What are the hydroxychloroquine (HCQ) levels in the blood of a patient with Systemic Lupus Erythematosus (SLE) according to the American College of Rheumatology (ACR)?

From the Guidelines

Hydroxychloroquine levels in blood should be monitored to ensure therapeutic levels are achieved, with a recommended level above 0.6 mg/l, to minimize the risk of lupus nephritis flares, as suggested by recent data 1. The management of systemic lupus erythematosus (SLE) involves the use of hydroxychloroquine (HCQ) as a key component of treatment, with the goal of achieving and maintaining low disease activity or remission.

• The typical dosing for hydroxychloroquine in SLE is 200-400 mg daily, with the goal of achieving and maintaining therapeutic blood levels.
• Blood level monitoring is particularly useful in patients who continue to have disease flares despite reported adherence to therapy, as subtherapeutic levels may indicate poor medication adherence or individual variations in drug metabolism.
• When interpreting results, it's essential to note that samples should be drawn at least 4-6 hours after the last dose to avoid measuring peak levels.
• Additionally, hydroxychloroquine has a long half-life (approximately 40-50 days), so blood levels reflect long-term adherence rather than just recent dosing.
• Regular monitoring of hydroxychloroquine levels can help clinicians make informed decisions about dosage adjustments and improve overall disease management in SLE patients, as supported by the 2024 KDIGO clinical practice guideline for the management of lupus nephritis 1.
• The recommended starting dose of hydroxychloroquine is around 5 mg/kg/d, with doses of 2–3 mg/kg/d potentially being associated with higher flare rates and inadequate blood levels 1.
• In patients with estimated glomerular filtration rate (eGFR) <30 ml/min per 1.73 m², the dose of hydroxychloroquine should be reduced by 25% to minimize the risk of toxicity 1.

From the FDA Drug Label

Following a single 200 mg oral dose of hydroxychloroquine sulfate to healthy male volunteers, whole blood hydroxychloroquine Cmax was 129.6 ng/mL In patients with rheumatoid arthritis, there was large variability as to the fraction of the dose absorbed (i.e. 30 to 100%), and mean hydroxychloroquine levels were significantly higher in patients with less disease activity.

The blood levels of hydroxychloroquine in patients with Systemic Lupus Erythematosus (SLE) are not directly stated in the provided drug label. However, based on the information provided for patients with rheumatoid arthritis, it can be inferred that:

• Blood levels of hydroxychloroquine may vary significantly in patients with SLE, similar to those with rheumatoid arthritis.
• Mean hydroxychloroquine levels may be higher in patients with less disease activity. However, without direct information on SLE patients, no specific conclusion can be drawn regarding the blood levels of hydroxychloroquine in these patients 2.

From the Research

Hydroxychloroquine Levels in Blood in Patients with SLE

• The American College of Rheumatology (ACR) recommends hydroxychloroquine (HCQ) as a standard treatment for systemic lupus erythematosus (SLE) 3.
• According to a 2015 study, the therapeutic range of HCQ blood levels is between 500-2000 ng/ml 4.
• A 2023 study found that higher HCQ blood levels were protective against flare occurrence in patients with SLE 5.
• The daily dose of HCQ associated with the best compromise between efficacy and safety is a matter of debate, with current guidelines recommending a dose of ≤5 mg/kg/day actual body weight 6.

Factors Affecting Hydroxychloroquine Blood Levels

• A 2015 study found that HCQ blood levels were similar regardless of height and ideal body weight, and that weight-based dosing (max 400 mg daily) is appropriate 4.
• The same study found that renal failure dosing led to suboptimum levels, and that measurement, counseling, and repeated testing can increase adherence rates 4.
• A 2024 study found that lower HCQ weight-based dose (≤5 vs >5 mg/kg/day) and non-weight-based dose (<400 vs 400 mg/day) were each associated with increased hospitalizations for active SLE 7.

Hydroxychloroquine Dosing and SLE Disease Activity

• A 2015 study found that disease activity decreased with increasing HCQ blood levels, and that there was a trend toward higher disease activity with lower HCQ levels 4.
• A 2023 study found that higher HCQ blood levels were protective against flare occurrence, and that patients with low oral HCQ dosage tend to have more flares 5.
• A 2024 study found that the use of lower doses of HCQ was associated with an increased risk of hospitalizations for active SLE 7.