Halofantrine

This is fast-acting, effective and has few side effects. The dose for an adult is 500 mg, repeated after 6 and 12 hours. It is recommended that non-immune individuals repeat this after one week. High-dose halofantrine is used in Thailand. Absorption is highly variable and is considerably increased if the medication is taken with fatty food. At present, however, the advice is to take Halfan® on an empty stomach. There is a syrup for children. The maximum concentration is reached 6 hours after oral ingestion. The half-life is 1-3 days for halofantrine itself and 2-4 days for the active (debutylated) metabolite (longer in active malaria than in healthy persons). [Desbutyl-halofantrine is being evaluated as a potential prophylactic agent]. Excretion is chiefly via the faeces.

In Southeast Asia resistance is common, but in other regions this problem is still limited. There is limited cross resistance with mefloquine. Cases of insufficient clinical response (5% of cases) are usually due to inadequate absorption. Sometimes Halfan® is used as the drug of first choice, or as a stand-by treatment for travellers, but this has been superseded by Malarone. It should be stressed that halofantrine cannot be given IV. Use in severe malaria might therefore be problematic (possibly via gastric tube). During treatment with halofantrine there is prolongation of the PR-interval and the QT time. Severe cardiac problems have been described in people who previously had a cardiac conduction disorder. Prolonged QT_c time, thiamine deficiency, conduction disturbances, ion deficiency (hypokalemia, hypomagnesaemia) and concomitant administration of quinine or mefloquine are contra-indications. If there is a falciparum malaria during mefloquine prophylaxis, Halfan® is not a good choice due to possible cross-resistance and cumulative cardiotoxicity. Other products which may also cause QT-time prolongation, such as cisapride [Prepulsid®], terfenadine [Triludan®], tricyclic antidepressants such as clomipramine [Anafranil®] and amitriptyline [Redomex®] are best avoided during Halfan® administration. An ECG is therefore advisable before administration of Halfan®. Halfan® cannot be used as prophylaxis. [A reminder: the QT-time is the time from the beginning of the Q-wave to the end of the T-wave. The correction for cardiac rate using Bazett’s formula (QT/RR) gives the QTc.] If there is a prolonged QT-time (longer than 440 msec) there is an increased risk of ventricular tachycardia, more specifically "torsade de pointes". This is characterised by polymorphous QRS complexes which vary in amplitude and appear to oscillate around the isoelectric line.

Category: Medicine Notes