levofolinic acid ๐Ÿถ Veterinary Use | 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
  • calcium levofolinate hydrate
A folate analog consisting of the pharmacologically active isomer of LEUCOVORIN.
  • Molecular weight: 473.45
  • Formula: C20H23N7O7
  • CLOGP: -1.98
  • 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 ยตM/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
S (Water solubility) 100 mg/mL Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Bocci G, Oprea TI, Benet LZ

Approvals:

DateAgencyCompanyOrphan
March 7, 2008 FDA SPECTRUM PHARMS
Sept. 21, 2018 PMDA Pfizer Japan Inc.

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
Neutrophil count decreased 251.82 29.87 115 5505 56291 63427111
Dermatitis acneiform 240.30 29.87 61 5559 4935 63478467
Paronychia 191.01 29.87 52 5568 5513 63477889
Neutropenia 138.02 29.87 118 5502 174887 63308515
Decreased appetite 128.29 29.87 133 5487 250919 63232483
Peripheral sensory neuropathy 116.83 29.87 38 5582 7413 63475989
Stomatitis 98.10 29.87 88 5532 138637 63344765
Hyperammonaemia 91.51 29.87 29 5591 5203 63478199
Diarrhoea 79.10 29.87 186 5434 715180 62768222
Mucosal inflammation 73.79 29.87 48 5572 46880 63436522
Neuropathy peripheral 72.29 29.87 68 5552 113599 63369803
Large intestine perforation 63.44 29.87 25 5595 8457 63474945
Drug ineffective 63.14 29.87 9 5611 1044756 62438646
Febrile neutropenia 62.51 29.87 64 5556 118385 63365017
Disease progression 62.40 29.87 65 5555 122693 63360709
Gastrointestinal perforation 59.60 29.87 19 5601 3472 63479930
Myelosuppression 54.65 29.87 31 5589 23672 63459730
Nausea 53.58 29.87 181 5439 854290 62629112
White blood cell count decreased 52.39 29.87 63 5557 139041 63344361
Diarrhoea haemorrhagic 51.74 29.87 22 5598 9020 63474382
Hypertransaminasaemia 51.26 29.87 20 5600 6589 63476813
Hypomagnesaemia 49.13 29.87 31 5589 28706 63454696
Extrasystoles 48.62 29.87 18 5602 5142 63478260
Dysentery 47.49 29.87 12 5608 949 63482453
Thrombocytopenia 46.66 29.87 62 5558 151095 63332307
Bone marrow failure 46.11 29.87 30 5590 29260 63454142
Posterior reversible encephalopathy syndrome 43.56 29.87 24 5596 17321 63466081
Hypertensive crisis 43.56 29.87 23 5597 15263 63468139
Anaemia 43.26 29.87 86 5534 293344 63190058
Palmar-plantar erythrodysaesthesia syndrome 39.77 29.87 25 5595 22990 63460412
Interstitial lung disease 37.33 29.87 36 5584 61872 63421530
Paraesthesia 36.11 29.87 56 5564 156910 63326492
Dry skin 36.05 29.87 34 5586 56853 63426549
Cholangitis 33.38 29.87 14 5606 5547 63477855
Cholinergic syndrome 33.35 29.87 8 5612 510 63482892
Metastases to peritoneum 32.40 29.87 12 5608 3430 63479972
Colon cancer 31.40 29.87 16 5604 9862 63473540

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 450.04 27.65 131 8808 6058 34941934
Paronychia 385.31 27.65 102 8837 3303 34944689
Interstitial lung disease 300.32 27.65 194 8745 65088 34882904
Neutrophil count decreased 245.05 27.65 156 8783 50948 34897044
Peripheral sensory neuropathy 240.44 27.65 83 8856 6677 34941315
Stomatitis 206.75 27.65 131 8808 42383 34905609
Neuropathy peripheral 179.01 27.65 157 8782 83106 34864886
Decreased appetite 162.97 27.65 206 8733 166186 34781806
Neutropenia 136.10 27.65 183 8756 156595 34791397
Hypomagnesaemia 133.50 27.65 78 8861 21773 34926219
Skin disorder 114.72 27.65 60 8879 13495 34934497
Hyperammonaemia 106.10 27.65 45 8894 6322 34941670
Diarrhoea 100.33 27.65 270 8669 389642 34558350
Gastrointestinal perforation 80.34 27.65 32 8907 3831 34944161
Palmar-plantar erythrodysaesthesia syndrome 69.86 27.65 47 8892 16748 34931244
Nausea 68.49 27.65 216 8723 339692 34608300
Drug ineffective 65.69 27.65 18 8921 456733 34491259
White blood cell count decreased 64.35 27.65 99 8840 95346 34852646
Leukopenia 63.09 27.65 79 8860 62777 34885215
Dry skin 63.06 27.65 57 8882 31230 34916762
Tumour perforation 57.70 27.65 14 8925 315 34947677
Dysgeusia 54.82 27.65 49 8890 26448 34921544
Hypersensitivity 53.87 27.65 72 8867 60963 34887029
Disease progression 52.70 27.65 97 8842 107980 34840012
Febrile neutropenia 51.29 27.65 110 8829 136739 34811253
Thrombocytopenia 50.09 27.65 118 8821 156129 34791863
Sciatic nerve palsy 50.03 27.65 9 8930 41 34947951
Transient aphasia 45.14 27.65 12 8927 393 34947599
Bone marrow failure 39.75 27.65 43 8896 29210 34918782
Hypertransaminasaemia 39.54 27.65 22 8917 5584 34942408
Myelosuppression 38.60 27.65 35 8904 19230 34928762
Intestinal ischaemia 37.74 27.65 24 8915 7770 34940222
Toxicity to various agents 37.16 27.65 4 8935 200358 34747634
Malaise 37.13 27.65 118 8821 185707 34762285
Disseminated intravascular coagulation 36.76 27.65 36 8903 21780 34926212
Erythema 36.29 27.65 74 8865 88706 34859286
Small intestinal perforation 35.02 27.65 15 8924 2156 34945836
Colony stimulating factor therapy 33.40 27.65 8 8931 170 34947822
Cholinergic syndrome 32.15 27.65 10 8929 577 34947415
Hypertension 31.30 27.65 91 8848 136352 34811640
Duodenal stenosis 30.67 27.65 8 8931 243 34947749
Malignant ascites 30.35 27.65 9 8930 441 34947551
Pulmonary artery thrombosis 29.76 27.65 10 8929 738 34947254
Peritonitis 29.44 27.65 28 8911 16337 34931655
Headache 28.54 27.65 8 8931 200627 34747365
Fixed eruption 28.26 27.65 12 8927 1688 34946304

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
Dermatitis acneiform 643.51 25.19 178 14114 9815 79720281
Paronychia 511.48 25.19 141 14151 7667 79722429
Neutrophil count decreased 459.54 25.19 256 14036 93703 79636393
Interstitial lung disease 324.75 25.19 219 14073 112381 79617715
Peripheral sensory neuropathy 316.48 25.19 110 14182 12923 79717173
Neutropenia 289.17 25.19 304 13988 287406 79442690
Decreased appetite 280.58 25.19 325 13967 342093 79388003
Neuropathy peripheral 260.74 25.19 210 14082 141095 79589001
Stomatitis 249.59 25.19 208 14084 146549 79583547
Hyperammonaemia 185.02 25.19 71 14221 11022 79719074
Diarrhoea 177.08 25.19 445 13847 880044 78850052
Hypomagnesaemia 153.83 25.19 99 14193 46812 79683284
Skin disorder 127.26 25.19 78 14214 33865 79696231
White blood cell count decreased 117.11 25.19 156 14136 188132 79541964
Gastrointestinal perforation 115.80 25.19 43 14249 6094 79724002
Drug ineffective 112.54 25.19 28 14264 1080885 78649211
Febrile neutropenia 112.11 25.19 170 14122 230829 79499267
Thrombocytopenia 109.15 25.19 181 14111 265078 79465018
Disease progression 104.42 25.19 146 14146 184216 79545880
Palmar-plantar erythrodysaesthesia syndrome 99.01 25.19 66 14226 33068 79697028
Nausea 93.69 25.19 378 13914 956818 78773278
Bone marrow failure 87.83 25.19 73 14219 51034 79679062
Leukopenia 87.34 25.19 106 14186 116407 79613689
Hypertransaminasaemia 85.28 25.19 42 14250 11882 79718214
Myelosuppression 85.16 25.19 65 14227 40231 79689865
Dry skin 82.89 25.19 80 14212 67915 79662181
Dysgeusia 76.81 25.19 71 14221 57106 79672990
Tumour perforation 69.79 25.19 16 14276 405 79729691
Cholinergic syndrome 63.68 25.19 18 14274 1069 79729027
Mucosal inflammation 61.95 25.19 72 14220 75508 79654588
Hypertensive crisis 61.14 25.19 41 14251 20729 79709367
Large intestine perforation 58.50 25.19 35 14257 14532 79715564
Dysentery 57.49 25.19 17 14275 1185 79728911
Disseminated intravascular coagulation 57.05 25.19 49 14243 35793 79694303
Headache 57.04 25.19 23 14269 653749 79076347
Paraesthesia 56.53 25.19 108 14184 176215 79553881
Arthralgia 55.20 25.19 17 14275 571786 79158310
Colon cancer 53.45 25.19 33 14259 14490 79715606
Metastases to liver 51.89 25.19 42 14250 28272 79701824
Sciatic nerve palsy 48.35 25.19 9 14283 77 79730019
Toxicity to various agents 47.56 25.19 9 14283 421531 79308565
Transient aphasia 47.35 25.19 12 14280 468 79729628
Hypertension 46.91 25.19 148 14144 330844 79399252
Proteinuria 46.84 25.19 42 14250 32460 79697636
Platelet count decreased 45.75 25.19 105 14187 194559 79535537
Metastases to peritoneum 45.59 25.19 20 14272 4352 79725744
Pain 45.29 25.19 36 14256 703766 79026330
Cholangitis 44.42 25.19 28 14264 12748 79717348
Malaise 43.30 25.19 188 14104 489681 79240415
Pulmonary artery thrombosis 42.64 25.19 14 14278 1378 79728718
Peritonitis 41.93 25.19 37 14255 27999 79702097
Small intestinal perforation 40.71 25.19 17 14275 3280 79726816
Hyperthermia 40.10 25.19 30 14262 18007 79712089
Malignant neoplasm progression 39.57 25.19 80 14212 135910 79594186
Metastases to lung 37.70 25.19 29 14263 18134 79711962
Pain in extremity 36.67 25.19 10 14282 364528 79365568
Malignant ascites 36.56 25.19 12 14280 1180 79728916
Erythema 36.45 25.19 105 14187 223185 79506911
Ileus 36.06 25.19 33 14259 26178 79703918
Pyrexia 36.03 25.19 226 14066 678483 79051613
Intestinal ischaemia 33.88 25.19 24 14268 13246 79716850
Colony stimulating factor therapy 32.16 25.19 9 14283 515 79729581
Nasopharyngitis 31.84 25.19 4 14288 253877 79476219
Anaphylactic shock 30.67 25.19 35 14257 35961 79694135
Extrasystoles 30.24 25.19 18 14274 7401 79722695
Hyperbilirubinaemia 30.14 25.19 29 14263 24489 79705607
Anaemia 29.30 25.19 157 14135 444858 79285238
Fall 28.81 25.19 27 14265 487602 79242494
Duodenal stenosis 28.55 25.19 9 14283 778 79729318
Altered state of consciousness 28.23 25.19 37 14255 43785 79686311
Necrotising fasciitis 28.16 25.19 16 14276 6034 79724062
Vomiting 27.75 25.19 209 14083 665619 79064477
Tumour necrosis 27.45 25.19 11 14281 1911 79728185
Drug intolerance 27.01 25.19 7 14285 264112 79465984
Neurotoxicity 26.66 25.19 31 14261 32487 79697609
Pulmonary venous thrombosis 26.17 25.19 6 14286 152 79729944
Acral peeling skin syndrome 26.07 25.19 5 14287 51 79730045
Fixed eruption 25.99 25.19 12 14280 2942 79727154
Dermatitis bullous 25.82 25.19 21 14271 14224 79715872
Enterocolitis 25.48 25.19 21 14271 14491 79715605

FDA Adverse Event Reporting System (Pediatric)

None

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
FDA EPC N0000178369 Folate Analog
CHEBI has role CHEBI:25212 metabolites
CHEBI has role CHEBI:35610 antineoplastic agents
MeSH PA D000931 Antidotes
MeSH PA D020011 Protective Agents

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Megaloblastic anemia indication 53165003 DOID:13382
Folic acid deficiency indication 190633005
Malignant tumor of stomach indication 363349007 DOID:10534
Small intestine cancer indication 363509000 DOID:10154
Methotrexate Toxicity indication
Adjunct to Fluorouracil Treatment of Colorectal Cancer indication
Pyrimethamine Toxicity indication
Trimethoprim Toxicity indication
Sulfadiazine Toxicity indication
Trimetrexate Toxicity indication
Bone Marrow Suppression due to Folic Acid Antagonism indication




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

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
419573-16-3 SECONDARY_CAS_RN
68538-85-2 SECONDARY_CAS_RN
4028507 VANDF
4028508 VANDF
CHEBI:63606 CHEBI
CHEMBL1908841 ChEMBL_ID
CHEMBL1908361 ChEMBL_ID
DB11596 DRUGBANK_ID
1648126 RXNORM
132962 MMSL
21723 MMSL
25218 MMSL
35726 MMSL
d05842 MMSL
005532 NDDF
005533 NDDF
395769006 SNOMEDCT_US
429990006 SNOMEDCT_US
433468002 SNOMEDCT_US
782479008 SNOMEDCT_US
C2721771 UMLSCUI
D058766 MESH_DESCRIPTOR_UI
FOZ PDB_CHEM_ID
CHEMBL3707343 ChEMBL_ID
135398559 PUBCHEM_CID
6883 INN_ID
WA16A5Y52X UNII

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 CALCIUM HUMAN PRESCRIPTION DRUG LABEL 1 14335-340 INJECTION, SOLUTION 10 mg INTRAVENOUS ANDA 24 sections
LEVOLEUCOVORIN CALCIUM HUMAN PRESCRIPTION DRUG LABEL 1 14335-341 INJECTION, SOLUTION 10 mg INTRAVENOUS ANDA 24 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
Biopar delta-FORTE HUMAN PRESCRIPTION DRUG LABEL 6 64661-793 CAPSULE 2.50 mg ORAL unapproved drug other 11 sections
Biopar delta-FORTE HUMAN PRESCRIPTION DRUG LABEL 6 64661-793 CAPSULE 2.50 mg ORAL unapproved drug other 11 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 HUMAN PRESCRIPTION DRUG LABEL 1 70121-1099 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 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 Calcium HUMAN PRESCRIPTION DRUG LABEL 1 70121-1572 INJECTION, SOLUTION 10 mg INTRAVENOUS ANDA 23 sections
Levoleucovorin Calcium HUMAN PRESCRIPTION DRUG LABEL 1 70121-1572 INJECTION, SOLUTION 10 mg INTRAVENOUS ANDA 23 sections
LEVOLEUCOVORIN CALCIUM HUMAN PRESCRIPTION DRUG LABEL 1 70436-209 INJECTION, SOLUTION 10 mg INTRAVENOUS ANDA 23 sections
LEVOLEUCOVORIN CALCIUM HUMAN PRESCRIPTION DRUG LABEL 1 70436-210 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 71288-104 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 72266-120 INJECTION 10 mg INTRAVENOUS ANDA 25 sections
Levoleucovorin HUMAN PRESCRIPTION DRUG LABEL 1 72266-121 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 72893-009 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS NDA 23 sections