Assessment of Long-Term Health Effects of Antimalarial Drugs When Used for Prophylaxis (2020) / Chapter Skim
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9 Chloroquine
9 Chloroquine
Pages 323-354
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From page 323... ...
. The once-weekly dosing regimen of chloroquine for malaria prophylaxis consists of one 500 mg salt (300 mg base)
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Serious adverse events (e.g., retinopathy, macular degeneration) have been reported in people using chloroquine for the treatment of rheumatoid arthritis and systemic lupus erythematosus; however, the chloroquine regimen for treating these diseases is 250 mg per day, a much higher dose than the once-weekly 500 mg dosing regimen used for malaria prophylaxis (Cabral et al., 2019)
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From page 325... ...
The adverse events listed in chloroquine's FDA package insert do not distinguish between adverse events experienced by those using chloroquine for malaria prophylaxis and those using it for malaria treatment, and the list of adverse events appears to be based on non-quantified postmarketing experience (FDA, 2018)
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From page 326... ...
If ocular toxicity is suspected in a chloroquine user, the drug should be stopped and the person observed closely since retinal changes and visual disturbances can progress after drug cessation. The label warns that chloroquine can cause severe hypoglycemia, including a loss of consciousness that could be life threatening in people treated with or without antidiabetic medications (FDA, 2018)
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has been discontinued. An effort has been made to limit the discussion below to label changes that refer to adverse events that occur in adults who use chloroquine as malaria prophylaxis (not for acute attacks of malaria or treatment for other conditions)
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The adverse reactions maculopathy and macular degeneration were noted to be potentially irreversible. In 2017 chloroquine became contraindicated for malaria prophylaxis in patients with retinal or visual field changes (FDA, 2017)
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Epidemiologic studies in which information was presented regarding adverse events occurring at least 28 days post-chloroquine-cessation are then summarized, with the emphasis on reported results of persistent or latent adverse events associated with the use of chloroquine, including the results of studies in which other antimalarial drugs were used as a comparison group.
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. Chloroquine users reported statistically significantly less dizziness than mefloquine users in the cohort studies (RR = 0.66, 95%CI 0.59–0.75; 56,710 participants)
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For example, in single cohort studies chloroquine users were less likely than mefloquine users to report alopecia (RR = 0.59, 95%CI 0.44–0.79) and visual impairment (RR = 1.10, 95%CI 0.01–2.44; 5 cohort tudies, s 58,847 participants)
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(2018) conducted a retrospective observational analysis of self-reported health outcomes associated with the use of antimalarial drugs in a cohort of U.S.
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The number of chloroquine users in this sample was small. It is noteworthy that adjusting for combat exposure consistently reduced the measures of association, potentially indicating a strong confounding effect of combat exposure.
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to compare the prevalence of selected health conditions after Peace Corps service between those who reported taking malaria prophylaxis (n = 5,055, 56.6%) and those who did not.
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Thus, the comparison group for each anti alarial m was a mixture of those who did not report taking any anti alarials and those who m reported taking antimalarial drugs other than the one being examined. Overall, there were few details of the limited analyses presented, which made it difficult to understand the groups that were being compared, how they differed with respect to important covariates, and what variables were included in the odels.
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The measures of immunity are intermediate, and the relationship to clinical outcomes is unknown. OTHER IDENTIFIED STUDIES OF CHLOROQUINE PROPHYLAXIS IN HUMAN POPULATIONS When reviewing full-text articles, the committee identified several epidemiologic articles on chloroquine use for malaria prophylaxis that could not be included because they either did not provide information on adverse events that occurred ≥28 days post-cessation of chloroquine or presented data that did not distinguish among adverse events that occurred during concurrent use of chloroquine or ≥28 days post-cessation of chloroquine.
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A detailed medical history was conducted that included medication exposures and completion of a visual examination. One participant was diagnosed with chloroquine etinopathy, r including blurred vision, blind spots, photophobia, eye pain, and clinical findings of ring scotoma, retinal pigment changes endothelial dystrophy, and macular degeneration; however, this patient used chloroquine for a connective tissue disorder, and not solely for malaria prophylaxis.
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. Chloroquine has not been found to have harmful effects on the fetus when it is used in the recommended doses for malaria prophylaxis (McGready et al., 2002; Villegas et al., 2007)
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for which the recommended doses are much higher than the dose used for malaria prophylaxis. It is postulated that retinal pigment changes may also be seen following short-term prophylactic dosing regimens (Rimpela et al., 2018)
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. SYNTHESIS AND CONCLUSIONS Even though chloroquine has been approved by FDA for malaria prophylaxis for more than 70 years, only three epidemiologic studies were identified that included some mention of adverse events or data collection that occurred ≥28 days post-cessation of chloroquine and that provided directly relevant information for assessing persistent or latent adverse events (Lege-Oguntoye et al., 1990; Schneiderman et al., 2018; Tan et al., 2017)
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Antimalarial medication use was grouped into mefloquine, chloroquine, doxycycline, primaquine, mefloquine in combination with other drugs, other antimalarials, and not specified or no antimalarial drug exposures. Health outcomes were self-reported using standardized instruments: the SF-12 for general health status, PCL-C for PTSD, and the PHQ.
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, and investigators examined and reported only intermediate measures of immunity with unknown clinical implications, limiting the information that could be gleaned from the study findings; therefore, this study was given less weight in the committee's forming of conclusions regarding the persistent or latent adverse events of chloroquine use as malaria prophylaxis. In addition to the epidemiologic studies, the committee also considered supplemental evidence, including recognized concurrent adverse events, case reports of persistent adverse events, studies of adverse events in pregnant women and people with comorbid conditions, and information from experimental animal models or cell cultures.
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From page 343... ...
Current evidence does not suggest further study of such an association is warranted, given the lack of evidence regarding biologic plausibility, adverse events associated with concurrent use, or findings from the existing epidemiologic studies. Psychiatric Disorders The FDA label or package insert for chloroquine lists psychosis, delirium, anxiety, agitation, insomnia, confusion, hallucinations, personality changes, and depression as potential psychiatric adverse events that may occur in individuals taking chloroquine.
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Based on the available evidence, the committee concludes that there is insufficient or inadequate evidence of an association between the use of chloroquine for malaria prophylaxis and persistent or latent psychiatric events. Current evidence does not suggest further study of such an association is warranted, given the lack of evidence regarding biologic plausibility, adverse events associated with concurrent use, or findings from the existing epidemiologic studies.
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From page 345... ...
Current evidence does not suggest further study of such an association is warranted, given the lack of evidence regarding biologic plausibility, adverse events associated with concurrent use, or findings from the existing epidemiologic studies. Eye Disorders There are known associations between eye disorders and concurrent use of chloroquine when used at higher doses than the recommended regimen for malaria prophylaxis or when a large cumulative dose is taken over an extended period of time.
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The individual was using chloroquine for malaria prophylaxis; however, the study states that chloroquine was being used simultaneously to treat a connective tissue disorder, indicating that it is likely the individual was receiving a greater dose of chloroquine than recommended for malaria prophylaxis. Experiments conducted in vitro and in animal models indicate that chloroquine's effects on lysosomal function or its binding to melanin can impair the health and viability of the retinal pigment epithelium.
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. Based on this evidence, the committee believed that immune dysfunction is likely not associated with the use of chloroquine for malaria prophylaxis.
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1979. The concentration of chloroquine in serum during short and long term malaria prophylaxis with standard and "double" dosage in non immunes: Clinical implications.
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2014. Compliance with long term malaria prophylaxis in British expatriates.
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1991. Effectiveness and tolerance of long-term malaria prophylaxis with mefloquine.
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1993. Long term malaria prophylaxis with weekly mefloquine.
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2017. Long term health outcomes among returned Peace Corps volunteers after malaria prophylaxis, 1995–2014.
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CHLOROQUINE 353 Woehrling, E
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