levofolinic acid Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
4384 80433-71-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • levoleucovorin calcium pentahydrate
  • levoleucovorin
  • calcium levofolinate
  • levoleucovorin calcium
  • levofolene
  • L-Folinic acid
  • levofolinic acid
  • sodium levofolinate
A folate analog consisting of the pharmacologically active isomer of LEUCOVORIN.
  • Molecular weight: 473.45
  • Formula: C20H23N7O7
  • CLOGP: -3.49
  • LIPINSKI: 2
  • HAC: 14
  • HDO: 7
  • TPSA: 215.55
  • ALOGS: -3.20
  • ROTB: 9

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
30 mg O
30 mg P
30 mg P

ADMET properties:

PropertyValueReference
MRTD (Maximum Recommended Therapeutic Daily Dose) 11.43 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution) 0.27 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 4.10 mL/min/kg Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1.10 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
March 7, 2008 FDA SPECTRUM PHARMS

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
Dermatitis acneiform 230.13 29.00 59 5045 4011 46676947
Neutrophil count decreased 225.85 29.00 105 4999 43321 46637637
Stomatitis 180.98 29.00 105 4999 68192 46612766
Paronychia 153.76 29.00 44 5060 4522 46676436
Colon cancer 142.29 29.00 49 5055 9220 46671738
Neutropenia 126.94 29.00 113 4991 143091 46537867
Decreased appetite 106.74 29.00 118 4986 193718 46487240
Peripheral sensory neuropathy 105.58 29.00 36 5068 6567 46674391
Hyperammonaemia 96.60 29.00 31 5073 4685 46676273
Gastrointestinal perforation 77.61 29.00 24 5080 3213 46677745
Diarrhoea 73.55 29.00 177 4927 559425 46121533
Neuropathy peripheral 71.12 29.00 67 5037 90826 46590132
Drug ineffective 53.48 29.00 6 5098 677832 46003126
Thrombocytopenia 52.79 29.00 67 5037 126514 46554444
Disease progression 50.77 29.00 56 5048 91244 46589714
Mucosal inflammation 49.52 29.00 38 5066 38938 46642020
Febrile neutropenia 49.13 29.00 56 5048 94571 46586387
White blood cell count decreased 47.73 29.00 60 5044 112171 46568787
Hypomagnesaemia 45.42 29.00 29 5075 22181 46658777
Bone marrow failure 44.58 29.00 32 5072 29637 46651321
Large intestine perforation 44.54 29.00 20 5084 7560 46673398
Disseminated intravascular coagulation 44.38 29.00 27 5077 18978 46661980
Hypertensive crisis 44.27 29.00 24 5080 13591 46667367
Palmar-plantar erythrodysaesthesia syndrome 42.56 29.00 27 5077 20424 46660534
Extrasystoles 42.44 29.00 17 5087 4852 46676106
Colorectal cancer 40.44 29.00 11 5093 936 46680022
Infusion related reaction 39.70 29.00 52 5052 101156 46579802
Dry skin 39.45 29.00 34 5070 40982 46639976
Interstitial lung disease 38.79 29.00 38 5066 53911 46627047
Skin disorder 35.72 29.00 25 5079 22238 46658720
Leukopenia 33.02 29.00 39 5065 68304 46612654
Leukoencephalopathy 31.54 29.00 13 5091 3991 46676967
Posterior reversible encephalopathy syndrome 31.52 29.00 20 5084 15121 46665837
Pyrexia 30.17 29.00 95 5009 348707 46332251
Hypertransaminasaemia 29.78 29.00 12 5092 3476 46677482

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
Dermatitis acneiform 500.48 28.15 144 8658 5545 29938131
Paronychia 426.92 28.15 111 8691 2900 29940776
Interstitial lung disease 375.08 28.15 228 8574 59969 29883707
Stomatitis 270.50 28.15 156 8646 37123 29906553
Neutrophil count decreased 244.12 28.15 153 8649 42301 29901375
Peripheral sensory neuropathy 213.35 28.15 76 8726 5825 29937851
Neuropathy peripheral 191.01 28.15 161 8641 70314 29873362
Decreased appetite 154.20 28.15 204 8598 149706 29793970
Hypomagnesaemia 132.39 28.15 74 8728 16524 29927152
Neutropenia 124.49 28.15 170 8632 128370 29815306
Colon cancer 121.63 28.15 56 8746 8316 29935360
Colorectal cancer 112.73 28.15 35 8767 1744 29941932
Hyperammonaemia 99.65 28.15 43 8759 5477 29938199
Diarrhoea 92.90 28.15 260 8542 333843 29609833
Gastrointestinal perforation 91.95 28.15 36 8766 3580 29940096
Dry skin 85.93 28.15 63 8739 22391 29921285
Skin disorder 85.10 28.15 49 8753 11559 29932117
Leukopenia 81.19 28.15 91 8711 56068 29887608
White blood cell count decreased 67.79 28.15 102 8700 83845 29859831
Nausea 63.44 28.15 211 8591 296746 29646930
Disease progression 62.99 28.15 96 8706 79778 29863898
Disseminated intravascular coagulation 62.64 28.15 52 8750 22119 29921557
Palmar-plantar erythrodysaesthesia syndrome 57.50 28.15 42 8760 14828 29928848
Drug ineffective 56.98 28.15 15 8787 340372 29603304
Dysgeusia 51.76 28.15 49 8753 24752 29918924
Hypersensitivity 46.95 28.15 68 8734 53960 29889716
Bone marrow failure 45.98 28.15 50 8752 29735 29913941
Thrombocytopenia 42.10 28.15 111 8691 136933 29806743
Toxicity to various agents 37.94 28.15 4 8798 177179 29766497
Necrotising fasciitis 37.72 28.15 19 8783 3430 29940246
Febrile neutropenia 37.52 28.15 91 8711 106602 29837074
Malaise 35.78 28.15 119 8683 166843 29776833
Rectal perforation 34.96 28.15 10 8792 374 29943302
Tumour perforation 33.25 28.15 9 8793 274 29943402
Small intestinal perforation 33.18 28.15 14 8788 1685 29941991
Rectal cancer 32.98 28.15 15 8787 2161 29941515
Colony stimulating factor therapy 32.52 28.15 8 8794 165 29943511
Fixed eruption 30.84 28.15 12 8790 1172 29942504
Duodenal stenosis 30.72 28.15 8 8794 209 29943467
Proteinuria 30.11 28.15 30 8772 16115 29927561
Malignant ascites 29.92 28.15 9 8793 402 29943274
Erythema 28.21 28.15 67 8735 77384 29866292
Cholinergic syndrome 28.19 28.15 9 8793 491 29943185

Pharmacologic Action:

SourceCodeDescription
ATC V03AF04 VARIOUS
ALL OTHER THERAPEUTIC PRODUCTS
ALL OTHER THERAPEUTIC PRODUCTS
Detoxifying agents for antineoplastic treatment
ATC V03AF10 VARIOUS
ALL OTHER THERAPEUTIC PRODUCTS
ALL OTHER THERAPEUTIC PRODUCTS
Detoxifying agents for antineoplastic treatment
FDA CS M0008658 Folic Acid
MeSH PA D000931 Antidotes
MeSH PA D020011 Protective Agents
FDA EPC N0000178369 Folate Analog
CHEBI has role CHEBI:25212 metabolites
CHEBI has role CHEBI:35610 cytostatic

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Megaloblastic anemia indication 53165003 DOID:13382
Folic acid deficiency indication 190633005
Adjunct to Fluorouracil Treatment of Colorectal Cancer indication
Sulfadiazine Toxicity indication
Pyrimethamine Toxicity indication
Bone Marrow Suppression due to Folic Acid Antagonism indication
Methotrexate Toxicity indication
Trimetrexate Toxicity indication
Trimethoprim Toxicity indication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.61 acidic
pKa2 5.29 acidic
pKa3 10.26 acidic
pKa4 12.96 acidic
pKa5 4.59 Basic
pKa6 2.23 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

None

External reference:

IDSource
4028507 VUID
N0000182085 NUI
68538-85-2 SECONDARY_CAS_RN
4028507 VANDF
4028508 VANDF
C2342719 UMLSCUI
CHEBI:63606 CHEBI
FOZ PDB_CHEM_ID
CHEMBL1908361 ChEMBL_ID
CHEMBL1908841 ChEMBL_ID
CHEMBL3707343 ChEMBL_ID
D058766 MESH_DESCRIPTOR_UI
DB11596 DRUGBANK_ID
135403647 PUBCHEM_CID
6883 INN_ID
990S25980Y UNII
1648126 RXNORM
132962 MMSL
21723 MMSL
35726 MMSL
d05842 MMSL
005532 NDDF
005533 NDDF
395769006 SNOMEDCT_US
429990006 SNOMEDCT_US
433468002 SNOMEDCT_US
782479008 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Levoleucovorin HUMAN PRESCRIPTION DRUG LABEL 1 0143-9558 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 23 sections
Levoleucovorin HUMAN PRESCRIPTION DRUG LABEL 1 0781-3201 INJECTION, SOLUTION 175 mg INTRAVENOUS ANDA 23 sections
LEVOLEUCOVORIN HUMAN PRESCRIPTION DRUG LABEL 1 16714-890 INJECTION, SOLUTION 175 mg INTRAVENOUS ANDA 25 sections
LEVOLEUCOVORIN HUMAN PRESCRIPTION DRUG LABEL 1 16714-915 INJECTION, SOLUTION 250 mg INTRAVENOUS ANDA 25 sections
LEVOLEUCOVORIN HUMAN PRESCRIPTION DRUG LABEL 1 43598-771 INJECTION, SOLUTION 175 mg INTRAVENOUS ANDA 25 sections
LEVOLEUCOVORIN HUMAN PRESCRIPTION DRUG LABEL 1 43598-773 INJECTION, SOLUTION 250 mg INTRAVENOUS ANDA 25 sections
LEVOLEUCOVORIN HUMAN PRESCRIPTION DRUG LABEL 1 50742-494 INJECTION, SOLUTION 10 mg INTRAVENOUS ANDA 21 sections
LEVOLEUCOVORIN HUMAN PRESCRIPTION DRUG LABEL 1 50742-495 INJECTION, SOLUTION 10 mg INTRAVENOUS ANDA 21 sections
Biopar delta-FORTE HUMAN PRESCRIPTION DRUG LABEL 6 64661-793 CAPSULE 2.50 mg ORAL unapproved drug other 11 sections
levoleucovorin Human Prescription Drug Label 1 68083-278 INJECTION 10 mg INTRAVENOUS ANDA 23 sections
levoleucovorin Human Prescription Drug Label 1 68083-279 INJECTION 10 mg INTRAVENOUS ANDA 23 sections
Levoleucovorin HUMAN PRESCRIPTION DRUG LABEL 1 70121-1099 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 23 sections
Levoleucovorin Calcium HUMAN PRESCRIPTION DRUG LABEL 1 70121-1572 INJECTION, SOLUTION 10 mg INTRAVENOUS ANDA 23 sections
Levoleucovorin HUMAN PRESCRIPTION DRUG LABEL 1 71288-104 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 24 sections
Levoleucovorin HUMAN PRESCRIPTION DRUG LABEL 1 71288-105 INJECTION, SOLUTION 10 mg INTRAVENOUS ANDA 24 sections
Levoleucovorin HUMAN PRESCRIPTION DRUG LABEL 1 72266-120 INJECTION 10 mg INTRAVENOUS ANDA 25 sections
Levoleucovorin HUMAN PRESCRIPTION DRUG LABEL 1 72266-121 INJECTION 10 mg INTRAVENOUS ANDA 25 sections
Fusilev Human Prescription Drug Label 1 72893-009 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS NDA 23 sections
Fusilev Human Prescription Drug Label 1 72893-013 INJECTION, SOLUTION 10 mg INTRAVENOUS NDA 23 sections
Fusilev Human Prescription Drug Label 1 72893-014 INJECTION, SOLUTION 10 mg INTRAVENOUS NDA 23 sections