The Canadian Rheumatology Association has recently updated its guidance on the safety of hydroxychloroquine when used to treat rheumatic diseases, providing important reassurance regarding ocular toxicity monitoring and cardiac safety at standard therapeutic doses.
Hydroxychloroquine, an antimalarial drug, is a cornerstone treatment for many rheumatic diseases, especially systemic lupus erythematosus (SLE) and rheumatoid arthritis. It is well-documented that hydroxychloroquine not only improves survival in SLE but also helps prevent disease flares, reduces organ damage, lowers cholesterol, improves glucose metabolism, and decreases cardiovascular and thromboembolic risks. Additionally, hydroxychloroquine has shown benefits in improving pregnancy outcomes for both mother and fetus. In rheumatoid arthritis, it remains a widely prescribed disease-modifying antirheumatic drug (DMARD).
Hydroxychloroquine Safety Monitoring
Monitoring for hydroxychloroquine safety is crucial, particularly regarding retinal toxicity. While rare, retinopathy is an irreversible complication that can lead to permanent vision loss if not detected early.
Risk factors for retinal toxicity include:
- Duration of hydroxychloroquine use
- Renal disease
- Concomitant use of tamoxifen
The American Academy of Ophthalmology recommends a baseline fundus examination before starting treatment to rule out pre-existing maculopathy. Following five years of continuous use, annual screening using visual field testing and spectral-domain optical coherence tomography (SD-OCT) is advised, especially in patients without major risk factors.
Despite these considerations, hydroxychloroquine safety remains strong. Other uncommon side effects, such as skin hyperpigmentation and myopathy (including cardiomyopathy), are possible but rare.
Cardiac Safety of Hydroxychloroquine
Concerns about hydroxychloroquine cardiac safety emerged during the COVID-19 pandemic, where the drug was used at much higher doses and often combined with azithromycin, a medication known to prolong the QT interval.
However, during regular rheumatology practice, where hydroxychloroquine is used at standard therapeutic doses, cardiac toxicity is rare. Studies show that only about 0.7% of patients with SLE experience QT prolongation, a rate comparable to that of the general population.
Possible risk factors for hydroxychloroquine cardiotoxicity include:
- Older age
- Pre-existing cardiac disease
- Renal insufficiency
It’s important to recognize that COVID-19 infection itself, alongside factors like hypokalemia, hypomagnesemia, and fever, contributed significantly to cardiac complications observed during the pandemic, rather than hydroxychloroquinealone.
Drug Interactions with Hydroxychloroquine
At therapeutic doses for rheumatic diseases, hydroxychloroquine typically does not cause significant drug interactions. Nonetheless, care must be taken with medications that also prolong the QT interval.
Common antidepressants such as bupropion, citalopram, escitalopram, fluoxetine, mirtazapine, paroxetine, sertraline, trazodone, and venlafaxine have been shown to only mildly prolong the QT interval when used alongside hydroxychloroquine, and are generally considered safe.
Recognizing potential hydroxychloroquine drug interactions ensures that patients continue to receive the full benefits of therapy without unnecessary risk.
Summary: Hydroxychloroquine Safety in Rheumatic Disease Treatment
The Canadian Rheumatology Association emphasizes that hydroxychloroquine safety remains strong when the drug is used appropriately under the guidance of a rheumatologist. Regular monitoring, particularly for ocular toxicity, and awareness of rare cardiac risks, help maintain its excellent safety profile.
The benefits of hydroxychloroquine, particularly in systemic lupus erythematosus, overwhelmingly outweigh its risks. When prescribed thoughtfully and monitored appropriately, hydroxychloroquine continues to be one of the safest and most effective treatments in rheumatology today.
Reference:
Canadian Rheumatology Association. Position statement on the safety of hydroxychloroquine in the treatment of rheumatic diseases. Version: 2.0 December 3, 2024. Published online March 2025. (accessed April 22, 2025).