What’s in a Label? Why the Package Insert for Plan B is Wrong… and Why It Matters.

When you open up the box for your medication and unfold the package insert it all looks so...scientific. All of those chemistry diagrams, tables and warnings. You'd assume that labels for FDA-approved medications must be accurate and up to date, right? Think again.

This article is published as part of our 2012 Back Up Your Birth Control series.

When you open up the box for your medication and unfold the package insert it all looks so… scientific. All of those chemistry diagrams, tables and warnings. You’d assume that labels for FDA-approved medications must be accurate and up-to-date, right?

Think again.

The labels for the emergency contraceptive pill Plan B One-Step and its generic cousins, Next Choice and Levonorgestrel Tablets, do not reflect the most current evidence about how the product works. The Plan B One-Step label says:

“Plan B One-Step is believed to act as an emergency contraceptive principally by preventing ovulation or fertilization (by altering tubal transport of sperm and/or ova). In addition, it may inhibit implantation (by altering the endometrium).”

This language was taken from the original Plan B label, approved in 1999, and reflects the understanding at the time of how Plan B might work. But the science has evolved considerably in the last 13 years.

Newer evidence, published since the Plan B label was approved, provides compelling evidence that levonorgestrel EC (LNG EC) works before ovulation, but not after. Two recent studies tested whether there might be an effect of LNG EC on the implantation of a fertilized egg. Together with over a dozen other studies on how LNG works, we now have strong evidence it has no effect on the implantation of a fertilized egg.

The two most recent studies included women coming to clinics for EC after unprotected sex, monitoring whether ovulation had occurred and recording which women took EC before ovulation and which took it after. In each study, none of the women who took LNG EC before ovulation became pregnant, but among those who took it on the day of ovulation or after, roughly the same number of pregnancies resulted that you’d expect to see with no use of emergency contraception. If LNG EC were effective in preventing implantation of a fertilized egg, the pregnancy rates for those women who took it after ovulation would surely be lower. (For the latest science on how EC works, read this statement from the International Consortium for Emergency Contraception and the International Federation of Gynecology & Obstetrics).

So why does it matter? The standard legal and medical definition of the beginning of pregnancy in the US is the implantation of a fertilized egg in the uterus. By that definition, even if LNG EC did interfere with implantation, it would not interrupt a pregnancy. But there have been aggressive efforts to legally define pregnancy as beginning with the fertilization of an egg, both at the state level in the United States (including a recent failed attempt in Mississippi to define a fertilized egg as a person, with full legal rights and protections) and in numerous cases in Latin America. Constitutional Courts in Ecuador, Chile, Argentina, Peru and Honduras have banned or severely restricted access to EC, based on the misunderstanding that LNG EC interrupts the implantation process. In many of these cases, the Plan B product label was offered as evidence. But a document that is based on incomplete or outdated science should not be offered as evidence of anything.

The intention of the FDA is to ensure that product labels include the most up-to-date science. An FDA guidance document for industry states:

“[O]nly reasonably well-characterized mechanisms should be described, and care must be taken to avoid speculative and undocumented suggestions of therapeutic advantages.”

The purported implantation effect of LNG EC is most certainly speculative, undocumented and not well-characterized. It is highly likely that the current evidence about how LNG EC works is sufficient for the FDA to approve a label change. But it is up to the company to request such a change – in the case of Plan B One-Step, Teva Pharmaceuticals.

For women who have had unprotected sex, and are holding out hope for a last chance to prevent pregnancy, LNG EC is an important option… and at this moment in history, at least one brand of LNG EC is available in most countries. But as it is currently written, the labels for LNG EC products are used to restrict access to EC for women who need it. Eventually, the label for the very product that women rely on to prevent pregnancy after sex might be the thing that makes LNG EC inaccessible. And that is why Teva, and all companies that market LNG EC products, should be invested in keeping their labels up-to-date.