial HIV treatment. [2009.07.31]
BACKGROUND: Abacavir sulfate/lamivudine (ABC/3TC) and tenofovir DF/emtricitabine (TDF/FTC) are widely used nucleoside reverse transcriptase inhibitors for initial HIV-1 treatment. This is the first completed, randomized clinical trial to directly compare the efficacy, safety, and tolerability of these agents, each in combination with lopinavir/ritonavir in antiretroviral-naive patients... CONCLUSION: Both ABC/3TC and TDF/FTC provided comparable antiviral efficacy, safety, and tolerability when each was combined with lopinavir/ritonavir in treatment-naive patients.
A combination drug of abacavir-lamivudine-zidovudine (Trizivir) for treating HIV infection and AIDS. [2009.07.08]
CONCLUSIONS: Our findings indicate that Trizivir remains a viable option for initiating antiretroviral therapy, especially in HIV-infected patients with pre-existing hyperlipidaemia and those who do not tolerate ritonavir.
A simplification trial switching from nucleoside reverse transcriptase inhibitors to once-daily fixed-dose abacavir/lamivudine or tenofovir/emtricitabine in HIV-1-infected patients with virological suppression. [2009.07.01]
BACKGROUND: Data comparing abacavir/lamivudine versus tenofovir/emtricitabine in antiretroviral-naive patients are controversial. We compared 48-week efficacy and safety of these combinations as substitutes of nucleosides in patients with virological suppression... CONCLUSIONS: In HIV-1-infected patients with virological suppression, abacavir/lamivudine did not meet the noninferiority outcome for treatment efficacy compared with tenofovir/emtricitabine.
Clinical Trials Related to Epivir (Lamivudine)
Effectiveness and Safety of Epivir/Ziagen/Zerit (3TC/ABC/d4T) Versus Epivir/Ziagen/Sustiva (3TC/ABC/EFV) Versus Epivir/Ziagen/Agenerase/Norvir (3TC/ABC/APV/RTV) in HIV Patients Who Have Never Received Treatment [Active, not recruiting]
The purpose of this study is to see how effective and safe it is to give 1 of the 3 following
treatments to patients who may not have received anti-HIV treatment: 1) lamivudine
(3TC)/abacavir (ABC)/stavudine (d4T); 2) 3TC/ABC/efavirenz (EFV); or 3) 3TC/ABC/amprenavir
(APV)/ritonavir (RTV).
Trial of Maraviroc (UK-427,857) in Combination With Zidovudine/Lamivudine Versus Efavirenz in Combination With Zidovudine/Lamivudine [Active, not recruiting]
Maraviroc (UK-427,857), a selective and reversible CCR5 coreceptor antagonist, has been shown
to be active in vitro against a wide range of clinical isolates (including those resistant to
existing classes). In HIV-1 infected patients, maraviroc (UK-427,857) given as monotherapy
for 10 days reduced HIV-1 viral load by up to 1. 6 log, consistent with currently available
agents. Safety and toleration have been studied in over 400 subjects for up to 28 days at
300 mg twice daily. No significant effects were seen on the QTc interval. The goal of this
study is to compare the safety and efficacy of maraviroc (UK-427,857) versus efavirenz, when
each are combined with two other antiretroviral agents, in patients who are previously naive
to antiretroviral therapy. This study will involve approximately 200 centers from around the
world to achieve a total randomized subject population of 1071 subjects. Patients will be
randomly assigned to one of three groups: maraviroc (UK-427,857) 300 mg once daily added to
zidovudine/lamivudine (300 mg/150 mg twice daily), Maraviroc (UK-427,857) 300 mg twice daily
added to zidovudine/lamivudine (300 mg/150 mg twice daily) or efavirenz (600 mg once daily)
added to zidovudine/lamivudine (300 mg/150 mg twice daily). The study will enroll over
approximately an 18 month period (5 months Phase 2b run-in, 13 months Phase 3) with 96 weeks
of treatment. This may be extended for an additional 3 years depending on the results at 96
weeks. Physical examinations will be performed at study entry, weeks 4, 8, 12, 16, 20, 24,
32, 40, 48, 60, 72, 84 and 96. Blood samples will also be taken at study entry, weeks 2, 4,
8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96. Additionally, blood samples will be drawn
twice, at least 30 minutes apart, at weeks 2 and 48 for maraviroc (UK-427,857)
pharmacokinetic analysis. As part of this clinical study a blood sample will be taken for
non-anonymized pharmacogenetic analysis. Patients will undergo a 12-lead electrocardiogram
at study entry, weeks 24, 48 and 96. A computerized tomography (CT) scan will also be
performed, at selected centers, at study entry and week 96. Patients will be asked to
complete a symptom distress questionnaire at study entry, weeks 12, 24, 48 and 96.
Induction/Simplification With Atazanavir + Ritonavir + Abacavir/Lamivudine Fixed-Dose Combination In HIV-1 Infection [Active, not recruiting]
This study was designed to test the efficacy, safety, tolerability and durability of the
antiviral response between atazanavir (ATV) + ritonavir (RTV) + abacavir/lamivudine(ABC/3TC)
each administered once daily (QD) for 36 weeks followed by randomization to either a
simplification regimen of ATV or continuation of ATV+RTV for an additional 48 weeks, each in
combination with ABC/3TC in antiretroviral (ART)-naive, HIV-1 infected, HLA-B*5701 negative
subjects.
Virologic and Immunologic Activity of Continued Lamivudine (3TC) Vs Delavirdine (DLV) in Combination With Indinavir (IDV) and Zidovudine (ZDV) or Stavudine (d4T) in 3TC-Experienced Subjects [Completed]
To compare the proportion of patients in the 2 zidovudine (ZDV)-containing arms who have a
plasma HIV RNA concentration below the limit of detection (defined as 500 copies/ml or less)
at Weeks 20 and 24 [AS PER AMENDMENT 8/24/98: HIV RNA concentration below the limit of
detection is now defined as 200 copies/ml or less]. To compare the safety and tolerability of
the different treatment regimens. To compare the decrease in plasma HIV-1 RNA and the change
in CD4 count from baseline to the average of Weeks 20 and 24 [AS PER AMENDMENT 12/19/97: and
to the average of Weeks 44 and 48; AS PER AMENDMENT 8/24/98: and the average of Weeks 88 and
96] in the 2 ZDV-containing arms. To study the emergence of resistance to ZDV, lamivudine
(3TC), stavudine (d4T), delavirdine (DLV), and indinavir (IDV) in treated patients. To
correlate the antiviral and immunologic activity and emergence of drug resistance with
pharmacologic parameters of study drugs. To delineate the pharmacokinetic interactions of IDV
and DLV. [AS PER AMENDMENT 12/19/97: To delineate the possible development of cellular
resistance to nucleoside analogs and the consequences of switching nucleoside study drugs on
intracellular phosphorylation.] To document rates and patterns of adherence over the course
of the study, from day of randomization through 48 weeks. [AS PER AMENDMENT 8/24/98: To
define long-term durability of the virologic activity of the different treatment regimens, as
defined by the proportion of patients with plasma HIV-1 RNA levels that remains below the
limit of detection. To define long-term tolerability of the different treatment regimens.]
Although a change in reverse transcriptase (RT) inhibitors is recommended when adding or
changing protease inhibitors in a treatment regimen, the choice of available RT inhibitors is
often limited by prior exposure, toxicity, or pharmacologic interaction with the protease
inhibitors. This study addresses the question of whether to continue 3TC or substitute the
nonnucleoside reverse transcriptase inhibitor (NNRTI) DLV when adding IDV to therapy for
patients previously treated with ddI or d4T plus 3TC who have greater than 500 copies/ml of
plasma HIV-1 RNA. Although the activity of DLV as monotherapy or in combination with
nucleoside reverse transcriptase inhibitors is of limited duration due to rapid emergence of
resistance, it is possible that DLV will contribute significantly to the activity of 3-drug
regimens that include a new RT inhibitor plus a protease inhibitor.
3TC (Lamivudine; GR109714X) Open-Label Program [Completed]
To make lamivudine (3TC) available to patients with progressive, symptomatic HIV disease who
cannot participate in a controlled clinical trial and who are refractory or unable to
tolerate other therapies. To collect data pertaining to the safety of 3TC at two dose levels.
To evaluate the effect of 3TC on markers of hepatitis B in co-infected patients at five to
ten selected sites.
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Page last updated: 2009-10-20
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