By Dr. Adam Urato
Last week the Food and Drug Administration published a final rule that will change how drug companies present information on the risks of medications during pregnancy. This is considered a very important step as there are approximately 6 million pregnancies in the U.S. every year and the average pregnant woman takes between three and five prescription drugs during the course of a pregnancy.
For decades, the public has relied on the FDA's Letter Category system in which a Category A drug was considered safe, Category D unsafe, with B and C falling in between, and Category X meaning contraindicated in pregnancy.
This past week the FDA announced that it is scrapping that letter system and replacing it with a new system that will offer descriptions about the effects of the drug during pregnancy and lactation. A third section (the "Females and Males of Reproductive Potential" subsection) will include information about pregnancy testing, contraception and about infertility as it relates to the drug.
So what exactly does all this mean for consumers?
As a Maternal-Fetal Medicine specialist, here's my read on the changes:
What this means is that men and women are going to have to actually go to the drug information label and read it. No longer will a pregnant woman simply be able to look up a drug and find out that it’s a Category D in pregnancy, for instance, and then avoid it.
And this is a major problem that I see with the new system: many patients and physicians do not take the time to read through the label prior to using a medication. A description-based system risks losing the benefit of warning that the current Letter System provides when the drug is simply listed as Category D or X.
Also, it seems that the drug companies themselves are going to be asked to write these pregnancy sections on the label. This strikes me as absurd.
In just the past few years pharmaceutical companies have agreed to pay over $13 billion to resolve U.S. Department of Justice allegations of fraudulent marketing practices. I can think of no group that the public would trust less to warn about the risks of medications during pregnancy than the drug companies themselves. Asking Pharma to warn us about medication risks would be like asking natural gas drilling companies to warn us about the risks of fracking. The warnings regarding the use of these drugs in pregnancy should be written by completely independent parties and based on the scientific evidence.
It goes without saying that pregnant women deserve good treatment and care and their health needs should not be ignored because they are pregnant. I take care of high-risk pregnant women on a daily basis and am frequently asked whether a certain medication or medical procedure is “safe” during pregnancy. I often counsel patients and referring physicians that “safe” is a relative term: if a pregnant woman needs a medication or procedure for her health and there is no “safer” alternative for her or her fetus, then that is the way she should be cared for.
No Perfect System
There are two big problems with the current Letter Category system. First, newer drugs are often assumed to be safe and can get a “better” letter grade simply because harm hasn’t been proven yet. A good example of this is the drug Latuda (lurasidone), which is an antipsychotic medication used to treat schizophrenia and bipolar depression. It has been used in the U.S. since 2013. It is considered FDA Category B, which is relatively reassuring, and drugs.com declares it is “not expected to harm an unborn baby.”
But Latuda is an antipsychotic drug. Its exact mechanisim of action is unknown, but it likely disrupts function at dopamine and serotonin receptors. The Latuda label information warns, in adults, of the association with stroke, neuroleptic malignant syndrome, tardive dyskinesia, hyperglycemia, hyperprolactinemia, leukopenia, seizures, orthostatic hypotension, syncope, body temperature dysregulation, and several other adverse effects.
If the dopamine and serotonin systems are important for fetal development (and they are), and if this drug crosses the placenta and disrupts those systems (and is known to cause problems in adults) what about that sounds like it would be safe for fetal development? In this case the Category B is misleading.
Second, in reality the letters are often being ignored. A good example of this is in my area of research: antidepressant use in pregnancy. Most antidepressants have a Category C designation. Category C means that animal studies have shown adverse effects but that there are no adequate studies in humans. The FDA Category C designation does not mean that the medications are safe for use in pregnancy. Yet, I have been told by many patients that the only counseling they received about continuing their antidepressant during pregnancy was that “these medications are safe.” Clearly there is a disconnect between the Category C designation and the public’s understanding.
Old System Had Benefits
A major benefit of the Letter Category system, however, was that the public was given proper warning about drugs that were categorized as D or X in pregnancy. Take, for example, the drug Accutane. This medication, used to treat acne, is Category X and there is widespread knowledge that it should not be used if a patient may become pregnant. Another example is with Paxil. This antidepressant was shown to be associated with heart defects and was given a Category D classification in 2005 and we have seen a significant decrease in its use during pregnancy in the subsequent years.
How To Navigate?
The easiest approach to medication use in pregnancy is to limit it whenever possible.
Medications, for the most part, are synthetic chemical compounds that are made in chemical factories. Human development is a process that has developed over millions of years without exposure to such chemical compounds.
Fetal systems like the serotonin, dopamine, endocrinologic system and many others are critical for normal development. Many medications cross the placenta, enter into the developing baby, and interfere with those very systems. However, this does not mean that medications cannot be used in pregnancy. Patients who need medication to control lupus, diabetes, or another illness, for instance, should work with their physicians to find the most appropriate medication to use during the pregnancy and they should be given good care and support. The new labeling information may prove quite helpful in these cases.
Dr. Adam Urato is a Maternal-Fetal Medicine specialist at MetroWest Medical Center and Tufts Medical Center.