Drug/Small Molecule:
chloroquine

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 annotates drug labels containing pharmacogenetic information approved by the US Food and Drug Administration (FDA), European Medicines Agency (EMA) and the Pharmaceuticals and Medical Devices Agency, Japan (PMDA). PharmGKB annotations provide a brief summary of the PGx in the label, an excerpt from the label and a downloadable highlighted label PDF file. A list of genes and phenotypes found within the label is mapped to label section headers and listed at the end of each annotation. PharmGKB also attempts to interpret the level of action implied in each label with the "PGx Level" tag.

Sources:

  • FDA Information is gathered from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" and from FDA-approved labels brought to our attention. Please note that drugs may be removed from or added to the FDA's Table without our knowledge. We periodically check the Table for changes and update PharmGKB accordingly. Drugs listed on the Table to our knowledge are tagged with the Biomarker icon. A drug label that has been removed from the Table will not have the Biomarker icon but will continue to have an annotation on PharmGKB stating the label has been removed from the FDA's Table. We acquire label PDF files from DailyMed.
  • EMA European Public Assessment Reports (EPARs) that contain PGx information were identified from [Article:24433361] and also by searching for drugs for which we have PGx-containing FDA drug labels.

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


last updated 10/25/2013

FDA Label for chloroquine and G6PD

Actionable PGx

Summary

The FDA-approved drug label for chloroquine (Aralan) states caution should be taken when administering treatment to G6PD deficient individuals due to the possibility of hematological effects. G6PD deficiency is a condition caused by variants in the G6PD gene which can be determined by enzymatic or genetic tests, however the drug label does not specifically mention testing.

Annotation

Excerpt from the chloroquine drug label:

Hematological Effects/Laboratory Tests
Complete blood cell counts should be made periodically if patients are given prolonged therapy. If any severe blood disorder appears which is not attributable to the disease under treatment, discontinuance of the drug should be considered. The drug should be administered with caution to patients having G-6-PD (glucose-6 phosphate dehydrogenase) deficiency.

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

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

Genes and/or phenotypes found in this label

  • Malaria
    • Indications & usage section, Dosage & administration section, Description section, Clinical pharmacology section
    • source: FDA Label
  • G6PD
    • 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.

? = Mouse-over for quick help

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 chloroquine variant annotations

Gene ? Variant?
(142)
Alternate Names ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA G6PD A- 202A_376G N/A N/A N/A
No VIP available CA No VIP available G6PD B (wildtype) 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 CA No VIP available G6PD Mediterranean Haplotype N/A N/A N/A
No VIP available CA 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
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 142
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Chloraquine
  • Chlorochine
  • Chloroquina
  • Chloroquine Phosphate
  • Chloroquinium
  • Chlorquin
  • Clorochina
  • Hydroxychloroquine Sulfate
Trade Names
  • 3377 RP opalate
  • Amokin
  • Aralen
  • Aralen HCl
  • Arechin
  • Arthrochin
  • Artrichin
  • Avlochlor
  • Avloclor
  • Bemaco
  • Bemaphate
  • Bemasulph
  • Benaquin
  • Bipiquin
  • Capquin
  • Chemochin
  • Chingamin
  • Chlorochin
  • Cidanchin
  • Cocartrit
  • Dawaquin
  • Delagil
  • Dichinalex
  • Elestol
  • Gontochin
  • Heliopar
  • Imagon
  • Iroquine
  • Klorokin
  • Lapaquin
  • Malaquin
  • Malaren
  • Malarex
  • Mesylith
  • Neochin
  • Nivachine
  • Nivaquine
  • Nivaquine B
  • Pfizerquine
  • Plaquenil
  • Quinachlor
  • Quinagamin
  • Quinagamine
  • Quinercyl
  • Quingamine
  • Quinilon
  • Quinoscan
  • Resochen
  • Resochin
  • Resoquina
  • Resoquine
  • Reumachlor
  • Reumaquin
  • Roquine
  • Sanoquin
  • Silbesan
  • Siragan
  • Solprina
  • Sopaquin
  • Tanakan
  • Tresochin
  • Trochin
Brand Mixture Names

PharmGKB Accession Id:
PA448948

Description

The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.

Source: Drug Bank

Indication

For the suppressive treatment and for acute attacks of malaria due to P. vivax, P.malariae, P. ovale, and susceptible strains of P. falciparum, Second-line agent in treatment of Rheumatoid Arthritis

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

The mechanism of plasmodicidal action of chloroquine is not completely certain. Like other quinoline derivatives, it is thought to inhibit heme polymerase activity. This results in accumulation of free heme, which is toxic to the parasites. nside red blood cells, the malarial parasite must degrade hemoglobin to acquire essential amino acids, which the parasite requires to construct its own protein and for energy metabolism. Digestion is carried out in a vacuole of the parasite cell.

During this process, the parasite produces the toxic and soluble molecule heme. The heme moiety consists of a porphyrin ring called Fe(II)-protoporphyrin IX (FP). To avoid destruction by this molecule, the parasite biocrystallizes heme to form hemozoin, a non-toxic molecule. Hemozoin collects in the digestive vacuole as insoluble crystals.

Chloroquine enters the red blood cell, inhabiting parasite cell, and digestive vacuole by simple diffusion. Chloroquine then becomes protonated (to CQ2+), as the digestive vacuole is known to be acidic (pH 4.7); chloroquine then cannot leave by diffusion. Chloroquine caps hemozoin molecules to prevent further biocrystallization of heme, thus leading to heme buildup. Chloroquine binds to heme (or FP) to form what is known as the FP-Chloroquine complex; this complex is highly toxic to the cell and disrupts membrane function. Action of the toxic FP-Chloroquine and FP results in cell lysis and ultimately parasite cell autodigestion. In essence, the parasite cell drowns in its own metabolic products.

Source: Drug Bank

Pharmacology

Chloroquine is the prototype anti malarial drug, most widely used to treat all types of malaria except for disease caused by chloroquine resistant Plasmodium falciparum. It is highly effective against erythrocytic forms of Plasmodium vivax, Plasmodium ovale and Plasmodium malariae, sensitive strains of Plasmodium falciparum and gametocytes of Plasmodium vivax. Being alkaline, the drug reaches high concentration within the food vacuoles of the parasite and raises its pH. It is found to induce rapid clumping of the pigment. Chloroquine inhibits the parasitic enzyme heme polymerase that converts the toxic heme into non-toxic hemazoin, thereby resulting in the accumulation of toxic heme within the parasite. It may also interfere with the biosynthesis of nucleic acids.

Source: Drug Bank

Food Interaction

Take with food to reduce irritation and increase bioavailability.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic (partially)

Source: Drug Bank

Protein Binding

~55% of the drug in the plasma is bound to nondiffusible plasma constituents

Source: Drug Bank

Absorption

Completely absorbed from gastrointestinal tract

Source: Drug Bank

Half-Life

1-2 months

Source: Drug Bank

Route of Elimination

Excretion of chloroquine is quite slow, but is increased by acidification of the urine.

Source: Drug Bank

Chemical Properties

Chemical Formula

C18H26ClN3

Source: Drug Bank

Isomeric SMILES

CCN(CC)CCCC(C)Nc1ccnc2c1ccc(c2)Cl

Source: OpenEye

Canonical SMILES

CCN(CC)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C1

Source: Drug Bank

Average Molecular Weight

319.872

Source: Drug Bank

Monoisotopic Molecular Weight

319.181525554

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
G6PD

Drug Targets

Gene Description
GSTA2 (source: Drug Bank)
HBA1 (source: Drug Bank)
HBA2 (source: Drug Bank)
TLR9 (source: Drug Bank)
TNF (source: Drug Bank)

Drug Interactions

Drug Description
chloroquine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine (source: Drug Bank)
chloroquine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine (source: Drug Bank)
chloroquine The antiacid decreases the absorption of chloroquine (source: Drug Bank)
chloroquine The antiacid decreases the absorption of chloroquine (source: Drug Bank)
aluminium The antiacid decreases the absorption of chloroquine (source: Drug Bank)
atomoxetine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine (source: Drug Bank)
atomoxetine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine (source: Drug Bank)
attapulgite The antiacid decreases the absorption of chloroquine (source: Drug Bank)
Calcium The antiacid decreases the absorption of chloroquine (source: Drug Bank)
Calcium The antiacid decreases the absorption of chloroquine (source: Drug Bank)
cyclosporine Increases the effect of cyclosporine (source: Drug Bank)
cyclosporine Increases the effect of cyclosporine (source: Drug Bank)
dihydroxyaluminium The antiacid decreases the absorption of chloroquine (source: Drug Bank)
kaolin The antiacid decreases the absorption of chloroquine (source: Drug Bank)
kaolin The antiacid decreases the absorption of chloroquine (source: Drug Bank)
Magnesium The antiacid decreases the absorption of chloroquine (source: Drug Bank)
Magnesium The antiacid decreases the absorption of chloroquine (source: Drug Bank)
magnesium oxide The antiacid decreases the absorption of chloroquine (source: Drug Bank)
mesoridazine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
mesoridazine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
praziquantel Markedly lower praziquantel levels (source: Drug Bank)
thioridazine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
thioridazine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
chloroquine Chloroquine increases the effect of cyclosporine (source: Drug Bank)
chloroquine Chloroquine increases the effect of cyclosporine (source: Drug Bank)
chloroquine The antiacid decreases the absorption of chloroquine (source: Drug Bank)
chloroquine The antiacid decreases the absorption of chloroquine (source: Drug Bank)
chloroquine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
chloroquine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
chloroquine Markedly lower praziquantel levels (source: Drug Bank)
chloroquine Chloroquine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy. (source: Drug Bank)
chloroquine Chloroquine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy. (source: Drug Bank)
chloroquine Chloroquine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Chloroquine is initiated, discontinued, or dose changed. (source: Drug Bank)
chloroquine Chloroquine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Chloroquine is initiated, discontinued, or dose changed. (source: Drug Bank)
chloroquine Telithromycin may reduce clearance of Chloroquine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Chloroquine if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank)
chloroquine Terbinafine may reduce the metabolism and clearance of Chloroquine. Consider alternate therapy or monitor for therapeutic/adverse effects of Chloroquine if Terbinafine is initiated, discontinued or dose changed. (source: Drug Bank)
chloroquine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
chloroquine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
chloroquine Chloroquine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank)
chloroquine The 2D6 inhibitor, Trazodone, may increase the efficacy of Chloroquine by decreasing Chloroquine metabolism and clearance. Monitor for changes in Chloroquine efficacy if Trazodone is initiated, discontinued or dose changed. (source: Drug Bank)
chloroquine The 2D6 inhibitor, Trazodone, may increase the efficacy of Chloroquine by decreasing Chloroquine metabolism and clearance. Monitor for changes in Chloroquine efficacy if Trazodone is initiated, discontinued or dose changed. (source: Drug Bank)
chloroquine Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of chloroquine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of chloroquine if voriconazole is initiated, discontinued or dose changed. (source: Drug Bank)

Curated Information ?

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

May Treat
May Prevent
Contraindicated With

Publications related to chloroquine: 26

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The genetics of pro-arrhythmic adverse drug reactions. British journal of clinical pharmacology. 2014. Petropoulou Evmorfia, et al. PubMed
No Dosing Guideline available No Drug Label available CA 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 CA 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 No VIP available No VIP available
A study of HLA class I and class II 4-digit allele level in Stevens-Johnson syndrome and toxic epidermal necrolysis. International journal of immunogenetics. 2011. Cristallo A 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
Drug-induced long QT syndrome. Pharmacological reviews. 2010. Kannankeril Prince, 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 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 No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Coprescription of tamoxifen and medications that inhibit CYP2D6. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2010. Sideras Kostandinos, 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 No Variant Annotation available No VIP available 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 No Variant Annotation available 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
Methylene blue for malaria in Africa: results from a dose-finding study in combination with chloroquine. Malaria journal. 2006. Meissner Peter E, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Safety of the combination of chloroquine and methylene blue in healthy adult men with G6PD deficiency from rural Burkina Faso. Tropical medicine & international health : TM & IH. 2005. Mandi Germain, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Safety of the methylene blue plus chloroquine combination in the treatment of uncomplicated falciparum malaria in young children of Burkina Faso [ISRCTN27290841]. Malaria journal. 2005. Meissner Peter E, 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
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 CA VA No VIP available No VIP available
Haemoglobinopathies and G.-6-P.D. deficiency in Laos. Lancet. 1978. Sicard D, 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 CA VA No VIP available No VIP available
Haemolytic effect of two sulphonamides evaluated by a new method. British journal of haematology. 1976. Gaetani G 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
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 No VIP available 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
National Drug Code Directory:
0024-0084-01
DrugBank:
DB00608
PDB:
CLQ
ChEBI:
3638
KEGG Compound:
C07625
KEGG Drug:
D02366
PubChem Compound:
2719
PubChem Substance:
46506925
9827
Drugs Product Database (DPD):
21261
BindingDB:
22985
ChemSpider:
2618
HET:
CLQ
Therapeutic Targets Database:
DAP001357
FDA Drug Label at DailyMed:
b48476e0-9f63-483e-89fe-1af123665951

Clinical Trials

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

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