From the Guidelines
The incidence rate of Hydroxychloroquine (Plaquenil) toxicity is approximately 1% for patients taking the medication for less than 5 years at recommended doses, increasing to about 2% after 10 years, and 20% after 20 years. For patients taking the medication for less than 5 years at recommended doses, the risk is less than 1% 1. However, this risk increases to about 2% after 10 years, and 20% after 20 years, and may exceed 50% after 20+ years of use at higher doses 1. The primary concern is retinal toxicity, which can lead to permanent vision loss if not detected early. Risk factors that increase toxicity include higher daily doses (especially exceeding 5 mg/kg of real body weight), renal impairment, concomitant tamoxifen use, and pre-existing macular disease. Hydroxychloroquine accumulates in melanin-containing tissues like the retina, where it can disrupt cellular metabolism and cause progressive damage to photoreceptors.
Key Considerations
- Regular ophthalmologic screening is essential, with baseline examination recommended within the first year of treatment and annual screening after 5 years of continuous use, or sooner for high-risk patients 1.
- Monitoring for ocular toxicity due to chloroquine and hydroxychloroquine has been recommended for every 6 to 12 months 1.
- The risk of toxicity is dependent on daily dose and duration of use, with the risk rising to almost 20% after 20 years 1.
Recommendations for Screening
- Baseline examination within the first year of treatment
- Annual screening after 5 years of continuous use
- Sooner for high-risk patients
- Monitoring for ocular toxicity every 6 to 12 months 1
From the Research
Incidence Rate of Hydroxychloroquine Toxicity
- The incidence of hydroxychloroquine retinopathy is exceedingly low, with less than 50 cases reported 2.
- A study found that the incidence of hydroxychloroquine-related retinopathy in patients treated with recommended dosages of the drug for a mean of 8.7 years was 0.5% 3.
- The risk of retinopathy is higher with increasing age, dose, and duration of usage 4.
- Other toxicities associated with hydroxychloroquine use include gastrointestinal effects, glucose abnormalities, dermatologic reactions, and neuropsychiatric events 4.
- Cardiotoxicity is a concern with hydroxychloroquine use, particularly when used in combination with azithromycin 4.
- Acute severe toxicity is associated with 10-30% mortality owing to a combination of direct cardiovascular effects and electrolyte derangements with resultant dysrhythmias 5.
Risk Factors for Hydroxychloroquine Toxicity
- Daily dosage of hydroxychloroquine
- Cumulative dosage
- Duration of treatment
- Coexisting renal or liver disease
- Patient age
- Concomitant retinal disease 2
Management of Hydroxychloroquine Toxicity
- Cessation of the drug is the only effective management of the toxicity 2.
- Regular screening may be necessary to detect reversible premaculopathy 2.
- Treatment in the emergency department is focused on decontamination, stabilization of cardiac dysrhythmias, hemodynamic support, electrolyte correction, and seizure prevention 5.