From the Guidelines
The incidence rate of retinal toxicity from Plaquenil (hydroxychloroquine) use is approximately 7.5% in patients using the drug for more than 5 years, with the risk being dose-dependent and closely correlated with real weight rather than ideal weight. The risk of retinal toxicity is a significant concern in patients taking Plaquenil, and it is essential to monitor these patients regularly to prevent permanent damage. According to a study published in Ophthalmology 1, the daily dose of hydroxychloroquine is the most critical determinant of risk, and patients taking 4.0 to 5.0 mg/kg of real weight have a markedly lower cumulative risk of toxicity than those using higher levels. Some key points to consider when assessing the risk of retinal toxicity in patients taking Plaquenil include:
- The risk of toxicity increases with longer duration of use, with Kaplan-Meier curves showing that patients staying with 5.0 mg/kg have less than 1% risk in the first 5 years of therapy and less than 2% up to 10 years 1.
- Other risk factors for retinal toxicity include kidney disease, concurrent tamoxifen use, and pre-existing retinal or macular disease.
- Early toxicity is often asymptomatic and may be reversible if detected promptly, but advanced damage is typically permanent.
- Regular screening is essential, with baseline examination recommended within the first year of treatment and then annually after 5 years of use (or sooner with risk factors) 1.
- The mechanism of toxicity involves hydroxychloroquine binding to melanin in the retinal pigment epithelium, causing cellular damage through disruption of lysosomal function and accumulation of lipofuscin, ultimately leading to photoreceptor degeneration. It is crucial to weigh the benefits of Plaquenil against the potential risks and to closely monitor patients for signs of retinal toxicity to minimize the risk of permanent damage.
From the FDA Drug Label
Irreversible retinal damage has been observed in some patients who had received hydroxychloroquine sulfate. Irreversible retinal damage was observed in some patients treated with hydroxychloroquine sulfate and it is related to cumulative dosage and treatment duration.
The incidence rate of retinal toxicity from Plaquenil (hydroxychloroquine) use is not explicitly stated in the FDA drug label. Key risk factors for retinal damage include:
- Daily hydroxychloroquine sulfate dosages ≥ 5 mg/kg of actual body weight
- Durations of use greater than five years
- Renal impairment
- Use of concomitant drug products such as tamoxifen citrate
- Concurrent macular disease 2 3
From the Research
Incidence Rate of Retinal Toxicity from Plaquenil (Hydroxychloroquine) Use
- The incidence of hydroxychloroquine (HCQ)-related retinal toxicity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) who are receiving recommended dosages of the drug (< or =6.5 mg/kg/day) is reported to be 0.5% 4.
- A study found that among patients who had taken a cumulative dose of less than 1,250 g, 7 of 67 eyes (10%) showed a characteristic mfERG defect, while in patients with a cumulative dosage of 1,250 g or more, 26 of 64 eyes (41%) showed one of these defects 5.
- The risk of hydroxychloroquine toxicity rises to nearly 1% with a total cumulative dose of 1,000 g, which is ∼5 years to 7 years of normal use 6.
- No HCQ retinal toxicity was noted in any of the 526 patients during the first 6 years of treatment, but 2 (3.4%) of the first 58 long-term (>6 years) treated patients developed HCQ-related maculopathy at 8 and 6.5 years of treatment 4.
- Known major risk factors for HCQ retinal toxicity include drug loads >300 mg/day (5 mg/kg/day), use for >5 years, a cumulative dose >1,000 g, underlying retinal disease or retinopathy, tamoxifen use, and renal disease 7, 8.