pyrimethamine 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) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.12 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 65 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 5.03 ┬ÁM/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
Drug reaction with eosinophilia and systemic symptoms 49.38 35.38 11 136 5507 2352431
Neutropenia 43.03 35.38 13 134 21535 2336403
Thrombocytopenia 40.14 35.38 12 135 19119 2338819
Nausea 39.76 35.38 19 128 112170 2245768

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 59.05 49.98 16 127 11341 1735297

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
FDA EPC N0000175934 Dihydrofolate Reductase Inhibitor Antimalarial
FDA MoA N0000000191 Dihydrofolate Reductase Inhibitors
CHEBI has role CHEBI:38068 antimalarial
CHEBI has role CHEBI:35820 antiprotozoal drug
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

Drug Use (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

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
Multidrug and toxin extrusion protein 1 Transporter INHIBITOR Ki 7.10 IUPHAR
Beta-hexosaminidase subunit alpha Unclassified IC50 5.51 CHEMBL
Beta-hexosaminidase subunit beta Unclassified 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
Dihydrofolate reductase Enzyme Ki 8.01 CHEMBL
Multidrug and toxin extrusion protein 1 Unclassified Ki 6.84 CHEMBL
Dihydrofolate reductase Enzyme IC50 5.30 CHEMBL
Dihydrofolate reductase Enzyme IC50 5.85 CHEMBL
Dihydrofolate reductase Unclassified Ki 8.92 CHEMBL
Solute carrier family 22 member 1 Unclassified Ki 5.44 CHEMBL
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme Ki 7.96 WOMBAT-PK
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme Ki 7.01 WOMBAT-PK
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme Ki 6.60 WOMBAT-PK
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme IC50 6.41 WOMBAT-PK
Multidrug and toxin extrusion protein 2 Unclassified INHIBITOR Ki 6.30 IUPHAR

External reference:

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

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Pyrimethamine HUMAN PRESCRIPTION DRUG LABEL 1 43598-672 TABLET 25 mg ORAL ANDA 12 sections
Daraprim HUMAN PRESCRIPTION DRUG LABEL 1 69413-330 TABLET 25 mg ORAL NDA 12 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 12 sections