New Risk Data Added to Contraceptive Patch Label

ROCKVILLE, MD. — The Food and Drug Administration has updated the product labeling for the Ortho Evra brand contraceptive patch to include under the warning section data from two studies, one of which indicates possible increased risk of deep vein thrombosis, MI, and other cardiovascular events in women using the patch—especially among smokers.

Acting Deputy Director of FDA's Office of Drug Evaluation III Daniel Shames discussed the studies and the new labeling in a conference call with news media.

The two studies were based on data obtained from large databases of medical insurance claims, he said. One of the studies, conducted by researchers at Boston University—and funded by Ortho Evra's manufacturer, Johnson & Johnson—concluded that women taking the drug had no more risk of thrombotic events (odds ratio 0.9) than women taking 35 mcg oral estradiol (Contraception 2006; 73:223–8).

The other study, by i3 Research, an Ingenix company, showed more than twice the risk (OR 2.4) for serious nonfatal blood clot as women on 35 mcg of estrogen and norgestimate; this study has yet to be published. Dr. Shames said participants in this study will be followed for another 18 months or 2 years. Ortho-Evra is marketed by Merck & Co and contains norelgestromin and ethinyl estradiol (EE).

Dr. Shames said the FDA has asked Merck to conduct studies with longer follow-up regarding serious blood clots and other adverse events, such as MI and stroke, noting that “blood clots occurring in the leg veins or in the lungs are serious and relatively rare events that have been considered a potential risk for all hormone therapies—in particular [in] women who smoke.

“Even though the results of the two studies are conflicting, the results of the second epidemiologic study is [sic] consistent with FDA's concern regarding the potential for Ortho Evra use to increase the risk of blood clots in some women,” he said. However, “Ortho Evra's risk-benefit profile is acceptable for a highly effective hormonal contraceptive.” Women should discuss concerns about adverse events with their health care provider, he said.

The patch was approved in 2001; in 2005 a warning was added noting that women using the patch might experience blood levels of the drug up to 60% higher than in women taking 35 mcg of oral EE.

In 1988, the FDA persuaded the three companies then producing oral contraceptives with more than 50 mcg of estrogen to remove those products from the market. Ortho Evra's product label was updated in November 2005 to disclose that although the peak level of estrogen imparted by the product in one study was 25% lower than that produced by 35 mg of oral EE, the steady-state concentration produced by Ortho Evra is 60% higher, at 56 mcg.

ROCKVILLE, MD. — The Food and Drug Administration has updated the product labeling for the Ortho Evra brand contraceptive patch to include under the warning section data from two studies, one of which indicates possible increased risk of deep vein thrombosis, MI, and other cardiovascular events in women using the patch—especially among smokers.

Acting Deputy Director of FDA's Office of Drug Evaluation III Daniel Shames discussed the studies and the new labeling in a conference call with news media.

The two studies were based on data obtained from large databases of medical insurance claims, he said. One of the studies, conducted by researchers at Boston University—and funded by Ortho Evra's manufacturer, Johnson & Johnson—concluded that women taking the drug had no more risk of thrombotic events (odds ratio 0.9) than women taking 35 mcg oral estradiol (Contraception 2006; 73:223–8).

The other study, by i3 Research, an Ingenix company, showed more than twice the risk (OR 2.4) for serious nonfatal blood clot as women on 35 mcg of estrogen and norgestimate; this study has yet to be published. Dr. Shames said participants in this study will be followed for another 18 months or 2 years. Ortho-Evra is marketed by Merck & Co and contains norelgestromin and ethinyl estradiol (EE).

Dr. Shames said the FDA has asked Merck to conduct studies with longer follow-up regarding serious blood clots and other adverse events, such as MI and stroke, noting that “blood clots occurring in the leg veins or in the lungs are serious and relatively rare events that have been considered a potential risk for all hormone therapies—in particular [in] women who smoke.

“Even though the results of the two studies are conflicting, the results of the second epidemiologic study is [sic] consistent with FDA's concern regarding the potential for Ortho Evra use to increase the risk of blood clots in some women,” he said. However, “Ortho Evra's risk-benefit profile is acceptable for a highly effective hormonal contraceptive.” Women should discuss concerns about adverse events with their health care provider, he said.

The patch was approved in 2001; in 2005 a warning was added noting that women using the patch might experience blood levels of the drug up to 60% higher than in women taking 35 mcg of oral EE.

In 1988, the FDA persuaded the three companies then producing oral contraceptives with more than 50 mcg of estrogen to remove those products from the market. Ortho Evra's product label was updated in November 2005 to disclose that although the peak level of estrogen imparted by the product in one study was 25% lower than that produced by 35 mg of oral EE, the steady-state concentration produced by Ortho Evra is 60% higher, at 56 mcg.

ROCKVILLE, MD. — The Food and Drug Administration has updated the product labeling for the Ortho Evra brand contraceptive patch to include under the warning section data from two studies, one of which indicates possible increased risk of deep vein thrombosis, MI, and other cardiovascular events in women using the patch—especially among smokers.

Acting Deputy Director of FDA's Office of Drug Evaluation III Daniel Shames discussed the studies and the new labeling in a conference call with news media.

The two studies were based on data obtained from large databases of medical insurance claims, he said. One of the studies, conducted by researchers at Boston University—and funded by Ortho Evra's manufacturer, Johnson & Johnson—concluded that women taking the drug had no more risk of thrombotic events (odds ratio 0.9) than women taking 35 mcg oral estradiol (Contraception 2006; 73:223–8).

The other study, by i3 Research, an Ingenix company, showed more than twice the risk (OR 2.4) for serious nonfatal blood clot as women on 35 mcg of estrogen and norgestimate; this study has yet to be published. Dr. Shames said participants in this study will be followed for another 18 months or 2 years. Ortho-Evra is marketed by Merck & Co and contains norelgestromin and ethinyl estradiol (EE).

Dr. Shames said the FDA has asked Merck to conduct studies with longer follow-up regarding serious blood clots and other adverse events, such as MI and stroke, noting that “blood clots occurring in the leg veins or in the lungs are serious and relatively rare events that have been considered a potential risk for all hormone therapies—in particular [in] women who smoke.

“Even though the results of the two studies are conflicting, the results of the second epidemiologic study is [sic] consistent with FDA's concern regarding the potential for Ortho Evra use to increase the risk of blood clots in some women,” he said. However, “Ortho Evra's risk-benefit profile is acceptable for a highly effective hormonal contraceptive.” Women should discuss concerns about adverse events with their health care provider, he said.

The patch was approved in 2001; in 2005 a warning was added noting that women using the patch might experience blood levels of the drug up to 60% higher than in women taking 35 mcg of oral EE.

In 1988, the FDA persuaded the three companies then producing oral contraceptives with more than 50 mcg of estrogen to remove those products from the market. Ortho Evra's product label was updated in November 2005 to disclose that although the peak level of estrogen imparted by the product in one study was 25% lower than that produced by 35 mg of oral EE, the steady-state concentration produced by Ortho Evra is 60% higher, at 56 mcg.