What are the considerations and potential adverse effects when prescribing Hydroxychloroquine (HCQ) for a young to middle-aged female patient with Systemic Lupus Erythematosus (SLE), particularly during pregnancy and lactation?

Hydroxychloroquine for Systemic Lupus Erythematosus: Prescribing Considerations, Adverse Effects, and Monitoring

Dosing and Administration

Hydroxychloroquine should be prescribed at ≤5 mg/kg/day based on actual body weight, with typical doses of 200-400 mg daily, to optimize efficacy while minimizing retinopathy risk. 1, 2

• The recommended starting dose is approximately 5 mg/kg/day (2.3 mg/kg actual body weight), which balances therapeutic benefit against toxicity 1
• Most patients with SLE respond effectively to 400 mg/day, with response rates ranging from 50-97% 3
• Dose reduction may be necessary in patients with hepatic or renal impairment 4

Pre-Treatment Screening

Before initiating hydroxychloroquine, screen for G6PD deficiency in men of African, Asian, or Middle Eastern origin to prevent hemolytic anemia, though recent data suggest this risk is lower than previously thought. 1

• Baseline ophthalmologic examination is no longer recommended by the Royal College of Ophthalmologists prior to initiating treatment 1
• Exclude known allergy to hydroxychloroquine or chloroquine, which is an absolute contraindication 1, 5, 4
• Document baseline renal and hepatic function 4

Ophthalmologic Monitoring

Annual ophthalmologic screening should begin after 1 year of therapy in patients with additional risk factors (eGFR <60 ml/min/1.73 m², concomitant tamoxifen use, or dose >5 mg/kg/day), or after 5 years in patients without risk factors. 1

• Retinopathy risk is dose-dependent and cumulative, affecting 0.5% after 6 years, 7.5% of long-term users generally, and >20% after 20 years of treatment 1
• The incidence of retinopathy is exceedingly low at recommended doses, with only one case reported across 852 patients in multiple studies 3
• Hydroxychloroquine can accumulate in lysosomes and cause phospholipidosis with zebra bodies in podocytes, mimicking Fabry disease 1

Common Adverse Effects

The most frequently reported adverse effects include:

• Skin rash and increased skin pigmentation 1
• Gastrointestinal symptoms (nausea, diarrhea), though less common than with chloroquine 6
• Muscle weakness 1
• Visual changes or vision loss (rare at recommended doses) 1

Cardiovascular Monitoring

• QRS or QTc prolongation can occur, particularly in overdose situations 4
• Severe toxicity may cause ventricular arrhythmias, torsade de pointes, and cardiac arrest 4
• Routine ECG monitoring is not required at therapeutic doses but should be considered in patients with pre-existing cardiac disease

Pregnancy and Lactation

Hydroxychloroquine should be continued throughout pregnancy in women with SLE, as discontinuation significantly increases disease flare risk without providing any fetal benefit. 1, 5

• The American College of Rheumatology strongly recommends continuing hydroxychloroquine during pregnancy if already prescribed, and conditionally recommends starting it if not contraindicated 1, 5
• Hydroxychloroquine reduces lupus flares during pregnancy, decreases rates of preterm birth and intrauterine growth retardation, and may reduce preeclampsia risk when combined with low-dose aspirin 1, 5, 4
• No retinal toxicity, ototoxicity, cardiotoxicity, or growth and developmental abnormalities have been observed in children exposed to hydroxychloroquine in utero 4
• Hydroxychloroquine has limited transfer into breast milk and is considered safe during breastfeeding 1, 4

Pregnancy-Specific Recommendations

• Combine hydroxychloroquine with low-dose aspirin (81-100 mg daily) starting before 16 weeks of gestation to reduce preeclampsia risk 1, 5
• Monitor disease activity at least once per trimester with CBC, urinalysis with protein:creatinine ratio, complement levels (C3/C4), and anti-dsDNA antibodies 1, 7
• Test for antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2GPI) once before or early in pregnancy 1

Renal and Hepatic Considerations

• Hydroxychloroquine is substantially excreted by the kidney, requiring dose reduction in renal impairment 4
• In patients with eGFR <60 ml/min/1.73 m², initiate ophthalmologic screening after 1 year rather than 5 years 1
• Dose adjustment is necessary in hepatic disease 4

Critical Pitfalls to Avoid

Never discontinue hydroxychloroquine when a patient becomes pregnant or is planning pregnancy, as this precipitates disease flares and increases maternal morbidity without providing fetal benefit. 5

• Do not use hydroxychloroquine doses exceeding 5 mg/kg/day actual body weight, as this significantly increases retinopathy risk 1, 2
• Do not delay ophthalmologic screening in high-risk patients (renal impairment, high doses, concomitant tamoxifen) 1
• Do not prescribe to patients with known G6PD deficiency without careful risk-benefit assessment, particularly in high-risk ethnic groups 1

Long-Term Benefits Supporting Continued Use

Beyond controlling disease activity, hydroxychloroquine provides multiple benefits that justify long-term use:

• Reduces SLE flare rates and allows glucocorticoid dose reduction 8, 2, 6
• Decreases organ damage accrual and improves long-term survival 2
• Provides antithrombotic effects, particularly in antiphospholipid antibody-positive patients 8, 6
• Improves lipid profiles and may reduce cardiovascular risk 2, 6
• Improves glycemic control and reduces risk of type 2 diabetes 6