For decades, the US Food and Drug Administration (FDA) has relied upon an alphabetic system for communicating the safety of drugs in pregnancy. Under this system, every medication is assigned to one of five categories: A, B, C, D or X. Drugs in category A are considered to be the safest for pregnant women; medications in this category have been well-studied and do not seem to pose a risk to a fetus. On the other hand, drugs that appear to present a serious danger to fetal health – with a risk that “clearly outweighs any potential benefit” – are placed in category X. Drugs in categories B, C and D fall somewhere in between.
Experts, however, have complained that this simple-seeming system is, in fact, too simple. “For years we have had these ABCDX categories, which really I think have sort of lulled clinicians and patients into thinking that if something has a B designation we know that it’s OK to use, and if something has a D designation you should never take it in pregnancy,” says Christina Chambers, a perinatal epidemiologist at the University of California, San Diego. “These categories may provide, on the one hand, more confidence than the data support for some drugs that have a B category, and may create more concern for a drug than the data show, even for drugs that have an X category.”
The FDA has come to agree with these concerns. In December 2014, the agency announced that it would be officially dropping the familiar letter-based system. As the agency wrote: “FDA has decided to eliminate the pregnancy categories because they are often viewed as confusing and overly simplistic and don’t effectively communicate the risk a drug may have during pregnancy and lactation and in females and males of reproductive potential.”
Rather than a standardised letter grade, drugs will now carry more narrative: detailed summaries of whatever information exists on the safety of compounds when used in pregnancy, during lactation, and in men and women of reproductive age. Each label will summarise the overall likelihood that a drug poses risks to a developing fetus and lay out how the dosing and timing of the medication may affect those risks. (A drug that is perfectly safe in the second and third trimester, for instance, may cause birth defects if taken during the first trimester.) Labels will also be required to describe any risks – to the mother or fetus – from whatever underlying disease the drug is designed to treat.
The American College of Obstetricians and Gynecologists has praised the new labelling rule, as have other experts. “It’s a huge improvement,” says Janine Polifka, who manages the Teratogen Information System (TERIS) at the University of Washington. “Eliminating those pregnancy categories is really going to be advantageous because they were so misleading.”
The new law also requires that labels prominently list any pregnancy registries that are currently tracking women who are taking a given medication – a move that researchers hope will spur more patients to volunteer for these studies. Some scientists also believe that the new labels could help raise awareness of how little is known about drug safety and dosing during pregnancy, ultimately driving a demand for more research.
“I think it will make it clear, when you look at that section of the label… where we really have gaps,” Chambers says. “So I think it will prompt greater interest in the need for systematically collecting this data and making it available to clinicians and patients.” All new drugs approved on or after 30 June 2015 will use the new system; manufacturers of older drugs will have several years to revise their labels.