Drug/Small Molecule:
mefloquine

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.



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.

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 Clinical Annotations available VA
G6PD deficiency N/A N/A N/A
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Mefloquine HCL
  • Mefloquine aziridine
  • Mefloquinone
Trade Names
  • Lariam
Brand Mixture Names

PharmGKB Accession Id:
PA450348

Description

A phospholipid-interacting antimalarial drug (antimalarials). It is very effective against plasmodium falciparum with very few side effects.

Source: Drug Bank

Indication

For the treatment of mild to moderate acute malaria caused by Mefloquineuine-susceptible strains of Plasmodium falciparum (both chloroquine-susceptible and resistant strains) or by Plasmodium vivax. Also for the prophylaxis of Plasmodium falciparum and Plasmodium vivax malaria infections, including prophylaxis of chloroquine-resistant strains of Plasmodium falciparum.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Mefloquine has been found to produce swelling of the Plasmodium falciparum food vacuoles. It may act by forming toxic complexes with free heme that damage membranes and interact with other plasmodial components.

Source: Drug Bank

Pharmacology

Mefloquine is an antimalarial agent which acts as a blood schizonticide. Mefloquine is active against the erythrocytic stages of Plasmodium species. However, the drug has no effect against the exoerythrocytic (hepatic) stages of the parasite. Mefloquine is effective against malaria parasites resistant to chloroquine. Mefloquine is a chiral molecule. According to some research, the (+) enantiomer is more effective in treating malaria, and the (-) enantiomer specifically binds to adenosine receptors in the central nervous system, which may explain some of its psychotropic effects.

Source: Drug Bank

Food Interaction

Avoid alcohol.|Take with a full glass of water.|Take with food.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. Two metabolites have been identified in humans. The main metabolite, 2,8-bis-trifluoromethyl-4-quinoline carboxylic acid, is inactive against Plasmodium falciparum. The second metabolite, an alcohol, is present in minute quantities.

Source: Drug Bank

Protein Binding

98%

Source: Drug Bank

Absorption

Well absorbed from the gastrointestinal tract. The presence of food significantly enhances the rate and extent of absorption.

Source: Drug Bank

Half-Life

2 to 4 weeks

Source: Drug Bank

Toxicity

Oral, rat: LD 50 = 880 mg/kg. Symptoms of overdose include nausea, vomiting, and weight loss.

Source: Drug Bank

Clearance

  • 30 mL/min

Source: Drug Bank

Route of Elimination

There is evidence that mefloquine is excreted mainly in the bile and feces. Urinary excretion of unchanged mefloquine and its main metabolite under steady-state condition accounted for about 9% and 4% of the dose, respectively.

Source: Drug Bank

Volume of Distribution

Source: Drug Bank

Chemical Properties

Chemical Formula

C17H16F6N2O

Source: Drug Bank

Isomeric SMILES

c1cc2c(cc(nc2c(c1)C(F)(F)F)C(F)(F)F)C(C3CCCCN3)O

Source: OpenEye

Canonical SMILES

OC(C1CCCCN1)C1=CC(=NC2=C1C=CC=C2C(F)(F)F)C(F)(F)F

Source: Drug Bank

Average Molecular Weight

378.3122

Source: Drug Bank

Monoisotopic Molecular Weight

378.116682374

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 No Clinical Annotation available No Variant Annotation available VIP No VIP available
ABCB1
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
G6PD

Drug Targets

Gene Description
ADORA2A (source: Drug Bank)
HBA1 (source: Drug Bank)
HBA2 (source: Drug Bank)

Drug Interactions

Drug Description
mefloquine Increased risk of cardiac toxicity (source: Drug Bank)
mefloquine Increased risk of cardiac toxicity (source: Drug Bank)
acenocoumarol Mefloquine can increase the anticoagulant effect (source: Drug Bank)
acenocoumarol Mefloquine may increase the anticoagulant effect of acenocoumarol. (source: Drug Bank)
anisindione Mefloquine may increase the anticoagulant effect of anisindione. (source: Drug Bank)
dicumarol Mefloquine can increase the anticoagulant effect (source: Drug Bank)
dicumarol Mefloquine may increase the anticoagulant effect of dicumarol. (source: Drug Bank)
halofantrine Increased risk of cardiac toxicity (source: Drug Bank)
halofantrine Increased risk of cardiac toxicity (source: Drug Bank)
rifampin Rifampin lowers mefloquine levels (source: Drug Bank)
rifampin Rifampin lowers mefloquine levels (source: Drug Bank)
ritonavir Mefloquine decreases the effect of ritonavir (source: Drug Bank)
ritonavir Mefloquine decreases the effect of ritonavir (source: Drug Bank)
warfarin Mefloquine can increase the anticoagulant effect (source: Drug Bank)
warfarin Mefloquine may increase the anticoagulant effect of warfarin. (source: Drug Bank)
ziprasidone Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
ziprasidone Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
mefloquine Rifampin lowers mefloquine levels (source: Drug Bank)
mefloquine Rifampin lowers mefloquine levels (source: Drug Bank)
mefloquine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. (source: Drug Bank)
mefloquine Telithromycin may reduce clearance of Mefloquine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Mefloquine if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank)
mefloquine May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration. (source: Drug Bank)
mefloquine May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration. (source: Drug Bank)
mefloquine Mefloquine increases the risk of seizure and is contraindicated in persons with a history of convulsions. Possible reduction in the therapeutic effect of Tiagabine when used for other indications may also occur. (source: Drug Bank)
mefloquine The p-glycoprotein inhibitor, Mefloquine, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided. (source: Drug Bank)
mefloquine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration. (source: Drug Bank)
mefloquine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. (source: Drug Bank)
mefloquine Mefloquine may decrease the serum concentration of Vigabatrin. This may increase the risk of seizure in patients receiving Vigabatrin to prevent seizures. Consider alternate therapy or monitor for changes in Vigabatrin serum concentration, therapeutic or adverse effects if Mefloquin is initiated, discontinued or dose changed. (source: Drug Bank)
mefloquine Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of mefloquine by decreasing its metabolism. Additive QTc prolongation may also occur. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of mefloquine if voriconazole is initiated, discontinued or dose changed. (source: Drug Bank)
mefloquine Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). (source: Drug Bank)
mefloquine Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated. (source: Drug Bank)
mefloquine Mefloquine may decrease the serum concentration and therapeutic effect of zonisamide. Concomitant therapy is contraindicated in patients with history of convulsions. (source: Drug Bank)
mefloquine Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). (source: Drug Bank)

Curated Information ?

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

May Treat
May Prevent
Contraindicated With

Publications related to mefloquine: 33

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 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 VIP No VIP available
Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenetics and genomics. 2011. Hodges Laura M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Histone deacetylase inhibitors induce a very broad, pleiotropic anticancer drug resistance phenotype in acute myeloid leukemia cells by modulation of multiple ABC transporter genes. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009. Hauswald Stefanie, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Genetic determinants of response to clopidogrel and cardiovascular events. The New England journal of medicine. 2009. Simon Tabassome, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Redox regulation of multidrug resistance in cancer chemotherapy: molecular mechanisms and therapeutic opportunities. Antioxidants & redox signaling. 2009. Kuo Macus Tien. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Several major antiepileptic drugs are substrates for human P-glycoprotein. Neuropharmacology. 2008. Luna-Tortós Carlos, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica; the fate of foreign compounds in biological systems. 2008. Zhou S-F. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression. Neuron. 2008. Uhr Manfred, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Citalopram enantiomers in plasma and cerebrospinal fluid of ABCB1 genotyped depressive patients and clinical response: a pilot study. Pharmacological research : the official journal of the Italian Pharmacological Society. 2008. Nikisch Georg, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Cobalamin potentiates vinblastine cytotoxicity through downregulation of mdr-1 gene expression in HepG2 cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2007. Marguerite Véronique, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Mechanism of inhibition of P-glycoprotein mediated efflux by vitamin E TPGS: influence on ATPase activity and membrane fluidity. Molecular pharmaceutics. 2007. Collnot Eva-Maria, 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
MDR1 gene polymorphisms are associated with neuropsychiatric adverse effects of mefloquine. Clinical pharmacology and therapeutics. 2006. Aarnoudse Albert L H 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
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 VIP No VIP available
Gefitinib modulates the function of multiple ATP-binding cassette transporters in vivo. Cancer research. 2006. Leggas Markos, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Impact of P-glycoprotein on clopidogrel absorption. Clinical pharmacology and therapeutics. 2006. Taubert Dirk, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Single nucleotide polymorphisms in human P-glycoprotein: its impact on drug delivery and disposition. Expert opinion on drug delivery. 2006. Dey Surajit. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Influence of lipid lowering fibrates on P-glycoprotein activity in vitro. Biochemical pharmacology. 2004. Ehrhardt Manuela, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Interactions of human P-glycoprotein with simvastatin, simvastatin acid, and atorvastatin. Pharmaceutical research. 2004. Hochman Jerome H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clinical pharmacology and therapeutics. 2004. Marzolini Catia, 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 VIP No VIP available
Genetic polymorphisms of the human MDR1 drug transporter. Annual review of pharmacology and toxicology. 2003. Schwab Matthias, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Pulmonary toxicity with mefloquine. The European respiratory journal. 2001. Udry E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein. Naunyn-Schmiedeberg's archives of pharmacology. 2001. Pauli-Magnus C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. The Journal of clinical investigation. 1999. Greiner B, 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 No Variant Annotation available VIP No VIP available
Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annual review of pharmacology and toxicology. 1999. Ambudkar S V, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Drug-induced pneumonia associated with hemizygote glucose-6-phosphate-dehydrogenase deficiency. European journal of haematology. 1998. Drent M. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Competitive, non-competitive and cooperative interactions between substrates of P-glycoprotein as measured by its ATPase activity. Biochimica et biophysica acta. 1997. Litman T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
P-glycoprotein structure and evolutionary homologies. Cytotechnology. 1993. Croop J M. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
A phase-III clinical trial of mefloquine in children with chloroquine-resistant falciparum malaria in Thailand. Bulletin of the World Health Organization. 1987. Chongsuphajaisiddhi T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Trials of mefloquine in vivax and of mefloquine plus 'fansidar' in falciparum malaria. Lancet. 1985. Harinasuta T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
A phase II clinical trial of mefloquine in patients with chloroquine-resistant falciparum malaria in Thailand. Bulletin of the World Health Organization. 1983. Harinasuta T, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
54868-5434-0
DrugBank:
DB00358
KEGG Compound:
C07633
KEGG Drug:
D04895
PubChem Compound:
4046
PubChem Substance:
46505610
9835
Drugs Product Database (DPD):
2244366
BindingDB:
50022889
ChemSpider:
3906
Therapeutic Targets Database:
DAP001310
FDA Drug Label at DailyMed:
1c47fd79-c0ca-42d6-9910-774272b25bc1

Clinical Trials

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

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