No Similar Changes To Ortho Evra Label In U.S. As Of Early December 2006

On November 23, 2006 Health Canada released a drug safety alert — which consisted of a so-called "Dear Doctor" letter and a public advisory for patients — about the norelgestromin and ethinyl estradiol transdermal system, better known as the birth control patch or, more simply, "the patch".

Although this announcement by Janssen-Ortho Inc., in consultation with Health Canada, focused on new safety information pertaining to its product Evra, the birth control patch that is marketed in Canada, their alert seems to be equally applicable to the Ortho Evra patch sold in the U.S.

The EVRA* transdermal system marketed in Canada contains 6.0 mg norelgestromin (NGMN) and 0.60 mg ethinyl estradiol (EE) and is approved for use in contraception (prevention of pregnancy). ORTHO EVRA® is the formulation of EVRA* marketed in the United States and contains 6.0 mg NGMN and 0.75mg EE. Although EVRA* and ORTHO EVRA® are manufactured differently and therefore contain different total amounts of estrogen, the risk of side effects reported for ORTHO EVRA® is considered to apply equally to the EVRA* formulation available in Canada.

This birth control patch warning in Canada started by addressing the situation which arose in September 2006 when we learned about two conflicting studies about Ortho Evra concerning whether there is any connection between Ortho Evra and serious blood clot side effects. 

The results of a recent study indicate that women using the ORTHO EVRA contraceptive patch (the formulation of EVRA marketed in the United States) had an increased risk of blood clots in the legs and lungs compared to women using an oral contraceptive. Another study indicated no difference in the risk of blood clots in the legs and lungs in women using ORTHO EVRA compared to women using an oral contraceptive.

Next, there are two new safety warnings about the Evra birth control patch set forth in this November 2006 Health Canada safety alert.

• "Women who are obese are at particularly high risk of blood clots."
• "Due to a theoretical risk of unintentional increase in estrogen exposure from the patch, patients are recommended not to expose the patch area to sources of heat such as sauna or whirlpool bath."

As of December 3, 2006, however, no corresponding warning about being overweight nor the sauna and whirlpool heat exposure had been issued by Ortho-McNeil Pharmaceutical — a Johnson & Johnson (J&J) company — for their Ortho Evra product in the U.S.  It is not clear at present whether J&J intends to revise the package insert, or label, for Ortho Evra to warn women that they are perhaps at an increased of developing serious blood clots if they are overweight or if the birth control patch is exposed to certain heated environments such as saunas and whirlpools.

Further comparing conduct in Canada and the U.S., in September 2006 J&J and the FDA did announce that the conflicting recent studies had caused a renewed concern about the association between Ortho Evra and certain blood clot disorders like pulmonary embolisms and deep vein thrombosis (DVT).  J&J did not, however, issue any Dear Doctor letter to U.S. health care providers then, nor have they done so since September.  One must wonder, why the difference?

(Posted by: Tom Lamb)