Taken in proper doses, chloroquine is an extraordinarily safe drug; however, its safety margin is narrow, and a single dose of 30 mg/kg may be fatal (Taylor and White, 2004). Acute chloroquine toxicity is encountered most frequently when therapeutic or high doses are administered too rapidly by parenteral routes. Toxic manifestations relate primarily to the cardiovascular system and the CNS. Cardiovascular effects include hypotension, vasodilation, suppressed myocardial function, cardiac arrhythmias, and eventual cardiac arrest. Confusion, convulsions, and coma indicate CNS dysfunction. Chloroquine doses of more than 5 g given parenterally usually are fatal. Prompt treatment with mechanical ventilation, epinephrine, and diazepam may be lifesaving.
Doses of chloroquine used for oral therapy of the acute malarial attack may cause GI upset, headache, visual disturbances, and urticaria. Pruritus also occurs, most commonly among dark-skinned persons. Prolonged medication with suppressive doses occasionally causes side effects such as headache, blurring of vision, diplopia, confusion, convulsions, lichenoid skin eruptions, bleaching of hair, widening of the QRS interval, and T-wave abnormalities. These complications usually disappear soon after the drug is withheld. Rare instances of hemolysis and blood dyscrasias have been reported. Chloroquine may cause discoloration of nail beds and mucous membranes. Chloroquine can interfere with the immunogenicity of certain vaccines (Horowitz and Carbonaro, 1992; Pappaioanou et al., 1986).
Irreversible retinopathy and ototoxicity can result from high daily doses (>250 mg) of chloroquine or hydroxychloroquine that lead to cumulative total doses of more than 1 g of base per kilogram body weight, such as those used for treatment of diseases other than malaria. Retinopathy presumably is related to drug accumulation in melanin-rich tissues and can be avoided if the daily dose is 250 mg or less (see Rennie, 1993). Prolonged therapy with high doses of 4-aminoquinoline also can cause toxic myopathy, cardiopathy, and peripheral neuropathy; these reactions improve if the drug is withdrawn promptly (Estes et al., 1987). Rarely, neuropsychiatric disturbances, including suicide, may be related to overdose.
Precautions and Contraindications :
This topic has been reviewed by Taylor and White (2004). Chloroquine is not recommended for treating individuals with epilepsy or myasthenia gravis. The drug should be used cautiously if at all in the presence of hepatic disease or severe gastrointestinal, neurological, or blood disorders. The dose must be adjusted in renal failure. In rare cases, chloroquine can cause hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency (see Primaquine below). Concomitant use of gold or phenylbutazone (no longer available in the United States) with chloroquine should be avoided because of the tendency of all three agents to produce dermatitis. Chloroquine should not be prescribed for patients with psoriasis or other exfoliative skin conditions because it causes severe reactions. It should not be used for malaria in patients with porphyria cutanea tarda but is used in smaller doses for treatment of the underlying disease . Chloroquine is an inhibitor of CYP2D6 and interacts with a variety of different agents. It should not be given with mefloquine because of increased risk of seizures. Most important, this antimalarial opposes the action of anticonvulsants and increases the risk of ventricular arrhythmias from coadministration with amiodarone or halofantrine. By increasing plasma levels of digoxin and cyclosporine, chloroquine also can increase the risk of toxicity from these agents. For patients receiving long-term, high-dose therapy, ophthalmological and neurological evaluations are recommended every 3 to 6 months.
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