FDA Updates Warnings for Combined Hormonal Contraceptives

The FDA has made the labels consistent for combined hormonal contraceptives about the risk these products have to women who have or have had breast cancer.

The FDA has updated the contraindications and warnings sections of several combined hormonal birth control products to include the risk these products have to women who have or have had breast cancer.

Currently, the prescribing information and patient information for the various products and the generics in this class contain different messages about this potential risk and the information is not current in all labeling, an FDA spokesperson said.

“We believe it is in the best interest of public health that providers and patients receive a consistent, clear, and current message on this potential risk across this drug class,” he told Formulary Watch.

After a review of the relevant studies, the FDA did not find consistent evidence of an increase in risk of breast cancer associated with the use of combined hormonal contraceptives (CHCs). Some studies reported no increased risk of breast cancer in those who ever used CHCs in the past compared with women who never used CHCs.

But the agency said some recent epidemiology studies suggested a small increased risk for current/recent use compared to those who never used CHCs, and a small increased risk for current users with longer duration of use (eight years or more). “We are requiring the labeling for all the CHC drugs to reflect the above findings from our updated review,” the spokesperson said.

The label changes impact the following products and their generics:

  • Loestrin 21 1.5/30 (norethindrone acetate and ethinyl estradiol), which is manufactured by Teva under the name of Junel 1/20.
  • Lo/Ovral (norgestrel and ethinyl estradiol), which was developed by Pfizer. The brand has been discontinued by the manufacturer, but generics are available, including Cryselle (from Teva), Elinest (Northstar), and Low-Ogesterel (Mayne).
  • Triphasil-21 (levonorgestrel and ethinyl estradiol - triphasic regimen), developed by Pfizer. The brand has been discontinued by the manufacturer, but generics are available, including Enpresse (Teva) and Trivora (Mayne).
  • Triphasil-28(levonorgestrel and ethinyl estradiol - triphasic regimen), developed by Pfizer. The brand has been discontinued by the manufacturer, but generics are available, including Enpresse (Teva) and Trivora (Mayne).
  • Twirla(levonorgestrel and ethinyl estradiol), developed by Agile Therapeutics
  • Tyblume (levonorgestrel and ethinyl estradiol), which was developed by Exeltis
  • Yasmin (drospirenone and ethinyl estradiol), which was developed by Bayer HealthCare)
  • Yaz (drospirenone and ethinyl estradiol), which was developed by Bayer HealthCare)

All of the therapies include information under the warning sections about the products being contraindicated in women who currently have or have had breast cancer because breast cancer may be hormonally sensitive. This section now includes a new paragraph that reads:

“Epidemiology studies have not found a consistent association between use of combined oral contraceptives (COCs) and breast cancer risk. Studies do not show an association between ever (current or past) use of COCs and risk of breast cancer. However, some studies report a small increase in the risk of breast cancer among current or recent users (<6 months since last use) and current users with longer duration of COC use.”

Under adverse events, all of these products now include a new section that reads:

“Five studies that compared breast cancer risk between ever-users (current or past use) of combined oral contraceptives (COCs) and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 - 1.12.

“Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs. One of these studies reported no association between breast cancer risk and COC use. The other two studies found an increased relative risk of 1.19 - 1.33 with current or recent use. Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8-10 years of COC use.”