title: Challenges of studying drugs in pregnancy for off-label indications: pravastatin for preeclampsia prevention.
abstract: Statins (3-hydroxy-3 methyl-glutaryl coenzyme-A reductase inhibitors) are the most commonly prescribed cholesterol-lowering medications due to their efficacy in reducing cardiovascular mortality and morbidities, tolerability, and safety profiles. Based on pathophysiologic similarities between cardiovascular disease and preeclampsia, a common and dangerous complication of pregnancy, there is an increasing interest in studying this class of medications during pregnancy to prevent and/or treat preeclampsia. Undergoing such a study, which entails the use of a pregnancy class X medication for an off-label indication in pregnancy, requires intensive multidisciplinary involvement of a group of experts in basic and clinical pharmacology, research methods, pregnancy physiology and maternal-fetal medicine, as well as U.S. Food and Drug Administration (FDA) regulatory guidelines and practice. Issues of potential fetal risk, altered maternal-fetal pharmacokinetics and pharmacodynamics, and regulatory challenges are real, and must be carefully considered in the process of research in this arena.
authors.affiliation: Department of Obstetrics and Gynecology, Columbia University Medical Center, 622 W 168th St, 16-66, New York, NY 10032. Electronic address: Klc2108@columbia.edu.
authors.forename: Kirsten Lawrence
authors.initials: KL
authors.lastname: Cleary
authors.affiliation: Research Triangle Institute International, Research Triangle Park, NC.
authors.forename: Kelly
authors.initials: K
authors.lastname: Roney
authors.affiliation: Department of Obstetrics & Gynecology, The University of Texas Medical Branch, Galveston, TX.
authors.forename: Maged
authors.initials: M
authors.lastname: Costantine
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology; D035843:Biomedical Research / Q000941:ethics / Q000331:legislation & jurisprudence / Q000379:methods*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D056687:Off-Label Use / Q000941:ethics / Q000331:legislation & jurisprudence; D017035:Pravastatin / Q000627:therapeutic use*; D011225:Pre-Eclampsia / Q000517:prevention & control*; D011247:Pregnancy
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin
keywords: maternal mortality; preeclampsia; prevention of preeclampsia; statins in pregnancy