Drug/Small Molecule:
halofantrine

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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?
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Halofantrina [INN-Spanish]
  • Halofantrine [Usan]
  • Halofantrinum [INN-Latin]
Trade Names
  • Halfan
Brand Mixture Names

PharmGKB Accession Id:
PA449839

Description

Halofantrine is a drug used to treat malaria. It belongs to the phenanthrene class of compounds that includes quinine and lumefantrine. It appears to inhibit polymerisation of heme molecules (by the parasite enzyme "heme polymerase"), resulting in the parasite being poisoned by its own waste. Halofantrine has been shown to preferentially block open and inactivated HERG channels leading to some degree of cardiotoxicity.

Source: Drug Bank

Indication

For treatment of Severe malaria

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 action of Halofantrine may be similar to that of chloroquine, quinine, and mefloquine; by forming toxic complexes with ferritoporphyrin IX that damage the membrane of the parasite.

Source: Drug Bank

Pharmacology

Halofantrine is a synthetic antimalarial which acts as a blood schizonticide. It is effective against multi drug resistant (including mefloquine resistant) P. falciparum malaria.

Source: Drug Bank

Food Interaction

Take on an empty stomach, bioavailability is 6 times higher when drug is taken with high fat meals. Risks of cardiac toxicity are then increased.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic

Source: Drug Bank

Protein Binding

60-70%;

Source: Drug Bank

Half-Life

6-10 days

Source: Drug Bank

Toxicity

Side effects incldue coughing noisy, rattling, troubled breathing, loss of appetite, aches and pain in joints, indigestion,and skin itching or rash.

Source: Drug Bank

Chemical Properties

Chemical Formula

C26H30Cl2F3NO

Source: Drug Bank

Isomeric SMILES

CCCCN(CCCC)CCC(c1cc2c(cc(cc2Cl)Cl)c3c1ccc(c3)C(F)(F)F)O

Source: OpenEye

Canonical SMILES

CCCCN(CCCC)CCC(O)C1=C2C=CC(=CC2=C2C=C(Cl)C=C(Cl)C2=C1)C(F)(F)F

Source: Drug Bank

Average Molecular Weight

500.424

Source: Drug Bank

Monoisotopic Molecular Weight

499.165654616

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Antiarrhythmic Pathway, Pharmacodynamics
    Pharmacodynamic pathway of antiarrhythmic drugs in a stylized cardiac myocyte.

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.

Drug Targets

Gene Description
KCNH2 (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)
mesoridazine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
mesoridazine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
quinupristin This combination presents an increased risk of toxicity (source: Drug Bank)
thioridazine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
thioridazine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
ziprasidone Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
ziprasidone Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
halofantrine Increased risk of cardiac toxicity (source: Drug Bank)
halofantrine Increased risk of cardiac toxicity (source: Drug Bank)
halofantrine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
halofantrine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
halofantrine This combination presents an increased risk of toxicity (source: Drug Bank)
halofantrine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. (source: Drug Bank)
halofantrine Telithromycin may reduce clearance of Halofantrine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Halofantrine if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank)
halofantrine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
halofantrine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
halofantrine 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)
halofantrine 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)
halofantrine 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)
halofantrine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. (source: Drug Bank)
halofantrine Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Halofantrine by decreasing its metabolism. Extreme caution with increased cardiac status monitoring should be used during concomitant therapy. (source: Drug Bank)
halofantrine Voriconazole may increase the serum concentration of halofantrine by decreasing its metabolism by CYP3A4. Concomitant therapy should be avoided due to the concentration-dependent risk of QTc prolongation related to halofantrine. (source: Drug Bank)
halofantrine 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)
halofantrine Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated. (source: Drug Bank)
halofantrine 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)

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

May Treat
Contraindicated With

Publications related to halofantrine: 3

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
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
Antimalarial drug toxicity: a review. Drug safety : an international journal of medical toxicology and drug experience. 2004. Taylor W Robert J, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01218
KEGG Compound:
C07634
PubChem Compound:
37393
PubChem Substance:
46506753
603092
Drugs Product Database (DPD):
2162857
BindingDB:
50096846
ChemSpider:
34303
Therapeutic Targets Database:
DAP000953

Clinical Trials

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

Common Searches

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