Pregnancy and Lactation Labeling Rule (PLLR): How to Read FDA Drug Safety Info

Before 2015, if you were pregnant and your doctor prescribed a medication, you might have seen a simple letter on the label: A, B, C, D, or X. That letter was supposed to tell you if it was safe. But it didn’t. Not really. It didn’t say how much risk, when it mattered, or what the real data showed. It just gave you a grade - and too often, that grade misled both patients and providers.

The FDA changed that. In December 2014, they rolled out the Pregnancy and Lactation Labeling Rule (PLLR), replacing the outdated letter system with clear, detailed narratives. This wasn’t just a tweak. It was a complete rewrite of how drug safety for pregnant and breastfeeding women is communicated. Today, every prescription drug label approved after June 30, 2001, follows this new format. And if you’re trying to understand whether a medication is safe during pregnancy or while breastfeeding, knowing how to read these sections can make all the difference.

What the PLLR Replaced - and Why It Wasn’t Enough

The old system - A, B, C, D, X - looked simple. But it was anything but helpful. Category A meant “safe in controlled studies.” Category X meant “dangerous.” But here’s the problem: most drugs didn’t have enough human data to even get a Category A. So they got stuck as Category C - “risk can’t be ruled out.” That didn’t mean the drug was risky. It just meant nobody had studied it well enough. And yet, many doctors avoided Category C drugs entirely, even when the benefits clearly outweighed the unknowns.

Take antidepressants. A woman with severe depression might be told to stop her medication because it’s Category C. But what if stopping it leads to a suicide attempt? The old system didn’t help weigh that trade-off. It didn’t mention that untreated illness carries its own risks. It didn’t explain how much of the drug passes into breast milk. It didn’t say whether the drug affects milk supply. And it didn’t tell you if there was a registry tracking outcomes in women who took it.

The PLLR fixed this by ditching the letters and forcing manufacturers to tell the full story - with data, context, and real-world evidence.

The Three Sections You Need to Know

Under the PLLR, all drug labels now have three new subsections under Section 8: 8.1 Pregnancy, 8.2 Lactation, and 8.3 Females and Males of Reproductive Potential. Each follows the same three-part structure: Risk Summary, Clinical Considerations, and Data. Let’s break them down.

8.1 Pregnancy: What You Need to Know

The Pregnancy section starts with the Risk Summary. This isn’t a vague warning. It’s a direct statement: “Use of this drug during pregnancy is associated with an increased risk of oligohydramnios.” Or: “No increased risk of major birth defects was observed in over 1,500 exposed pregnancies.”

Then comes the Clinical Considerations. This is where context kicks in. Does the drug cross the placenta? Does it affect amniotic fluid levels? Is there a safe window for use? What happens if you stop it mid-pregnancy? Are there dose adjustments needed in the third trimester? Does it affect labor or delivery? The label now answers these questions - not with guesses, but with what’s known from human studies, animal data, and pharmacological principles.

Finally, the Data section shows the evidence. It doesn’t just say “studies show.” It tells you how many women were studied, what outcomes were tracked, and whether the data came from registries, case reports, or controlled trials. For example: “Among 217 pregnant women exposed to Drug X in the first trimester, 4 had neural tube defects (1.8%), compared to a background rate of 0.1% in the general population.” That’s the kind of detail you need to make a decision.

8.2 Lactation: Breastfeeding and Medications

Many women are told to stop breastfeeding when they start a new medication. But that’s not always necessary - and the old system didn’t help them figure out why.

The Lactation section now tells you: How much of the drug gets into breast milk? Is it measurable? Is it absorbed by the baby’s gut? Is there any documented effect on the infant? Does the drug reduce milk supply?

For example, a label might say: “Maternal serum levels of Drug Y are 2.5 times higher than milk levels. Estimated infant dose is 0.3% of the maternal weight-adjusted dose. No adverse effects reported in 35 breastfed infants.” That’s actionable. You can use that to decide whether to breastfeed, pump and dump, or switch meds.

Some labels even include advice like: “Avoid breastfeeding for 4-6 hours after dosing to minimize infant exposure.” That’s not speculation. It’s based on pharmacokinetic studies.

8.3 Females and Males of Reproductive Potential

This section is often overlooked, but it’s critical. It tells you whether the drug requires pregnancy testing before starting, what kind of contraception is needed, and whether it causes infertility or birth defects in offspring if taken by men.

For drugs like isotretinoin (Accutane), it says: “Pregnancy must be excluded before starting. Two forms of contraception required. Monthly pregnancy tests.” For others, like certain antivirals, it might say: “Male partners should use condoms during treatment due to potential sperm effects.”

This section turns reproductive safety from a woman’s issue into a shared responsibility - and gives clear, enforceable guidance.

Why the PLLR Is Better - And How It’s Being Used

One of the biggest wins of the PLLR is that it forces manufacturers to include information about the risks of not treating the illness. A woman with epilepsy who stops her seizure medication because she’s pregnant might have a seizure that harms her baby. The PLLR now requires labels to say: “Untreated epilepsy increases the risk of fetal loss and congenital malformations.” That’s life-saving context.

Another improvement? Pregnancy exposure registries. Before the PLLR, these were optional. Now, if a drug has enough use in pregnancy to warrant tracking, the label must say: “A pregnancy exposure registry is available at [website].” These registries collect real-world data from thousands of women - data that helps future patients.

And the FDA doesn’t let labels sit outdated. If new safety data emerges - say, a study shows a drug causes heart defects in infants - the label must be updated within months. That’s a huge shift from the old system, where outdated warnings could stay on shelves for years.

What to Do When You’re Pregnant or Breastfeeding

Here’s how to use the PLLR sections in real life:

1. Ask for the full prescribing information - not just the patient leaflet. The PLLR details are in the professional label, not the consumer summary.
2. Start with the Risk Summary - is the risk clearly stated? Is it high, moderate, or low? Don’t skip this.
3. Check the Clinical Considerations - does it say anything about timing? Dose changes? Effects on labor? These matter.
4. Look for the Data section - if it says “limited data,” that’s not a green light. It’s a red flag to proceed with caution.
5. Ask about the registry - if one exists, sign up. Your data helps others.
6. Don’t assume breastfeeding is unsafe - check the Lactation section. Many drugs are compatible.

And remember: if a drug’s label says “no human data,” that doesn’t mean it’s dangerous. It just means we don’t know yet. That’s different from “known to cause harm.”

What’s Still Missing - And What’s Next

The PLLR isn’t perfect. Some labels still use vague language like “potential risk” without quantifying it. Others don’t clearly explain how animal data translates to humans. And while the FDA and EMA (Europe’s agency) both have similar goals, their wording often differs - leading to confusion for global patients and prescribers.

But progress is real. More labels now include specific outcomes: amniotic fluid levels, infant weight gain, developmental milestones. More include data from registries. More mention the risks of stopping treatment.

The future? Better harmonization with global regulators. More use of real-world data from electronic health records. And eventually, dynamic labeling that updates in real time as new evidence emerges.

For now, the PLLR is the best tool we have. It doesn’t give you a simple answer. But it gives you the information to find your own - with your doctor, your values, and your health in mind.