ADVERSE REACTIONS
Normal Subjects
The following adverse events were reported in normal subjects given HALFAN 1,000 mg to 1,500 mg in a single dosing course.
Gastrointestinal
Abdominal pain (10%), anorexia (5%), diarrhea (5%), nausea (10%), vomiting (10%).
Central Nervous System
Dizziness (5%), headache (5%).
Clinical Trials
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 repeatedly.
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 patients.
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.
Dermatologic
Rash.
Gastrointestinal
Abdominal distention, anorexia, constipation, dyspepsia.
Mucous Membrane
Stomatitis.
Musculoskeletal
Arthralgia, back pain.
Central Nervous System
Asthenia, confusion, convulsions, depression, paresthesia, sleep disorder.
Renal
Urinary frequency.
Special Senses
Abnormal vision, tinnitus.
Laboratory
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.
Postmarketing Experience
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 pre-existing prolongation of QT interval.1
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