Chloroquine and Hydroxychloroquine Toxicity Treatment & Management

Updated: Nov 03, 2015
  • Author: Manolette R Roque, MD, MBA, FPAO; Chief Editor: Hampton Roy, Sr, MD  more...
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Approach Considerations

Withdrawal of the medication and shifting to another form of treatment is the standard of care. Coordination with the rheumatologist or the dermatologist is warranted for comprehensive care of the patient.

If serious toxic symptoms occur from overdosage or sensitivity, it has been suggested that ammonium chloride (8 g daily in divided doses for adults) be administered orally 3-4 times/wk for several months after therapy has been stopped. Acidification of the urine with ammonium chloride increases renal excretion of the 4-aminoquinoline compounds by 20-90%. In patients with impaired renal function and/or metabolic acidosis, caution must be taken.



During therapy, patients should be monitored on an annual basis. The clinician should record any visual symptoms, visual acuity, and fundus examination results. After 5 years of treatment, annual screenings should include an ocular examination, 10-2 threshold field testing, and one of the objective tests (ie, SD-OCT, mfERG, fundus autofluorescence).

Ophthalmologists should know the latest guidelines. Ophthalmologists are held to the position on hydroxychloroquine by the American Academy of Ophthalmology.

The most important factor in avoiding toxicity with long-term therapy appears to be the daily dose. If the daily dose is below the stated threshold levels, then the chance of encountering any retinopathy is small. However, it is essential that the clinician discuss the early symptoms of toxicity with the patient. A high index of suspicion of toxicity would justify the performance of expensive ancillary procedures to detect possible retinopathy.

It is important to understand that at the present time, no criterion standard exists for identification of the ocular toxicity prior to its clinical manifestation. This has led to controversy regarding the recommendations for ophthalmologic examinations for screening patients on hydroxychloroquine. Current guidelines need to be improved to prevent permanent retinopathy from these medications.

The recommended safe threshold dose has been reported as 3.5 mg/kg/d for chloroquine and 6.5 mg/kg/d for hydroxychloroquine. These dosages are based on lean body weight. A body mass index calculator used by endocrinologists is helpful in calculating the recommended dose.

The standard ideal weight, which factors in height, is calculated as follows:

  • For women, the ideal weight is 100 lb for 5 feet, plus 5 lb per extra inch of height.
  • For men, the ideal weight is 110 lb for 5 feet, plus 5 lb per extra inch of height.
  • Note: 1 kg = 2.2 lb

In addition, pediatric and elderly patients should be considered at high risk for toxicity and should be monitored closely. Dose adjustments should be made in patients with renal impairment or hepatic insufficiency.

The National Registry of Drug-Induced Ocular Side Effects is a resource for soliciting information about, and contributing reports of, suspected drug toxicities. To access the Registry, go to The service is free, although American Academy of Ophthalmology membership is required for entry.


Long-Term Monitoring

A yearly visual field examination is useful to detect changes from hydroxychloroquine. Multifocal ERG assessment is a required element in the preferred practice pattern of patients treated with antimalarial agents. Whenever abnormalities are noted, additional testing should be obtained. Humphrey visual field central 10-2 white-on-white pattern should be repeated promptly if central or parafoveal changes are seen, even if these appear to be nonspecific. If the findings are reproducible, objective testing should be repeatedly performed.

If toxicity is suspected, more frequent and detailed examinations should be conducted. Once toxicity is confirmed, the prescribing physician should be informed and hydroxychloroquine therapy should be discontinued unless it is medically critical and the patient has been informed of the visual risk.

Once retinal toxicity is identified, the drug is discontinued and other immunosuppressive agents are substituted. Chloroquine and/or hydroxychloroquine clear very slowly from the body, so the full effects may not manifest for 3-6 months. Slow, continued deterioration of visual function may occur even after the drug is discontinued.

A small case series study revealed evidence of retinal toxicity that included difficulty with reading, variation in fundus findings from normal to bull’s eye maculopathy, electroretinogram (ERG) findings of reduced rod and cone function, and abnormal visual fields. Cessation of the study drug did not result in sustained improved visual function: 6 of 16 patients had progressive loss of retinal function despite cessation of the study drug. [8]

The authors recommend that patients be reevaluated 3 months after a diagnosis of toxicity is made, even after discontinuation of drug use. Annual examinations are recommended until the findings have clearly stabilized.