Mirena intrauterine system seeks U.S. nod

American women might have another option in long-term intrauterine devices if Wayne, NJ-based Berlex Laboratories’ receives approval for the Mirena levonorgestrel intrauterine system (IUS) from the Food and Drug Administration.

A unique intrauterine contraceptive that delivers a 20 mcg daily dose of locally acting hormone directly in the uterus, Mirena is now used by more than 1.4 million women in Europe, Asia, and Latin America. The company bills the device as an IUS rather than an intrauterine device (IUD) due to its hormone reservoir.

News of the February filing of a new drug application with the federal regulatory agency has been met with enthusiasm by national family planning experts, who have been calling for U.S. introduction of the device since it debuted overseas in 1990. (Contraceptive Technology Update has covered Mirena in these issues: January 1997, p. 4, a complete overview; and June 1999, p. 65, an announcement of Berlex’s evaluation of the device for possible U.S. marketing.)

"It would be wonderful for American women to have access to two outstanding IUDs which provide protection equal to that of a sterilization procedure but are totally reversible," says Allan Rosenfield, MD, dean of the Joseph L. Mailman School of Public Health, DeLamar Professor of Public Health at Columbia University in New York City, and professor of obstetrics and gynecology in Columbia University’s School of Medicine.

"To my mind, this device and the Copper T 380A are ideal, safe, and highly effective contraceptive methods and should be widely available," he says. The Copper T 380A is marketed in the United States as the ParaGard by Ortho-McNeil Pharmaceuticals in Raritan, NJ.

Mirena would be a welcome addition to the menu of contraceptive options for U.S. women, agrees Andrew Kaunitz, MD, professor and assistant chair in the obstetrics and gynecology department at the University of Florida Health Science Center/Jacksonville and director of menopause and gynecology services at the Medicus Women’s Diagnostic Center in Jacksonville.

"Mirena provides the convenience and high contraceptive efficacy characteristic of IUDs while reducing menstrual flow and cramps," Kaunitz observes. "These characteristics would expand the number of IUD users among my patients."

The clinical safety and efficacy information presented to the FDA is based on the European patient experience database, says Herman Ellman, MD, Berlex’s director of medical science liaison. The database includes results from more than 20 studies conducted by Leiras, the Finnish company that developed the Mirena in conjunction with the New York City-based Population Council, as well as several investigator-sponsored studies.

Berlex is planning to conduct studies of Mirena in the United States, says Wendy Neininger, director of corporate communications. However, those studies are not part of the new drug application, which already has been submitted, she notes.

According to Contraceptive Technology, over the long run, the levonorgestrel IUD is the single most effective method available in the world today, followed closely by the Copper T 380A.1 Over seven years of wear, the cumulative probability of pregnancy with the levonorgestrel IUD is only 1.1%; for the Copper T, it is 1.7%.1

Proposed recommended patient profile labeling for the Mirena is similar to that for the ParaGard, says Ellman. Such labeling recommends the device for women who have had at least one child, are in a stable, mutually monogamous relationship, and have no history of pelvic inflammatory disease. Berlex is seeking a U.S. indication of five years’ use for the device, which is similar to its current indication in other countries, he confirms.

Women’s health providers are intrigued with Mirena’s many uses, notes Robert Hatcher, MD, MPH, professor of gynecology and obstetrics at Emory University School of Medicine in Atlanta.

"It dramatically decreases menstrual blood loss, is beneficial in the management of the No. 1 cause of hysterectomies in the U.S., leiomyomata [fibroids], and it may be used as the progestin in women on estrogen replacement therapy who have an intact uterus," he notes.

Berlex is seeking U.S. approval for only the contraceptive indication of the device, says Neininger. Some European countries have given approval for the device’s therapeutic use in the management of dysfunctional uterine bleeding, she confirms.

Mirena’s insertion procedure is easy, but it is different from previous devices and will require hands-on instruction, observes Anita Nelson, MD, professor in the obstetrics and gynecology department at the University of California in Los Angeles (UCLA) and medical director of the women’s health care clinic and nurse practitioner training program at Harbor-UCLA Medical Center in Torrance.

A new proprietary device developed by Leiras should aid in inserting the IUS, reports Don Atkinson, Berlex director of marketing for the female health care division. The new introducer will debut in Europe and the United States, but its debut has not been scheduled.

Fewer than 1% of U.S. women at risk for pregnancy currently use an IUD,2 so Berlex recognizes that many providers may have limited or no experience with IUD products, says Atkinson. Appropriate physician education and patient support programs will accompany the product upon approval, Neininger says.

References

1. Hatcher RA, Trussell J, Stewart F, et al. Contraceptive Technology. 17th ed. New York City: Ardent Media; 1998.

2. Abma JC, Chandra A, Mosher WD, et al. Fertility, family planning, and women’s health: New data from the 1995 National Survey of Family Growth. Vit Health Statistics 1997; Series 12, No. 19.