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    Hydroxychloroquine (Plaquenil) Dosing Calculator

    Calculates maximum daily dose of hydroxychloroquine to reduce risk of retinopathy.
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    IMPORTANT

    This calculator is for double-checking hydroxychloroquine dosing, and should NOT be used as the primary means for ordering.

    When to Use
    Pearls/Pitfalls
    Why Use

    Use in an outpatient setting for adult patients taking hydroxychloroquine (Plaquenil).

    • The current American Academy of Ophthalmology (AAO) guidelines, published in 2016, recommend a maximum daily hydroxychloroquine dose of ≤5.0 mg/kg of real weight. These guidelines were established to minimize the likelihood of permanent vision loss related to hydroxychloroquine retinopathy. 
    • The 2016 revision was prompted by a study by Melles and Marmor in 2014 which suggested that hydroxychloroquine retinopathy is more common than previously thought. They demonstrated that a daily consumption of 5.0 mg/kg real body weight or less is associated with a low risk for up to 10 years. However, there is significant variability in individuals that develop hydroxychloroquine retinopathy.
    • This study was performed only in adult patients.
    • The American College of Rheumatology updated their guidelines in August 2016 to acknowledge the American Academy of Ophthalmology’s position, but does not specify a preferred dosing regimen.
    • Doses must be adjusted for renal insufficiency.
    • Patients with underlying retinal or macular disease may be at a higher risk for toxicity.
    • Patients who are undergoing tamoxifen therapy for breast cancer have a higher risk for toxicity.
    • An appropriate dose is required to minimize the risk of hydroxychloroquine related retinopathy and to permit long-term use in most patients. 
    • The overall risk of developing hydroxychloroquine retinopathy in patients on long-term therapy is 7.5% with the risk increasing with higher doses and long-term use.
    • Calculation of appropriate dose of hydroxychloroquine can minimize the risk of hydroxychloroquine retinopathy since vision loss is irreversible and there is no therapy to treat the resulting retinopathy.
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    Next Steps
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    Management

    • Doses should be adjusted in conjunction with the prescribing physician to minimize the risk of vision loss and to ensure that the medical risks of medication adjustment are managed.
    • Recommended screening consists of automated visual fields (appropriate to race) and spectral-domain optical coherence tomography (SD-OCT).
    • Other objective testing to be performed as needed or, if available, a multifocal electroretinogram or fundus autofluorescence.
    • Ophthalmoscopy is not a recommended screening tool because photoreceptor damage can be detected by the above techniques before being clinically visible.

    Critical Actions

    If a patient is on a dose that exceeds 5 mg/kg/day of real body weight, the prescribing physician should be contacted to ensure that the dose can be adjusted and medical risks are managed.

    Formula

    Maximum daily hydroxychloroquine dose = 5.0 mg/kg

    Facts & Figures

    Interpretation:

    Mean daily dose 10-year risk of retinopathy 20-year risk of retinopathy
    4-5 mg/kg 2% 20%
    >5 mg/kg 10% 40%

    Evidence Appraisal

    Previous guidelines were published by the American Academy of Ophthalmology in 2011, which recommended a daily dose of 6.5 mg/kg based on ideal body weight. The updated 2016 guidelines reflect a large retrospective case-control study performed by Melles and Marmor in 2014, which found that hydroxychloroquine retinopathy was more common than previously recognized.

    Melles and Marmor demonstrated that patients who were on a mean daily dose exceeding 5 mg/kg had a 10% cumulative risk of developing retinopathy within 10 years, which rose to 40% after 20 years.

    Patients on an intermediate dose of 4-5 mg/kg had a 2% cumulative risk within 10 years and 20% risk after 20 years. 

    While tamoxifen is also known to cause retinal toxicity, Melles and Marmor also found that patients who were on tamoxifen for breast cancer therapy had a significantly higher risk of developing hydroxychloroquine retinopathy (odds ratio of 4.59).

    While the guidelines recommend caution in using hydroxychloroquine in patients with pre-existing retinal or macular disease, there is no clear evidence for increased risk, although it is reasonable that pre-existing retinal disease can confound screening tests.

    These studies were performed in adults, and therefore these guidelines do not apply to pediatric populations.

    Dr. Ronald B. Melles

    About the Creator

    Ronald B. Melles, MD, is an ophthalmologist and researcher at Kaiser Permanente Redwood City Medical Center in Redwood City, California. Dr. Melles has published extensively on hydroxychloroquine retinopathy.

    To view Dr. Ronald B. Melles's publications, visit PubMed

    Content Contributors
    Reviewed By
    • Joshua Young, MD