Drug/Small Molecule:
primaquine

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 gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.


last updated 12/20/2013

FDA Label for primaquine and G6PD

This label is on the FDA Biomarker List
Actionable PGx

Summary

Primaquine is used to prevent vivax malaria relapse. Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency who are treated with primaquine are at risk of moderate to severe hemolytic reactions. Patients with cytochrome b5 reductase deficiency (CYB5R3, also known as NADH methemoglobin reductase) who are treated with primaquine are at risk of methemoglobinemia.

Annotation

The label emphasizes caution prior to initiating treatment with primaquine for G6PD deficient individuals or CYB5R3 deficient individuals. Excerpt from the primaquine drug label:

If primaquine phosphate is prescribed for (1) an individual who has shown a previous idiosyncrasy to primaquine phosphate (as manifested by hemolytic anemia, methemoglobinemia, or leukopenia), (2) an individual with a family or personal history of favism, or (3) an individual with erythrocytic glucose-6-phosphate dehydrogenase (G-6-PD) deficiency or nicotinamide adenine dinucleotide (NADH) methemoglobin reductase deficiency, the person should be observed closely for tolerance. The drug should be discontinued immediately if marked darkening of the urine or sudden decrease in hemoglobin concentration or leukocyte count occurs.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the primaquine drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Anemia, Hemolytic
    • Warnings section, Adverse reactions section
    • source: FDA Label
  • Malaria
    • Indications & usage section
    • source: FDA Label
  • CYB5R3
    • Adverse reactions section, Precautions section, toxicity
    • source: FDA Label
  • G6PD
    • Warnings section, Adverse reactions section, Precautions section, toxicity
    • source: FDA Label

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?
Molecular Genetics Laboratory ARUP Laboratories, Glucose-6-Phosphate Dehydrogenase (G6PD) 2 Mutations G6PDA- 202A_376G , rs1050829 , rs1050828

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.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? 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 B (wildtype) N/A N/A N/A
No VIP available No VIP available VA G6PD Mediterranean, Dallas, Panama' Sassari, Cagliari, Birmingham 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
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
Trade Names
  • Neo-Quipenyl
  • Primachin
Brand Mixture Names

PharmGKB Accession Id:
PA451103

Description

An aminoquinoline that is given by mouth to produce a radical cure and prevent relapse of vivax and ovale malarias following treatment with a blood schizontocide. It has also been used to prevent transmission of falciparum malaria by those returning to areas where there is a potential for re-introduction of malaria. Adverse effects include anemias and GI disturbances. (From Martindale, The Extra Pharmacopeia, 30th ed, p404)

Source: Drug Bank

Indication

For the treatment of malaria.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Primaquine's mechanism of action is not well understood. It may be acting by generating reactive oxygen species or by interfering with the electron transport in the parasite. Also, although its mechanism of action is unclear, primaquine may bind to and alter the properties of protozoal DNA.

Source: Drug Bank

Pharmacology

Primaquine is an antimalarial agent and is the essential co-drug with chloroquine in treating all cases of malaria. In the blood, malaria parasites break down a part of the red blood cells known as haemoglobin. When this happens haemoglobin is divided into two parts; haem and globin. Haem is toxic to the malaria parasite. To prevent it from being damaged, the malaria parasite produces an chemical which converts the toxic haem into a non-toxic product. Primaquine acts by interfering with a part of the parasite (mitochondria) that is responsible for supplying it with energy. Without energy the parasite dies. This stops the infection from continuing and allows the person to recover. Primaquine kills the intrahepatic form of Plasmodium vivax and Plasmodium ovale, and thereby prevents the development of the erythrocytic forms that are responsible for relapses (it also kills gametocytes). Primaquine is not used in the prevention of malaria, only in the treatment. It has insignificant activity against the asexual blood forms of the parasite and therefore it is always used in conjunction with a blood schizonticide and never as a single agent. Primaquine has gametocytocidal activity against all plasmodia, including P. falciparum.

Source: Drug Bank

Food Interaction

Take with food to decrease dyspepsia.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Half-Life

3.7-7.4 hours

Source: Drug Bank

Chemical Properties

Chemical Formula

C15H21N3O

Source: Drug Bank

Isomeric SMILES

CC(CCCN)Nc1cc(cc2c1nccc2)OC

Source: OpenEye

Canonical SMILES

COC1=CC(NC(C)CCCN)=C2N=CC=CC2=C1

Source: Drug Bank

Average Molecular Weight

259.3467

Source: Drug Bank

Monoisotopic Molecular Weight

259.168462309

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 DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYB5R3
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
CYP1A2
G6PD
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
IKBKG

Drug Targets

Gene Description
HBA1 (source: Drug Bank)
KRT7 (source: Drug Bank)
NQO2 (source: Drug Bank)

Drug Interactions

Drug Description
primaquine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine (source: Drug Bank)
primaquine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine (source: Drug Bank)
atomoxetine The CYP2D6 inhibitor could increases the effect and toxicity of atomoxetine (source: Drug Bank)
atomoxetine The CYP2D6 inhibitor could increases the effect and toxicity of atomoxetine (source: Drug Bank)
primaquine The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by strong CYP1A2 inhibitors such as Primaquine. Consider modifying therapy to avoid Tacrine toxicity. Monitor the efficacy and toxicity of Tacrine if Primaquine is initiated, discontinued or if the dose is changed. (source: Drug Bank)
primaquine The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by strong CYP1A2 inhibitors such as Primaquine. Consider modifying therapy to avoid Tacrine toxicity. Monitor the efficacy and toxicity of Tacrine if Primaquine is initiated, discontinued or if the dose is changed. (source: Drug Bank)
primaquine The strong CYP1A2 inhibitor, Primaquine, may decrease the metabolism and clearance of Thiothixene, a CYP1A2 substrate. Consider alternate therapy or monitor for changes in Thiothixene therapeutic and adverse effects if Primaquine is initiated, discontinued or dose changed. (source: Drug Bank)
primaquine The strong CYP1A2 inhibitor, Primaquine, may decrease the metabolism and clearance of Thiothixene, a CYP1A2 substrate. Consider alternate therapy or monitor for changes in Thiothixene therapeutic and adverse effects if Primaquine is initiated, discontinued or dose changed. (source: Drug Bank)
primaquine Primaquine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration. (source: Drug Bank)

Curated Information ?

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

May Treat
May Prevent
Contraindicated With

Publications related to primaquine: 33

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests. Malaria journal. 2013. Domingo Gonzalo J, et al. PubMed
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
The metabolism of primaquine to its active metabolite is dependent on CYP 2D6. Malaria journal. 2013. Pybus Brandon S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
An in vivo drug screening model using glucose-6-phosphate dehydrogenase deficient mice to predict the hemolytic toxicity of 8-aminoquinolines. The American journal of tropical medicine and hygiene. 2013. Zhang Peng, 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
Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP 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
Blue cures blue but be cautious. Journal of pharmacy & bioallied sciences. 2011. Sikka Pranav, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: very important pharmacogene information for CYP1A2. Pharmacogenetics and genomics. 2011. Thorn Caroline F, 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
Prospective-retrospective biomarker analysis for regulatory consideration: white paper from the industry pharmacogenomics working group. Pharmacogenomics. 2011. Patterson Scott D, 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
A research agenda for malaria eradication: diagnoses and diagnostics. PLoS medicine. 2011. malERA Consultative Group on Diagnoses and Diagnostics, 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
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP 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
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 No Clinical Annotation available VA No VIP available No VIP available
Clinical aspects of hemolysis in patients with P. vivax malaria treated with primaquine, in the Brazilian Amazon. The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases. 2010. Ramos Júnior Wilson M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Cytochrome P(450)-dependent toxic effects of primaquine on human erythrocytes. Toxicology and applied pharmacology. 2009. Ganesan Shobana, 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
Allelic heterogeneity of G6PD deficiency in West Africa and severe malaria susceptibility. European journal of human genetics : EJHG. 2009. Clark Taane G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Omeprazole transactivates human CYP1A1 and CYP1A2 expression through the common regulatory region containing multiple xenobiotic-responsive elements. Biochemical pharmacology. 2008. Yoshinari Kouichi, 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
Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008. Cappellini M D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Prevalence and significance of G6PD deficiency in patients of an urban HIV clinic. Journal of the International Association of Physicians in AIDS Care (Chicago, Ill. : 2002). 2008. Tungsiripat Marisa, 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
G6PD deficiency: the genotype-phenotype association. Blood reviews. 2007. Mason Philip J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I. The American journal of tropical medicine and hygiene. 2006. Hill David R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Safety and tolerability of elubaquine (bulaquine, CDRI 80/53) for treatment of Plasmidium vivax malaria in Thailand. The Korean journal of parasitology. 2006. Krudsood Srivicha, 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
Primaquine-induced hemolytic anemia: role of membrane lipid peroxidation and cytoskeletal protein alterations in the hemotoxicity of 5-hydroxyprimaquine. The Journal of pharmacology and experimental therapeutics. 2005. Bowman Zachary S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Haemolytic potential of three chemotherapeutic agents and aspirin in glucose-6-phosphate dehydrogenase deficiency. Eastern Mediterranean health journal = La revue de santé de la Méditerranée orientale = al-Majallah al-ṣiḥḥīyah li-sharq al-mutawassiṭ. 1999. Ali N 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
G6PD deficiency. Blood. 1994. Beutler E. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Drug-induced haemolysis and renal failure in children with glucose-6-phosphate dehydrogenase deficiency in Afghanistan. Annals of tropical paediatrics. 1990. Choudhry V P, 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
Glucose-6-phosphate dehydrogenase deficiency. WHO Working Group. Bulletin of the World Health Organization. 1989. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacokinetics of primaquine in man: identification of the carboxylic acid derivative as a major plasma metabolite. British journal of clinical pharmacology. 1984. Mihaly G W, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Methaemoglobin reduction test: a new, simple, in vitro test for identifying primaquine-sensitivity. Bulletin of the World Health Organization. 1960. BREWER G 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
The hemolytic effect of primaquine and related compounds: a review. Blood. 1959. BEUTLER E. PubMed
Enzymatic deficiency in primaquine-sensitive erythrocytes. Science (New York, N.Y.). 1956. ALVING A S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Toxicity of primaquine in Caucasians. Journal of the American Medical Association. 1952. CLAYMAN C B, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Toxicity of primaquine in Negroes. Journal of the American Medical Association. 1952. HOCKWALD R S, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01087
ChEBI:
8405
KEGG Compound:
C07627
PubChem Compound:
4908
PubChem Substance:
46508222
9829
Drugs Product Database (DPD):
2017776
BindingDB:
50203193
ChemSpider:
4739
Therapeutic Targets Database:
DAP000216

Clinical Trials

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

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