indication

For treatment of Severe malaria

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.

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.

toxicity

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

biotransformation

Hepatic

half life

6-10 days

drug interactions

Artemether: Halofantrine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.

Bicalutamide: CYP3A4 Inhibitors like bicalutamide may increase the serum concentration of halofantrine. Extreme caution, with possibly increased monitoring of cardiac status (e.g., ECG), should be used with concurrent use of halofantrine with any moderate CYP3A4 inhibitor(s).

Clotrimazole: CYP3A4 Inhibitors (Moderate) such as clotrmazole may increase the serum concentration of halofantrine. Extreme caution, with possibly increased monitoring of cardiac status (e.g., ECG), should be used with concurrent use of halofantrine with any moderate CYP3A4 inhibitor(s).

Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Concurrent use of orally inhaled fluticasone with strong CYP3A4 inhibitors is not recommended.

Lumefantrine: Halofantrine may increase the adverse effects of lumefantrine. Additive QTc-prolongation may occur. Combination therapy is contraindicated and therapies should not be administered within one month of each other due to the long half-life of lumefantrine.

Mefloquine: Increased risk of cardiac toxicity

Mesoridazine: Increased risk of cardiotoxicity and arrhythmias

Posaconazole: Contraindicated co-administration

Quinupristin: This combination presents an increased risk of toxicity

Tacrolimus: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Telithromycin: 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.

Thioridazine: Increased risk of cardiotoxicity and arrhythmias

Thiothixene: May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.

Toremifene: 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.

Trimipramine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Verapamil: 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.

Voriconazole: 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.

Vorinostat: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Ziprasidone: Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.

Zuclopenthixol: 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).