Bulletin: FDA issues approvable status for single-rod contraceptive implant
American women are one step closer to having a contraceptive implant option with the recent Food and Drug Administration (FDA) issuance of approvable status for Implanon, the single-rod contraceptive implant from Organon (West Orange, NJ).
According to the FDA, an approvable letter signals that the agency is prepared to approve the product dependent on the company meeting specified conditions.
Organon is in the process of meeting those requests, states Frances DeSena, company spokeswoman.
"Our next step is to provide FDA with the information they have requested so that we are can obtain approval," says DeSena. "Based on that approval, Organon plans to launch sometime in the first half of 2005."
Implanon is inserted under the skin of the upper arm, and provides contraception for up to three years. Consisting of a nonbiodegradable rod measuring 40 mm in length and 2 mm in diameter, the device releases the progestin etonogestrel at an average release rate of 40 mcg per day. Since the device does not contain estrogen, women who do not tolerate or are contraindicated to estrogen use may safely use it.
In a three-year study investigating the contraceptive efficacy and tolerability of Implanon, findings indicate that the device was well tolerated and had excellent, reversible, contraceptive efficacy.1 Irregular bleeding was the primary reason for discontinuation (19%). Adverse events, other than bleeding irregularities, were generally mild to moderate in intensity and resulted in 9.3% of discontinuations.1 The most commonly reported nonbleeding adverse events were breast pain (16%), acne (12.6%), vaginitis (12%), and pharyngitis (10.5%).1 There is a rapid return to fertility in those women without fertility problems when the implant is discontinued.2
Bleeding disturbances are the main adverse events associated with implantable contraceptives.3 Other minor risks relate to the insertion and removal procedures, which require adequately trained providers as well as aseptic techniques.3 Provider education will be an important aspect of product introduction should Implanon receive FDA final approval. Organon is developing educational models on insertion and removal techniques to ensure clinicians are familiar and comfortable with the device.
"Organon is committed to conducting comprehensive training programs to ensure health care providers are instructed on the use of Implanon; we will also be providing education to consumers as well," states DeSena. Pending a decision from the FDA, the company will launch a web site and toll-free number for consumers and health care providers, she adds.
Option would be welcome
While 1 million to 2 million women in the United States currently use progestin-only injections (depot medroxyprogesterone acetate or DMPA, Depo-Provera, Pfizer, New York City), progestin-only implant contraception options have been lacking since the 2000 removal of six-rod Norplant implant from U.S. pharmacy shelves. (Wyeth Pharmaceuticals, Madison, NJ, suspended shipment of implants in August 2000 when concerns arose about efficacy of suspect lots. While the lots were found effective in July 2002, the manufacturer chose not to reintroduce the product in the United States.
"Implanon represents a great improvement over the six-capsule Norplant system," states 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.
"It is a single-rod system with unsurpassed efficacy which is placed in less than one minute and can be removed in two to three minutes," she says.
Implanon is different from Norplant; it is longer and stiffer, due to its ethyl vinyl acetate composition, observes David Archer, MD, professor of obstetrics and gynecology and director of the Clinical Research Center at the Eastern Virginia Medical Center in Norfolk. Insertion and removal times are quicker since the system consists of one rod, he notes.
"We still receive calls from women interested in Norplant," states Archer, who serves on an advisory committee to Organon for physician training in implanting and removing the device. "There is a group of women who are interested in long-term progestin-only implants for contraception."
How will it work?
Three conditions must be met to ensure method success if Implanon is indeed released in the United States, says Nelson:
- Clinician training is imperative, not only for insertion and removal techniques, but for counseling as well.
- The side effects of the method need to be understood, especially the unpredictable spotting and bleeding.
- Women must have access to providers who are able to remove the implants upon their request.
Carrie Cwiak, MD, MPH, assistant professor of obstetrics and gynecology at Emory University in Atlanta, says, "I think one lesson we can learn from the Norplant experience is the importance of getting insertion and removal training before using Implanon clinically."
Implanon offers the options many women want in a contraceptive method: high efficacy and no need to adhere to a daily schedule for dosing, says Linda Dominguez, RNC, NP, assistant medical director of the Albuquerque-based Planned Parenthood of New Mexico.
"The three years of effectiveness matches the birth spacing rate that many women tell clinicians they are planning — maybe a baby in two or three years,’" she observes. "And many previous implant users have been waiting, with literally open arms, for this new product."
1. Croxatto HB. Clinical profile of Implanon: A single-rod etonogestrel contraceptive implant. Eur J Contracept Reprod Health Care 2000; 5 Suppl 2:21-28.
2. Croxatto HB, Urbancsek J, Massai R, et al. A multicentre efficacy and safety study of the single contraceptive implant Implanon. Implanon Study Group. Hum Reprod 1999; 14:976-981.
3. Brache V, Faundes A, Alvarez F. Risk-benefit effects of implantable contraceptives in women. Expert Opin Drug Saf 2003; 2:321-332.