ranolazine Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
2359 95635-55-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • ranolazine hydrochloride
  • ranolazine
  • ranexa
  • renexa
  • ranolazine HCl
An acetanilide and piperazine derivative that functions as a SODIUM CHANNEL BLOCKER and prevents the release of enzymes during MYOCARDIAL ISCHEMIA. It is used in the treatment of ANGINA PECTORIS.
  • Molecular weight: 427.55
  • Formula: C24H33N3O4
  • CLOGP: 1.01
  • LIPINSKI: 0
  • HAC: 7
  • HDO: 2
  • TPSA: 74.27
  • ALOGS: -3.59
  • ROTB: 9

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
1.50 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 6 % Benet LZ, Broccatelli F, Oprea TI
BA (Bioavailability) 42.50 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 1.20 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 9.50 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.38 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1.80 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Jan. 27, 2006 FDA GILEAD

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
Angina pectoris 123.79 19.41 64 6652 28661 53313689
Electrocardiogram QT prolonged 102.20 19.41 72 6644 56331 53286019
Bradycardia 98.05 19.41 77 6639 70979 53271371
Chest pain 80.70 19.41 109 6607 190076 53152274
Torsade de pointes 67.83 19.41 33 6683 12972 53329378
Dizziness 61.85 19.41 141 6575 372118 52970232
Tonic clonic movements 48.23 19.41 14 6702 1308 53341042
Coronary artery disease 45.55 19.41 36 6680 33401 53308949
Chromaturia 45.22 19.41 27 6689 15923 53326427
Stent placement 41.55 19.41 16 6700 3571 53338779
Drug interaction 35.09 19.41 82 6634 219247 53123103
Syncope 32.74 19.41 54 6662 111939 53230411
Catheterisation cardiac 32.37 19.41 14 6702 4200 53338150
Hyperkalaemia 30.73 19.41 36 6680 54220 53288130
Urinary straining 29.77 19.41 5 6711 33 53342317
Hypotension 29.29 19.41 84 6632 253992 53088358
Therapeutic response unexpected 28.83 19.41 21 6695 17249 53325101
Serum serotonin increased 26.78 19.41 6 6710 197 53342153
Product residue present 26.13 19.41 12 6704 4144 53338206
Hypersensitivity pneumonitis 24.64 19.41 10 6706 2560 53339790
Ventricular tachycardia 23.91 19.41 19 6697 17743 53324607
Left ventricular hypertrophy 23.52 19.41 12 6704 5211 53337139
Sinus bradycardia 22.67 19.41 17 6699 14584 53327766
Myocardial infarction 21.45 19.41 42 6674 99312 53243038
Myopathy 21.39 19.41 14 6702 9678 53332672
Nodal rhythm 20.92 19.41 8 6708 1752 53340598
Hypoglycaemia 20.76 19.41 31 6685 58982 53283368
Cardiac arrest 20.71 19.41 40 6676 93627 53248723
Sinus arrest 20.56 19.41 8 6708 1836 53340514
Dyspnoea 20.00 19.41 134 6582 586098 52756252
Pulseless electrical activity 19.53 19.41 12 6704 7442 53334908

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
Angina pectoris 154.94 18.29 100 8747 31326 32473353
Dizziness 142.44 18.29 225 8622 209393 32295286
Chest pain 123.55 18.29 160 8687 123977 32380702
Syncope 83.07 18.29 112 8735 90012 32414667
Drug interaction 68.91 18.29 170 8677 218015 32286664
Coronary artery disease 53.90 18.29 67 8780 49639 32455040
Rhabdomyolysis 46.46 18.29 73 8774 67192 32437487
Chromaturia 45.44 18.29 35 8812 14443 32490236
Stent placement 45.35 18.29 23 8824 4552 32500127
Bradycardia 36.64 18.29 68 8779 71494 32433185
Cardiac failure congestive 34.26 18.29 73 8774 84779 32419900
Death 33.27 18.29 197 8650 382320 32122359
Dyspnoea 33.13 18.29 189 8658 361856 32142823
Electrocardiogram QT prolonged 28.71 18.29 44 8803 39597 32465082
Cardiac failure 28.33 18.29 71 8776 91602 32413077
Ventricular tachycardia 26.96 18.29 34 8813 25522 32479157
Myocardial infarction 26.74 18.29 85 8762 125591 32379088
Vertigo 25.13 18.29 32 8815 24251 32480428
Product residue present 24.57 18.29 13 8834 2805 32501874
Pyrexia 24.23 18.29 31 8816 319937 32184742
Tremor 24.12 18.29 62 8785 81215 32423464
Hypotension 23.90 18.29 119 8728 215991 32288688
Presyncope 23.17 18.29 26 8821 17275 32487404
Angina unstable 19.04 18.29 20 8827 12335 32492344
Loss of consciousness 18.54 18.29 57 8790 82650 32422029

Pharmacologic Action:

SourceCodeDescription
ATC C01EB18 CARDIOVASCULAR SYSTEM
CARDIAC THERAPY
OTHER CARDIAC PREPARATIONS
Other cardiac preparations
FDA EPC N0000175427 Anti-anginal
MeSH PA D002317 Cardiovascular Agents
MeSH PA D049990 Membrane Transport Modulators
MeSH PA D026941 Sodium Channel Blockers
FDA MoA N0000182137 Cytochrome P450 2D6 Inhibitors
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000187061 Organic Cation Transporter 2 Inhibitors
FDA MoA N0000190114 Cytochrome P450 3A Inhibitors
CHEBI has role CHEBI:38070 antiarrhythmic agent
CHEBI has role CHEBI:38633 Na channel blocker

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Angina pectoris indication 194828000
Cirrhosis of liver contraindication 19943007 DOID:5082
Torsades de pointes contraindication 31722008
Kidney disease contraindication 90708001 DOID:557
Prolonged QT interval contraindication 111975006
Congenital long QT syndrome contraindication 442917000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.4 acidic
pKa2 6.91 Basic
pKa3 2.91 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Sodium channel protein type 5 subunit alpha Ion channel BLOCKER IC50 5.17 CHEMBL CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 4.92 WOMBAT-PK
Multidrug resistance protein 1 Transporter WOMBAT-PK
Voltage-gated sodium channel Nav1.5 cardiac isoform Unclassified IC50 5.16 CHEMBL

External reference:

IDSource
4025078 VUID
N0000175343 NUI
D05700 KEGG_DRUG
95635-56-6 SECONDARY_CAS_RN
4025078 VANDF
C0073633 UMLSCUI
CHEBI:87681 CHEBI
CHEMBL1404 ChEMBL_ID
CHEMBL1526084 ChEMBL_ID
CHEMBL537649 ChEMBL_ID
D000069458 MESH_DESCRIPTOR_UI
DB00243 DRUGBANK_ID
56959 PUBCHEM_CID
7291 IUPHAR_LIGAND_ID
5946 INN_ID
A6IEZ5M406 UNII
356778 RXNORM
20936 MMSL
309260 MMSL
75657 MMSL
d05719 MMSL
011195 NDDF
420365007 SNOMEDCT_US
420624001 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Ranolazine Human Prescription Drug Label 1 27241-125 TABLET, EXTENDED RELEASE 500 mg ORAL ANDA 27 sections
Ranolazine Human Prescription Drug Label 1 27241-126 TABLET, EXTENDED RELEASE 1000 mg ORAL ANDA 27 sections
Ranolazine HUMAN PRESCRIPTION DRUG LABEL 1 42291-773 TABLET, FILM COATED, EXTENDED RELEASE 500 mg ORAL ANDA 22 sections
Ranolazine HUMAN PRESCRIPTION DRUG LABEL 1 42291-774 TABLET, FILM COATED, EXTENDED RELEASE 1000 mg ORAL ANDA 22 sections
Ranolazine HUMAN PRESCRIPTION DRUG LABEL 1 42571-324 TABLET, EXTENDED RELEASE 500 mg ORAL ANDA 26 sections
Ranolazine HUMAN PRESCRIPTION DRUG LABEL 1 42571-325 TABLET, EXTENDED RELEASE 1000 mg ORAL ANDA 26 sections
Ranexa HUMAN PRESCRIPTION DRUG LABEL 1 43353-880 TABLET, FILM COATED, EXTENDED RELEASE 500 mg ORAL NDA 28 sections
Ranolazine HUMAN PRESCRIPTION DRUG LABEL 1 45963-418 TABLET, FILM COATED, EXTENDED RELEASE 500 mg ORAL ANDA 27 sections
Ranolazine HUMAN PRESCRIPTION DRUG LABEL 1 45963-419 TABLET, FILM COATED, EXTENDED RELEASE 1000 mg ORAL ANDA 27 sections
RANOLAZINE HUMAN PRESCRIPTION DRUG LABEL 1 50228-423 TABLET, FILM COATED, EXTENDED RELEASE 500 mg ORAL ANDA 27 sections
RANOLAZINE HUMAN PRESCRIPTION DRUG LABEL 1 50228-424 TABLET, FILM COATED, EXTENDED RELEASE 1000 mg ORAL ANDA 27 sections
RANOLAZINE HUMAN PRESCRIPTION DRUG LABEL 1 51407-225 TABLET, FILM COATED, EXTENDED RELEASE 500 mg ORAL ANDA 27 sections
RANOLAZINE HUMAN PRESCRIPTION DRUG LABEL 1 51407-226 TABLET, FILM COATED, EXTENDED RELEASE 1000 mg ORAL ANDA 27 sections
Ranolazine HUMAN PRESCRIPTION DRUG LABEL 1 60687-549 TABLET, EXTENDED RELEASE 500 mg ORAL ANDA 27 sections
Ranexa HUMAN PRESCRIPTION DRUG LABEL 1 61958-1001 TABLET, FILM COATED, EXTENDED RELEASE 500 mg ORAL NDA 29 sections
Ranexa HUMAN PRESCRIPTION DRUG LABEL 1 61958-1002 TABLET, FILM COATED, EXTENDED RELEASE 1000 mg ORAL NDA 29 sections
Ranexa HUMAN PRESCRIPTION DRUG LABEL 1 61958-1003 TABLET, FILM COATED, EXTENDED RELEASE 500 mg ORAL NDA 28 sections
Ranexa HUMAN PRESCRIPTION DRUG LABEL 1 61958-1004 TABLET, FILM COATED, EXTENDED RELEASE 1000 mg ORAL NDA 28 sections
Ranolazine HUMAN PRESCRIPTION DRUG LABEL 1 63304-017 TABLET, EXTENDED RELEASE 500 mg ORAL ANDA 27 sections
Ranolazine HUMAN PRESCRIPTION DRUG LABEL 1 63304-018 TABLET, EXTENDED RELEASE 1000 mg ORAL ANDA 27 sections
Ranolazine HUMAN PRESCRIPTION DRUG LABEL 1 65162-376 TABLET, FILM COATED, EXTENDED RELEASE 500 mg ORAL ANDA 27 sections
Ranolazine HUMAN PRESCRIPTION DRUG LABEL 1 65162-379 TABLET, FILM COATED, EXTENDED RELEASE 1000 mg ORAL ANDA 27 sections
Ranolazine Human Prescription Drug Label 1 67877-525 TABLET, FILM COATED, EXTENDED RELEASE 500 mg ORAL ANDA 25 sections
Ranolazine Human Prescription Drug Label 1 67877-526 TABLET, FILM COATED, EXTENDED RELEASE 1000 mg ORAL ANDA 25 sections
Ranexa HUMAN PRESCRIPTION DRUG LABEL 1 68151-5004 TABLET, FILM COATED, EXTENDED RELEASE 500 mg ORAL NDA 27 sections
RANOLAZINE HUMAN PRESCRIPTION DRUG LABEL 1 68180-354 TABLET, FILM COATED, EXTENDED RELEASE 500 mg ORAL ANDA 26 sections
RANOLAZINE HUMAN PRESCRIPTION DRUG LABEL 1 68180-355 TABLET, FILM COATED, EXTENDED RELEASE 1000 mg ORAL ANDA 26 sections
Ranolazine HUMAN PRESCRIPTION DRUG LABEL 1 68462-319 TABLET, FILM COATED, EXTENDED RELEASE 500 mg ORAL ANDA 28 sections
Ranolazine HUMAN PRESCRIPTION DRUG LABEL 1 68462-320 TABLET, FILM COATED, EXTENDED RELEASE 1000 mg ORAL ANDA 28 sections
Ranolazine HUMAN PRESCRIPTION DRUG LABEL 1 69097-221 TABLET, FILM COATED, EXTENDED RELEASE 500 mg ORAL ANDA 25 sections