FDA requests removal of strongest warning against using statins during pregnancy
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The FDA is requesting that manufacturers of statins remove its strongest warning from current prescribing information, which states that these medications should never be used during pregnancy.
Most patients should still stop statins, also referred to as cholesterol-lowering HMG-CoA reductase inhibitors, once they learn they are pregnant. In addition, many patients can discontinue statins temporarily while breastfeeding, but patients who require statins after giving birth should not breastfeed and should use alternatives such as infant formula to feed their babies.
However, because statins may prevent serious or potentially fatal events for a small group of very high-risk pregnant patients and their fetuses, it is no longer appropriate to state that these drugs should never be used in pregnant women.
FDA’s actions
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.
FDA’s requested changes include removing the contraindication against using these medicines in all pregnant women. A contraindication is FDA’s strongest warning and is only added to the prescribing information when a medicine should not be used because the risk clearly outweighs any possible benefit. Removing the contraindication will apply to the entire class of statin drugs.
The removal of the contraindication will enable health care professionals and patients to make individual decisions about the benefits and risks of statin use during pregnancy, especially for patients who are at very high risk for myocardial infarction (MI) or stroke, such as patients with homozygous familial hypercholesterolemia and those who have previously had MI or stroke.
Statins are safe to prescribe in patients who are not pregnant but may become pregnant. Thus, we hope the removal will reassure patients and providers that inadvertent exposure to statin therapy in early pregnancy (before the pregnancy is recognized) is unlikely to cause harm to the developing fetus.
Statins as treatment for cholesterol and CV events
Statins are a class of drugs approved to lower cholesterol levels and reduce risk for CV events in various patient populations. First approved in 1987, statins are now widely used, with more than one-quarter of U.S. adults taking these medications.
Statins decrease LDL cholesterol. Statins can also lower the risk for MI and stroke in patients who have heart disease or risk factors for heart disease.
Common adverse effects of statins include headache, nausea, muscle pain, diarrhea and constipation.
Medicines in the statin class include atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin. Statins are marketed as single-ingredient products and in combination with other medicines. They are available as brand-name and generic products.
Deciding whether to use statins during pregnancy
Health care professionals should discontinue statin therapy in most pregnant patients as treatment of hyperlipidemia is generally not necessary during pregnancy. Atherosclerosis is a chronic process and temporary discontinuation of lipid-lowering drugs during pregnancy should have little impact on long-term therapy.
However, health care providers should consider the therapeutic needs of the individual patient during pregnancy. As mentioned, statin use during pregnancy may prevent serious or potentially fatal events in a small group of very high-risk pregnant patients and their fetuses. This may include those at very high risk for MI or stroke, such as patients with homozygous familial hypercholesterolemia and those who have previously had MI or stroke.
People who can become pregnant who are taking statins should talk to their health care provider if they are pregnant or suspect they are pregnant about whether to stop statin use.
Lactation
Patients who require statins after giving birth should not breastfeed because the medication may pass into the breastmilk. Patients should discuss their options with their health care professionals. The statin may be temporarily stopped until the patient is no longer breastfeeding. Alternatively, patients who require ongoing statin treatment can use breastmilk alternatives such as infant formula to feed their baby.
The rationale for the revisions
When FDA approved the first statin in 1987, the prescribing information came with our strongest warning recommending against use during pregnancy and breastfeeding. This was based on safety signals from animal data at drug exposures higher than human doses; the potential concern that lowering cholesterol may negatively affect the fetus or infant; and the perspective 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.
Since then, multiple randomized trials and meta-analyses have shown the benefit of statin therapy on the prevention of CV events. Meanwhile, human data from published observational studies of statin use in pregnant women have not identified a drug-associated risk for major birth defects (structural changes in one or more parts of the body that are present at birth and have a serious, adverse effect on the health, development or functional ability of the infant) when controlling for other risks, such as diabetes. The available evidence is insufficient to determine if there is a drug-associated risk for miscarriage. Overall, animal data also suggest limited potential of statins to cause birth defects or miscarriage and limited potential to affect nervous system development in a fetus. Nevertheless, statins decrease the synthesis of cholesterol and possibly other biologically active substances derived from cholesterol. Therefore, statins may cause fetal harm when administered to pregnant patients based on the mechanism of action.
The revised labeling language bridges these findings. Statins are not indicated in most pregnant patients because of the potential risk, but contraindicating statins in all pregnant patients, particularly those at high risk for CV events without appropriate therapy, is not warranted.
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John Sharretts, MD, is deputy director of the Division of Diabetes, Lipid Disorders and Obesity in the FDA’s Center for Drug Evaluation and Research.
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