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| {{Drugbox| | | __NOTOC__ |
| |IUPAC_name = L</small>-2',3'-dideoxy-3'-thiacytidine | | {{Lamivudine}} |
| | image=Lamivudine.svg
| | '''''For patient information, click <u>[[Lamivudine (patient information)|here]]</u>'''''. |
| | CAS_number=134678-17-4
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| | ATC_prefix=J05
| | {{CMG}} |
| | ATC_suffix=AF05
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| | ATC_supplemental=
| | ==Overview== |
| | PubChem=60825
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| | DrugBank=APRD00681
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| | C=8 | H=11 | N=3 | O=3 | S=1
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| | molecular_weight = 229.26 g/mol
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| | bioavailability = 86%
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| | metabolism =
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| | protein_bound = Less than 36%
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| | elimination_half-life = 5 to 7 hours
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| | excretion = [[Kidney|Renal]] (circa 70%)
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| | pregnancy_AU = B3
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| | pregnancy_US = C
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| | legal_US = Rx-only
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| | legal_UK = POM
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| | routes_of_administration = Oral
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| }}
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| <!-- FAIR USE of Lamivudine.gif: see image description page at http://en.wikipedia.org/wiki/Image:Lamivudine.gif for rationale -->
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| '''Lamivudine''' (2',3'-dideoxy-3'-thia[[cytidine]], commonly called '''3TC''') is a potent [[reverse transcriptase inhibitor|nucleoside analog reverse transcriptase inhibitor]] (nRTI). | | '''Lamivudine''' (2',3'-dideoxy-3'-thia[[cytidine]], commonly called '''3TC''') is a potent [[reverse transcriptase inhibitor|nucleoside analog reverse transcriptase inhibitor]] (nRTI). |
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| 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. | | 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. |
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| ==History== | | ==Category== |
| Lamivudine was invented by [[Bernard Belleau]] and Nghe Nguyen-Ga at the Montreal-based IAF BioChem International, Inc. laboratories in 1989. Initially designed as an antiviral agent, the drug's effectiveness for treating HIV in combination with AZT was discovered by [[Yung-Chi (Tommy) Cheng]] at [[Yale University]]. The drug was later licensed to the British pharmaceutical company Glaxo for a 14 percent royalty.
| | Antiretroviral |
| | | ==US Brand Names== |
| Lamivudine was approved by the [[Food and Drug Administration]] (FDA) on [[November 17]] [[1995]] for use with [[zidovudine]] (AZT) and again in 2002 as a once-a-day dosed medication. The fifth antiretroviral drug on the market, it was the last NRTI for three years while the approval process switched to [[protease inhibitor (pharmacology)|protease inhibitors]]. According to the manufacturer's 2004 annual report, its patent will expire in the United States in 2010 and in Europe in 2011.
| | EPIVIR<sup>®</sup> |
| | | ==FDA Package Insert== |
| ==Mechanism of action==
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| Lamivudine is an [[analog (chemistry)|analogue]] of [[cytidine]]. It can inhibit both types (1 and 2) of [[HIV]] [[reverse transcriptase]] and also the reverse transcriptase of [[hepatitis B]]. It needs to be phosphorylated to its triphosphate form before it is active. 3TC-triphosphate also inhibits cellular [[DNA polymerase]].
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| Lamivudine is administered orally, and it is rapidly absorbed with a bio-availability of over 80%. Some research suggests that lamivudine can cross the [[blood-brain barrier]]. Lamivudine is often given in combination with [[zidovudine]], with which it is highly synergistic. Lamivudine treatment has been shown to restore zidovudine sensitivity of previously resistant HIV. Several mutagenicity tests show that lamivudine should not show [[mutagen]]ic activity in therapeutic doses.
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| '''== Physical Interaction with Tenofovir DF''' ==
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| Lamivudine shows brownish coloration with tenofovir disoproxil fumarate, reason behind this is still unknown.
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| ==Resistance==
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| :''See also: [[resistance mutation]]''
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| In HIV, high level resistance is associated with the M184V/I mutation in the [[reverse transcriptase]] gene. [[GlaxoSmithKline]] sought to perpetuate the fiction that the M184V mutation reduces "viral fitness", because of the finding that continued lamivudine treatment causes the HIV viral load to rebound but at a much lower level, and that withdrawal of lamivudine results in a higher viral load rebound with rapid loss of the M184V mutation; GSK therefore argued that there is theoretical benefit in continuing lamivudine treatment even in the presence of high level resistance, because the resistant virus is "less fit". The COLATE study has shown definitively that there is no benefit to continuing lamivudine treatment in patients with lamivudine resistance.<ref>{{cite journal | author=Fox Z, Dragsted UB, Gerstoft J, ''et al.'' | title=A randomized trial to evaluate continuation versus discontinuation of lamivudine in individuals failing a lamivudine-containing regimen: The COLATE trial | journal=Antiviral Therapy | volume=11 | pages=761–70 | year=2006 | id=PMID 17310820 }}</ref> A better explanation of the data is that lamivudine continues to have a partial anti-viral effect even in the presence of the M184V mutation.
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| In hepatitis B, lamivudine resistance was first described in the YMDD locus of the HBV reverse transcriptase gene. The HBV reverse transcriptase gene is 344 amino acids long and occupies codons 349 to 692 on the viral genome. The most commonly encountered resistance mutations are M204V/I/S. Other resistance mutations are L80V/I, V173L and L180M.<ref>{{cite journal | author=Koziel MJ, Peters MG | year=2007 | journal=N Engl J Med | volume=356 | pages=1445–54 | issue=14 | title=Viral hepatitis in HIV infection }}</ref>
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| ==Dosing==
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| For adults with HIV (or children over 12), the dose is 300mg once daily, or 150mg twice a day. Lamivudine is never used on its own in the treatment of HIV.
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| For the treatment of adults with hepatitis B, the dose is 100mg once daily. If co-infected with HIV, then the dose is as for HIV.
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| ==Presentation==
| | ''' [[Lamivudine description|Description]]''' |
| [[Image:Lamivudine.gif|thumb|81px|Epivir logo]] | | '''| [[Lamivudine clinical pharmacology|Clinical Pharmacology]]''' |
| *'''Epivir''' 150 mg or 300 mg tablets (GlaxoSmithKline; US and UK) for the treatment of HIV;
| | '''| [[Lamivudine microbiology|Microbiology]]''' |
| *'''Epivir-HBV''' 100 mg tablets (GlaxoSmithKline; US only) for the treatment of hepatitis B;
| | '''| [[Lamivudine indications and usage|Indications and Usage]]''' |
| *'''Zeffix''' 100 mg tablets (GlaxoSmithKline; UK only) for the treatment of hepatitis B.
| | '''| [[Lamivudine contraindications|Contraindications]]''' |
| | | '''| [[Lamivudine warnings and precautions|Warnings and Precautions]]''' |
| Lamivudine is also available in fixed combinations with other HIV drugs: | | '''| [[Lamivudine adverse reactions|Adverse Reactions]]''' |
| *[[Combivir]] (with [[zidovudine]]);
| | '''| [[Lamivudine drug interactions|Drug Interactions]]''' |
| *[[Kivexa]] (with [[abacavir]]);
| | '''| [[Lamivudine overdosage|Overdosage]]''' |
| *[[Trizivir]] (with [[zidovudine]] and [[abacavir]]).
| | '''| [[Lamivudine clinical studies|Clinical Studies]]''' |
| | '''| [[Lamivudine dosage and administration|Dosage and Administration]]''' |
| | '''| [[Lamivudine how supplied|How Supplied]]''' |
| | '''| [[Lamivudine labels and packages|Labels and Packages]]''' |
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| | ==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== | | ==References== |
| {{Reflist}} | | {{Reflist|2}} |
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| ==External links==
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| * [http://www.gsk.com/products/prescription_medicines/uk/epivir.htm Epivir] (manufacturer's website)
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| * [http://www.hepatitisbhelp.com/index.html Epivir-HBV] (manufacturer's website)
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| * {{DailyMed|2552|Epivir}}
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| * {{DailyMed|2841|Epivir-HBV}}
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| {{-}}
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| {{Antivirals}}
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| [[Category:Antiretroviral drugs]]
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| [[de:Lamivudin]] | | [[Category:Antiretroviral]] |
| [[fr:Lamivudine]] | | [[Category:Wikinfect]] |
| [[ja:ラミブジン]]
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| [[th:ลามิวูดีน]]
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| [[zh:拉米夫定]]
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| {{WikiDoc Help Menu}}
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| {{WikiDoc Sources}}
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For patient information, click here.
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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