The following adverse events were reported in normal subjects given Halfan 1000 mg to
1500 mg in a single dosing course.
Gastrointestinal: Abdominal pain (10%), anorexia (5%), diarrhea (5%), nausea (10%),
Central Nervous System: Dizziness (5%), headache (5%).
In clinical trials involving 933 patients treated with three 500 mg doses (500 mg every 6
hours), the following clinical adverse events were reported.
There were no deaths or permanent disabilities thought related to drug toxicity. Five
patients discontinued medication due to adverse events. Three patients vomited medicine
Though temporally related to drug administration, the relationship of the following serious
adverse events to malaria or underlying illness as opposed to drug toxicity could not be
established. Two patients had decreased consciousness; other serious adverse events
reported during clinical trials included convulsions (3 cases), stomatitis (3 cases),
moderately severe diarrhea (2 cases), pulmonary edema (1 case), tetany (1 case),
hypertensive crisis (1 case), cerebrovascular accident (1 case).
The most frequently reported adverse events thought possibly- or probably-related to
halofantrine were: abdominal pain (8.5%), diarrhea (6.0%), dizziness (4.5%), vomiting
(4.3%), nausea (3.4%), cough (3.0%), headache (3.0%), pruritus (2.6%), rigors (1.7%) and
myalgias (1.3%). These events are also characteristic of malaria.
Pruritus was reported in a higher proportion of highly pigmented patients than in other
Adverse events thought possibly- or probably-related to halofantrine affecting <1% of
patients studied in the clinical trials included:
Body as a Whole: Fatigue, malaise.
Cardiovascular: Chest pain, palpitations, postural hypotension.
Gastrointestinal: Abdominal distention, anorexia, constipation, dyspepsia.
Mucous Membrane: Stomatitis.
Musculoskeletal: Arthralgia, back pain.
Central Nervous System: Asthenia, confusion, convulsions, depression, paresthesia,
Renal: Urinary frequency.
Special Senses: Abnormal vision, tinnitus.
The most frequently noted laboratory abnormalities that occurred following drug
administration in the clinical trials were decreased hematocrit, elevated hepatic
transaminases, decreased and increased white blood cell counts, and decreased platelet
counts. These alterations returned to normal limits within 2 to 3 weeks post-infection. The
causal relationship of these changes to Halfan is unclear, as these laboratory
abnormalities can also occur with acute malaria.
Halofantrine was marketed in Europe starting in 1988. The following additional adverse
experiences have been reported in postmarketing surveillance outside the United States:
Facial edema and urticaria (allergic/anaphylactic reactions) in rare cases.
Hemolysis/hemolytic anemia (including immune hemolytic anemia) which may compromise
renal function have been reported in patients with malaria who have been treated with
halofantrine. Hemolytic reactions may also be observed in patients with malaria in the
absence of halofantrine.
Prolongation of QT interval has been reported. There have been rare reports of serious
ventricular dysrhythmias sometimes associated with death. These cases have occurred
particularly under certain conditions which include uses of doses higher than
recommended, recent or concomitant treatment with mefloquine, or presence of preexisting
prolongation of QT interval.1