pyrimethamine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
2332 58-14-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • pyrimethamine
  • chloridin
  • chloridine
  • diaminopyritamin
  • pirimecidan
  • pirimetamin
  • pyrimethamin
One of the FOLIC ACID ANTAGONISTS that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis.
  • Molecular weight: 248.71
  • Formula: C12H13ClN4
  • CLOGP: 3
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 2
  • TPSA: 77.82
  • ALOGS: -3.14
  • ROTB: 2
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
75 mg O
75 mg O
75 mg P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Bocci G, Oprea TI, Benet LZ
S (Water solubility) 0.18 mg/mL Bocci G, Oprea TI, Benet LZ
EoM (Fraction excreted unchanged in urine) 65 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 5.03 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 90 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.43 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.05 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.10 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 140 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Jan. 23, 1953 FDA AMEDRA 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
Pancytopenia 93.62 37.10 40 942 96893 63391147
Drug reaction with eosinophilia and systemic symptoms 84.34 37.10 28 954 33808 63454232
Cerebral toxoplasmosis 55.01 37.10 10 972 968 63487072
Bone marrow failure 48.89 37.10 18 964 29272 63458768
Hepatocellular injury 42.66 37.10 16 966 27365 63460675
Neutropenia 38.11 37.10 27 955 174978 63313062

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
Pancytopenia 61.04 36.65 41 1347 95116 34860427
Enterocutaneous fistula 45.02 36.65 10 1378 1025 34954518
Immune reconstitution inflammatory syndrome 41.89 36.65 15 1373 8744 34946799
Urinary tract inflammation 41.39 36.65 7 1381 169 34955374
Neuropsychiatric symptoms 40.80 36.65 9 1379 893 34954650
Myopia 38.74 36.65 9 1379 1127 34954416

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
Pancytopenia 137.12 33.40 74 2144 165671 79576499
Drug reaction with eosinophilia and systemic symptoms 80.26 33.40 38 2180 64206 79677964
Cerebral toxoplasmosis 66.58 33.40 15 2203 2347 79739823
Bone marrow failure 63.09 33.40 30 2188 51077 79691093
Neutropenia 53.76 33.40 52 2166 287658 79454512
Hepatocellular injury 49.91 33.40 25 2193 47568 79694602
Immune reconstitution inflammatory syndrome 47.84 33.40 17 2201 13824 79728346
Mycobacterial infection 45.34 33.40 12 2206 3656 79738514
Enterocutaneous fistula 42.19 33.40 10 2208 1951 79740219
Urinary tract inflammation 41.15 33.40 7 2211 253 79741917
Lymphopenia 40.96 33.40 19 2199 30538 79711632
Pulmonary venous thrombosis 37.33 33.40 6 2212 152 79742018
Myopia 37.05 33.40 9 2209 1947 79740223
Conductive deafness 34.70 33.40 6 2212 239 79741931
Neuropsychiatric symptoms 34.57 33.40 8 2210 1407 79740763
Toxic skin eruption 33.46 33.40 15 2203 22278 79719892

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC P01BD01 ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
ANTIPROTOZOALS
ANTIMALARIALS
Diaminopyrimidines
ATC P01BD51 ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
ANTIPROTOZOALS
ANTIMALARIALS
Diaminopyrimidines
ATC P01BF04 ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
ANTIPROTOZOALS
ANTIMALARIALS
Artemisinin and derivatives, combinations
ATC P01BF09 ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
ANTIPROTOZOALS
ANTIMALARIALS
Artemisinin and derivatives, combinations
FDA MoA N0000000191 Dihydrofolate Reductase Inhibitors
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000962 Antimalarials
MeSH PA D000977 Antiparasitic Agents
MeSH PA D000981 Antiprotozoal Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D005493 Folic Acid Antagonists
CHEBI has role CHEBI:35820 antiprotozoal drugs
CHEBI has role CHEBI:38068 antimalarials
CHEBI has role CHEBI:50683 dihydrofolic acid reductase inhibitors
FDA EPC N0000175934 Dihydrofolate Reductase Inhibitor Antimalarial

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

DiseaseRelationSNOMED_IDDOID
Malaria indication 61462000 DOID:12365
Toxoplasmosis indication 187192000 DOID:9965
Toxoplasmosis associated with acquired immunodeficiency syndrome indication 421666009
Chloroquine-Resistant Plasmodium Falciparum Malaria Prevention indication
Chloroquine Resistant Plasmodium Falciparum Malaria indication
Encephalitis due to Toxoplasmosis indication
Toxoplasmosis Prevention off-label use
Pneumocystis Carinii Pneumonia Prevention off-label use
Third trimester pregnancy contraindication 41587001
Acute nephropathy contraindication 58574008
Epilepsy contraindication 84757009 DOID:1826
Megaloblastic anemia due to folate deficiency contraindication 85649008 DOID:14026
Kidney disease contraindication 90708001 DOID:557
Anemia due to enzyme deficiency contraindication 111577008
Deficiency of glucose-6-phosphate dehydrogenase contraindication 124134002 DOID:2862
Folic acid deficiency contraindication 190633005
Disease of liver contraindication 235856003 DOID:409
Anemia contraindication 271737000 DOID:2355
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Bone marrow depression contraindication 307762000
Porphyria contraindication 418470004




🐶 Veterinary Drug Use

SpeciesUseRelation
Horses Myeloencephalitis (EPM) caused by Sarcocystis neurona Indication

🐶 Veterinary products

ProductApplicantIngredients
ReBalance Pegasus Laboratories Inc. 2

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 6.94 Basic
pKa2 0.6 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
Dihydrofolate reductase Enzyme Ki 8.10 CHEMBL
Cytochrome P450 2C9 Enzyme Ki 4.29 WOMBAT-PK
Solute carrier family 22 member 1 Transporter IC50 4.87 CHEMBL
Multidrug and toxin extrusion protein 1 Transporter INHIBITOR Ki 7.10 IUPHAR
Beta-hexosaminidase subunit alpha Enzyme IC50 5.51 CHEMBL
Beta-hexosaminidase subunit beta Enzyme IC50 5.35 CHEMBL
Muscarinic acetylcholine receptor M1 GPCR Ki 8.72 PDSP
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme INHIBITOR Ki 9.72 CHEMBL CHEMBL
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme IC50 6.41 WOMBAT-PK
Dihydrofolate reductase Enzyme Ki 8.01 CHEMBL
Dihydrofolate reductase Enzyme IC50 5.85 CHEMBL
Dihydrofolate reductase Enzyme Ki 8.92 CHEMBL
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme Ki 6.60 WOMBAT-PK
Dihydrofolate reductase Enzyme IC50 5.30 CHEMBL
Dihydrofolate reductase Enzyme Ki 8.92 CHEMBL
Pteridine reductase 1 Enzyme IC50 4.87 CHEMBL
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme Ki 7.01 WOMBAT-PK
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme Ki 7.96 WOMBAT-PK
Solute carrier family 22 member 1 Transporter Ki 5.44 CHEMBL
Multidrug and toxin extrusion protein 1 Unclassified Ki 6.84 CHEMBL
Dihydrofolate reductase Enzyme IC50 7 CHEMBL
Multidrug and toxin extrusion protein 2 Unclassified INHIBITOR Ki 6.30 IUPHAR
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme Ki 9.07 CHEMBL

External reference:

IDSource
4017802 VUID
N0000146163 NUI
D00488 KEGG_DRUG
4017802 VANDF
C0034283 UMLSCUI
CHEBI:8673 CHEBI
CP6 PDB_CHEM_ID
CHEMBL36 ChEMBL_ID
DB00205 DRUGBANK_ID
D011739 MESH_DESCRIPTOR_UI
4993 PUBCHEM_CID
4800 IUPHAR_LIGAND_ID
2215 INN_ID
Z3614QOX8W UNII
9010 RXNORM
5396 MMSL
72370 MMSL
d00364 MMSL
002948 NDDF
373769001 SNOMEDCT_US
59589008 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Pyrimethamine HUMAN PRESCRIPTION DRUG LABEL 1 0480-3720 TABLET 25 mg ORAL ANDA 18 sections
Pyrimethamine HUMAN PRESCRIPTION DRUG LABEL 1 43598-672 TABLET 25 mg ORAL ANDA 24 sections
Pyrimethamine HUMAN PRESCRIPTION DRUG LABEL 1 43598-672 TABLET 25 mg ORAL ANDA 24 sections
pyrimethamine HUMAN PRESCRIPTION DRUG LABEL 1 47781-925 TABLET 25 mg ORAL ANDA 22 sections
pyrimethamine HUMAN PRESCRIPTION DRUG LABEL 1 47781-925 TABLET 25 mg ORAL ANDA 22 sections
Pyrimethamine HUMAN PRESCRIPTION DRUG LABEL 1 48102-026 TABLET 25 mg ORAL ANDA 23 sections
Pyrimethamine Human Prescription Drug Label 1 59651-590 TABLET 25 mg ORAL ANDA 22 sections
Daraprim HUMAN PRESCRIPTION DRUG LABEL 1 69413-330 TABLET 25 mg ORAL NDA 23 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70260-426 CAPSULE 25 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70260-427 CAPSULE 25 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70260-428 CAPSULE 50 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70260-429 CAPSULE 50 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70260-430 CAPSULE 12.50 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70260-480 CAPSULE 50 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70271-426 CAPSULE 25 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70271-427 CAPSULE 25 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70271-428 CAPSULE 50 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70271-429 CAPSULE 50 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70271-430 CAPSULE 12.50 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70271-480 CAPSULE 50 mg ORAL unapproved drug other 1 sections
Pyrimethamine HUMAN PRESCRIPTION DRUG LABEL 1 72647-330 TABLET 25 mg ORAL NDA authorized generic 23 sections