Implanon status report: Not on U.S. market yet

A new single-rod progestin contraceptive implant from Netherlands-based Organon NV is poised for market introduction in the United Kingdom and the Netherlands, and it may enter the approval process soon for use in the United States. Organon is committed to bringing the Implanon system to the United States, says Nancy Alexander, PhD, associate director of medical services for contraception in the company’s U.S. branch.

While Organon considers the timing of Implanon’s entrance in the federal Food and Drug Administration (FDA) approval process, Wyeth-Ayerst Laboratories of Philadelphia already has FDA clearance in hand to market its two-rod levonorgestrel implant system. Indeed, the company has had such approval since 1996.

Wyeth-Ayerst is continuing to conduct additional research and development pertinent to that approval, and until that research is complete, the company will not market the product, according to a press statement issued through company spokeswoman Audrey Ashby. The company’s research includes an assessment of potential design changes in the trocar insertion device for the two-rod implant.

Some family planners have referred to the new Wyeth-Ayerst product as Norplant II. However, the product is yet unnamed, says Ashby, and is described by Wyeth-Ayerst simply as the two-rod levonorgestrel implant.

Benefits of implants

Subdermal contraception provides women with extremely effective, convenient, and safe birth control, notes Andrew Kaunitz, MD, prof essor and assistant chair of the OB/GYN department of the University of Florida Health Sciences Center in Jacksonville.

The principal setbacks associated with the Norplant six-rod implant system have been insertions performed with incorrect technique and difficult removals, which often relate to such insertions, says Kaunitz. Second generation implants, including Implanon, address these concerns.

"Insertion of this single-rod implant system is easy and facilitated by a dedicated introducer instrument," he observes. "Removal is easier and quicker than the original six-implant Norplant system. For these reasons, U.S. clinicians and their patients should be looking forward to the availability of Implanon and, when it is marketed, the two-rod levonorgestrel system."

Alexander, who observed insertions and removals of Implanon in Indonesia, remarks on the advantages of the single-rod implant:

"We do believe that the single rod is so much easier to implant, as well as to remove. I think the device for implanting makes it more difficult to insert it incorrectly. And the removal has to be easier with just one rod."

The Implanon system relies on the progestin 3-keto-desogestrel contained in a single capsule of ethylene vinyl acetate for its contraceptive efficacy. It is inserted beneath the skin and is effective for three years. In a study using 68 mg of the progestin, the drug showed rapid absorption, reaching stable levels in about one month and rapid elimination upon removal.1

In an overview of 13 studies, Implanon showed high contraceptive effectiveness, with zero pregnancies during 53,530 cycles.2 Side effects associated with the method include acne and weight gain.3 The implant has been studied for three years of use. "It is reversible and convenient, and its compliance is adherent independent," notes Alexander. "It is extremely effective."

A five-year trial of the two-rod contraceptive implant, conducted among 594 women in the United States and the Dominican Republic, reported a cumulative pregnancy rate of 0.8 per 100, with an annual average pregnancy rate below 2 per 1,000 women.4 Prolonged bleeding/spotting and irregular bleeding were the most frequently cited medical reasons for removal.

A randomized three-year clinical trial compared the experiences of 600 women using the two-rod levonorgestrel rod implants with a control group of 598 women using Norplant.5 No pregnancies occurred in either group.

Research is continuing on other forms of progestin subdermal contraceptives. The Population Council in New York City continues to evaluate the use of the progestin Nestorone in a subdermal contraceptive. Phase II clinical trials of Nestorone have been completed, with no pregnancies observed in 1,570 woman-months of use.6

Scientists also are looking at a single-rod implant system, Uniplant, which releases nomegestrol acetate. In a study of 1,803 women in a nine-country clinical trial, 15 pregnancies were recorded in a 12-month period with a net cumulative pregnancy rate of 0.94%.7 A total of 276 women discontinued prior to completing one year of study, with menstrual-related side effects listed for most of the medical discontinuations. Uniplant is being evaluated for one year of use.

References

1. Pasquale SA, Sinofsky FE. Pharmacology of Implanon — A two-year study evaluating absorption, stabilization of levels and elimination rate. Presented at the annual meeting of the American Society of Reproductive Medicine. Boston; 1996.

2. Croxatto HB, Makarainen L. The pharmacodynamics and efficacy of Implanon. An overview of the data. Contraception 1998; 58(6 Suppl):91S-97S.

3. Urbancsek J. An integrated analysis of nonmenstrual adverse events with Implanon. Contraception 1998; 58(6 Suppl):109S-115S.

4. Sivin I, Alvarez F, Mishell DR Jr., et al. Contraception with two levonorgestrel rod implants. A 5-year study in the United States and Dominican Republic. Contraception 1998; 58:275-282.

5. Sivin I, Viegas O, Campodonico I, et al. Clinical per formance of a new two-rod levonorgestrel contraceptive implant: A three-year randomized study with Norplant implants as controls. Contraception 1997; 55:73-80.

6. Peralta O, Diaz S, Croxatto H. Subdermal contraceptive implants. J Steroid Biochem Mol Biol 1995; 53:223-226.

7. Coutinho EM, de Souza JC, Athayde C, et al. Multicenter clinical trial on the efficacy and acceptability of a single contraceptive implant of nomegestrol acetate, Uniplant. Contraception 1996; 53:121-125.