Details of the Drug

General Information of Drug (ID: DM92S6N)

• Drug Name: Levamlodipine
• Synonyms: Levamlodipine (hypertension); S-amlodipine gentisate; Levamlodipine (hypertension), SK Chemicals; S-amlodipine (hypertension), SK Chemicals

Indication

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Phase 4	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 408.9
  Logarithm of the Partition Coefficient (xlogp); 3
  Rotatable Bond Count (rotbonds); 10
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 7
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 3-4 h [2]
  Bioavailability: The bioavailability of drug is 34% [2]
  Clearance: The apparent oral clearance of drug is 6.9 +/- 1.6 mL/min/kg [3]
  Elimination: The drug is 60% eliminated in urine with 10% eliminated as the unmetabolized form [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 30 - 50 hours [4]
  Metabolism: The drug is metabolized via the liver [4]
  Vd: The volume of distribution (Vd) of drug is 21 L/kg [3]
• Chemical Identifiers:
  Formula: C20H25ClN2O5
  IUPAC Name: 3-O-ethyl 5-O-methyl (4S)-2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
  Canonical SMILES: CCOC(=O)C1=C(NC(=C([C@@H]1C2=CC=CC=C2Cl)C(=O)OC)C)COCCN
  InChI: InChI=1S/C20H25ClN2O5/c1-4-28-20(25)18-15(11-27-10-9-22)23-12(2)16(19(24)26-3)17(18)13-7-5-6-8-14(13)21/h5-8,17,23H,4,9-11,22H2,1-3H3/t17-/m0/s1
  InChIKey: HTIQEAQVCYTUBX-KRWDZBQOSA-N
• Cross-matching ID:
  PubChem CID: 9822750
  ChEBI ID: CHEBI:53796
  CAS Number: 103129-82-4
  DrugBank ID: DB09237
  TTD ID: D0I2WV
  INTEDE ID: DR0931

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Voltage-gated L-type calcium channel (L-CaC)	TTXHYV6	NOUNIPROTAC	Modulator	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[6]

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Levamlodipine caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[7]
Arn-509	DMT81LZ	Major	Increased metabolism of Levamlodipine caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[8]
Gilteritinib	DMTI0ZO	Moderate	Decreased metabolism of Levamlodipine caused by Gilteritinib mediated inhibition of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[9]
Emapalumab	DMZG5WL	Moderate	Altered metabolism of Levamlodipine due to Emapalumab alters the formation of CYP450 enzymes.	Adaptive immunity immunodeficiency [4A01]	[9]
Troleandomycin	DMUZNIG	Moderate	Decreased metabolism of Levamlodipine caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[10]
Erdafitinib	DMI782S	Moderate	Increased metabolism of Levamlodipine caused by Erdafitinib mediated induction of CYP450 enzyme.	Bladder cancer [2C94]	[11]
Tucatinib	DMBESUA	Moderate	Decreased metabolism of Levamlodipine caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[10]
PF-04449913	DMSB068	Moderate	Decreased metabolism of Levamlodipine caused by PF-04449913 mediated inhibition of CYP450 enzyme.	Chronic myelomonocytic leukaemia [2A40]	[12]
Osilodrostat	DMIJC9X	Moderate	Decreased metabolism of Levamlodipine caused by Osilodrostat mediated inhibition of CYP450 enzyme.	Cushing syndrome [5A70]	[9]
Lumacaftor	DMCLWDJ	Major	Increased metabolism of Levamlodipine caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[8]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of Levamlodipine caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[10]
Polatuzumab vedotin	DMF6Y0L	Moderate	Decreased metabolism of Levamlodipine caused by Polatuzumab vedotin mediated inhibition of CYP450 enzyme.	Diffuse large B-cell lymphoma [2A81]	[13]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Levamlodipine caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[14]
Ripretinib	DM958QB	Moderate	Decreased metabolism of Levamlodipine caused by Ripretinib mediated inhibition of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[15]
Avapritinib	DMK2GZX	Moderate	Decreased metabolism of Levamlodipine caused by Avapritinib mediated inhibition of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[9]
Levobetaxolol	DMSREPX	Moderate	Increased risk of cardiac depression by the combination of Levamlodipine and Levobetaxolol.	Glaucoma [9C61]	[16]
MK-1439	DM215WE	Minor	Decreased metabolism of Levamlodipine caused by MK-1439 mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[17]
Lesinurad	DMUR64T	Moderate	Increased metabolism of Levamlodipine caused by Lesinurad mediated induction of CYP450 enzyme.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[18]
PF-06463922	DMKM7EW	Moderate	Decreased metabolism of Levamlodipine caused by PF-06463922 mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[19]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Levamlodipine caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[20]
LGX818	DMNQXV8	Moderate	Increased metabolism of Levamlodipine caused by LGX818 mediated induction of CYP450 enzyme.	Melanoma [2C30]	[21]
Ubrogepant	DM749I3	Moderate	Decreased metabolism of Levamlodipine caused by Ubrogepant mediated inhibition of CYP450 enzyme.	Migraine [8A80]	[22]
Siponimod	DM2R86O	Major	Increased risk of atrioventricular block by the combination of Levamlodipine and Siponimod.	Multiple sclerosis [8A40]	[15]
Ozanimod	DMT6AM2	Moderate	Increased risk of atrioventricular block by the combination of Levamlodipine and Ozanimod.	Multiple sclerosis [8A40]	[23]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Levamlodipine caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[10]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Levamlodipine caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[24]
Darolutamide	DMV7YFT	Minor	Decreased metabolism of Levamlodipine caused by Darolutamide mediated inhibition of CYP450 enzyme.	Prostate cancer [2C82]	[25]
Ixekizumab	DMXW92T	Moderate	Altered metabolism of Levamlodipine due to Ixekizumab alters the formation of CYP450 enzymes.	Psoriasis [EA90]	[9]
Sarilumab	DMOGNXY	Moderate	Altered metabolism of Levamlodipine due to Sarilumab alters the formation of CYP450 enzymes.	Rheumatoid arthritis [FA20]	[9]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Levamlodipine caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[10]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Levamlodipine caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[9]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Levamlodipine caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[15]
LEE011	DMMX75K	Moderate	Decreased metabolism of Levamlodipine caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[10]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Levamlodipine caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[26]

References

• [1] ClinicalTrials.gov (NCT01131546) Efficacy and Safety of Levamlodipine Besylate Compared to Amlodipine Maleate in Patients With Essential Hypertension. U.S. National Institutes of Health.
• [2] Cada DJ, Baker DE: Oritavancin diphosphate. Hosp Pharm. 2014 Dec;49(11):1049-60. doi: 10.1310/hjp4911-1049.
• [3] Laufen H, Leitold M: Enantioselective disposition of oral amlodipine in healthy volunteers. Chirality. 1994;6(7):531-6. doi: 10.1002/chir.530060704.
• [4] FDA Approved Drug Products: Conjupri Levamlodipine Oral Tablets
• [5] Effects of (S)-amlodipine and (R)-amlodipine on L-type calcium channel current of rat ventricular myocytes and cytosolic calcium of aortic smooth muscle cells. Pharmazie. 2008 Jun;63(6):470-4.
• [6] Amlodipine metabolism in human liver microsomes and roles of CYP3A4/5 in the dihydropyridine dehydrogenation. Drug Metab Dispos. 2014 Feb;42(2):245-9.
• [7] Product Information. Tibsovo (ivosidenib). Agios Pharmaceuticals, Cambridge, MA.
• [8] Product Information. Mycobutin (rifabutin). Pharmacia and Upjohn, Kalamazoo, MI.
• [9] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [10] Canadian Pharmacists Association.
• [11] Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
• [12] Product Information. Daurismo (glasdegib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
• [13] Product Information. Polivy (polatuzumab vedotin). Genentech, South San Francisco, CA.
• [14] Product Information. Tazverik (tazemetostat). Epizyme, Inc, Cambridge, MA.
• [15] Cerner Multum, Inc. "Australian Product Information.".
• [16] Henry M, Kay MM, Viccellio P "Cardiogenic shock associated with calcium-channel and beta blockers: reversal with intravenous calcium chloride." Am J Emerg Med 3 (1985): 334-6. [PMID: 2860911]
• [17] Product Information. Pifeltro (doravirine). Merck & Company Inc, Whitehouse Station, NJ.
• [18] Product Information. Zurampic (lesinurad). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
• [19] Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
• [20] Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
• [21] Product Information. Braftovi (encorafenib). Array BioPharma Inc., Boulder, CO.
• [22] Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
• [23] Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
• [24] EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
• [25] Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
• [26] Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.