Halofantrine adverse reactions

Halofantrine
HALFAN® FDA Package Insert
Description
Clinical Pharmacology
Microbiology
Indications and Usage
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Overdosage
Dosage and Administration
How Supplied

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Adverse Reactions

Normal Subjects

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%), 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: Chestpain,palpitations,posturalhypotension.

Dermatologic: Rash.

Gastrointestinal: Abdominaldistention,anorexia,constipation,dyspepsia.

Mucous Membrane: Stomatitis.

Musculoskeletal: Arthralgia, back pain.

CentralNervousSystem: Asthenia,confusion,convulsions,depression,paresthesia, sleep disorder.

Renal: Urinaryfrequency.

Special Senses: Abnormalvision,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.

References

Adapted from the FDA Package Insert.