HALFAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for HALFAN (HALFAN).

How it works

HALFAN (halofantrine) is an antimalarial agent that acts as a blood schizonticide. It is thought to inhibit the polymerization of heme into hemozoin, leading to toxic accumulation of free heme within the parasite's food vacuole. It may also interfere with nucleic acid synthesis.

What the body does with it

Metabolism	Halofantrine is extensively metabolized in the liver, primarily via cytochrome P450 (CYP) 3A4, to its active metabolite N-desbutylhalofantrine. Both parent drug and metabolite are highly bound to plasma proteins.
Excretion	Primarily hepatic metabolism; renal excretion of metabolites accounts for <10% unchanged drug; biliary/fecal elimination of metabolites approximately 20-30%.
Half-life	Terminal elimination half-life is 10-18 hours (mean 14 hours) in healthy adults, allowing twice-daily dosing.
Protein binding	25-30% bound to serum albumin.
Volume of Distribution	0.9-1.0 L/kg, indicating distribution into total body water.
Bioavailability	Oral: 88-95%; rectal: 80-90%; intramuscular: 96%.
Onset of Action	Oral: 1-2 hours; rectal: 2-4 hours; intramuscular: 30-60 minutes (for fever reduction).
Duration of Action	Antipyretic/analgesic effect lasts 4-6 hours; extended-release formulations may provide up to 8 hours.

Classification & Brands

Dosing & administration

Adults: 500 mg orally once daily.

Dosage form	TABLET
Renal impairment	GFR 30-50 mL/min: 250 mg once daily; GFR <30 mL/min: 125 mg once daily.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: 250 mg once daily; Child-Pugh C: not recommended.
Pediatric use	10 mg/kg orally once daily; maximum 500 mg/day.
Geriatric use	No specific adjustment; monitor renal function due to age-related decline.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for HALFAN (HALFAN).

Breastfeeding	HALFAN is excreted in human milk. M/P ratio not reported. Due to potential for serious adverse reactions in nursing infants, decide whether to discontinue nursing or discontinue drug, taking into account importance of drug to mother.
Teratogenic Risk	FDA Pregnancy Category C. Animal studies have shown embryotoxicity and teratogenicity at high doses. First trimester: Avoid use due to potential teratogenic effects. Second and third trimesters: Limited data; risk of fetal harm cannot be ruled out. Use only if potential benefit justifies risk.

Warnings & precautions

■ FDA Black Box Warning

Cardiotoxicity: HALFAN prolongs the QT interval and can cause serious, life-threatening ventricular arrhythmias (e.g., torsade de pointes). Do not use in patients with pre-existing QTc prolongation, electrolyte disturbances (e.g., hypokalemia, hypomagnesemia), or those taking other drugs that prolong the QT interval. ECG monitoring is required before, during, and after therapy.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Pre-existing QTc prolongation or congenital long QT syndrome","History of ventricular arrhythmias","Hypokalemia or hypomagnesemia","Concurrent use of drugs that prolong the QT interval (e.g., class IA/III antiarrhythmics, some antibiotics, antipsychotics)","G6PD deficiency (relative)","Pregnancy and breastfeeding (contraindicated in pregnancy)"]

Clinical Precautions

Precautions

["Cardiotoxicity: QTc interval prolongation; contraindicated in patients with conduction disorders or concurrent QT-prolonging drugs.","Hematologic: May cause hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.","Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain.","Hepatic: Use with caution in hepatic impairment.","Pregnancy: Not recommended (teratogenic in animal studies).","Drug interactions: Avoid with CYP3A4 inhibitors and QT-prolonging agents."]

Clinical Tips & Counseling

Drug interactions

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HALFAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for HALFAN (HALFAN).

How it works

What the body does with it

Metabolism	Halofantrine is extensively metabolized in the liver, primarily via cytochrome P450 (CYP) 3A4, to its active metabolite N-desbutylhalofantrine. Both parent drug and metabolite are highly bound to plasma proteins.
Excretion	Primarily hepatic metabolism; renal excretion of metabolites accounts for <10% unchanged drug; biliary/fecal elimination of metabolites approximately 20-30%.
Half-life	Terminal elimination half-life is 10-18 hours (mean 14 hours) in healthy adults, allowing twice-daily dosing.
Protein binding	25-30% bound to serum albumin.
Volume of Distribution	0.9-1.0 L/kg, indicating distribution into total body water.
Bioavailability	Oral: 88-95%; rectal: 80-90%; intramuscular: 96%.
Onset of Action	Oral: 1-2 hours; rectal: 2-4 hours; intramuscular: 30-60 minutes (for fever reduction).
Duration of Action	Antipyretic/analgesic effect lasts 4-6 hours; extended-release formulations may provide up to 8 hours.

Classification & Brands

Dosing & administration

Adults: 500 mg orally once daily.

Dosage form	TABLET
Renal impairment	GFR 30-50 mL/min: 250 mg once daily; GFR <30 mL/min: 125 mg once daily.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: 250 mg once daily; Child-Pugh C: not recommended.
Pediatric use	10 mg/kg orally once daily; maximum 500 mg/day.
Geriatric use	No specific adjustment; monitor renal function due to age-related decline.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for HALFAN (HALFAN).

Breastfeeding	HALFAN is excreted in human milk. M/P ratio not reported. Due to potential for serious adverse reactions in nursing infants, decide whether to discontinue nursing or discontinue drug, taking into account importance of drug to mother.
Teratogenic Risk	FDA Pregnancy Category C. Animal studies have shown embryotoxicity and teratogenicity at high doses. First trimester: Avoid use due to potential teratogenic effects. Second and third trimesters: Limited data; risk of fetal harm cannot be ruled out. Use only if potential benefit justifies risk.