Drug/Small Molecule:
methylene blue

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 12/17/2013

FDA Label for methylene blue and G6PD

This label is on the FDA Biomarker List
Actionable PGx

Summary

Although the methylene blue drug label does not specifically mention genetic testing, precaution prior to initiating treatment with methylene blue is highlighted for G6PD deficient individuals, a condition caused by variants in the G6PD gene which can be determined by enzymatic or genetic tests.

Annotation

Excerpt from the methylene blue drug label:

Methylene blue should be avoided in patients with G6PD deficiency due to the risk of paradoxical methemoglobinemia and hemolysis.

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

DailyMed link to the label

*Disclaimer: The contents of this page are the sole responsibility of PharmGKB.

Genes and/or phenotypes found in this label

  • Methemoglobinemia
    • Indications & usage section
    • source: FDA Label
  • G6PD
    • Precautions section, toxicity
    • source: PharmGKB

European Medicines Agency (EMA) Label for methylene blue and BLVRB, CYB5R3, G6PD

Actionable PGx

Summary

The EMA European Public Assessment Report (EPAR) for methylthioninium chloride Proveblue (also known as methylene blue) contains information regarding contraindication of the drug in patients with G6PD deficiency due to risk of hemolytic anemia, and in patients with a deficiency in NADPH reductase (encoded by the BLVRB gene). The label also states that failure to respond to the drug may indicate a deficiency in cytochrome b5 reductase (CYB5R3) or G6PD.

Annotation

Excerpts from the methylthioninium chloride Proveblue (methylene blue) EPAR:

Contraindications

  • Hypersensitivity to the active substance, or to any other thiazine dyes
  • Patients with Glucose-6-phosphate dehydrogenase deficiency (G6PD) due to the risk of
    haemolytic anaemia
  • Patients with sodium nitrite-induced methaemoglobinaemia
  • Patients with methaemoglobinaemia due to chlorate poisoning
  • Deficiency in NADPH reductase.


Failure to respond to methylthioninium chloride suggests cytochrome b5 reductase deficiency, glucose-6- phosphate dehydrogenase deficiency or sulfhaemoglobinemia. Alternative treatment options should be considered.

This information is highlighted in the following sections:
Contraindications, special warnings and precautions for use, package leaflet: information for the user.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the methylthioninium chloride Proveblue (methylene blue) EMA drug label.

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


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 CA VA G6PD A-202A_376G N/A N/A N/A
No VIP available CA VA G6PD B (wildtype) N/A N/A N/A
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138

Overview

Generic Names
  • aniline violet
  • methylthionine chloride
  • methylthioninium chloride
  • tetrametylthionine chloride
Trade Names
  • Urolene Blue
  • methylthioninium chloride Proveblue
Brand Mixture Names

PharmGKB Accession Id:
PA450457

Other Vocabularies

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Methylene Blue Pathway, Pharmacodynamics
    A stylized diagram showing the mechanisms that can cause methemoglobin production in erythrocytes and the control mechanisms to prevent methemoglobinemia, including methylene blue treatment which requires NADPH from the Pentose Phosphate Pathway.
  1. Oxidative Stress Regulatory Pathway (Erythrocyte)
    A simplified diagram to show several of the regulatory mechanisms that prevent oxidative stress in red blood cells, many of which require NADPH from the Pentose Phosphate Pathway.
  1. Pentose Phosphate Pathway (Erythrocyte)
    A simplified diagram to show the role of G6PD in generating NADPH in red blood cells - this can then be utilized in the Oxidative Stress Regulatory and Methylene Blue Pathways.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

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
BLVRB
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYB5R3
G6PD
No related drugs are available.

Curated Information ?

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

May Treat
May Prevent
Induces
Contraindicated With

Publications related to methylene blue: 29

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PharmGKB summary: methylene blue pathway. Pharmacogenetics and genomics. 2013. McDonagh Ellen M, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Haemolysis risk in methylene blue treatment of G6PD-sufficient and G6PD-deficient West-African children with uncomplicated falciparum malaria: a synopsis of four RCTs. Pharmacoepidemiology and drug safety. 2012. Müller Olaf, 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 and safety of methylene blue. Drug safety : an international journal of medical toxicology and drug experience. 2012. Müller Olaf, 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 CA VA No VIP available No VIP available
A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2011. Vadhan-Raj S, 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
Exchange transfusion as treatment for rasburicase induced methemoglobinemia in a glucose-6-phosphate dehydrogenase deficient patient. Pediatric blood & cancer. 2008. Bhat Priya, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Aniline-induced methaemoglobinaemia in a glucose-6-phosphate dehydrogenase enzyme deficient patient. Anaesthesia and intensive care. 2007. Mullick P, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Recognition and management of methemoglobinemia and hemolysis in a G6PD-deficient patient on experimental anticancer drug Triapine. American journal of hematology. 2006. Foltz Lynda M, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA 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
Drug-induced haemolysis and methaemoglobinaemia in glucose 6-phosphate dehydrogenase deficiency. British journal of haematology. 2005. Dalal Bukal I, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Postoperative methemoglobinemia with associated G-6-P-D deficiency in infant cardiac surgery--enigmas in diagnosis and management. Paediatric anaesthesia. 2005. Maddali Madan Mohan, et al. PubMed
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
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 CA VA No VIP available No VIP available
Prolonged hemolysis and methemoglobinemia following organic copper fungicide ingestion. Veterinary and human toxicology. 2004. Yang Chen-Chang, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Hemolytic anemia after methylene blue therapy for aniline-induced methemoglobinemia. Veterinary and human toxicology. 2002. Liao Yao-Pan, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Metoclopramide-induced methemoglobinemia in a patient with co-existing deficiency of glucose-6-phosphate dehydrogenase and NADH-cytochrome b5 reductase: failure of methylene blue treatment. Haematologica. 2001. Karadsheh N S, et al. PubMed
Methylene blue-induced hyperbilirubinemia in neonatal glucose-6-phosphate dehydrogenase (G6PD) deficiency. The Journal of maternal-fetal medicine. 2000. Gauthier T W. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Methemoglobinemia: etiology, pharmacology, and clinical management. Annals of emergency medicine. 1999. Wright R O, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Methemoglobinemia: etiology, pharmacology, and clinical management. Annals of emergency medicine. 1999. Wright R O, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Methemoglobinemia induced by methylene blue pertubation during laparoscopy. Acta anaesthesiologica Scandinavica. 1998. Bilgin H, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Treatment of high-risk, refractory acquired methemoglobinemia with automated red blood cell exchange. Journal of clinical apheresis. 1998. Golden P 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
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
Concise review: methemoglobinemia. American journal of hematology. 1993. Mansouri 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
Glucose-6-phosphate dehydrogenase deficiency. WHO Working Group. Bulletin of the World Health Organization. 1989. PubMed
Failure of methylene blue treatment in toxic methemoglobinemia. Association with glucose-6-phosphate dehydrogenase deficiency. Annals of internal medicine. 1971. Rosen P 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
TPNH-methemoglobin reductase deficiency: a new red-cell enzyme defect. The Journal of laboratory and clinical medicine. 1967. Sass 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
METHEMOGLOBIN REDUCTION. STUDIES OF THE INTERACTION BETWEEN CELL POPULATIONS AND OF THE ROLE OF METHYLENE BLUE. Blood. 1963. BEUTLER 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
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

Clinical Trials

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

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