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

Stem definition	Drug id	CAS RN
antihyperlipidaemic substances, HMG CoA reductase inhibitors	2214	147511-69-1

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: nisvastatin itavastatin pitavastatin calcium hydrate pitavastatin pitavastatin calcium livalo	Pitavastatin competitively inhibits HMG-CoA reductase, which is a rate-determining enzyme involved with biosynthesis of cholesterol, in a manner of competition with the substrate so that it inhibits cholesterol synthesis in the liver. As a result, the expression of LDL-receptors followed by the uptake of LDL from blood to liver is accelerated and then the plasma TC decreases. Further, the sustained inhibition of cholesterol synthesis in the liver decreases levels of very low density lipoproteins. Molecular weight: 421.47 Formula: C25H24FNO4 CLOGP: 3.59 LIPINSKI: 0 HAC: 5 HDO: 3 TPSA: 90.65 ALOGS: -5.03 ROTB: 8 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

nisvastatin
itavastatin
pitavastatin calcium hydrate
pitavastatin
pitavastatin calcium
livalo

Pitavastatin competitively inhibits HMG-CoA reductase, which is a rate-determining enzyme involved with biosynthesis of cholesterol, in a manner of competition with the substrate so that it inhibits cholesterol synthesis in the liver. As a result, the expression of LDL-receptors followed by the uptake of LDL from blood to liver is accelerated and then the plasma TC decreases. Further, the sustained inhibition of cholesterol synthesis in the liver decreases levels of very low density lipoproteins.

Molecular weight: 421.47
Formula: C25H24FNO4
CLOGP: 3.59
LIPINSKI: 0
HAC: 5
HDO: 3
TPSA: 90.65
ALOGS: -5.03
ROTB: 8

Status: OFP

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

Drug dosage:

Dose	Unit	Route
2	mg	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	4	Hosey CM, Chan R, Benet LZ
Vd (Volume of distribution)	0.90 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	5.85 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.01 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	4.60 hours	Lombardo F, Berellini G, Obach RS
BA (Bioavailability)	0.60 %	Kawashima H, Watanabe R, Esaki T, Kuroda M, Nagao C, Natsume-Kitatani Y, Ohashi R, Komura H, Mizuguchi K
BA (Bioavailability)	0.80 %	Kawashima H, Watanabe R, Esaki T, Kuroda M, Nagao C, Natsume-Kitatani Y, Ohashi R, Komura H, Mizuguchi K

Approvals:

Date	Agency	Company	Orphan
Aug. 3, 2009	FDA	KOWA CO
June 26, 2015	PMDA	Kowa Company, Ltd.

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
Myalgia	139.04	17.01	118	6519	146411	63335974
Hepatic function abnormal	94.87	17.01	55	6582	37087	63445298
Cerebral infarction	84.86	17.01	44	6593	23849	63458536
Rhabdomyolysis	49.09	17.01	39	6598	43912	63438473
Renal impairment	40.46	17.01	48	6589	88307	63394078
Liver disorder	40.37	17.01	38	6599	53649	63428736
Haemorrhage subcutaneous	39.59	17.01	14	6623	2969	63479416
Interstitial lung disease	39.41	17.01	40	6597	61868	63420517
Altered state of consciousness	38.49	17.01	27	6610	25203	63457182
Blood creatine phosphokinase increased	33.97	17.01	27	6610	30403	63451982
Anaemia	31.51	17.01	84	6553	293346	63189039
Muscle spasms	30.72	17.01	57	6580	156093	63326292
Platelet count decreased	28.86	17.01	47	6590	116075	63366310
Vulvovaginal inflammation	28.20	17.01	8	6629	831	63481554
Akinesia	27.08	17.01	9	6628	1584	63480801
Lymphocyte stimulation test positive	27.08	17.01	7	6630	512	63481873
Enterocolitis	23.73	17.01	13	6624	7845	63474540
Decreased appetite	22.17	17.01	67	6570	250985	63231400
Alanine aminotransferase increased	21.81	17.01	39	6598	103731	63378654
Glucose-6-phosphate dehydrogenase deficiency	21.56	17.01	5	6632	232	63482153
Aspartate aminotransferase increased	20.36	17.01	35	6602	90242	63392143
Toxic encephalopathy	20.19	17.01	11	6626	6568	63475817
Hypoglycaemia	20.17	17.01	28	6609	60037	63422348
Pemphigoid	19.06	17.01	11	6626	7333	63475052
Dyspnoea at rest	18.88	17.01	9	6628	4070	63478315
Cardiac failure acute	18.88	17.01	12	6625	9511	63472874
Vessel puncture site haematoma	18.49	17.01	4	6633	135	63482250
Gastric dysplasia	18.02	17.01	3	6634	23	63482362
Drug eruption	17.27	17.01	18	6619	28676	63453709

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
Hepatic function abnormal	126.01	17.63	88	6664	44275	34905904
Interstitial lung disease	116.10	17.63	98	6654	65184	34884995
Myalgia	102.18	17.63	102	6650	84008	34866171
Cerebral infarction	93.53	17.63	61	6691	27394	34922785
Blood creatine phosphokinase increased	83.10	17.63	69	6683	44788	34905391
Rhabdomyolysis	47.41	17.63	62	6690	68101	34882078
Liver disorder	39.93	17.63	40	6712	32957	34917222
Cardiac failure	36.32	17.63	64	6688	91184	34858995
Angina pectoris	34.28	17.63	36	6716	31327	34918852
Visceral pain	30.76	17.63	6	6746	62	34950117
Hyperuricaemia	30.15	17.63	19	6733	8024	34942155
Immune-mediated myositis	29.16	17.63	12	6740	2071	34948108
Aspartate aminotransferase increased	24.98	17.63	46	6706	67737	34882442
Renal impairment	22.92	17.63	54	6698	94459	34855720
Bronchitis chronic	22.48	17.63	9	6743	1447	34948732
Subdural haematoma	21.53	17.63	23	6729	20398	34929781
Urine ketone body present	20.91	17.63	8	6744	1140	34949039
Decreased appetite	20.83	17.63	75	6677	166317	34783862
Death	20.78	17.63	28	6724	398021	34552158
Anaemia	19.61	17.63	93	6659	233242	34716937
Pemphigoid	19.58	17.63	15	6737	8651	34941528
Pyelonephritis	19.18	17.63	13	6739	6202	34943977
Drug-induced liver injury	18.14	17.63	25	6727	28807	34921372

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
Hepatic function abnormal	210.67	14.55	136	12550	72971	79658731
Myalgia	166.75	14.55	175	12511	185466	79546236
Cerebral infarction	164.56	14.55	98	12588	45578	79686124
Interstitial lung disease	146.07	14.55	130	12556	112470	79619232
Blood creatine phosphokinase increased	101.29	14.55	84	12602	66006	79665696
Rhabdomyolysis	86.73	14.55	94	12592	103037	79628665
Liver disorder	71.61	14.55	72	12614	72345	79659357
Renal impairment	58.08	14.55	96	12590	157687	79574015
Anaemia	47.48	14.55	167	12519	444848	79286854
Cardiac failure	46.31	14.55	86	12600	154756	79576946
Angina pectoris	44.94	14.55	48	12638	51684	79680018
Hyperuricaemia	44.24	14.55	26	12660	11773	79719929
Decreased appetite	42.25	14.55	135	12551	342283	79389419
Aspartate aminotransferase increased	40.20	14.55	76	12610	138565	79593137
Pemphigoid	38.02	14.55	26	12660	15289	79716413
Altered state of consciousness	36.90	14.55	40	12646	43782	79687920
Platelet count decreased	36.06	14.55	89	12597	194575	79537127
Alanine aminotransferase increased	35.19	14.55	79	12607	162491	79569211
Toxicity to various agents	32.85	14.55	13	12673	421527	79310175
Drug ineffective	32.65	14.55	78	12608	1080835	78650867
Immune-mediated myositis	31.84	14.55	14	12672	3453	79728249
Drug eruption	30.03	14.55	36	12650	43899	79687803
Visceral pain	29.50	14.55	6	12680	96	79731606
Cardiac failure acute	28.85	14.55	24	12662	18905	79712797
Completed suicide	28.45	14.55	3	12683	245764	79485938
Haemorrhage subcutaneous	27.47	14.55	14	12672	4795	79726907
Lymphocyte stimulation test positive	26.38	14.55	9	12677	1124	79730578
Akinesia	26.04	14.55	12	12674	3300	79728402
Colon cancer	25.49	14.55	20	12666	14503	79717199
Subdural haematoma	25.26	14.55	28	12658	31406	79700296
Blood lactate dehydrogenase increased	24.99	14.55	31	12655	39139	79692563
Muscle spasms	24.40	14.55	72	12614	174658	79557044
Upper respiratory tract inflammation	23.79	14.55	12	12674	4023	79727679
Pyelonephritis	23.38	14.55	22	12664	20366	79711336
Enterocolitis	23.37	14.55	19	12667	14493	79717209
Urine ketone body present	22.19	14.55	11	12675	3554	79728148
Embolic cerebral infarction	21.63	14.55	8	12678	1263	79730439
Hypoglycaemia	21.55	14.55	49	12637	101545	79630157
Diabetes mellitus	21.51	14.55	42	12644	78348	79653354
Embolic stroke	21.13	14.55	14	12672	7812	79723890
Immobilisation syndrome	19.59	14.55	6	12680	532	79731170
Vulvovaginal inflammation	19.50	14.55	6	12680	540	79731162
Prostate cancer	19.12	14.55	25	12661	33243	79698459
Spinal compression fracture	18.87	14.55	18	12668	16940	79714762
Pneumonia bacterial	18.69	14.55	19	12667	19312	79712390
Acute myocardial infarction	18.43	14.55	39	12647	76997	79654705
Pancreatic carcinoma	18.21	14.55	16	12670	13561	79718141
Diverticulum intestinal haemorrhagic	18.16	14.55	10	12676	4001	79727701
Gastric cancer	17.82	14.55	14	12672	10165	79721537
Myopathy	17.71	14.55	19	12667	20544	79711158
Glucose-6-phosphate dehydrogenase deficiency	17.43	14.55	5	12681	353	79731349
Confusional state	17.40	14.55	15	12671	317982	79413720
Blood triglycerides increased	17.35	14.55	19	12667	21021	79710681
Pneumonia aspiration	17.31	14.55	35	12651	66932	79664770
Cerebral haemorrhage	17.17	14.55	32	12654	57641	79674061
Bronchitis chronic	17.13	14.55	10	12676	4472	79727230
Glycosylated haemoglobin increased	16.95	14.55	18	12668	19242	79712460
Erythema multiforme	16.43	14.55	17	12669	17634	79714068
Gastric dysplasia	16.14	14.55	3	12683	29	79731673
Hyperglycaemia	16.13	14.55	35	12651	70300	79661402
Femoral neck fracture	15.92	14.55	13	12673	9971	79721731
Gamma-glutamyltransferase increased	15.86	14.55	30	12656	54650	79677052
Ketosis	15.25	14.55	6	12680	1120	79730582
Vessel puncture site haematoma	15.14	14.55	4	12682	208	79731494
Infusion related reaction	15.03	14.55	9	12677	230228	79501474
Hyperkalaemia	14.88	14.55	46	12640	114352	79617350
Therapeutic product effect decreased	14.59	14.55	4	12682	163859	79567843

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	C10AA08	CARDIOVASCULAR SYSTEM LIPID MODIFYING AGENTS LIPID MODIFYING AGENTS, PLAIN HMG CoA reductase inhibitors
FDA MoA	N0000000121	Hydroxymethylglutaryl-CoA Reductase Inhibitors
FDA EPC	N0000175589	HMG-CoA Reductase Inhibitor
MeSH PA	D000924	Anticholesteremic Agents
MeSH PA	D000963	Antimetabolites
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D019161	Hydroxymethylglutaryl-CoA Reductase Inhibitors
MeSH PA	D000960	Hypolipidemic Agents
MeSH PA	D057847	Lipid Regulating Agents
CHEBI has role	CHEBI:22586	antioxidants

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

Disease	Relation	SNOMED_ID	DOID
Hypercholesterolemia	indication	13644009
Mixed hyperlipidemia	indication	267434003
Familial hypercholesterolemia	indication	398036000	DOID:13810
Dehydration	contraindication	34095006
Hypothyroidism	contraindication	40930008	DOID:1459
Low blood pressure	contraindication	45007003
Acute infectious disease	contraindication	63171007
Disorder of muscle	contraindication	129565002	DOID:423
Liver function tests abnormal	contraindication	166603001
Impaired renal function disorder	contraindication	197663003
Hemorrhagic cerebral infarction	contraindication	230706003
Disease of liver	contraindication	235856003	DOID:409
Sepsis syndrome	contraindication	238150007
Rhabdomyolysis	contraindication	240131006
Pregnancy, function	contraindication	289908002
Surgical procedure	contraindication	387713003
Breastfeeding (mother)	contraindication	413712001
Traumatic injury	contraindication	417746004
Uncontrolled Epilepsy	contraindication

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	4.05	acidic
pKa2	13.01	acidic
pKa3	13.99	acidic
pKa4	5.11	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
EQ 1MG BASE	LIVALO	KOWA CO	N022363	Aug. 3, 2009	RX	TABLET	ORAL	7022713	Feb. 19, 2024	ADJUNCTIVE THERAPY TO DIET TO REDUCE ELEVATED TOTAL CHOLESTEROL, LOW-DENSITY LIPOPROTEIN CHOLESTEROL, APOLIPOPROTEIN B, TRIGLYCERIDES AND TO INCREASE HDL-C IN ADULT PATIENTS WITH PRIMARY HYPERLIPIDEMIA OR MIXED DYSLIPIDEMIA
EQ 2MG BASE	LIVALO	KOWA CO	N022363	Aug. 3, 2009	RX	TABLET	ORAL	7022713	Feb. 19, 2024	ADJUNCTIVE THERAPY TO DIET TO REDUCE ELEVATED TOTAL CHOLESTEROL, LOW-DENSITY LIPOPROTEIN CHOLESTEROL, APOLIPOPROTEIN B, TRIGLYCERIDES AND TO INCREASE HDL-C IN ADULT PATIENTS WITH PRIMARY HYPERLIPIDEMIA OR MIXED DYSLIPIDEMIA
EQ 4MG BASE	LIVALO	KOWA CO	N022363	Aug. 3, 2009	RX	TABLET	ORAL	7022713	Feb. 19, 2024	ADJUNCTIVE THERAPY TO DIET TO REDUCE ELEVATED TOTAL CHOLESTEROL, LOW-DENSITY LIPOPROTEIN CHOLESTEROL, APOLIPOPROTEIN B, TRIGLYCERIDES AND TO INCREASE HDL-C IN ADULT PATIENTS WITH PRIMARY HYPERLIPIDEMIA OR MIXED DYSLIPIDEMIA

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
3-hydroxy-3-methylglutaryl-coenzyme A reductase	Enzyme	P04035	HMDH_HUMAN	INHIBITOR	IC50	8.17	WOMBAT-PK	CHEMBL
Retinoic acid receptor RXR-alpha	Nuclear hormone receptor	P19793	RXRA_HUMAN		Kd	4.88	CHEMBL
Nuclear receptor subfamily 4 group A member 2	Nuclear other	P43354	NR4A2_HUMAN		EC50	6.92	CHEMBL
3-hydroxy-3-methylglutaryl-coenzyme A reductase	Enzyme		HMDH_RAT		IC50	4.98	CHEMBL

External reference:

ID	Source
4029463	VUID
N0000180308	NUI
D01862	KEGG_DRUG
147526-32-7	SECONDARY_CAS_RN
4029463	VANDF
4037418	VANDF
C1101838	UMLSCUI
CHEBI:32020	CHEBI
PV9	PDB_CHEM_ID
CHEMBL1201753	ChEMBL_ID
CHEMBL1237061	ChEMBL_ID
DB08860	DRUGBANK_ID
C108475	MESH_SUPPLEMENTAL_RECORD_UI
5282452	PUBCHEM_CID
3035	IUPHAR_LIGAND_ID
7730	INN_ID
M5681Q5F9P	UNII
861612	RXNORM
173089	MMSL
27200	MMSL
33902	MMSL
d07637	MMSL
013206	NDDF
013429	NDDF
443585001	SNOMEDCT_US
443586000	SNOMEDCT_US
700402009	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
ZYPITAMAG	HUMAN PRESCRIPTION DRUG LABEL	1	25208-201	TABLET, FILM COATED	2 mg	ORAL	NDA	26 sections
ZYPITAMAG	HUMAN PRESCRIPTION DRUG LABEL	1	25208-201	TABLET, FILM COATED	2 mg	ORAL	NDA	26 sections
ZYPITAMAG	HUMAN PRESCRIPTION DRUG LABEL	1	25208-202	TABLET, FILM COATED	4 mg	ORAL	NDA	26 sections
ZYPITAMAG	HUMAN PRESCRIPTION DRUG LABEL	1	25208-202	TABLET, FILM COATED	4 mg	ORAL	NDA	26 sections
Livalo	HUMAN PRESCRIPTION DRUG LABEL	1	66869-104	TABLET, FILM COATED	1.05 mg	ORAL	NDA	32 sections
Livalo	HUMAN PRESCRIPTION DRUG LABEL	1	66869-104	TABLET, FILM COATED	1.05 mg	ORAL	NDA	32 sections
Livalo	HUMAN PRESCRIPTION DRUG LABEL	1	66869-204	TABLET, FILM COATED	2.09 mg	ORAL	NDA	32 sections
Livalo	HUMAN PRESCRIPTION DRUG LABEL	1	66869-204	TABLET, FILM COATED	2.09 mg	ORAL	NDA	32 sections
Livalo	HUMAN PRESCRIPTION DRUG LABEL	1	66869-404	TABLET, FILM COATED	4.18 mg	ORAL	NDA	32 sections
Livalo	HUMAN PRESCRIPTION DRUG LABEL	1	66869-404	TABLET, FILM COATED	4.18 mg	ORAL	NDA	32 sections
ZYPITAMAG	HUMAN PRESCRIPTION DRUG LABEL	1	70771-1117	TABLET, FILM COATED	2 mg	ORAL	NDA	1 sections
ZYPITAMAG	HUMAN PRESCRIPTION DRUG LABEL	1	70771-1117	TABLET, FILM COATED	2 mg	ORAL	NDA	1 sections
ZYPITAMAG	HUMAN PRESCRIPTION DRUG LABEL	1	70771-1118	TABLET, FILM COATED	4 mg	ORAL	NDA	1 sections
ZYPITAMAG	HUMAN PRESCRIPTION DRUG LABEL	1	70771-1118	TABLET, FILM COATED	4 mg	ORAL	NDA	1 sections