lapatinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
tyrosine kinase inhibitors	1548	231277-92-2

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: lapatinib tosilate hydrate lapatinib tosilate lapatinib GW 572016X tyverb lapatinib ditosylate GW572016F lapatinib ditosilate lapatinib ditosilate hydrate lapatinib ditosylate hydrate	A quinazoline derivative that inhibits EPIDERMAL GROWTH FACTOR RECEPTOR and HER2 (RECEPTOR, ERBB-2) tyrosine kinases. It is used for the treatment of advanced or metastatic breast cancer, where tumors overexpress HER2. Molecular weight: 581.06 Formula: C29H26ClFN4O4S CLOGP: 5.82 LIPINSKI: 2 HAC: 8 HDO: 2 TPSA: 106.35 ALOGS: -4.42 ROTB: 11 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

lapatinib tosilate hydrate
lapatinib tosilate
lapatinib
GW 572016X
tyverb
lapatinib ditosylate
GW572016F
lapatinib ditosilate
lapatinib ditosilate hydrate
lapatinib ditosylate hydrate

A quinazoline derivative that inhibits EPIDERMAL GROWTH FACTOR RECEPTOR and HER2 (RECEPTOR, ERBB-2) tyrosine kinases. It is used for the treatment of advanced or metastatic breast cancer, where tumors overexpress HER2.

Molecular weight: 581.06
Formula: C29H26ClFN4O4S
CLOGP: 5.82
LIPINSKI: 2
HAC: 8
HDO: 2
TPSA: 106.35
ALOGS: -4.42
ROTB: 11

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
1.25	g	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	0.00 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	1 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	30.73 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	0 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

Date	Agency	Company	Orphan
June 10, 2008	EMA
March 13, 2007	FDA	NOVARTIS PHARMS CORP

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Palmar-plantar erythrodysaesthesia syndrome	1776.19	20.05	563	22311	19535	50562715
Diarrhoea	1457.85	20.05	1535	21339	586941	49995309
Disease progression	778.19	20.05	503	22371	95363	50486887
Metastases to central nervous system	595.48	20.05	215	22659	11067	50571183
Malignant neoplasm progression	359.21	20.05	275	22599	67849	50514401
Neutropenia	297.90	20.05	350	22524	147615	50434635
Paronychia	282.63	20.05	98	22776	4466	50577784
Metastases to liver	257.83	20.05	142	22732	19962	50562288
Metastases to lung	251.26	20.05	115	22759	10905	50571345
Dehydration	232.45	20.05	314	22560	152135	50430115
Metastases to bone	190.09	20.05	112	22762	17883	50564367
Ejection fraction decreased	187.10	20.05	112	22762	18408	50563842
Skin toxicity	185.67	20.05	69	22805	3844	50578406
Vomiting	176.56	20.05	531	22343	460227	50122023
Breast cancer metastatic	169.10	20.05	86	22788	10278	50571972
Blood bilirubin increased	161.34	20.05	126	22748	31912	50550338
Metastases to lymph nodes	149.80	20.05	70	22804	6954	50575296
Skin fissures	141.62	20.05	72	22802	8596	50573654
Death	134.79	20.05	386	22488	324993	50257257
Mucosal inflammation	126.96	20.05	121	22753	40021	50542229
Gastrointestinal toxicity	126.41	20.05	55	22819	4622	50577628
Jaundice	120.36	20.05	98	22776	26331	50555919
Metastases to skin	110.57	20.05	36	22838	1347	50580903
Dry skin	108.66	20.05	115	22759	43076	50539174
Stomatitis	107.08	20.05	176	22698	101168	50481082
Rash	104.55	20.05	432	22442	437039	50145211
Hypokalaemia	104.21	20.05	161	22713	87831	50494419
Hepatic function abnormal	100.47	20.05	97	22777	32584	50549666
Nausea	89.23	20.05	583	22291	704815	49877435
Febrile neutropenia	86.62	20.05	157	22717	97510	50484740
Lymphangiosis carcinomatosa	83.08	20.05	28	22846	1168	50581082
Hepatotoxicity	78.44	20.05	78	22796	27148	50555102
Pyrexia	77.35	20.05	358	22516	379845	50202405
Haematotoxicity	75.21	20.05	46	22828	7849	50574401
Decreased appetite	73.10	20.05	228	22646	200695	50381555
Alanine aminotransferase increased	72.02	20.05	137	22737	88222	50494028
Drug hypersensitivity	70.38	20.05	14	22860	250996	50331254
Cardiotoxicity	69.65	20.05	42	22832	6985	50575265
Hyperbilirubinaemia	67.11	20.05	46	22828	9524	50572726
Drug ineffective	62.75	20.05	178	22696	819155	49763095
Weight increased	61.56	20.05	9	22865	201882	50380368
Condition aggravated	61.07	20.05	29	22845	297029	50285221
Joint swelling	56.80	20.05	20	22854	245266	50336984
Arthralgia	54.73	20.05	71	22803	438631	50143619
Pleural effusion	54.08	20.05	116	22758	81338	50500912
Fall	53.28	20.05	44	22830	334888	50247362
Dermatitis acneiform	52.92	20.05	29	22845	4028	50578222
Therapeutic product effect decreased	49.51	20.05	3	22871	136047	50446203
Completed suicide	47.72	20.05	3	22871	131886	50450364
Skin exfoliation	47.67	20.05	67	22807	33545	50548705
Maternal exposure during pregnancy	46.71	20.05	8	22866	159770	50422480
Neoplasm progression	45.70	20.05	61	22813	29096	50553154
Off label use	44.07	20.05	93	22781	474333	50107917
Superior vena cava syndrome	41.26	20.05	14	22860	596	50581654
Breast cancer	40.61	20.05	71	22803	42819	50539431
Neurotoxicity	40.19	20.05	41	22833	14699	50567551
Asthenia	40.16	20.05	264	22610	318778	50263472
Biliary dilatation	40.06	20.05	19	22855	1950	50580300
Aspartate aminotransferase increased	39.60	20.05	100	22774	77898	50504352
Cellulitis	39.37	20.05	94	22780	70704	50511546
Neoplasm	38.07	20.05	27	22847	5901	50576349
Metastasis	37.90	20.05	24	22850	4351	50577899
Product dose omission issue	37.66	20.05	18	22856	183820	50398430
Onychalgia	37.64	20.05	14	22860	781	50581469
Sinusitis	37.62	20.05	15	22859	170543	50411707
Leukopenia	36.84	20.05	89	22785	67439	50514811
Glossodynia	35.56	20.05	5	22869	115564	50466686
Pain	35.07	20.05	139	22735	578764	50003486
Neuropathy peripheral	34.37	20.05	109	22765	96648	50485602
Second primary malignancy	34.36	20.05	27	22847	6887	50575363
Transaminases	34.12	20.05	8	22866	84	50582166
Nail disorder	34.01	20.05	31	22843	9677	50572573
Ascites	33.47	20.05	59	22815	35802	50546448
Limbal stem cell deficiency	33.30	20.05	6	22868	13	50582237
Hypertension	33.22	20.05	28	22846	211175	50371075
Feeling abnormal	33.11	20.05	8	22866	125484	50456766
Thrombocytopenia	32.59	20.05	129	22745	127544	50454706
Musculoskeletal stiffness	32.35	20.05	9	22865	128472	50453778
Radiation necrosis	31.82	20.05	10	22864	333	50581917
Metastatic neoplasm	31.04	20.05	20	22854	3734	50578516
Drug interaction	30.74	20.05	27	22847	199594	50382656
Onycholysis	30.70	20.05	14	22860	1314	50580936
Therapeutic product effect incomplete	30.53	20.05	3	22871	91512	50490738
Recurrent cancer	29.88	20.05	15	22859	1742	50580508
Metastases to spine	28.26	20.05	17	22857	2814	50579436
Left ventricular dysfunction	28.23	20.05	29	22845	10477	50571773
Tumour marker increased	28.21	20.05	19	22855	3821	50578429
Nail infection	28.18	20.05	15	22859	1966	50580284
Pericardial effusion	27.73	20.05	45	22829	25544	50556706
Breast neoplasm	27.72	20.05	13	22861	1300	50580950
Injection site pain	27.53	20.05	8	22866	111016	50471234
Radiation pneumonitis	27.52	20.05	13	22861	1322	50580928
Neoplasm malignant	27.48	20.05	43	22831	23672	50558578
Plantar erythema	27.10	20.05	8	22866	215	50582035
Erythema	26.81	20.05	134	22740	146280	50435970
Performance status decreased	26.37	20.05	17	22857	3178	50579072
Exposure during pregnancy	26.10	20.05	11	22863	121004	50461246
Infusion related reaction	26.02	20.05	23	22851	169534	50412716
Brain oedema	26.00	20.05	30	22844	12340	50569910
Breast cancer recurrent	25.98	20.05	18	22856	3790	50578460
Wound	25.55	20.05	8	22866	105786	50476464
Swelling	25.50	20.05	32	22842	200840	50381410
Discomfort	24.78	20.05	9	22865	108371	50473879
Botryomycosis	24.40	20.05	5	22869	26	50582224
Arthritis	23.93	20.05	5	22869	86716	50495534
Anal erythema	23.93	20.05	7	22867	182	50582068
Dyschezia	23.82	20.05	13	22861	1791	50580459
Skin mass	23.27	20.05	19	22855	5116	50577134
Neoplasm recurrence	23.06	20.05	14	22860	2355	50579895
Ingrowing nail	22.98	20.05	13	22861	1919	50580331
Asthma	22.97	20.05	6	22868	89331	50492919
Alopecia	22.71	20.05	48	22826	244999	50337251
Abdominal pain	21.96	20.05	182	22692	236046	50346204
Anxiety	21.81	20.05	29	22845	177577	50404673
Central nervous system lesion	21.63	20.05	24	22850	9465	50572785
Brain neoplasm	21.53	20.05	16	22858	3757	50578493
Contusion	21.45	20.05	12	22862	112171	50470079
Bone cancer metastatic	21.38	20.05	6	22868	134	50582116
Disease recurrence	21.33	20.05	35	22839	20046	50562204
Jaundice cholestatic	21.27	20.05	18	22856	5093	50577157
Psoriasis	21.18	20.05	3	22871	68997	50513253
Hyperhidrosis	21.17	20.05	7	22867	89419	50492831
General physical health deterioration	21.08	20.05	123	22751	142311	50439939
Hormone receptor positive breast cancer	20.98	20.05	8	22866	478	50581772
Malignant pleural effusion	20.73	20.05	13	22861	2317	50579933
Abdominal discomfort	20.13	20.05	47	22827	231594	50350656

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Duodenal ulcer perforation	52.66	33.86	12	1076	1494	29571945
Diarrhoea	43.87	33.86	57	1031	332641	29240798
Metastases to lung	36.85	33.86	13	1075	7842	29565597

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Palmar-plantar erythrodysaesthesia syndrome	1116.28	20.04	371	15167	28448	64454746
Diarrhoea	1014.11	20.04	1038	14500	721666	63761528
Disease progression	497.38	20.04	348	15190	141332	64341862
Metastases to central nervous system	367.86	20.04	135	15403	13777	64469417
Malignant neoplasm progression	270.46	20.04	221	15317	112650	64370544
Metastases to lung	237.59	20.04	101	15437	15163	64468031
Metastases to liver	197.09	20.04	102	15436	23839	64459355
Dehydration	167.25	20.04	232	15306	216531	64266663
Breast cancer metastatic	161.85	20.04	62	15476	7107	64476087
Paronychia	160.50	20.04	60	15478	6432	64476762
Metastases to bone	150.96	20.04	81	15457	20354	64462840
Vomiting	140.71	20.04	367	15171	550750	63932444
Ejection fraction decreased	135.37	20.04	85	15453	28622	64454572
Gastrointestinal toxicity	134.54	20.04	50	15488	5272	64477922
Metastases to lymph nodes	123.53	20.04	54	15484	8663	64474531
Metastases to skin	122.00	20.04	34	15504	1418	64481776
Neutropenia	104.41	20.04	198	15340	239426	64243768
Skin toxicity	100.43	20.04	43	15495	6559	64476635
Skin fissures	96.72	20.04	48	15490	10258	64472936
Mucosal inflammation	86.06	20.04	90	15448	62494	64420700
Death	81.43	20.04	278	15260	482427	64000767
Nausea	80.32	20.04	387	15151	785413	63697781
Blood bilirubin increased	74.22	20.04	80	15458	57473	64425721
Hypokalaemia	72.96	20.04	116	15422	121787	64361407
Rash	71.17	20.04	257	15281	458292	64024902
Hepatotoxicity	68.86	20.04	65	15473	39897	64443297
Lymphangiosis carcinomatosa	68.52	20.04	23	15515	1798	64481396
Jaundice	67.10	20.04	70	15468	48442	64434752
Cardiotoxicity	62.89	20.04	36	15502	10238	64472956
Haematotoxicity	62.82	20.04	39	15499	12857	64470337
Dry skin	60.56	20.04	68	15470	51093	64432101
Stomatitis	59.74	20.04	100	15438	109505	64373689
Hyperbilirubinaemia	51.64	20.04	42	15496	21163	64462031
Asthenia	41.42	20.04	208	15330	427836	64055358
Condition aggravated	41.39	20.04	19	15519	372407	64110787
Dermatitis acneiform	39.77	20.04	25	15513	8418	64474776
Onycholysis	36.47	20.04	14	15524	1612	64481582
Decreased appetite	36.38	20.04	149	15389	281140	64202054
Biliary dilatation	35.24	20.04	15	15523	2253	64480941
Tumour marker increased	35.15	20.04	17	15521	3433	64479761
Drug interaction	35.06	20.04	22	15516	362061	64121133
Metastases to spine	34.27	20.04	17	15521	3626	64479568
Transaminases	34.03	20.04	7	15531	76	64483118
Onychalgia	33.73	20.04	11	15527	786	64482408
Drug hypersensitivity	33.62	20.04	8	15530	237807	64245387
Fall	33.14	20.04	31	15507	416795	64066399
Limbal stem cell deficiency	32.62	20.04	6	15532	34	64483160
Abdominal pain	31.73	20.04	154	15384	312221	64170973
Weight increased	30.50	20.04	7	15531	213341	64269853
Hepatic function abnormal	30.23	20.04	55	15483	64258	64418936
Hormone receptor positive breast cancer	29.27	20.04	8	15530	310	64482884
Second primary malignancy	29.12	20.04	24	15514	12313	64470881
Neoplasm progression	27.29	20.04	41	15497	40923	64442271
Metastasis	27.17	20.04	17	15521	5678	64477516
Breast cancer recurrent	27.14	20.04	13	15525	2570	64480624
Neurotoxicity	26.73	20.04	33	15505	27371	64455823
Disease recurrence	26.11	20.04	35	15503	31475	64451719
Osteonecrosis of jaw	25.32	20.04	39	15499	39786	64443408
Metastases to the mediastinum	25.17	20.04	8	15530	526	64482668
Recurrent cancer	25.11	20.04	12	15526	2361	64480833
Pyrexia	24.97	20.04	224	15314	558420	63924774
Botryomycosis	23.93	20.04	5	15533	59	64483135
Cholangitis	23.40	20.04	20	15518	10782	64472412
Pleural effusion	23.06	20.04	75	15463	126484	64356710
Pericardial effusion	22.96	20.04	37	15501	39217	64443977
Left ventricular dysfunction	22.60	20.04	24	15514	16930	64466264
Hypertension	22.13	20.04	18	15520	259243	64223951
Breast cancer	22.07	20.04	31	15507	29117	64454077
Arthralgia	22.03	20.04	46	15492	442214	64040980
Neoplasm	21.63	20.04	16	15522	7015	64476179
Skin mass	21.48	20.04	16	15522	7090	64476104
Cellulitis	21.29	20.04	60	15478	93597	64389597
Radiation pneumonitis	21.28	20.04	12	15526	3316	64479878
Joint swelling	20.94	20.04	13	15525	215369	64267825
Nail disorder	20.82	20.04	17	15521	8607	64474587
Plantar erythema	20.69	20.04	6	15532	289	64482905
Performance status decreased	20.66	20.04	14	15524	5350	64477844
Gastric neoplasm	20.55	20.04	6	15532	296	64482898
Metastatic neoplasm	20.54	20.04	13	15525	4429	64478765
Onychoclasis	20.14	20.04	13	15525	4579	64478615

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01EH01	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS Human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors
FDA MoA	N0000175076	Protein Kinase Inhibitors
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D047428	Protein Kinase Inhibitors
FDA EPC	N0000175605	Kinase Inhibitor

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID
HER2-positive carcinoma of breast	indication	427685000
Torsades de pointes	contraindication	31722008
Hypokalemia	contraindication	43339004
Hepatic failure	contraindication	59927004
Interstitial pneumonia	contraindication	64667001
Left heart failure	contraindication	85232009
Prolonged QT interval	contraindication	111975006
Liver function tests abnormal	contraindication	166603001
Hypomagnesemia	contraindication	190855004
Drug-induced hepatitis	contraindication	235876009
Pregnancy, function	contraindication	289908002
Severe diarrhea	contraindication	409587002
Breastfeeding (mother)	contraindication	413712001
Congenital long QT syndrome	contraindication	442917000

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	5.62	Basic
pKa2	4.99	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Epidermal growth factor receptor	Kinase	P00533	EGFR_HUMAN	INHIBITOR	Kd	9.04	CHEMBL	CHEMBL
Receptor tyrosine-protein kinase erbB-2	Kinase	P04626	ERBB2_HUMAN	INHIBITOR	Kd	8.15	CHEMBL	CHEMBL
Platelet-derived growth factor receptor beta	Kinase	P09619	PGFRB_HUMAN		IC50	5.07	CHEMBL
Tyrosine-protein kinase ABL1	Kinase	P00519	ABL1_HUMAN		IC50	4.64	CHEMBL
Solute carrier organic anion transporter family member 1B1	Transporter	Q9Y6L6	SO1B1_HUMAN				WOMBAT-PK
Cyclin-dependent kinase 2	Kinase	P24941	CDK2_HUMAN		IC50	4.96	CHEMBL
Insulin receptor	Kinase	P06213	INSR_HUMAN	AGONIST	IC50	4.77	CHEMBL
Receptor tyrosine-protein kinase erbB-4	Kinase	Q15303	ERBB4_HUMAN		Kd	7.27	CHEMBL
Serine/threonine-protein kinase 10	Kinase	O94804	STK10_HUMAN		Kd	5.59	CHEMBL
Receptor-interacting serine/threonine-protein kinase 2	Kinase	O43353	RIPK2_HUMAN		Kd	5.44	CHEMBL
STE20-like serine/threonine-protein kinase	Kinase	Q9H2G2	SLK_HUMAN		Kd	5.48	CHEMBL
Dual specificity mitogen-activated protein kinase kinase 7	Kinase	O14733	MP2K7_HUMAN		Kd	5.36	CHEMBL
Receptor tyrosine-protein kinase erbB-3	Kinase	P21860	ERBB3_HUMAN		Kd	5.26	CHEMBL
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta	Kinase	O00750	P3C2B_HUMAN		Kd	6.17	CHEMBL
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma	Kinase	O75747	P3C2G_HUMAN		Kd	5.12	CHEMBL
Phosphatidylinositol 4-kinase beta	Kinase	Q9UBF8	PI4KB_HUMAN		Kd	6.03	CHEMBL
Multidrug resistance protein 1	Transporter	P08183	MDR1_HUMAN				WOMBAT-PK
Dual specificity mitogen-activated protein kinase kinase 5	Kinase	Q13163	MP2K5_HUMAN		Kd	5.96	CHEMBL
ATP-binding cassette sub-family G member 2	Transporter	Q9UNQ0	ABCG2_HUMAN				WOMBAT-PK
Tubulin alpha-1A chain	Structural		TBA1A_RAT		Kd	7.27	CHEMBL

External reference:

ID	Source
4026029	VUID
N0000179782	NUI
D04024	KEGG_DRUG
388082-78-8	SECONDARY_CAS_RN
4026029	VANDF
C1506770	UMLSCUI
FMM	PDB_CHEM_ID
CHEMBL554	ChEMBL_ID
CHEMBL1201179	ChEMBL_ID
D000077341	MESH_DESCRIPTOR_UI
DB01259	DRUGBANK_ID
5692	IUPHAR_LIGAND_ID
8378	INN_ID
0VUA21238F	UNII
208908	PUBCHEM_CID
480167	RXNORM
339254	MMSL
d06672	MMSL
012020	NDDF
012022	NDDF
425466009	SNOMEDCT_US
425820005	SNOMEDCT_US
426238006	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
TYKERB	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0671	TABLET	250 mg	ORAL	NDA	34 sections
TYKERB	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0671	TABLET	250 mg	ORAL	NDA	34 sections
Lapatinib	Human Prescription Drug Label	1	68180-801	TABLET	250 mg	ORAL	ANDA	28 sections