Halfan (Halofantrine Hydrochloride) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies of halofantrine hydrochloride in animals have not been performed to evaluate carcinogenic potential.

Genotoxicity of halofantrine hydrochloride was evaluated in 5 assay test systems including an Ames test, a gene mutation test in Chinese hamster ovary cells, a chromosomal aberration analysis in Chinese hamster ovary cells, a micronucleus test in mice, and a dominant lethal assay. No mutagenic potential was demonstrated in any of these test systems.

Halofantrine hydrochloride did not adversely affect male or female fertility in the rat at an oral dose of 30 mg/kg (1/6 of the maximum recommended human dose based on mg/m²).

Pregnancy

Teratogenic Effects

Pregnancy Category C : In pregnant rabbits, maternal-lethal doses (decremental dose schedule of 360 to 120 mg/kg, equivalent to 3.6 times to 1.2 times the maximum recommended human dose, respectively, based on mg/m²) were associated with abortion and an increased incidence of skeletal malformations, but oral doses up to 60 mg/kg (6/10 of the maximum recommended human dose based on mg/m²) did not produce maternal or fetal developmental toxicity.

Non-teratogenic Effects

In reproduction teratology studies in the rat, oral doses ≥30 g/kg (1/6 of the maximum recommended human dose based on mg/m²) produced postimplantation embryonic death and reduced fetal weight and viability. Halofantrine hydrochloride at doses of 15 mg/kg/day (1/10 of the maximum recommended human dose based on mg/m²) had no embryotoxicity or teratogenicity. These effects occurred at and below doses that produced overt maternal toxicity in the rats.

Halofantrine has been shown to be embryocidal in rats. There are no adequate and well-controlled studies in pregnant women. HALFAN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

OVERDOSAGE

In case of overdosage, vomiting should be induced, in conjunction with appropriate supportive measures, which should include ECG monitoring. The possibility of neurologic toxicity, especially decreased consciousness and seizures, should be evaluated. Dehydration secondary to gastrointestinal toxicity with diarrhea and vomiting may require treatment with intravenous fluid therapy.

Gastrointestinal distress with abdominal pain, vomiting, cramping, and diarrhea occurs at doses higher than the recommended therapeutic regimen. Palpitations have also been reported at these higher doses.

CONTRAINDICATIONS

HALFAN is contraindicated in patients with a known family history of congenital QTc prolongation. (See BOXED WARNING.) Use of this drug is contraindicated in patients with a known hypersensitivity to halofantrine.