Drug/Small Molecule:
pyrimethamine

PharmGKB contains no dosing guidelines for this drug/small molecule. To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB has no annotated drug labels with pharmacogenomic information for this drug/small molecule. If you know of a drug label with PGx, send us a message.

Links to Unannotated Labels

These links are to labels associated with pyrimethamine that have not been annotated by PharmGKB.

  1. DailyMed - DrugLabel PA166105230

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all pyrimethamine variant annotations

Gene ? Variant?
(142)
Alternate Names ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No VIP available VA G6PD A- 202A_376G N/A N/A N/A
No VIP available No VIP available VA G6PD Canton, Taiwan-Hakka, Gifu-like, Agrigento-like N/A N/A N/A
No VIP available No Clinical Annotations available VA
G6PD deficiency N/A N/A N/A
No VIP available CA VA
rs1050828 153764217C>T, 16571G>A, 202G>A, 292G>A, 4682155C>T, Asahi, G6PD:202G>A, Val68Met, Val98Met
C > T
Not Available
Val68Met
VIP No Clinical Annotations available No Variant Annotations available
rs1138272 12659374C>T, 341C>T, 67353579C>T, 7514C>T, A114V, Ala114Val, GSTP1: A114V, GSTP1: C341T
C > T
Missense
Ala114Val
VIP No Clinical Annotations available No Variant Annotations available
rs1695 12658484A>G, 313A>G, 6624A>G, 67352689A>G, GSTP1*2, GSTP1*B, GSTP1: I105V, GSTP1:A313G, GSTP1:I105V, GSTP1:Ile105Val, Ile105Val, Part of haplotypes GSTP1*B and GSTP1*C, rs1695:A>G
A > G
Missense
Ile105Val
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 142
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • CD
  • Chloridin
  • Chloridine
  • Chloridyn
  • Diaminopyritamin
  • Ethylpyrimidine
  • Pirimetamin
  • Pirimetamina
  • Primethamine
  • Pyremethamine
  • Pyrimethamin
  • Pyrimethamine Hcl
Trade Names
  • Darachlor
  • Daraclor
  • Darapram
  • Daraprim
  • Daraprime
  • Disulone
  • Erbaprelina
  • Fansidar
  • Khloridin
  • Malacid
  • Malocid
  • Malocide
  • Maloprim
  • Pirimecidan
  • Tindurin
  • Tinduring
Brand Mixture Names
  • Fansidar Tablets (Pyrimethamine + Sulfadoxine)
  • Quinnoxine-S (Pyrimethamine + Sulfaquinoxaline)
  • Sulfaquinoxaline-S Liq (Pyrimethamine + Sulfaquinoxaline)

PharmGKB Accession Id:
PA451193

Description

One of the folic acid antagonists that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis.

Source: Drug Bank

Indication

For the treatment of toxoplasmosis and acute malaria; For the prevention of malaria in areas non-resistant to pyrimethamine

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Pyrimethamine inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are essential for DNA synthesis and cell multiplication. This leads to failure of nuclear division at the time of schizont formation in erythrocytes and liver.

Source: Drug Bank

Pharmacology

Pyrimethamine is an antiparasitic compound commonly used as an adjunct in the treatment of uncomplicated, chloroquine resistant, P. falciparum malaria. Pyrimethamine is a folic acid antagonist and the rationale for its therapeutic action is based on the differential requirement between host and parasite for nucleic acid precursors involved in growth. This activity is highly selective against plasmodia and Toxoplasma gondii. Pyrimethamine possesses blood schizonticidal and some tissue schizonticidal activity against malaria parasites of humans. However, the 4-amino-quinoline compounds are more effective against the erythrocytic schizonts. It does not destroy gametocytes, but arrests sporogony in the mosquito. The action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides.

Source: Drug Bank

Food Interaction

Take with food to reduce irritation.|Folic acid needs increased.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic

Source: Drug Bank

Protein Binding

87%

Source: Drug Bank

Absorption

Well absorbed with peak levels occurring between 2 to 6 hours following administration

Source: Drug Bank

Half-Life

96 hours

Source: Drug Bank

Chemical Properties

Chemical Formula

C12H13ClN4

Source: Drug Bank

Isomeric SMILES

CCc1c(c(nc(n1)N)N)c2ccc(cc2)Cl

Source: OpenEye

Canonical SMILES

CCC1=C(C(N)=NC(N)=N1)C1=CC=C(Cl)C=C1

Source: Drug Bank

Average Molecular Weight

248.711

Source: Drug Bank

Monoisotopic Molecular Weight

248.082874143

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
G6PD
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
GSTP1
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
IKBKG

Drug Targets

Gene Description
DHFR (source: Drug Bank)

Drug Interactions

Drug Description
pyrimethamine Pyrimethamine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy. (source: Drug Bank)
pyrimethamine Pyrimethamine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy. (source: Drug Bank)
pyrimethamine Pyrimethamine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Pyrimethamine is initiated, discontinued, or dose changed. (source: Drug Bank)
pyrimethamine Pyrimethamine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Pyrimethamine is initiated, discontinued, or dose changed. (source: Drug Bank)
pyrimethamine Pyrimethamine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to pyrimethamine: 13

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Humanized mouse model of glucose 6-phosphate dehydrogenase deficiency for in vivo assessment of hemolytic toxicity. Proceedings of the National Academy of Sciences of the United States of America. 2013. Rochford Rosemary, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Emerging Transporters of Clinical Importance: An Update from the International Transporter Consortium. Clinical pharmacology and therapeutics. 2013. Hillgren Kathleen M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PharmGKB summary: very important pharmacogene information for G6PD. Pharmacogenetics and genomics. 2012. McDonagh Ellen M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence-based review. Drug safety : an international journal of medical toxicology and drug experience. 2010. Youngster Ilan, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A-) individuals. Antimicrobial agents and chemotherapy. 2010. Shekalaghe Seif A, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
High risk of severe anaemia after chlorproguanil-dapsone+artesunate antimalarial treatment in patients with G6PD (A-) deficiency. PloS one. 2008. Fanello Caterina I, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Sulfadoxine-pyrimethamine pharmacokinetics in malaria: pediatric dosing implications. Clinical pharmacology and therapeutics. 2006. Barnes Karen I, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Comparison of chlorproguanil-dapsone with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in young African children: double-blind randomised controlled trial. Lancet. 2004. Alloueche A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Antimalarial drug toxicity: a review. Drug safety : an international journal of medical toxicology and drug experience. 2004. Taylor W Robert J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Chlorproguanil-dapsone versus sulfadoxine-pyrimethamine for sequential episodes of uncomplicated falciparum malaria in Kenya and Malawi: a randomised clinical trial. Lancet. 2002. Sulo J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Management of a case of chloroquine-resistant falciparum malaria in a pregnant woman with glucose-6-phosphate dehydrogenase (G6PD) deficiency. American journal of perinatology. 1999. Cultrera R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Drug-induced haemolysis in glucose-6-phosphate dehydrogenase deficiency. British medical journal. 1976. Chan T K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
A comparative evaluation of sulfalene-trimethoprim and sulphormethoxine-pyrimethamine against falciparum malaria in Thailand. The American journal of tropical medicine and hygiene. 1973. Chin W, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0173-0201-55
DrugBank:
DB00205
PDB:
CP6
ChEBI:
8673
KEGG Compound:
C07391
KEGG Drug:
D00488
PubChem Compound:
4993
PubChem Substance:
46505987
9595
Drugs Product Database (DPD):
4774
BindingDB:
18512
ChemSpider:
4819
HET:
CP6
Therapeutic Targets Database:
DAP000633
FDA Drug Label at DailyMed:
bf0d869c-83c5-4129-c4a5-7515f7554831

Clinical Trials

These are trials that mention pyrimethamine and are related to either pharmacogenetics or pharmacogenomics.

Common Searches

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.