Details of the Drug

General Information of Drug (ID: DMI347A)

Drug Name

Lamivudine

Synonyms

lamivudine; 134678-17-4; Epivir; Zeffix; Heptovir; Epivir-HBV; Hepitec; Heptodin; BCH-189; 3TC; Heptivir; CIS-LAMIVUDINE; (-)-2'-Deoxy-3'-thiacytidine; 4-amino-1-((2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl)pyrimidin-2(1H)-one; GR-109714X; 3'-Thia-2',3'-dideoxycytidine; (-)-BCH-189; Lamivudine [USAN:BAN:INN]; GR109714X; beta-L-3'-Thia-2',3'-dideoxycytidine; beta-L-2',3'-Dideoxy-3'-thiacytidine; (-)NGPB-21; 136891-12-8; 2',3'-Dideoxy-3'-thiacytidine; (-)-BCH 189; UNII-2T8Q726O95; HSDB 7155; GR 109714X; DTHC; LMV; Lamivir; Zefix; BCH 189; BCH189; BCH-790; DRG-0126; Epivir (TN); Epivir(TM); GG-714; HHA & 3TC; HHA & Lamivudine; Heptovir (TN); Lamivudine & GNA; Zeffix (TN); Epivir-HBV (TN); Lamivudine [USAN:INN:BAN]; Lamivudine (JAN/USP/INN); Lamivudine, (2S-cis)-Isomer; Beta-L-2',3'-Dideoxy-3'-thiacytidine; Beta-L-3'-Thia-2',3'-dideoxycytidine; Beta-L-(-)-2',3'-dideoxy-3'-thiacytidine & Sho-Saiko-To; (+/-)-(Cis)-1-[2-(Hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine; (+/-)-3TC; (+/-)-BCH-189; (+/-)-SddC; (-)-(2'R,5'S)-1-[2'-Hydroxymethyl-5'-(1,3-oxathiolanyl)]cytosine; (-)-1-((2R,5S)-2-(Hydroxymethyl)-1,3-oxathiolan-5-yl)cytosine; (-)-1-[(2R,5S)-2-(Hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine; (-)-NGPB-21; (-)-SddC; (-)-beta-L-2',3'-Dideoxy-3'-thiacytidine; (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one; 2',3' Dideoxy 3' thiacytidine; 2(1H)-Pyrimidinone, 4-amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl], (+/-)-(Cis); 2(1H)-Pyrimidinone, 4-amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl], (-)-(2R,5S); 2(1H)-Pyrimidinone, 4-amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl], (-)-(2R,5S) & Galanthus Nivalis Agglutinin (GNA); 2(1H)-Pyrimidinone, 4-amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl], (-)-(2R,5S) & Hippeastrum hybrid agglutinin(HHA); 3TC & GNA; 3TC & SST; 3TC (AIDS INITIATIVE) (AIDS INITIATIVE); 3TC and NV-01; 3TC, Zeffix, Heptovir, Epivir, Epivir-HBV, Lamivudine; 4-Amino-1-((2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl)-2(1H)-pyrimidinone; 4-amino-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2(1H)-one; 4-amino-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one; Efavirenz/lamivudine/tenofovir fumarate

Indication

Disease Entry	ICD 11	Status	REF
Chronic HBV infection	1E51.0Z	Approved	[1]
Chronic hepatitis B virus infection	N.A.	Approved	[2]
Human immunodeficiency virus infection	1C62	Approved	[1]
Human immunodeficiency virus-1 infection	1C62	Approved	[3]
Diarrhea	ME05.1	Investigative	[2]
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Therapeutic Class

Anti-HIV Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

229.26

Logarithm of the Partition Coefficient (xlogp)

-0.9

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [4]
Bioavailability: 86% of drug becomes completely available to its intended biological destination(s) [5]
Clearance: The renal clearance of drug is 199.7 +/- 56.9 mL/min []
Elimination: 67% of drug is excreted from urine in the unchanged form [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 5 - 7 hours [6]
Metabolism: The drug is metabolized via sulfotransferases []
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 21.80938 micromolar/kg/day [7]
Unbound Fraction: The unbound fraction of drug in plasma is 0.94% [6]
Vd: The volume of distribution (Vd) of drug is 1.3 +/- 0.4 L/kg []
Water Solubility: The ability of drug to dissolve in water is measured as 70 mg/mL [4]

Chemical Identifiers

Formula: C8H11N3O3S
IUPAC Name: 4-amino-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one
Canonical SMILES: C1[C@H](O[C@H](S1)CO)N2C=CC(=NC2=O)N
InChI: InChI=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+/m0/s1
InChIKey: JTEGQNOMFQHVDC-NKWVEPMBSA-N

Cross-matching ID

PubChem CID: 60825
ChEBI ID: CHEBI:63577
CAS Number: 134678-17-4
DrugBank ID: DB00709
TTD ID: D07TQV
VARIDT ID: DR00116
INTEDE ID: DR0912
ACDINA ID: D00347

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human immunodeficiency virus Reverse transcriptase (HIV RT)	TT84ETX	POL_HV1B1	Modulator	[8]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[9]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[10]
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[11]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Phosphorylcholine transferase A (PCYT1A)	DEQYXD4	PCY1A_HUMAN	Substrate	[12]
Phosphorylethanolamine transferase (PCYT2)	DEIX1PO	PCY2_HUMAN	Substrate	[12]
Deoxy-5'-nucleotidase 1 (NT5C)	DE4E31Z	NT5C_HUMAN	Substrate	[13]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Actin, aortic smooth muscle (ACTA2)	OTEDLG8E	ACTA_HUMAN	Gene/Protein Processing	[14]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Protein Interaction/Cellular Processes	[15]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L)	OTJKOMXE	BNI3L_HUMAN	Gene/Protein Processing	[16]
Collagen alpha-1(III) chain (COL3A1)	OTT1EMLM	CO3A1_HUMAN	Gene/Protein Processing	[14]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Gene/Protein Processing	[17]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Gene/Protein Processing	[17]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Gene/Protein Processing	[17]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Protein Interaction/Cellular Processes	[16]
G1/S-specific cyclin-D2 (CCND2)	OTDULQF9	CCND2_HUMAN	Gene/Protein Processing	[17]
G1/S-specific cyclin-E2 (CCNE2)	OTBBUKQQ	CCNE2_HUMAN	Gene/Protein Processing	[17]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Lamivudine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Lamivudine and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[18]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Lamivudine and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[19]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Lamivudine and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[20]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Lamivudine and Cannabidiol.	Epileptic encephalopathy [8A62]	[21]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Lamivudine and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[22]
Cobicistat	DM6L4H2	Moderate	Decreased metabolism of Lamivudine caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[18]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Lamivudine and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[23]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Lamivudine and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[24]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Lamivudine and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[25]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Lamivudine and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[26]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Lamivudine and Idelalisib.	Mature B-cell leukaemia [2A82]	[27]
Orlistat	DMRJSP8	Moderate	Altered absorption of Lamivudine caused by Orlistat.	Obesity [5B80-5B81]	[28]
Leflunomide	DMR8ONJ	Major	Increased risk of hepatotoxicity by the combination of Lamivudine and Leflunomide.	Rheumatoid arthritis [FA20]	[24]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Lamivudine and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[21]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Isomalt	E00383	88735	Binding agent; Coating agent; Diluent; Flavoring agent; Suspending agent
Isopropyl alcohol	E00070	3776	Antimicrobial preservative; Solvent
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Crospovidone	E00626	Not Available	Disintegrant
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 400	E00653	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polysorbate 80	E00665	Not Available	Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Water	E00035	962	Solvent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Lamivudine 150 mg tablet	150 mg	Oral Tablet	Oral
Lamivudine 100 mg tablet	100 mg	Oral Tablet	Oral
Lamivudine 300 mg tablet	300 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
2	Lamivudine FDA Label
3	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4	BDDCS applied to over 900 drugs
5	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
6	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
7	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
8	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
9	Relevance of the organic cation transporters 1 and 2 for antiretroviral drug therapy in human immunodeficiency virus infection. Drug Metab Dispos. 2008 Aug;36(8):1616-23.
10	The effect of ABCG2 V12M, Q141K and Q126X, known functional variants in vitro, on the disposition of lamivudine. Br J Clin Pharmacol. 2007 Nov;64(5):645-54.
11	Genetic variants of organic cation transporter 1 (OCT1) and OCT2 significantly reduce lamivudine uptake. Biopharm Drug Dispos. 2012 Apr;33(3):170-8.
12	Model for intracellular Lamivudine metabolism in peripheral blood mononuclear cells ex vivo and in human immunodeficiency virus type 1-infected adolescents. Antimicrob Agents Chemother. 2006 Aug;50(8):2686-94.
13	Nucleoside and nucleotide HIV reverse transcriptase inhibitors: 25 years after zidovudine. Antiviral Res. 2010 Jan;85(1):39-58.
14	Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B. J Hepatol. 2001 Dec;35(6):749-55. doi: 10.1016/s0168-8278(01)00218-5.
15	Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. doi: 10.1080/15216540400016286.
16	Nucleoside reverse transcriptase inhibitors induce a mitophagy-associated endothelial cytotoxicity that is reversed by coenzyme Q10 cotreatment. Toxicol Sci. 2013 Aug;134(2):323-34. doi: 10.1093/toxsci/kft105. Epub 2013 May 2.
17	Zidovudine induces S-phase arrest and cell cycle gene expression changes in human cells. Mutagenesis. 2005 Mar;20(2):139-46. doi: 10.1093/mutage/gei019. Epub 2005 Mar 22.
18	Cerner Multum, Inc. "Australian Product Information.".
19	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
20	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
21	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
22	Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
23	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
24	Canadian Pharmacists Association.
25	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
26	Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
27	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
28	MHRA. Medicines and Healthcare Products Regulatory Agency "Orlistat: theoretical interaction with antiretroviral HIV medicines.".