Contraceptive implants: Single-rod Implanon headed to United States
Contraceptive implants: Single-rod Implanon headed to United States
Providers look to 2004 debut — hold continues on Norplant shipments
What options can you now offer to women who seek effective birth control, but who have contraindications to estrogen-based methods or a history of compliance issues with other contraceptives?
Progestin-only contraceptive implants offer safe, long-term birth control; however, no implants have been available in the United States since August 2000 when Philadelphia-based Wyeth-Ayerst Pharmaceuticals discontinued shipments of its Norplant six-rod levonorgestrel implant. The company halted distribution when questions arose over the effectiveness of suspect lots of the contraceptive implant. (Contraceptive Technology Update reported on the shipment suspension in the article "Check Norplant stock, Company says: Recent batches may be ineffective" in the October 2000 issue, p. 117.)
Wyeth-Ayerst Pharmaceuticals is not selling or distributing Norplant at this time, confirms Doug Petkus, company spokesman. The company is in ongoing discussions with the Food and Drug Administration (FDA) regarding the implant, he states.
"Physicians have been advised to suggest to current Norplant users that backup contraception should be used," reports Petkus. "We have advised physicians not to schedule new insertions until further notice."
What then is on the U.S. horizon for contraceptive implants? Look to 2004 for the debut of Implanon, a single-rod progestin implant, says Edio Zampaglione, MD, associate director of the contraception division of Organon Pharmaceuticals in West Orange, NJ. Implanon is marketed in 17 countries; more than 725,000 implants have been inserted since its introduction in 1999, he says. (CTU provided an overview of Implanon in the August 1999 article, "Implanon status report: Not on U.S. market yet," p. 87.)
Reports on Implanon have consistently shown a high level of overall patient satisfaction and acceptance with an extremely low failure rate, Zampag-lione observes. A key point about Implanon is that there is a rapid return to fertility when use of the implant is discontinued, he notes.
What are the options?
Several forms of contraceptive implants are available around the world. In addition to Norplant and Implanon, Jadelle, the two-rod levonorgestrel implant developed by the New York City-based Population Council, is registered in Europe, North America, and some developing countries.1 (CTU reported on Jadelle in its May 2001 article "What to expect in the next five years? Innovative contraceptive delivery," p. 49.) In addition, two generic levonorgestrel implants similar to Norplant and Jadelle are manufactured and marketed in China, with the six-month Nestorone Elcometrine implant registered in Brazil.1
U.S. family planners may recognize Jadelle as Wyeth-Ayerst Pharmaceuticals’ Norplant II, which was approved by the FDA in 1996. However, the company has suspended all U.S. development work pertaining to this product until it completes its discussions with the FDA about the current six-rod Norplant system, says Petkus.
Due to their simpler insertion and removal capabilities, it is expected that Jadelle and Implanon will replace Norplant in the coming years, states Olav Meirik, MD, PhD, senior research associate at Instituto Chileno de Medicina Reproductiva in Santiago, Chile. Meirik makes this observation following a 2001 review of implant contraceptives convened by the Special Programme of Research, Development and Research Training in Human Reproduction at the Geneva-based World Health Organization (WHO). (The entire January 2002 issue of Contraception contains the published research presented at the WHO meeting.)
Implants probably are the most efficacious method of all reversible contraceptives, says Meirik. However, the bleeding disturbances associated with their use are problematic for many women and require that potential users are well-informed and counseled before deciding on implants for contraception, he states.
To begin and end use of implant contraceptives, women are dependent on skilled and experienced family planning providers, says Meirik. The need for appropriate counseling and insertion and removal of implants place particular demands on family planning services for the provision of these contraceptives, he comments.
Insertion made easy
Clinicians need to know that Implanon will provide a better bleeding pattern than Norplant and will be much easier to insert and remove, says Philip Darney, MD, MSc, professor at the University of California, San Francisco, and chief of the department of OB/GYN at San Francisco General Hospital Medical Center.
Organon is developing a number of programs where clinicians will get didactic as well as hands-on training on the insertion and removal of Impla-non using lifelike models, reports Zampaglione.
"The insertion technique is very different from other implants available, and this will be stressed during the training sessions," states Zampaglione. "There also will be appropriate follow-up to ensure that all clinicians are very familiar and comfortable with the insertion and removal of Implanon."
Such training will be an important aspect in the successful introduction of Implanon as a U.S. contraceptive option.
"The failure’ of Norplant in some European countries and in North America was, in my opinion, because training of providers in counseling and insertion-removal techniques was incomplete," comments Meirik.
What to expect?
Implanon consists of a single, covered rod containing 68 mg of etonogestrel, the 3-keto metabolite of desogestrel, with an initial release rate of around 60 mcg/day that decreases to about 30 mcg/day at the end of two years.2 The implant provides contraception for three years.
The chief advantages of Implanon are its trouble-free use, its absence of estrogen, and its high efficacy rating, says Darney. Studies undertaken during the development of Implanon involved 1,176 women in at least 10 countries and contributed 4,103 women-years of use in which no pregnancies occurred.3
Expect bleeding irregularities with Implanon, the same as those shared by other progestin-only implants, says David Archer, MD, professor of obstetrics and gynecology and director of the clinical research center at the Eastern Virginia Medical School in Norfolk.
Like Norplant, Implanon induces vaginal bleeding irregularities.4 The incidence of amenorrhea increases to 30%-40% during the first three months of use and remains at that level thereafter. About half of the users experience infrequent bleeding during the first three months, but this percentage declines to 30% by six months.5 In studies comparing Implanon to Norplant, Implanon was consistently shown to induce more amenorrhea and less frequent bleeding than Norplant.6,7 The incidence of prolonged bleeding is similar with both implants and decreases over time.4
The Bethesda, MD-based National Institutes of Health has issued a request for clinical trials of new therapeutic interventions in an effort to control the irregular bleeding found in implants, a chief reason for user discontinuation, notes Archer.
"I believe that there is a need for this type of long-acting implant for American women," says Archer. "I hope that we will see a resurrection in the interest level in this form of highly effective contraception."
References
1. Meirik O. Implantable contraceptives for women. Contraception 2002; 65:1-2.
2. Jordan A. Toxicology of progestogens of implantable contraceptives for women. Contraception 2002; 65:3-8.
3. Croxatto HB, Makarainen L. The pharmacodynamics and efficacy of Implanon. Contraception 1998; 58:91S-97S.
4. Hickey M, d’Arcangues C. Vaginal bleeding disturbances and implantable contraceptives. Contraception 2002; 65:75-84.
5. Edwards JE, Moore A. Implanon. A review of clinical studies. Br J Fam Plann 1999; 24(4 Suppl):3-16.
6. Affandi B. An integrated analysis of vaginal bleeding patterns in clinical trials of Implanon. Contraception 1998; 58(6 Suppl):99S-107S.
7. Zheng SR, Zheng HM, Qian SZ, et al. A randomized multicenter study comparing the efficacy and bleeding pattern of a single-rod (Implanon) and a six-capsule (Norplant) hormonal contraceptive implant. Contraception 1999; 60:1-8.
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