Halofantrine with chloroquine

Adverse effects. Halofantrine may cause gastrointestinal symptoms pruritis occurs but to a lesser extent than with chloroquine which may be reason for it to be preferred. It prolongs the cardiac QT interval and may predispose to hazardous arrhythmia. The drug should therefore not be taken ... 

Sowunmi A, Fehintola FA, Ogundahunsi OA, Ofi AB, Happi TC, Oduola AM. Comparative cardiac effects of halofantrine and chloroquine plus chlorpheniramine in children with acute uncomphcated falciparum malaria. Trans R Soc Trop Med Hyg 1999 93(l) 78-83. 

Adverse effects with the dosages originally recommended have in general been mild, no more than nausea, diarrhea, headache, and pruritus (SEDA-13, 820) (2-4). Pruritus occurred markedly less often with halofantrine than with chloroquine (SEDA-16, 306). A comparison between high-dose chloroquine (35 mg/kg total in three daily doses) and halofantrine in the standard dose (total 25 mg/kg given at 6-hour intervals) in patients 4—14 years old showed a fairly similar frequency of adverse effects. Itching was a common adverse effect of chloroquine (4). 

Early laboratory studies suggested cross-resistance of halofantrine with mefloquine. In rats, parasites that are resistant to mefloquine, quinine, chloroquine, and amodiaquine are also markedly resistant to halofantrine (13). 

Sporadic resistance to mefloquine has been reported from many areas. At present, resistance appears to be uncommon except in regions of Southeast Asia with high rates of multidrug resistance (especially border areas of Thailand). Mefloquine resistance appears to be associated with resistance to quinine and halofantrine but not with resistance to chloroquine. 

In parallel, extensive studies on P. falciparum field isolates in Gabon [140-142], Senegal [143], Cambodia [118, 119, 144], and the Thailand Burmese border [145] corroborated the efficacy of FQ on the parasite whatever its resistance level to chloroquine or to other commonly used antimalarials mefloquine, quinine, halofantrine, and artemisinin derivatives [146, 147]. The cross reactivity observed in some studies with CQ was limited and it was demonstrated that it was caused by differences in initial parasitemia among isolates at the start of the assays [141]. Independance of susceptibility of P. falciparum with phenotypic variation of pfcrt gene, responsible for CQ resistance, could be suspected from these results, but this was demonstrated at the molecular level on Cambodia isolates [148] and extended further on other genes currently involved in resistance to aminoquinoline antimalarials [89, 90]. 

Chlorphenamine enhances the efficacy of chloroquine in acute uncomplicated falciparum malaria, but the disposition of chloroquine in these circumstances is unpredictable. Chloroquine (25 mg/kg) was given orally over 3 days in combination with chlorphenamine to Nigerian children with parasitemia (45). The peak whole blood chloroquine concentration was increased and the time to peak concentration shortened. In small trials there seemed to be an increase in QT interval with this combination, but less than with halofantrine (46). However, in other studies, the addition of chlorphenamine to chloroquine did not amplify the cardiac effects of chloroquine (46). 

There is an increased risk of dysrhythmias, including torsade de pointes, when halofantrine is combined with qui-nine/quinidine or chloroquine and any other drug that prolongs the QT interval (52). 

Clinically important, potentially hazardous interactions with amiodarone, astemizole, bepridil, carbamazepine, chloroquine, cisapride, clarithromycin, dihydroergotamine, disopyramide, ergotamine, grapefruit juice, halofantrine, haloperidol, itraconazole, ketoconazole, methadone, moxifloxacin, phenobarbital, phenytoin, pimozide, procainamide, quinidine, rifampicin, ritonavir, sotalol, St John s wort, telithromycin, terfenadine, voriconazole... 

Halofantrine is a potent blood schizontocidal agent with high activity against chloroquine-resistant and chloroquine-sensitive P, falciparum. The drug has been used at a dose of Ig/adult given daily for 3 days no phototoxicity or gastrointestinal problems were observed [138,139],... 

Halofantrine, a synthetic phenanthrene-methanol, is a recently introduced antimalarial drug which is a blood schizonticide. The drug is effective against chloroquine-resistant P. falciparum but has been associated with cardiotoxicity, so it must be used with caution (76). 

An isolated report describes life-threatening hypoglycaemia in a 3-year-old boy, with uncomplicated malaria, 90 minutes after he took sulfadox-ine-pyrimethaniine (Fansidar). Mefloquine has been reported to reduce plasma glucose levels in healthy subjects. Artemisinin derivatives such as artemether may be associated with fewer episodes of hypoglycaemia than quinine in children with severe malaria. Chloroquine, amo-diaquine and halofantrine do not apparently stimulate the release of insulin. ... 

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