Action and Spectrum

Actions and Spectrum 

Actions: 

halofantrine’s primary mode of action involves interfering with the ability of the malaria parasite (Plasmodium falciparum) to multiply within red blood cells. It affects the parasite’s ion channels, specifically those related to calcium transport, which disrupts the parasite’s normal cellular processes. This disruption leads to the parasite’s death, helping to control and treat malaria infections. 

Spectrum: 

halofantrine was primarily used against Plasmodium falciparum, the most severe and deadly malaria parasite species. It was effective against both drug-sensitive and some drug-resistant strains of Plasmodium falciparum. However, its use could have been improved due to the emergence of resistant strains, safety concerns, and potential interactions with other medications. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Chest Pain 

Ventricular arrhythmias 

Orthostatic hypertension 

Cerebrovascular accident 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindications: 

• QT prolongation 
• Pre-existing cardiac conditions 
• Concomitant medicines 

Cautions: 

• Cardiac Monitoring 
• Electrolyte imbalance 
• Medication interaction 
• Baseline ECG 

Pregnancy / Lactation

Pregnancy consideration:  

Pregnancy Category: C 

Breastfeeding warnings:  

No data is available regarding the excretion of drug in breast milk.  

Pregnancy category: 

Category A: well-controlled and satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: No data is available for the drug under this category. 

Pharmacology

Pharmacology:  

halofantrine interferes with the parasite’s calcium-dependent ion channels, particularly those regulating calcium fluxes across the parasite’s membranes. This disruption affects the parasite’s normal cellular functions, leading to growth inhibition and death of the Plasmodium falciparum parasite.Top of Form 

Pharmacodynamics: 

halofantrine blocks the HERG channels that are already inactivated, causing cardiotoxicity.  

Pharmacokinetics: 

Absorption 

halofantrine is administered orally in tablet form. It is absorbed from the gastrointestinal tract, and its absorption is influenced by the presence of food in the stomach. Taking halofantrine with food can enhance its absorption. 

Distribution 

Once absorbed, halofantrine is distributed throughout the bloodstream. It crosses the blood-brain barrier and can reach therapeutic concentrations in the central nervous system, making it effective against cerebral malaria. 

Metabolism 

halofantrine undergoes extensive metabolism in the liver by the enzyme cytochrome P450 3A4 (CYP3A4). This metabolism results in the formation of an active metabolite, N-desbutyl-halofantrine. 

Elimination and Excretion 

Metabolized halofantrine and its metabolites are primarily excreted in the feces. Only a small portion is excreted in the urine. 

Adminstartion

Patient Information Leaflet

Patient information leaflet 

Generic Name: halofantrine 

Pronounced as: hal-oh-FAN-treen 

Why do we use halofantrine? 

halofantrine is used as an antimalarial medication to treat malaria caused by the Plasmodium falciparum parasite, which is responsible for severe cases of the disease. It is effective against both the asexual blood stages of the parasite.