What are the guidelines for using Hydroxychloroquine (HCQ) in pregnancy?

Hydroxychloroquine in Pregnancy

Hydroxychloroquine should be continued throughout pregnancy in women already taking it for autoimmune conditions, and should be started if not already prescribed, as it reduces disease flares and improves pregnancy outcomes without increasing the risk of major birth defects. 1, 2, 3

Primary Recommendations

For women with systemic lupus erythematosus (SLE) or lupus nephritis:

• Continue hydroxychloroquine throughout pregnancy if already taking it 1, 2
• Start hydroxychloroquine if not already prescribed, unless contraindicated by allergy or intolerance 2, 3
• Hydroxychloroquine reduces lupus flares during pregnancy, with cessation associated with significantly increased disease activity 1, 2
• The drug decreases rates of preterm birth and intrauterine growth retardation 1, 2

For women with antiphospholipid syndrome (APS):

• Add hydroxychloroquine to standard anticoagulation therapy (aspirin + heparin/LMWH) for refractory obstetric APS when pregnancy loss occurs despite standard treatment 4
• Consider adding hydroxychloroquine to prophylactic-dose heparin/LMWH and low-dose aspirin for primary APS 4

Timing and Dosing

Initiation timing:

• Start hydroxychloroquine before 16 weeks of gestation to maximize reduction in pregnancy complications 1, 3
• Typical doses are 200-400 mg daily (approximately 5 mg/kg/day), which have been extensively studied 1, 2

Combination therapy:

• Add low-dose aspirin (81-100 mg daily) in the first trimester for all SLE patients 1, 3
• This combination may reduce risk of preeclampsia and intrauterine growth retardation 1, 2

Safety Profile

Maternal and fetal safety:

• Prolonged clinical experience over decades and published epidemiologic studies have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal/fetal outcomes 5
• One large real-world study of 288 pregnancies exposed to chloroquine/hydroxychloroquine found no increased risk of prematurity, low birth weight, or major congenital malformations 6
• A systematic review of over 250 pregnancies with hydroxychloroquine exposure found no increase in birth defects, with no retinal or ototoxicity detected in exposed children 7

Important caveat regarding recent data:

• One 2021 study using Medicaid and MarketScan databases (2045 exposed pregnancies) found a small increased risk of major congenital malformations with first-trimester hydroxychloroquine exposure (adjusted relative risk 1.26,95% CI 1.04-1.54), particularly at doses ≥400 mg daily (adjusted relative risk 1.33) 8
• However, this risk was small, and the study authors concluded that for most patients with autoimmune rheumatic disorders, the benefits of treatment during pregnancy likely outweigh this risk 8
• The FDA label states that available data have not identified a drug-associated risk of major birth defects or adverse outcomes 5

Absolute Contraindications

Do not use hydroxychloroquine if:

• Known allergy to hydroxychloroquine or chloroquine 2, 5
• Severe adverse effects or intolerance to hydroxychloroquine 2
• G6PD deficiency is a relative contraindication due to hemolysis risk, though recent data suggest lower risk than previously thought 1, 2

Monitoring During Pregnancy

Disease activity monitoring:

• Monitor at least once per trimester with complete blood count, urinalysis with protein:creatinine ratio, serum C3/C4 complement levels, and anti-dsDNA antibody titers 1, 3
• Increase monitoring frequency based on individual disease activity 3

Ocular monitoring:

• Baseline examination is not required prior to initiating treatment 1
• Yearly monitoring should begin after 1 year of therapy in patients with additional risk factors (eGFR <60 ml/min per 1.73 m², dose >5 mg/kg/day) or after 5 years otherwise 1

Breastfeeding

Hydroxychloroquine is compatible with breastfeeding:

• The drug is present in human milk at low levels 5
• No adverse reactions, retinal toxicity, ototoxicity, cardiotoxicity, or developmental abnormalities have been observed in breastfed infants 5
• Hydroxychloroquine has limited transfer into breast milk and is considered safe 1

Critical Pitfall to Avoid

Never discontinue hydroxychloroquine when a patient becomes pregnant or is planning pregnancy. This can precipitate disease flares and increase maternal morbidity without providing any fetal benefit. 2 The drug has a satisfactory safety profile in both mother and fetus, and withdrawal is associated with increased lupus activity. 1