Is Plaquenil (hydroxychloroquine) safe to use during pregnancy?

From the Guidelines

Plaquenil (hydroxychloroquine) is considered safe to use during pregnancy, and it is recommended to continue its use in pregnant women with autoimmune conditions, as the benefits of controlling these conditions typically outweigh potential risks. The medication has been shown to cross the placenta, but extensive clinical experience, as reported in the 2024 KDIGO clinical practice guideline for the management of lupus nephritis 1, has not demonstrated significant harm to the developing fetus. In fact, discontinuing hydroxychloroquine during pregnancy may lead to disease flares that could pose greater risks to both mother and baby.

The usual dosage remains 200-400 mg daily, as prescribed before pregnancy. Hydroxychloroquine helps control inflammation and immune system activity, which can improve pregnancy outcomes in women with autoimmune disorders. Some studies suggest it may even reduce the risk of preterm birth and intrauterine growth retardation, as mentioned in the 2024 KDIGO guideline 1. While any medication during pregnancy should be approached with caution, hydroxychloroquine has one of the better safety profiles among disease-modifying antirheumatic drugs, with decades of use supporting its relative safety during pregnancy.

Key points to consider when using Plaquenil during pregnancy include:

• The medication is considered safe and should be continued in pregnant women with autoimmune conditions, as stated in the 2024 KDIGO guideline 1 and also supported by the 2023 KDOQI US commentary on the 2021 KDIGO clinical practice guideline for the management of glomerular diseases 1.
• The benefits of controlling autoimmune conditions with hydroxychloroquine typically outweigh potential risks.
• Discontinuing hydroxychloroquine during pregnancy may lead to disease flares that could pose greater risks to both mother and baby.
• Hydroxychloroquine has been shown to reduce the risk of preterm birth and intrauterine growth retardation, as reported in the 2024 KDIGO guideline 1.

From the FDA Drug Label

Risk Summary Prolonged clinical experience over decades of use and available data from published epidemiologic and clinical studies with hydroxychloroquine sulfate use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal, or fetal outcomes Data from published epidemiologic and clinical studies have not established an association with hydroxychloroquine sulfate use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes Hydroxychloroquine readily crosses the placenta with cord blood levels corresponding to maternal plasma levels. No retinal toxicity, ototoxicity, cardiotoxicity, or growth and developmental abnormalities have been observed in children who were exposed to hydroxychloroquine in utero

Plaquenil (hydroxychloroquine) use in pregnancy appears to be relatively safe, as there is no established association with major birth defects, miscarriage, or adverse maternal or fetal outcomes, according to available data from epidemiologic and clinical studies 2. However, it is essential to consider the risks and benefits of using hydroxychloroquine during pregnancy, especially in women with underlying conditions such as malaria, rheumatoid arthritis, or systemic lupus erythematosus.

• Key points:
  • No drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
  • Hydroxychloroquine crosses the placenta, but no retinal toxicity, ototoxicity, cardiotoxicity, or growth and developmental abnormalities have been observed in exposed children
  • Available data have methodological limitations, including small sample size and study design

From the Research

Safety of Plaquenil in Pregnancy

• The safety of Plaquenil (hydroxychloroquine) in pregnancy has been evaluated in several studies 3, 4.
• A study published in the American Journal of Obstetrics and Gynecology in 2021 found that hydroxychloroquine use during the first trimester of pregnancy was associated with a small increase in the risk of major congenital malformations 3.
• Another study published in Birth Defects Research in 2021 found that the observed birth defects among women taking hydroxychloroquine were varied and did not present a clear pattern, suggesting no meaningful evidence for the risk of specific birth defects 4.
• However, a study published in the Journal of Midwifery & Women's Health in 2002 noted that understanding the FDA categorization of agents and basic teratology associated with drugs can assist professionals in recognizing which pharmaceuticals should be used or avoided during pregnancy 5.

Risk of Congenital Malformations

• The study published in the American Journal of Obstetrics and Gynecology in 2021 found that the adjusted relative risk of major congenital malformations associated with hydroxychloroquine use during the first trimester was 1.26 (95% confidence interval, 1.04-1.54) 3.
• The study also found that the risk of malformations was higher with daily doses of ≥400 mg (adjusted relative risk, 1.33; 95% confidence interval, 1.08-1.65) compared to daily doses of <400 mg (adjusted relative risk, 0.95; 95% confidence interval, 0.60-1.50) 3.

Other Considerations

• Hydroxychloroquine has been associated with irreversible visual loss due to retinal toxicity, particularly with long-term use 6, 7.
• A study published in the Annals of Internal Medicine in 2023 found that the cumulative incidence of hydroxychloroquine retinopathy was 8.6% after 15 years of use, and higher doses were associated with a greater risk of incident retinopathy 6.
• The study published in Eye in 2017 noted that hydroxychloroquine retinopathy is far more common than previously considered, with an overall prevalence of 7.5% in patients taking hydroxychloroquine for greater than 5 years 7.