Details of the Drug

General Information of Drug (ID: DM0L594)

• Drug Name: Ivabradine
• Synonyms: Ivabradine; 155974-00-8; Procoralan; Corlanor; Corlentor; UNII-3H48L0LPZQ; S 16257; S-16257; S-16257-2; S 16257-2; 3H48L0LPZQ; CHEMBL471737; CHEBI:85966; C27H36N2O5; 7,8-Dimethoxy-3-(3-(((4,5-dimethoxybenzocyclobutan-1-yl)methyl)methylamino)propyl)-1,3,4,5-tetrahydro-2H-benzazepin-2-one; S-16260-2; s16257; (S)-3-(3-(((3,4-Dimethoxybicyclo(4.2.0)octa-1,3,5-trien-7-yl)methyl)methylamino)propyl)-1,3,4,5-tetrahydro-7,8-dimethoxy-2H-3-benzazepin-2-one; Ivabradine [INN]

Indication

Disease Entry	ICD 11	Status	REF
Angina pectoris	BA40	Approved	[1]
Chronic heart failure	BD1Z	Approved	[2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 468.6
  Logarithm of the Partition Coefficient (xlogp); 2.4
  Rotatable Bond Count (rotbonds); 10
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 6
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
  Clearance: The renal clearance of drug is 70 mL/min []
  Elimination: 4% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 2 hours [4]
  Metabolism: The drug is metabolized via oxidation in the gut and liver by cytochrome P450 3A4 enzyme []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.4573 micromolar/kg/day [5]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.28% [4]
  Vd: The volume of distribution (Vd) of drug is 100 L []
• Chemical Identifiers:
  Formula: C27H36N2O5
  IUPAC Name: 3-[3-[[(7S)-3,4-dimethoxy-7-bicyclo[4.2.0]octa-1,3,5-trienyl]methyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepin-4-one
  Canonical SMILES: CN(CCCN1CCC2=CC(=C(C=C2CC1=O)OC)OC)C[C@H]3CC4=CC(=C(C=C34)OC)OC
  InChI: InChI=1S/C27H36N2O5/c1-28(17-21-11-20-14-25(33-4)26(34-5)16-22(20)21)8-6-9-29-10-7-18-12-23(31-2)24(32-3)13-19(18)15-27(29)30/h12-14,16,21H,6-11,15,17H2,1-5H3/t21-/m1/s1
  InChIKey: ACRHBAYQBXXRTO-OAQYLSRUSA-N
• Cross-matching ID:
  PubChem CID: 132999
  ChEBI ID: CHEBI:85966
  CAS Number: 155974-00-8
  DrugBank ID: DB09083
  TTD ID: D0S9QA
  INTEDE ID: DR0897
  ACDINA ID: D00338
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Hyperpolarization cyclic nucleotide-gated channel (HCN)	TTKLW9S	NOUNIPROTAC	Inhibitor	[6]
Sinus node I(f) channel (SA node IfC)	TTFCQYU	NOUNIPROTAC	Modulator	[7]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[8]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Gene/Protein Processing	[9]

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Major	Increased risk of ventricular arrhythmias by the combination of Ivabradine and Ivosidenib.	Acute myeloid leukaemia [2A60]	[10]
Arn-509	DMT81LZ	Major	Increased metabolism of Ivabradine caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[10]
Gilteritinib	DMTI0ZO	Major	Increased risk of ventricular arrhythmias by the combination of Ivabradine and Gilteritinib.	Acute myeloid leukaemia [2A60]	[10]
Oliceridine	DM6MDCF	Major	Increased risk of ventricular arrhythmias by the combination of Ivabradine and Oliceridine.	Acute pain [MG31]	[10]
Levalbuterol	DM5YBO1	Moderate	Increased risk of prolong QT interval by the combination of Ivabradine and Levalbuterol.	Asthma [CA23]	[11]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Ivabradine caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[12]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Ivabradine caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[10]
Tucatinib	DMBESUA	Major	Decreased metabolism of Ivabradine caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[12]
PF-04449913	DMSB068	Major	Increased risk of ventricular arrhythmias by the combination of Ivabradine and PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[10]
Osilodrostat	DMIJC9X	Major	Increased risk of ventricular arrhythmias by the combination of Ivabradine and Osilodrostat.	Cushing syndrome [5A70]	[10]
Lumacaftor	DMCLWDJ	Major	Increased metabolism of Ivabradine caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[10]
MK-8228	DMOB58Q	Major	Decreased metabolism of Ivabradine caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[10]
Deutetrabenazine	DMUPFLI	Major	Increased risk of ventricular arrhythmias by the combination of Ivabradine and Deutetrabenazine.	Dystonic disorder [8A02]	[10]
Ingrezza	DMVPLNC	Major	Increased risk of ventricular arrhythmias by the combination of Ivabradine and Ingrezza.	Dystonic disorder [8A02]	[10]
Stiripentol	DMMSDOY	Major	Decreased metabolism of Ivabradine caused by Stiripentol mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[10]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of Ivabradine caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[10]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Ivabradine caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[10]
Fostemsavir	DM50ILT	Major	Increased risk of ventricular arrhythmias by the combination of Ivabradine and Fostemsavir.	Human immunodeficiency virus disease [1C60-1C62]	[10]
Berotralstat	DMWA2DZ	Major	Decreased metabolism of Ivabradine caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[10]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Ivabradine caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[10]
Osimertinib	DMRJLAT	Major	Increased risk of ventricular arrhythmias by the combination of Ivabradine and Osimertinib.	Lung cancer [2C25]	[10]
Selpercatinib	DMZR15V	Major	Increased risk of ventricular arrhythmias by the combination of Ivabradine and Selpercatinib.	Lung cancer [2C25]	[10]
IPI-145	DMWA24P	Major	Decreased metabolism of Ivabradine caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[10]
LGX818	DMNQXV8	Major	Increased risk of ventricular arrhythmias by the combination of Ivabradine and LGX818.	Melanoma [2C30]	[10]
Siponimod	DM2R86O	Major	Increased risk of atrioventricular block by the combination of Ivabradine and Siponimod.	Multiple sclerosis [8A40]	[12]
Ozanimod	DMT6AM2	Major	Increased risk of ventricular arrhythmias by the combination of Ivabradine and Ozanimod.	Multiple sclerosis [8A40]	[13]
Fedratinib	DM4ZBK6	Major	Decreased metabolism of Ivabradine caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[10]
Rucaparib	DM9PVX8	Major	Increased risk of ventricular arrhythmias by the combination of Ivabradine and Rucaparib.	Ovarian cancer [2C73]	[10]
Triclabendazole	DMPWGBR	Major	Increased risk of ventricular arrhythmias by the combination of Ivabradine and Triclabendazole.	Parasitic worm infestation [1F90]	[10]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Ivabradine caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[14]
Macimorelin	DMQYJIR	Major	Increased risk of ventricular arrhythmias by the combination of Ivabradine and Macimorelin.	Pituitary gland disorder [5A60-5A61]	[10]
Lefamulin	DME6G97	Major	Decreased metabolism of Ivabradine caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[15]
Relugolix	DMK7IWL	Major	Increased risk of ventricular arrhythmias by the combination of Ivabradine and Relugolix.	Prostate cancer [2C82]	[10]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Ivabradine caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[10]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Ivabradine caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[10]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Ivabradine caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[10]
LEE011	DMMX75K	Major	Decreased metabolism of Ivabradine caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[15]
Pitolisant	DM8RFNJ	Major	Increased risk of ventricular arrhythmias by the combination of Ivabradine and Pitolisant.	Somnolence [MG42]	[10]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Ivabradine caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[16]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Ivabradine caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[10]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Maltitol	E00423	493591	Binding agent; Coating agent; Diluent; Flavoring agent
Dextrin	E00359	62698	Binding agent; Diluent; Microencapsulating agent; Stiffening agent; Suspending agent; Viscosity-controlling agent
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Glycerin	E00026	753	Antimicrobial preservative; Emollient; Flavoring agent; Humectant; Lubricant; Plasticizing agent; Solvent; Suppository base; Tonicity agent; Viscosity-controlling agent
Hypromellose	E00634	Not Available	Coating agent
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 6000	E00655	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
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
Colcothar yellow	E00436	518696	Colorant
Haematite red	E00236	14833	Colorant
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Pregelatinized starch	E00674	Not Available	Binding agent; Diluent; Disintegrant

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Ivabradine Hydrochloride eq 5mg base tablet	eq 5mg base	Tablet	Oral
Ivabradine Hydrochloride eq 7.5mg base tablet	eq 7.5mg base	Tablet	Oral
Ivabradine 5 mg tablet	5 mg	Oral Tablet	Oral
Ivabradine 7.5 mg tablet	7.5 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2357).
• [2] Ivabradine FDA Label
• [3] BDDCS applied to over 900 drugs
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] 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
• [6] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [7] Ivabradine - the first selective sinus node If channel inhibitor in the treatment of stable angina. Int J Clin Pract. 2006 February; 60(2): 222-228.
• [8] Ivabradine: new drug. Best avoided in stable angina. Prescrire Int. 2007 Apr;16(88):53-6.
• [9] Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
• [10] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [11] Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
• [12] Cerner Multum, Inc. "Australian Product Information.".
• [13] Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
• [14] Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
• [15] Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67. [PMID: 19667002]
• [16] Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.