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

Stem definitionDrug idCAS RN
antihyperlipidaemic substances, HMG CoA reductase inhibitors 2214 147511-69-1

Description:

MoleculeDescription

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:

DoseUnitRoute
2 mg O

ADMET properties:

PropertyValueReference
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

Approvals:

DateAgencyCompanyOrphan
Aug. 3, 2009 FDA KOWA CO

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Myalgia 102.50 17.31 96 5667 124223 50475138
Hepatic function abnormal 81.20 17.31 49 5714 32632 50566729
Cerebral infarction 71.34 17.31 39 5724 21565 50577796
Liver disorder 47.50 17.31 37 5726 37185 50562176
Rhabdomyolysis 43.84 17.31 36 5727 38991 50560370
Haemorrhage subcutaneous 39.78 17.31 14 5749 2687 50596674
Altered state of consciousness 35.15 17.31 25 5738 21885 50577476
Blood creatine phosphokinase increased 33.17 17.31 26 5737 26341 50573020
Vulvovaginal inflammation 30.15 17.31 8 5755 594 50598767
Renal impairment 30.11 17.31 40 5723 75621 50523740
Interstitial lung disease 27.39 17.31 32 5731 53144 50546217
Lymphocyte stimulation test positive 26.66 17.31 7 5756 499 50598862
Anaemia 25.85 17.31 75 5688 252381 50346980
Enterocolitis 24.88 17.31 13 5750 6554 50592807
Akinesia 22.95 17.31 8 5755 1491 50597870
Glucose-6-phosphate dehydrogenase deficiency 21.65 17.31 5 5758 209 50599152
Alanine aminotransferase increased 21.30 17.31 37 5726 88322 50511039
Hypoglycaemia 20.81 17.31 28 5735 53553 50545808
Dyspnoea at rest 19.11 17.31 9 5754 3638 50595723
Drug eruption 18.94 17.31 18 5745 23588 50575773
Oropharyngeal discomfort 18.62 17.31 9 5754 3849 50595512
Toxic encephalopathy 18.31 17.31 10 5753 5505 50593856
Gastric dysplasia 18.27 17.31 3 5760 19 50599342
Aspartate aminotransferase increased 17.94 17.31 32 5731 77966 50521395
Platelet count decreased 17.86 17.31 37 5726 100689 50498672
Pemphigoid 17.67 17.31 10 5753 5897 50593464

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hepatic function abnormal 113.34 15.84 80 5889 39179 29529379
Interstitial lung disease 108.24 15.84 91 5878 57627 29510931
Cerebral infarction 87.15 15.84 57 5912 24618 29543940
Blood creatine phosphokinase increased 75.95 15.84 64 5905 40580 29527978
Myalgia 74.66 15.84 83 5886 73936 29494622
Rhabdomyolysis 44.53 15.84 58 5911 60750 29507808
Liver disorder 38.54 15.84 37 5932 27712 29540846
Angina pectoris 36.55 15.84 36 5933 27814 29540744
Cardiac failure 32.84 15.84 58 5911 79229 29489329
Hyperuricaemia 32.10 15.84 19 5950 6870 29561688
Renal impairment 25.65 15.84 53 5916 81280 29487278
Aspartate aminotransferase increased 25.11 15.84 44 5925 59681 29508877
Bronchitis chronic 23.26 15.84 9 5960 1265 29567293
Urine ketone body present 21.28 15.84 8 5961 1040 29567518
Immune-mediated myositis 21.26 15.84 9 5960 1594 29566964
Subdural haematoma 21.09 15.84 22 5947 18171 29550387
Death 18.81 15.84 25 5944 342059 29226499
Alanine aminotransferase increased 18.67 15.84 43 5926 70901 29497657
Pemphigoid 18.54 15.84 14 5955 7567 29560991
Pyelonephritis 17.90 15.84 12 5957 5381 29563177
Anaemia 17.88 15.84 84 5885 200867 29367691
Drug eruption 17.21 15.84 19 5950 16722 29551836
Pulmonary sepsis 16.80 15.84 8 5961 1866 29566692
Thrombotic cerebral infarction 16.75 15.84 5 5964 319 29568239
Prostate cancer 16.59 15.84 23 5946 25504 29543054
Drug-induced liver injury 16.36 15.84 21 5948 21634 29546924
Colon cancer 16.25 15.84 13 5956 7642 29560916
Decreased appetite 16.16 15.84 65 5904 145277 29423281
Blood ketone body increased 15.94 15.84 5 5964 377 29568181
Glycosylated haemoglobin increased 15.86 15.84 14 5955 9412 29559146

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hepatic function abnormal 181.90 14.89 122 11030 64191 64423389
Cerebral infarction 143.48 14.89 89 11063 40955 64446625
Interstitial lung disease 122.87 14.89 115 11037 97617 64389963
Myalgia 114.59 14.89 139 11013 158478 64329102
Blood creatine phosphokinase increased 91.59 14.89 78 11074 58480 64429100
Liver disorder 77.22 14.89 68 11084 53283 64434297
Rhabdomyolysis 77.17 14.89 87 11065 91639 64395941
Renal impairment 50.98 14.89 87 11065 134930 64352650
Angina pectoris 47.12 14.89 48 11104 45033 64442547
Hyperuricaemia 45.77 14.89 26 11126 10165 64477415
Anaemia 39.31 14.89 149 11003 378531 64109049
Aspartate aminotransferase increased 37.30 14.89 71 11081 119717 64367863
Cardiac failure 37.03 14.89 75 11077 132298 64355282
Alanine aminotransferase increased 35.64 14.89 76 11076 138955 64348625
Altered state of consciousness 35.39 14.89 38 11114 37864 64449716
Pemphigoid 35.13 14.89 24 11128 12962 64474618
Drug ineffective 33.45 14.89 59 11093 840188 63647392
Decreased appetite 31.94 14.89 114 11038 281175 64206405
Drug eruption 31.59 14.89 35 11117 36101 64451479
Toxicity to various agents 31.10 14.89 12 11140 363501 64124079
Platelet count decreased 29.29 14.89 79 11073 167632 64319948
Completed suicide 28.18 14.89 3 11149 224411 64263169
Haemorrhage subcutaneous 27.66 14.89 14 11138 4347 64483233
Blood lactate dehydrogenase increased 25.47 14.89 30 11122 33048 64454532
Enterocolitis 25.14 14.89 19 11133 11999 64475581
Immune-mediated myositis 24.31 14.89 11 11141 2667 64484913
Prostate cancer 24.26 14.89 23 11129 19772 64467808
Subdural haematoma 24.22 14.89 27 11125 28027 64459553
Colon cancer 24.16 14.89 19 11133 12720 64474860
Akinesia 22.85 14.89 11 11141 3068 64484512
Diabetes mellitus 22.68 14.89 41 11111 66433 64421147
Gastric cancer 22.46 14.89 14 11138 6479 64481101
Urine ketone body present 22.10 14.89 11 11141 3296 64484284
Lymphocyte stimulation test positive 22.06 14.89 8 11144 1098 64486482
Embolic stroke 22.03 14.89 14 11138 6697 64480883
Cardiac failure acute 21.98 14.89 20 11132 16324 64471256
Hypoglycaemia 21.72 14.89 48 11104 89844 64397736
Pyelonephritis 21.04 14.89 20 11132 17246 64470334
Upper respiratory tract inflammation 20.71 14.89 11 11141 3771 64483809
Vulvovaginal inflammation 19.77 14.89 6 11146 474 64487106
Pneumonia bacterial 19.44 14.89 18 11134 15017 64472563
Pancreatic carcinoma 18.66 14.89 15 11137 10358 64477222
Glycosylated haemoglobin increased 18.47 14.89 18 11134 16001 64471579
Embolic cerebral infarction 18.32 14.89 7 11145 1112 64486468
Blood triglycerides increased 17.75 14.89 19 11133 18847 64468733
Bronchitis chronic 17.57 14.89 10 11142 3922 64483658
Glucose-6-phosphate dehydrogenase deficiency 17.41 14.89 5 11147 326 64487254
Myopathy 16.98 14.89 18 11134 17662 64469918
Cerebral haemorrhage 16.77 14.89 31 11121 51059 64436521
Acute myocardial infarction 16.58 14.89 37 11115 69681 64417899
Diverticulum intestinal haemorrhagic 16.48 14.89 9 11143 3260 64484320
Immobilisation syndrome 16.46 14.89 5 11147 396 64487184
Gastric dysplasia 16.29 14.89 3 11149 25 64487555
Hyperkalaemia 16.02 14.89 46 11106 101083 64386497
Spinal compression fracture 15.92 14.89 16 11136 14759 64472821
Dyslipidaemia 15.86 14.89 13 11139 9229 64478351
Gamma-glutamyltransferase increased 15.38 14.89 29 11123 48481 64439099
Erythema multiforme 15.11 14.89 16 11136 15685 64471895

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
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 (View source of the data)

DiseaseRelationSNOMED_IDDOID
Hypercholesterolemia indication 13644009
Mixed hyperlipidemia indication 267434003
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 levelDissociation constantType (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 strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 1MG BASE LIVALO KOWA CO N022363 Aug. 3, 2009 RX TABLET ORAL 7022713 Feb. 19, 2024 ADJUNCITVE 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 ADJUNCITVE 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 ADJUNCITVE 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)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 1MG BASE LIVALO KOWA CO N022363 Aug. 3, 2009 RX TABLET ORAL May 16, 2022 NEW PATIENT POPULATION
EQ 2MG BASE LIVALO KOWA CO N022363 Aug. 3, 2009 RX TABLET ORAL May 16, 2022 NEW PATIENT POPULATION
EQ 4MG BASE LIVALO KOWA CO N022363 Aug. 3, 2009 RX TABLET ORAL May 16, 2022 NEW PATIENT POPULATION
EQ 1MG BASE LIVALO KOWA CO N022363 Aug. 3, 2009 RX TABLET ORAL Nov. 16, 2022 PEDIATRIC EXCLUSIVITY
EQ 2MG BASE LIVALO KOWA CO N022363 Aug. 3, 2009 RX TABLET ORAL Nov. 16, 2022 PEDIATRIC EXCLUSIVITY
EQ 4MG BASE LIVALO KOWA CO N022363 Aug. 3, 2009 RX TABLET ORAL Nov. 16, 2022 PEDIATRIC EXCLUSIVITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
3-hydroxy-3-methylglutaryl-coenzyme A reductase Enzyme INHIBITOR IC50 8.17 WOMBAT-PK CHEMBL
Retinoic acid receptor RXR-alpha Nuclear hormone receptor Kd 4.88 CHEMBL
3-hydroxy-3-methylglutaryl-coenzyme A reductase Enzyme IC50 4.98 CHEMBL

External reference:

IDSource
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:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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
Livalo HUMAN PRESCRIPTION DRUG LABEL 1 66869-104 TABLET, FILM COATED 1.05 mg ORAL NDA 26 sections
Livalo HUMAN PRESCRIPTION DRUG LABEL 1 66869-204 TABLET, FILM COATED 2.09 mg ORAL NDA 26 sections
Livalo HUMAN PRESCRIPTION DRUG LABEL 1 66869-404 TABLET, FILM COATED 4.18 mg ORAL NDA 26 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