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

Stem definition	Drug id	CAS RN
	2332	58-14-0

Description:

Molecule	Description
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

Molecule

Description

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:

Dose	Unit	Route
75	mg	O
75	mg	O
75	mg	P

ADMET properties:

Property	Value	Reference
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 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:

Date	Agency	Company	Orphan
Jan. 23, 1953	FDA	AMEDRA PHARMS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Pancytopenia	90.92	39.63	39	898	88676	56202454
Drug reaction with eosinophilia and systemic symptoms	85.38	39.63	28	909	30276	56260854
Cerebral toxoplasmosis	76.18	39.63	13	924	813	56290317
Bone marrow failure	48.22	39.63	18	919	28268	56262862
Hepatocellular injury	42.02	39.63	16	921	26498	56264632

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Pancytopenia	60.61	33.75	39	1177	87277	31608851
Toxoplasmosis	53.94	33.75	12	1204	1285	31694843
Enterocutaneous fistula	47.22	33.75	10	1206	850	31695278
Immune reconstitution inflammatory syndrome	39.57	33.75	14	1202	8164	31687964
Myopia	39.56	33.75	9	1207	1064	31695064
Pulmonary venous thrombosis	37.42	33.75	6	1210	107	31696021
Cerebral toxoplasmosis	36.12	33.75	9	1207	1568	31694560
Optic neuropathy	34.97	33.75	9	1207	1784	31694344

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Pancytopenia	134.06	31.20	71	1931	151036	70775406
Cerebral toxoplasmosis	90.96	31.20	19	1983	2061	70924381
Drug reaction with eosinophilia and systemic symptoms	83.46	31.20	38	1964	57975	70868467
Bone marrow failure	63.89	31.20	30	1972	48980	70877462
Hepatocellular injury	50.34	31.20	25	1977	46066	70880376
Toxoplasmosis	49.23	31.20	12	1990	2598	70923844
Immune reconstitution inflammatory syndrome	48.66	31.20	17	1985	12973	70913469
Mycobacterial infection	45.77	31.20	12	1990	3476	70922966
Enterocutaneous fistula	43.48	31.20	10	1992	1688	70924754
Neutropenia	39.29	31.20	42	1960	257114	70669328
Pulmonary venous thrombosis	38.69	31.20	6	1996	118	70926324
Myopia	37.48	31.20	9	1993	1828	70924614
Toxic skin eruption	34.70	31.20	15	1987	20147	70906295
Crystalluria	32.57	31.20	7	1995	868	70925574
Optic neuropathy	32.43	31.20	9	1993	3224	70923218

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
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|

Disease	Relation	SNOMED_ID	DOID
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

Species	Use	Relation
Horses	Myeloencephalitis (EPM) caused by Sarcocystis neurona	Indication

🐶 Veterinary products

Product	Applicant	Ingredients
ReBalance	Pegasus Laboratories Inc.	2

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (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)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
25MG	PYRIMETHAMINE	ALVOGEN	A211271	July 27, 2021	RX	TABLET	ORAL	April 2, 2022	COMPETITIVE GENERIC THERAPY

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Dihydrofolate reductase	Enzyme	P00374	DYR_HUMAN		Ki	8.10	CHEMBL
Cytochrome P450 2C9	Enzyme	P11712	CP2C9_HUMAN		Ki	4.29	WOMBAT-PK
Solute carrier family 22 member 1	Transporter	O15245	S22A1_HUMAN		IC50	4.87	CHEMBL
Multidrug and toxin extrusion protein 1	Transporter	Q96FL8	S47A1_HUMAN	INHIBITOR	Ki	7.10	IUPHAR
Beta-hexosaminidase subunit alpha	Enzyme	P06865	HEXA_HUMAN		IC50	5.51	CHEMBL
Beta-hexosaminidase subunit beta	Enzyme	P07686	HEXB_HUMAN		IC50	5.35	CHEMBL
Muscarinic acetylcholine receptor M1	GPCR	P11229	ACM1_HUMAN		Ki	8.72	PDSP
Bifunctional dihydrofolate reductase-thymidylate synthase	Enzyme		DRTS_PLAFK	INHIBITOR	Ki	9.72	CHEMBL	CHEMBL
Bifunctional dihydrofolate reductase-thymidylate synthase	Enzyme		DRTS_TOXGO		IC50	6.41	WOMBAT-PK
Dihydrofolate reductase	Enzyme		DYR_PNECA		Ki	8.01	CHEMBL
Dihydrofolate reductase	Enzyme		DYR_RAT		IC50	5.85	CHEMBL
Dihydrofolate reductase	Enzyme		DYR_ECOLI		Ki	8.92	CHEMBL
Bifunctional dihydrofolate reductase-thymidylate synthase	Enzyme		DRTS_LEIMA		Ki	6.60	WOMBAT-PK
Dihydrofolate reductase	Enzyme		DYR_CANAX		IC50	5.30	CHEMBL
Dihydrofolate reductase	Enzyme		B0BL08_ECOLX		Ki	8.92	CHEMBL
Pteridine reductase 1	Enzyme		PTR1_LEIMA		IC50	4.87	CHEMBL
Bifunctional dihydrofolate reductase-thymidylate synthase	Enzyme		DRTS_TRYCR		Ki	7.01	WOMBAT-PK
Bifunctional dihydrofolate reductase-thymidylate synthase	Enzyme		DRTS_TRYBB		Ki	7.96	WOMBAT-PK
Solute carrier family 22 member 1	Transporter		S22A1_MOUSE		Ki	5.44	CHEMBL
Multidrug and toxin extrusion protein 1	Unclassified		S47A1_MOUSE		Ki	6.84	CHEMBL
Dihydrofolate reductase	Enzyme		DYR_BOVIN		IC50	7	CHEMBL
Multidrug and toxin extrusion protein 2	Unclassified		S47A2_MOUSE	INHIBITOR	Ki	6.30	IUPHAR
Bifunctional dihydrofolate reductase-thymidylate synthase	Enzyme		Q8I1R6_PLAF7		Ki	9.07	CHEMBL

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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	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