Pregnancy-associated exposure reduction to medications used for antiphospholipid syndrome: a systematic review.

Objectives: Pregnancy-associated hypercoagulability and potential changes in drug disposition increase the risk of anticoagulant treatment failure for pregnant women with antiphospholipid syndrome (APS), which is characterised by thrombotic and obstetric complications. We conducted a systematic review of pregnancy-associated pharmacokinetic (PK) changes of medications commonly used for APS. Methods: We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Pharmaceutical Abstracts. Publications of PK assessment in pregnant individuals compared to nonpregnant controls were included. Six target drugs in 3 groups were low-dose aspirin, heparins (unfractionated heparin and low molecular weight heparin), and antimalarial (hydroxychloroquine and chloroquine). PK parameters in pregnancy including apparent clearance (CL) were compared to those of the nonpregnant state. Results: In 3460 screened publications, we identified 12 articles. Of the 3 drug groups, only heparins included studies of pregnant women with APS. Despite the diverse PK profiles of these drugs, all 6 drugs showed statistically significant changes of 1.5- to 2-fold represented by decreased area under the curve, lower peak concentration, and/or increased CL with large interindividual variations. Details of postpartum recovery profiles of the PK changes were not reported in any of the studies. Conclusions: Limited evidence shows the reduction of exposure to APS medications during pregnancy, implying a higher risk of therapeutic failure. Although the clinical impact of the PK changes awaits sufficiently powered studies, the lack of PK data in pregnancy and postpartum remains a significant challenge in women's health.