How to use hydroxychloroquine (Antimalarial) in patients with Impaired renal function (Chronic Kidney Disease, CKD)?

From the Guidelines

Hydroxychloroquine dosing should be reduced in patients with impaired renal function, specifically by 25% when the estimated glomerular filtration rate (eGFR) falls below 30 ml/min per 1.73 m², as recommended by the kdigo 2024 clinical practice guideline for the management of lupus nephritis 1.

Key Considerations

• The recommended starting dose of hydroxychloroquine is around 5 mg/kg/d, and doses of 2–3 mg/kg/d may not achieve adequate blood levels and could be associated with higher flare rates 1.
• In patients with eGFR <30 ml/min per 1.73 m², the dose of hydroxychloroquine should be reduced by 25% 1.
• Regular monitoring of renal function is essential, with assessments every 3-6 months depending on the severity of kidney disease.
• Additionally, these patients should undergo more frequent ophthalmologic examinations, as hydroxychloroquine can accumulate in tissues when renal clearance is reduced, potentially increasing the risk of retinopathy 1.

Important Factors

• Hydroxychloroquine is partially eliminated by the kidneys (approximately 40-50%), which explains why dose adjustment is necessary in severe renal impairment.
• The medication has a very long half-life (40-50 days), so changes in dosing may take weeks to reach steady state.
• If signs of toxicity develop (visual changes, muscle weakness, or cardiac symptoms), the medication should be temporarily discontinued and the patient reassessed.

Screening and Monitoring

• Updated guidelines from the Royal College of Ophthalmologists in the United Kingdom published in 2020 do not recommend baseline examination prior to initiating treatment, and yearly monitoring should begin after 1 year of therapy in patients with additional risk factors (concomitant tamoxifen use; estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m²; dose of hydroxychloroquine >5 mg/kg/d; use of chloroquine) or after 5 years of therapy otherwise 1.
• Recent data showed that hydroxychloroquine retinopathy in long-term users is more common than previously perceived, affecting 0.5% after 6 years of treatment, increasing to 7.5% of long-term users in general, and could be >20% when treatment duration is over 20 years 1.

From the FDA Drug Label

A reduction in the dosage of hydroxychloroquine sulfate may be necessary in patients with hepatic or renal disease. In general, dose selection in geriatric patients should start with the lowest recommended dose, taking into consideration the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. Nevertheless, this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function

Key Considerations:

• A reduction in dosage may be necessary for patients with renal disease.
• Dose selection should consider decreased hepatic, renal, or cardiac function.
• Impaired renal function increases the risk of toxic reactions.

Clinical Decision: When using hydroxychloroquine in patients with Chronic Kidney Disease (CKD), it is essential to consider a reduced dosage to minimize the risk of toxic reactions due to the drug's substantial excretion by the kidney 2.

From the Research

Hydroxychloroquine Use in Patients with Chronic Kidney Disease (CKD)

• Hydroxychloroquine is an antimalarial drug that has been used to treat various conditions, including systemic lupus erythematosus and lupus nephritis 3.
• In patients with CKD, the use of hydroxychloroquine requires careful consideration due to the potential risk of adverse effects, such as irreversible and progressive retinal toxicity and cardiomyopathy 3.
• However, research suggests that hydroxychloroquine may have a protective effect on the kidneys, with a lower risk of incident CKD in patients with rheumatoid arthritis who use the drug 4.

Dosing and Monitoring

• The dosing of hydroxychloroquine in patients with CKD requires adjustment to avoid toxicity, with monitoring of blood levels and renal function recommended 3, 5.
• Clinicians should be aware of the potential for drug interactions and adjust the dose of hydroxychloroquine accordingly, taking into account the patient's renal function and other medications being used 5.

Management of CKD

• The management of CKD involves a comprehensive approach, including cardiovascular risk reduction, treatment of albuminuria, and avoidance of potential nephrotoxins 6.
• Patients with CKD require regular monitoring for complications, such as hyperkalemia, metabolic acidosis, and anemia, and may require adjustments to their medication regimen 6.
• Drug stewardship is an important aspect of CKD management, with a focus on maximizing medication safety and effectiveness while minimizing potential harms 5.

Anticoagulation in Patients with CKD

• The use of anticoagulants, such as direct oral anticoagulants (DOACs), in patients with CKD requires careful consideration due to the potential risk of bleeding and other adverse effects 7.
• DOACs may be preferred over warfarin in patients with moderate-to-severe CKD, with appropriate dose adjustment and monitoring of renal function and bleeding risk 7.