Lamivudine

verifiedfields	changed
verifiedrevid	477168974
width	155
tradename	Epivir, Epivir-HBV, Zeffix, others
medlineplus	a696011
dailymedid	Lamivudine
pregnancy au	B3
routes of administration	By mouth
atc prefix	J05
atc suffix	AF05
legal uk	POM
legal us	Rx-only
legal ca	Rx-only
legal ca comment	‡R1R‡
legal us comment	‡R2R‡‡R3R‡
legal eu	Rx-only
bioavailability	86%
protein bound	Less than 36%
elimination half-life	5 to 7 hours
excretion	Kidney (circa 70%)
cas number	134678-17-4
pubchem	60825
drugbank	DB00709
chemspiderid	66068
unii	2T8Q726O95
kegg	D00353
chembl	141
pdb ligand	3TC
niaid chemdb	000388
synonyms	(−)-L-2′,3′-dideoxy-3′-thiacytidine
iupac name	2',3'-dideoxy-3'-thiacytidine
c	8
h	11
n	3
o	3
s	1
smiles	O=C1/N=C(/N)\C=C/N1[C@@H]2O[C@@H](SC2)CO
stdinchi	1S/C8H11N3O3S/c9-5-1-2-11(8(13)10-5)6-4-15-7(3-12)14-6/h1-2,6-7,12H,3-4H2,(H2,9,10,13)/t6-,7+/m1/s1
stdinchikey	JTEGQNOMFQHVDC-RQJHMYQMSA-N

Lamivudine, commonly called 3TC, is an antiretroviral medication used to prevent and treat HIV/AIDS.[4] It is also used to treat chronic hepatitis B when other options are not possible.[4] It is effective against both HIV-1 and HIV-2.[4] It is typically used in combination with other antiretrovirals such as zidovudine, dolutegravir, and abacavir.[4] Lamivudine may be included as part of post-exposure prevention in those who have been potentially exposed to HIV.[4] Lamivudine is taken by mouth as a liquid or tablet.[4]

Medical uses

Lamivudine (Epivir) is indicated in combination with other antiretroviral agents for the treatment of HIV‑1 infection.[2][8] Lamivudine (Epivir HBV) is indicated for the treatment of chronic hepatitis B virus infection associated with evidence of hepatitis B viral replication and active liver inflammation.[3][9]

Lamivudine has been used for treatment of chronic hepatitis B at a lower dose than for treatment of HIV/AIDS. It improves the seroconversion of e-antigen positive hepatitis B and also improves histology staging of the liver. Long-term use of lamivudine leads to emergence of a resistant hepatitis B virus (YMDD) mutant.[10] Despite this, lamivudine is still used widely as it is well tolerated.[11]

Resistance

In HIV, high level resistance is associated with the M184V/I mutation in the reverse transcriptase gene as reported by Raymond Schinazi's group at Emory University. GlaxoSmithKline claimed 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 may be benefit in continuing lamivudine treatment even in the presence of high level resistance, because the resistant virus is "less fit". The COLATE study has suggested that there is no benefit to continuing lamivudine treatment in patients with lamivudine resistance.[12]

In hepatitis B, lamivudine resistance was first described in the YMDD (tyrosine-methionine-aspartate-aspartate) 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.[13] The change in amino acid sequence from YMDD to YIDD results in a 3.2 fold reduction in the error rate of the reverse transcriptase, which correlates with a significant growth disadvantage of the virus. Other resistance mutations are L80V/I, V173L and L180M.[14]

Lamivudine

Medical uses

Resistance

Side effects

Mechanism of action

History

Formulations

References