FDA Asks Statin Makers to Remove the Strongest Warning Against Use in Pregnancy (2021)

Table of Contents

1. What the FDA Did on July 20, 2021
2. What a Contraindication Is, and Why the FDA Removed This One
3. Who the FDA Had in Mind
4. Which Medicines Are Covered
5. What Statins Are, in the FDA’s Words
6. Why the Warning Was There: 1987 to 2021
7. The Evidence the FDA Reviewed: Birth Defects
8. The Evidence on Miscarriage
9. What the FDA Still States About Pregnancy and Breastfeeding
10. What the Request Does Not Do
11. Dates and Legal Status as of October 18, 2026
12. How It Fits Other FDA Pregnancy-Labeling Actions
13. Primary Documents
14. Key Research Papers
15. Connections
16. Featured Videos

1. What the FDA Did on July 20, 2021

The announcement came as a Drug Safety Communication, the form the FDA uses to tell the public and health care professionals about new safety information on a medicine. It is titled “FDA requests removal of strongest warning against using cholesterol-lowering statins during pregnancy; still advises most pregnant patients should stop taking statins,” with the subtitle “Breastfeeding not recommended in patients who require statins.”

The FDA wrote that it “is requesting removal of its strongest warning against using cholesterol-lowering statin medicines in pregnant patients.” It explained the basis in one sentence: “We have conducted a comprehensive review of all available data and are requesting that statin manufacturers make this change to the prescribing information as part of FDA’s ongoing effort to update the pregnancy and breastfeeding information for all prescription medicines.”

The prescribing information is the official label written for health care professionals, which sets out what a medicine is approved for and its warnings. The FDA described the change it asked for as “revisions to the information about use in pregnancy in the prescribing information of the entire class of statin medicines,” including “removing the contraindication against using these medicines in all pregnant patients.” The request went to the manufacturers of every statin, not to one product.

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2. What a Contraindication Is, and Why the FDA Removed This One

The FDA’s own definition, from the same communication: “A contraindication is FDA’s strongest warning and is only added when a medicine should not be used because the risk clearly outweighs any possible benefit.” Before the change, the statin labels, in the FDA’s words, stated “that statins should never be used in patients during pregnancy.”

The FDA’s reasoning for removing it: “Because the benefits of statins may include prevention of serious or potentially fatal events in a small group of very high-risk pregnant patients, contraindicating these drugs in all pregnant women is not appropriate.”

In other words, the FDA did not find that statins had become safe in pregnancy. It found that a blanket “never” no longer matched the evidence, because for a small number of patients the balance of benefit and risk may differ. The FDA stated that it “expects removing the contraindication will enable health care professionals and patients to make individual decisions about benefit and risk, especially for those at very high risk of heart attack or stroke.”

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3. Who the FDA Had in Mind

The communication names two groups of patients at very high risk:

• patients with homozygous familial hypercholesterolemia (the condition is described on the site’s Familial Hypercholesterolemia page); and
• patients who have previously had a heart attack or stroke. The section written for health care professionals describes this group as patients “with established cardiovascular disease.”

For these patients, the FDA wrote, health care professionals can “consider the ongoing therapeutic needs of the individual patient, particularly those at very high risk for cardiovascular events during pregnancy.”

The FDA also addressed patients who are not pregnant but could become pregnant: “Statins are safe to use in patients who are not pregnant but may become pregnant.” It stated its hope that the revised labels would help reassure health care professionals on that point, and help them reassure patients who took a statin early in pregnancy, before the pregnancy was recognized, “that the medicine is unlikely to harm the unborn baby.”

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4. Which Medicines Are Covered

The request covers the whole statin class. The FDA lists the medicines in the class as:

• atorvastatin (alone and combined with amlodipine)
• fluvastatin
• lovastatin
• pitavastatin
• pravastatin
• rosuvastatin (alone and combined with ezetimibe)
• simvastatin (alone and combined with ezetimibe)

The FDA notes that statins “are marketed as single-ingredient products and in combination with other medicines” and are “available as brand-name and generic products.” The combinations listed above are the ones that appear in the FDA’s table of FDA-approved statin medicines in the communication.

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5. What Statins Are, in the FDA’s Words

The communication describes statins as “a class of prescription medicines that have been used for decades to lower low-density lipoprotein (LDL-C or ‘bad’) cholesterol in the blood.” According to the FDA, they work “by reducing the amount of cholesterol made by the liver and helping the liver remove cholesterol already in the blood.”

The FDA adds that statins “also can lower the risk for heart attack and stroke in those who have heart disease or risk factors for it,” and that they “may help stabilize the plaques that can build up inside blood vessel walls,” plaques that can interfere with blood flow to the heart and brain. That plaque build-up is the subject of the site’s Atherosclerosis page.

The communication lists the common side effects of statins as headache, nausea, muscle pain, diarrhea and constipation.

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6. Why the Warning Was There: 1987 to 2021

The FDA gives the history in its “What did FDA review?” section. When it approved the first statin in 1987, “the medicine came with our strongest warning recommending against use during pregnancy and breastfeeding.” The FDA lists three reasons for that warning at the time:

• safety signals from animal data at drug exposures higher than human doses;
• a potential concern that lowering cholesterol may negatively affect the unborn baby or infant; and
• the view that short-term use during pregnancy and breastfeeding did not provide a substantial benefit to the mother.

“All statins approved subsequently have carried the same warning,” the FDA wrote. It then describes what changed in the decades since: “multiple randomized trials and meta-analyses have demonstrated the benefit of statin therapy on the prevention of cardiovascular events,” and published observational studies in pregnant women did not identify a drug-associated risk of major birth defects (section 7).

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7. The Evidence the FDA Reviewed: Birth Defects

The communication’s Data Summary says the FDA “reviewed data from case series and prospective and retrospective observational cohort studies over decades of use of statins in pregnant women,” citing 15 references. An observational study follows what happens to people who took a medicine in ordinary life, rather than assigning it at random; a confounder is another factor, such as diabetes, that can affect the outcome and has to be accounted for.

The FDA’s summary of those studies: “Multiple larger, well-designed, and controlled observational studies did not find an increase in major birth defects associated with use of statins during pregnancy.”

The largest study it describes is a 2015 cohort study linked to Medicaid records:

• Size: 1,152 pregnant women exposed to statins compared with 886,996 controls.
• Method: propensity-score methods were used to control for maternal age, diabetes, hypertension, obesity, and alcohol and tobacco use.
• Result: the relative risk of congenital malformations with first-trimester statin use was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, “particularly pre-existing diabetes.” A relative risk of 1.0 would mean no difference between the groups; the FDA reports that the study “did not find a significant teratogenic effect” (a teratogenic effect is one that causes birth defects). There were also no statistically significant increases in any of the organ-specific malformations assessed.
• Exposure pattern: in most pregnancies, statin treatment had started before pregnancy and was stopped at some point in the first trimester once the pregnancy was identified.
• Limitations the FDA lists: reliance on physician coding to define a malformation, no control for certain confounders such as body mass index, use of prescription dispensing as proof that a statin was taken, and no information on non-live births.

The FDA also “re-reviewed nonclinical data from statin development programs” (the animal studies done when the medicines were developed). It concluded that “the totality of the data suggests a limited potential for statins to cause malformations or embryofetal lethality, and limited potential to affect nervous system development.”

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8. The Evidence on Miscarriage

On miscarriage, the FDA’s conclusion is that the published data “are insufficient to determine if there is a drug-associated risk of miscarriage.” Its Data Summary sets out why the studies disagree:

• Many older studies did not report or discuss the miscarriage rate. Three studies that included miscarriage in their analyses did not find an increased risk once adjustments were made for confounders.
• A 2009 study reported an adjusted risk ratio for terminations of 2.48 (95% CI 1.65–3.73), but it did not separate elective terminations from miscarriages. The FDA notes that a higher rate of elective terminations “would be expected in a study of pregnant women exposed to a drug contraindicated during pregnancy.”
• A meta-analysis of six small observational studies reported a risk ratio of miscarriage of 1.35 (95% CI 1.04–1.75). The FDA writes that many of the included studies were older and “did not control for multiple confounders that are known to increase the risk of miscarriage.”
• A 2017 retrospective cohort study looked at fetal loss as its main outcome, comparing 281 statin-exposed pregnant women with 2,643 controls matched for maternal age, diabetes, hypertension and body mass index. It found a miscarriage rate of 25% in the statin-exposed group versus 21% in controls, an adjusted hazard ratio of 1.64 (95% CI 1.1–2.46). The FDA notes that the authors acknowledged possible remaining confounding, because the study did not control for the type or severity of diabetes, and possible misclassification of smoking and alcohol use.

The section written for health care professionals states it plainly: “There is insufficient evidence to determine whether statins can cause miscarriage.” Pregnancy loss in general is described on the site’s Recurrent Pregnancy Loss page.

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9. What the FDA Still States About Pregnancy and Breastfeeding

Removing the contraindication did not remove every pregnancy caution. The statements below are the FDA’s own, from the same communication:

• Most pregnant patients: “Despite the change, most patients should stop statins once they learn they are pregnant.” For health care professionals, the FDA wrote that they “should discontinue statin therapy in most pregnant patients.”
• Why a pause is usually possible: “Because of the chronic nature of cardiovascular disease, treatment of hyperlipidemia is not generally necessary during pregnancy.” The FDA adds that atherosclerosis “is a chronic process and the temporary discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients.” (Hyperlipidemia means high levels of fats such as cholesterol in the blood.)
• Possible harm remains on the label: because statins decrease the body’s production of cholesterol “and possibly other biologically active substances derived from cholesterol,” the FDA states that “statins may cause fetal harm when administered to pregnant patients.”
• Breastfeeding: the FDA states that patients “should not breastfeed when taking a statin because the medicine may pass into breast milk and pose a risk to the baby,” and that “Some statins have been shown to pass into human milk.” According to the FDA, many patients can stop statins temporarily until breastfeeding ends, while patients who require ongoing statin treatment are described as needing infant formula or other alternatives instead.
• Telling a clinician: the FDA’s patient section asks patients taking statins to tell their health care professionals about a known or suspected pregnancy, and states that the health care professional “will be able to advise whether you should stop taking the medicine.”

These are the FDA’s statements, reported here as information; decisions about any medicine in pregnancy or while breastfeeding belong with a clinician. The FDA also asks patients and professionals to report side effects from statins to its MedWatch program.

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10. What the Request Does Not Do

• It does not endorse statin use in pregnancy. The FDA still states that most patients “should stop statins once they learn they are pregnant” (section 9).
• It does not change the breastfeeding position. Breastfeeding remains “not recommended” in the FDA’s words for patients who require a statin.
• It does not settle the miscarriage question. The FDA states that the data are insufficient to determine whether there is a drug-associated risk (section 8).
• It does not say statins cannot harm an unborn baby. The FDA still states that statins “may cause fetal harm” because of how they work.
• It is not a new rule. It is a labeling request to the makers of the statin class, announced in a Drug Safety Communication, not a regulation published in the Federal Register.
• It does not remove statins from the market or change what they are approved for. The communication concerns only the pregnancy and breastfeeding information in the label.

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11. Dates and Legal Status as of October 18, 2026

• 1987: the FDA approves the first statin, with its strongest warning against use in pregnancy and breastfeeding; every later statin carries the same warning.
• July 20, 2021: the FDA issues the Drug Safety Communication and requests that statin manufacturers remove the pregnancy contraindication from the prescribing information of the whole class.
• August 30, 2021: the date the FDA gives for the current content of the communication page.

Status as of October 18, 2026: the request stands. No later FDA document reversing or changing it was found. A check of the Federal Register (the U.S. government’s daily publication of rules and official notices) for FDA documents on statins and pregnancy from July 2021 through October 18, 2026 returned none; a labeling request of this kind is not published there, so it has no rulemaking docket. The dates on which each statin’s label was revised are kept in the FDA’s drug-label database, which was not read for this page, so no revision date is given here.

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12. How It Fits Other FDA Pregnancy-Labeling Actions

The FDA itself places this change inside a larger project: it describes the statin request as “part of FDA’s ongoing effort to update the pregnancy and breastfeeding information for all prescription medicines.” The statin class was one group of medicines in that effort; the communication does not list the others.

The statin request removed a warning rather than adding one, and it applied to a whole class of medicines at once. Another 2021 labeling action, which added warnings, is reported on the page on the boxed warnings required on JAK inhibitors.

Pregnancy labeling came up again in a later FDA action reported on its own page, the 2025 acetaminophen-in-pregnancy label change. Other 2021 FDA drug actions are listed on the FDA Actions of 2021 hub, among them the varenicline nitrosamine recall and limit and the accelerated approval of aducanumab.

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13. Primary Documents

1. U.S. Food and Drug Administration. FDA requests removal of strongest warning against using cholesterol-lowering statins during pregnancy; still advises most pregnant patients should stop taking statins. Drug Safety Communication, July 20, 2021; content current as of August 30, 2021. No Federal Register citation or docket (a labeling request, not a rule) — fda.gov Drug Safety Communication
2. U.S. Food and Drug Administration. Drug Safety Communication of July 20, 2021, printable version (PDF), linked from the communication page — fda.gov Drug Safety Communication PDF

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Key Research Papers

1. Bateman BT, Hernandez-Diaz S, Fischer MA, Seely EW, Ecker JL, Franklin JM, Desai RJ, Allen-Coleman C, Mogun H, Avorn J, Huybrechts KF (2015). Statins and congenital malformations: cohort study. BMJ 350:h1035 — PubMed PMID: 25784688
2. McGrogan A, Snowball J, Charlton RA (2017). Statins during pregnancy: a cohort study using the General Practice Research Database to investigate pregnancy loss. Pharmacoepidemiology and Drug Safety 26(7):843-852 — PubMed PMID: 28176447
3. Winterfeld U, Allignol A, Panchaud A, Rothuizen LE, Merlob P, Cuppers-Maarschalkerweerd B, Vial T, Stephens S, Clementi M, De Santis M, Pistelli A, Berlin M, Eleftheriou G, Maňáková E, Buclin T (2013). Pregnancy outcome following maternal exposure to statins: a multicentre prospective study. BJOG 120(4):463-471 — PubMed PMID: 23194157
4. Toleikyte I, Retterstøl K, Leren TP, Iversen PO (2011). Pregnancy outcomes in familial hypercholesterolemia: a registry-based study. Circulation 124(15):1606-1614 — PubMed PMID: 21911783
5. Ofori B, Rey E, Bérard A (2007). Risk of congenital anomalies in pregnant users of statin drugs. British Journal of Clinical Pharmacology 64(4):496-509 — PubMed PMID: 17506782
6. Chang JC, Chen YJ, Chen IC, Lin WS, Chen YM, Lin CH (2021). Perinatal Outcomes After Statin Exposure During Pregnancy. JAMA Network Open 4(12):e2141321 — PubMed PMID: 34967881
7. Karadas B, Uysal N, Erol H, Acar S, Koc M, Kaya-Temiz T, Koren G, Kaplan YC (2022). Pregnancy outcomes following maternal exposure to statins: A systematic review and meta-analysis. British Journal of Clinical Pharmacology 88(9):3962-3976 — PubMed PMID: 35639354
8. Hirsch A, Ternovsky N, Zwas DR, Rotem R, Amir O, Hirsh Raccah B (2022). The effect of statins exposure during pregnancy on congenital anomalies and spontaneous abortions: A systematic review and meta-analysis. Frontiers in Pharmacology 13:1003060 — PubMed PMID: 36249743

The first five papers are among the studies the FDA cites in its Data Summary: the 2015 Medicaid-linked cohort study of birth defects, the 2017 cohort study of pregnancy loss, a multicentre prospective study, a registry study of pregnancies in familial hypercholesterolemia, and a 2007 study of congenital anomalies. The last three were published after the FDA’s July 2021 request: a cohort study of perinatal outcomes and two systematic reviews with meta-analyses of statin exposure in pregnancy.

PubMed Topic Searches

1. PubMed: statins in pregnancy and congenital malformations
2. PubMed: statins in pregnancy and miscarriage
3. PubMed: familial hypercholesterolemia and pregnancy
4. PubMed: statins and breastfeeding

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Connections

• FDA Actions of 2021
• FDA and Regulation
• Cholesterol Management
• Familial Hypercholesterolemia
• Atherosclerosis
• Heart Attack
• Stroke
• Reproductive Medicine
• Recurrent Pregnancy Loss
• JAK Inhibitor Boxed Warnings (2021)
• Varenicline Nitrosamine Recall and Limit (2021)
• Aducanumab Accelerated Approval (2021)
• Propylhexedrine Inhaler Abuse Warning (2021)
• Acetaminophen-in-Pregnancy Label Change (2025)

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