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Guidelines for the treatment of malaria – 2 edition

in the liver, mainly to monodesethylchloroquine, which has similar activity against
P. falciparum.

Toxicity

Chloroquine has a low safety margin and is very dangerous in overdosage. Larger doses
of chloroquine are used for the treatment of rheumatoid arthritis than for malaria, so
adverse effects are seen more frequently in patients with the former. The drug is generally
well tolerated. The principle limiting adverse effects in practice are the unpleasant
taste, which may upset children, and pruritus, which may be severe in dark-skinned
patients (6). Other less common side effects include headache, various skin eruptions
and gastrointestinal disturbances, such as nausea, vomiting and diarrhoea. More rarely
central nervous system toxicity including, convulsions and mental changes may occur.
Chronic use (>5 years continuous use as prophylaxis) may lead to eye disorders, including
keratopathy and retinopathy. Other uncommon effects include myopathy, reduced
hearing, photosensitivity and loss of hair. Blood disorders, such as aplastic anaemia, are
extremely uncommon (7).

Acute overdosage is extremely dangerous and death can occur within a few hours. The
patient may progress from feeling dizzy and drowsy with headache and gastrointestinal
upset, to developing sudden visual loss, convulsions, hypokalaemia, hypotension and
cardiac arrhythmias. There is no specific treatment, although diazepam and epinephrine
(adrenaline) administered together are beneficial (8,9).

Drug interactions

Major interactions are very usual. There is a theoretical increased risk of arrhythmias when
chloroquine is given with halofantrine or other drugs that prolong the electrocardiograph
QT interval; a possible increased risk of convulsions with mefloquine; reduced absorption
with antacids; reduced metabolism and clearance with cimetidine; an increased risk of
acute dystonic reactions with metronidazole; reduced bioavailability of ampicillin and
praziquantel; reduced therapeutic effect of thyroxine; a possible antagonistic effect on
the antiepileptic effects of carbamazepine and sodium valproate; and increased plasma
concentrations of cyclosporine.

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