UK Warns Pregnant Women About Taking Pregabalin

By Pat Anson, PNN Editor

Health officials in the UK are warning women of childbearing age that pregabalin (Lyrica), a drug commonly prescribed for pain, anxiety and epilepsy, raises the risk of major birth defects.

A recent study in four Nordic countries of over 2,700 pregnancies found that 5.6% of babies born to women who took pregabalin in the first three months of pregnancy had birth abnormalities. That compares to 4.1% of babies whose mothers did not use pregabalin.  

“The study showed that taking pregabalin during early pregnancy was associated with a slightly increased chance of having a baby who is born with a physical birth abnormality. It is important to note that this study could not show that pregabalin was the cause of the physical birth abnormalities,” the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) said in a new safety alert.

The birth defects associated with pregabalin primarily involved the nervous system, eyes, face, urinary system and genitals. The MHRA – which regulates drugs in the UK – cautioned pregnant women not to stop taking pregabalin without talking to a doctor first.

“If you think you may be pregnant and are currently taking pregabalin, you should set up an appointment with your GP, specialist or nurse at your earliest opportunity, to discuss any concerns you may have. However, do continue to take pregabalin as prescribed until you can speak to them,” the MHRA alert said. “Untreated epilepsy, pain, or anxiety could be harmful to you and your unborn baby. It is important that you talk to your healthcare professional before stopping pregabalin or making any changes to your usual medicines.”

An international study in 2016 also linked pregabalin to birth defects. Women taking pregabalin were found to be six times more likely to have a baby with a major birth defect, including abnormalities in the heart, central nervous system (CNS) and other organs.

Pregabalin Concerns

In recent years, pregabalin has come under increased scrutiny in the UK.  In 2021, the MHRA said pregabalin was associated with serious breathing problems in people over age 65 and in patients with compromised respiratory systems.

Doctors in Northern Ireland were also told last year not to prescribe pregabalin for neuropathic pain due to a “significant increase” in drug-related deaths involving the drug.

In 2019, pregabalin and gabapentin (Neurontin) were both rescheduled as Class C drugs in the UK due to a rising number of overdose deaths. Health experts said the medications cause “an elevated mood in users” and could have serious side effects when combined with other drugs.

Lyrica and Neurontin are two of Pfizer’s top selling drugs and generate billions of dollars in annual sales. They belong to a class of nerve medication called gabapentinoids that were originally developed to treat seizures, but are now widely prescribed as an alternative to opioid painkillers. A 2019 study found little evidence that gabapentinoids should be used to treat pain and said their effectiveness was often exaggerated by prescribing guidelines.

In the United States, where Lyrica is approved for fibromyalgia, neuropathic pain, seizures and postherpetic neuralgia, the FDA’s lengthy warning label states that “there are no adequate and well-controlled studies with Lyrica in pregnant women,” but at the same time cautions that “Lyrica may harm your unborn baby.”  

An earlier warning label said it was “not known if Lyrica will harm your unborn baby.”

Acetaminophen May Harm Male Fetuses

By Pat Anson, Editor

The pain reliever acetaminophen may inhibit the sexual development of male babies whose mothers take the over-the-counter drug while pregnant, according to a new study by Danish researchers. The study only involved laboratory rodents, but one researcher called the findings “very worrying” and said pregnant women should think carefully before using the painkiller.

Acetaminophen – which is more commonly known as paracetamol outside the U.S. -- is used by over half the pregnant women in the United States and European Union. It is the active ingredient in Tylenol, Excedrin, and hundreds of pain medications.

Previous research has already indicated that acetaminophen can suppress the development testosterone in male fetuses. It has also been linked to autism and attention deficit problems in young children.

The new study, published in the journal Reproduction, involved mouse fetuses that were exposed to acetaminophen at varying doses. The dose that produced the most effect was three times higher than the maximum recommended daily dose in humans.

Researchers evaluated the male rodents' behavior after their birth, studying their aggressiveness toward other male mice, their ability to mark their territory, and their ability to mate. They were found wanting in all three areas.

The abnormal behavior was apparently caused by lower levels of testosterone, the male sex hormone that fuels the development and programming of the male body and brain. Testosterone also controls sex drive and the production of sperm.

"We have demonstrated that a reduced level of testosterone means that male characteristics do not develop as they should. This also affects sex drive," said Dr. David Møbjerg Kristensen of the Department of Biomedical Sciences at the University of Copenhagen. "Mice exposed to paracetamol at the fetal stage were simply unable to copulate in the same way as our control animals. Male programming had not been properly established during their fetal development, and this could be seen long afterwards in their adult life. It is very worrying."

When the brains of the mice exposed to acetaminophen were analyzed, researchers found significantly fewer neurons in the brain region that controls sex drive.

“These findings add to the growing body of evidence suggesting the need to limit the widespread exposure and use of APAP (acetaminophen) by pregnant women,” said Kristensen.

A study published last year in JAMA Pediatrics  linked prenatal use of acetaminophen to a higher risk of behavior problems, hyperactivity and emotional problems in children. The pain reliever has also long been associated with liver injury and allergic reactions such as skin rash.

The FDA label for products containing acetaminophen warns about the risk of liver damage and other side effects, but does not specifically warn pregnant women about using the pain reliever. The agency said in 2015 that the evidence was “too limited” to justify such a warning.  

In its 2016 opioid prescribing guidelines, the CDC recommends acetaminophen as an alternative to opioid pain medication. The guideline only briefly mentions that acetaminophen was involved in nearly 900 overdose deaths in 2010 and can cause liver problems. The guideline does warn pregnant women -- at length -- that opioids can cause birth defects, poor fetal growth, still births and neonatal opioid withdrawal syndrome.