Chloroquine adverse effects

Hydroxychloroquine (Plaquenil), like chloroquine, is a 4-aminoquinoline derivative used for the suppressive and acute treatment of malaria. It also has been used for rheumatoid arthritis and discoid and systemic lupus erythematosus. Hydroxychloroquine has not been proved to be more effective than chloroquine. Adverse reactions associated with its use are similar to those described for chloroquine. The drug should not be used in patients with psoriasis or porphyria, since it may exacerbate these conditions. 

Chloroquine and related antimalarials are effective in rheumatoid arthritis and lupus erythematosus, but their mode of action is not known. The anthelmintic drug levamisole (186) is also effective but adverse effects limit its use. 

Adverse Effects. The most serious problem associated with chloroquine is the possibility of toxicity to the retina and subsequent visual disturbances. This issue is usually insignificant, however, when this drug is used for short periods in relatively low doses (see Chapter 16). Other relatively mild side effects may occur, including gastrointestinal distress (nausea, vomiting, stomach cramps, diarrhea), behavior and mood changes (irritability, confusion, nervousness, depression), and skin disorders (rashes, itching, discoloration). 

Hydroxychloroquine (Plaquenil) is derived chemically from chloroquine and is similar to it in clinical use, mechanism of action, and adverse effects. Hydroxychloroquine does not have any distinct therapeutic advantages over chloroquine, but it may be substituted in certain individuals who do not respond well to chloroquine. 

Chloroquine is a 4-aminoquinoline used in the treatment and prophylaxis of malaria and hepatic amebiasis, as well as rheumatoid arthritis. Adverse effects are generally less common and less severe. Frequent effects include headache, GI disturbances, and diarrhea. Large doses may cause blurred vision and difficulty focusing. A common adverse effect on the eye is retinopathy. Parenteral therapy with chloroquine can be hazardous, and rapid intravenous injections may result in cardiovascular toxicity. Acute overdose is extremely dangerous death may occur within a few hours. Chloroquine should be used cautiously in patients with liver and kidney impairment. Chloroquine may aggravate the condition of myasthenia... 

Some adverse effects commonly associated with chloroquine. 

The pharmacology of these drugs, which are also used in the treatment of malaria, is presented on p. 351. The mechanism of their anti-inflammatory activity is uncertain. Besides inhibiting nucleic acid synthesis, they are known to stabilize lysosomal membranes and trap free radicals. In treating inflammatory disorders, they are reserved for rheumatoid arthritis that has been unresponsive to the NSAIDs or else they are used in conjunction with an NSAID, which allows a lower dose of chloroquine or hydroxychloroquine to be administered. These drugs have been shown to slow progression of erosive bone lesions and may induce remission. They do cause serious adverse effects (see p. 351). 

A postal survey of the incidence of psychiatric disturbances in 2500 returning Israeli travellers (505) showed that travellers with this class of adverse effects were more likely to have taken mefloquine than other antimalarial drugs. Of 117 travellers with psychiatric adverse effects, 115 had taken mefloquine compared with 948/1340 for the entire cohort. This was a retrospective postal study with a response rate of 54% (1340 out of 2500), and of those who responded 71% had taken mefloquine, 5% had taken chloroquine, and 24% had taken no prophylaxis. In this study 11% (117) of the respondents reported psychiatric disturbances, mainly sleep disturbance, fatigue, vivid dreams, or lack of mood. Only 16 of the respondents had symptoms lasting 2 months or more. Those who had had a psychiatric disturbance were also more likely to have been female and to have taken recreational drug use. 

CHLOROQUINE H2 RECEPTOR BLOCKERS -CIMETIDINE t efficacy and adverse effects of chloroquine Inhibition of metabolism and excretion Consider ranitidine as an alternative or take cimetidine at least 2 hours after chloroquine... 

Adverse effects are infrequent at doses normally Report 1993 Chloroquine poisoning. Lancet 307 49. 

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 ... 

Amopyroquine is a 4-aminoquinoline, structurally related to amodiaquine. It is not a new compound, but it is of renewed interest as a result of the extensive occurrence of resistance to chloroquine and the adverse effects of prophylactic amodiaquine. In a study in 152 patients with malaria, the efficacy of a 12 mg/kg, given as two intramuscular injections of 6 mg/kg 24 hours apart, was described as good (1). AU the patients became apyrexial and there was clearance of parasites on day 7 in 143 cases the nine who retained a low level of parasitemia were all children. In 50% of the cases, the parasite had been chloroquine-resistant. The drug was well tolerated, and there were no major adverse effects. 

More than one mechanism may underlie the cardiac adverse effects of chloroquine. Severe hypokalemia after a single large dose of chloroquine has been documented, and some studies show a correlation between plasma potassium concentrations and the severity of the cardiac effects (6). 

Syncope occurred in a hypertensive 48-year-old man who took oral chloroquine sulfate (total 600 mg base) while also taking amlodipine 5 mg/day (44). Chloroquine and amlodipine both cause vasodilatation, perhaps by release of nitric oxide, and the syncope in this case was probably due to a synergistic mechanism. Malaria itself can also provoke orthostatic reactions, which may be why syncope is not a reported adverse effect of chloroquine. However, in this patient malaria had been excluded. 

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). 

Lumefantrine is a synthetic aminoalcohol fluorene derivative, related to halofantrine and mefloquine (1). It was highly effective in uncomplicated chloroquine-resistant malaria tropica in an open, non-comparative trial in 102 patients in China when given in four oral doses over 48 hours (2). No significant adverse effects have been reported. It has also been marketed in a combination of artemether (20 mg) plus lumefantrine (120 mg). 

In an open, randomized trial in 260 Tanzanian children, lumefantrine was superior to chloroquine and did not produce major adverse effects (7). 

The adverse effects of mefloquine have been extensively reviewed both for prophylaxis (when rare neuropsychiatric adverse effects make its use controversial) and in treatment doses, when it has been linked to an increased incidence of the postmalaria neurological syndrome. A retrospective review of 5120 Itahan soldiers showed an overall chemoprophylaxis curtailment rate of less than 1%, which was not significantly different from the combination of chloroquine and proguanil (11). A semi-systematic review also suggested no significant difference in tolerabihty compared with other antimalarial drugs (12). 

WR-243251 is a floxacrine analogue, a dihydroacridine-dione. It is active in vitro against chloroquine-resistant, mefloquine-resistant, and pyrimethamine-resistant strains of malaria (1). By analogy to quinacrine and floxacrine, there is concern about possible dermatological, cardiac, and neuropsychiatric toxicity and vascular adverse effects. 

The authors of the report attribute the dystonia to an interaction between metronidazole and chloroquine as she had taken both drugs alone without adverse effect. However, they do not fiilly assess the possible contribution of promethazine, which is known to cause dystonias. It is therefore possible that the reaction seen was an adverse effect of the promethazine, or perhaps even an interaction between promethazine and chloroquine. No general recommendations can therefore be made from this single report. 

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