HALFAN
Clinical safety rating
cautionComprehensive clinical and safety monograph for HALFAN (HALFAN).
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.
| 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. |
| Molecular Weight | 254.3 Da |
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. |
| 1st trimester | Contraindicated due to teratogenicity risk (e.g., cardiovascular and neural tube defects). |
| 2nd trimester | Contraindicated due to risk of fetal cardiotoxicity and electrolyte disturbances. |
| 3rd trimester | Contraindicated due to risk of neonatal cardiotoxicity, hypoglycemia, and electrolyte disturbances. |
Clinical note
Comprehensive clinical and safety monograph for HALFAN (HALFAN).
| Placental transfer | Crosses placenta; therapeutic levels in fetal plasma. |
| Breastfeeding | Excreted into breast milk; potential for severe adverse effects in nursing infants. Not recommended. |
| Lactation Rating | L5 (Contraindicated) |
| 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. |
| Fetal Monitoring | Monitor maternal liver function tests (LFTs), renal function, and complete blood count (CBC) periodically. Consider fetal ultrasound for growth and anatomy if exposure during first trimester. Monitor for maternal hypotension, bradycardia, and arrhythmias. |
| Fertility Effects | Animal studies have shown impaired fertility at high doses. Human data insufficient. May cause reversible reduction in sperm count or ovarian function. Advise patients seeking pregnancy to weigh risks. |
■ 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.
| Serious Effects |
Known hypersensitivityCardiac glycoside toxicityHypokalemiaHypercalcemiaHypomagnesemiaRenal impairmentConcomitant use with other cardiotonic glycosides
| 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. |
| Food/Dietary | Take with a high-fat meal (e.g., full yogurt, burger, nuts) to increase absorption by up to 10-fold. Grapefruit juice may increase halofantrine levels; avoid concurrent use. Avoid alcohol due to additive QT-prolonging effects. |
| Clinical Pearls | Halofantrine (Halfan) is reserved for chloroquine-resistant Plasmodium falciparum malaria due to risk of fatal cardiotoxicity (QT prolongation, ventricular arrhythmias). Must obtain baseline ECG and monitor QTc; contraindicated if QTc >450 ms, family history of sudden death, or concurrent use of other QT-prolonging drugs. Administer with fatty food to enhance absorption, but food content may increase risk of arrhythmias. Do not repeat therapy within 6 weeks due to cumulative toxicity. |
| Patient Advice | Take with a full meal high in fat to improve absorption. · Complete the full course even if symptoms improve. · Report immediately any chest pain, palpitations, fainting, or irregular heartbeat. · Avoid use with certain anti-malarials (e.g., quinine, mefloquine) and other drugs that affect heart rhythm. · Inform doctor if you have a personal or family history of heart problems, fainting, or electrolyte disturbances. · Do not use during pregnancy or breastfeeding unless specifically directed. |
Loading safety data…