New year, new option: Cyclo-Provera awaits word
American women who want reliable contraception but have trouble remembering to take a daily pill may have another option this year if Cyclo-Provera receives approval from the U.S. Food and Drug Administration. Pharmacia and Upjohn of Kalamazoo, MI, which holds U.S. marketing rights for the combined injectable contraceptive, filed a new drug application with the FDA in September 1997, and company officials hope to receive approval this year, says company spokeswoman Liz Jakeway. The company plans to file for mutual recognition in European markets upon FDA approval, she says.
Enrollment for a company-sponsored clinical trial of the drug had just closed at Contraceptive Technology Update’s press time, confirms Kathy Arbogast, RN, clinical research coordinator at the clinical research unit of the Jones Institute for Reproductive Medicine at the Eastern Virginia Medical School in Norfolk. The facility is one of 44 sites involved with the nationwide study, which enrolled 1,200 women and is scheduled to run for 60 weeks.
Cyclo-Provera uses the same progestin, depomedroxyprogesterone acetate (DMPA), as Depo-Provera. However, it uses a lower dose 25 mg and combines it with 5 mg of estradiol cypionate to improve the control of the menstrual cycle.1 (See a review of Cyclo-Provera in the June 1996 issue of CTU, pp. 71-72.)
The drug, which is marketed outside the United States under the name Cyclofem, has been used mainly in China and Latin America. It provides very effective pregnancy prevention for a 30-day period. A similar monthly injectable, Mesigyna, marketed by Schering AG in Berlin, Germany, combines 50 mg of the progestin norethisterone enanthate with 5 mg of estradiol valerate. The World Health Organization (WHO) in Geneva, Switzerland, has conducted multinational studies on both drugs, and the two have been introduced in several countries.
In issuing its medical eligibility criteria, WHO lists Cyclofem as appropriate for most women who want effective, reversible contraception and who are not at risk for most cardiovascular complications.2 Its estrogen has a shorter lifespan and is less potent than those found in combined oral contraceptives (OCs), so its restrictions vary somewhat from those for combined OCs.
For example, WHO guidelines say the advantages outweigh the risks for smokers under age 35 or for light smokers over 35, as well as for those with mild hypertension (blood pressure below 160/100), current or medically treated gall bladder disease, or mild cirrhosis (compensated). However, WHO states that the risks outweigh the advantages for heavy smokers (more than 20 cigarettes daily) above age 35, those with a history of hypertension or blood pressure of 160/100 or 180/110, and those with severe cirrhosis (decompensated) or liver tumors (benign).
Good cycle control a key benefit
When the initial injection of Cyclo-Provera is given, the estrogen level goes up, then drops after two weeks, with the woman then menstruating, says David Archer, MD, professor of obstetrics and gynecology at the Jones Institute for Reproductive Medicine at the Eastern Virginia Medical School in Norfolk and one of the investigators for the U.S. study. The second injection is scheduled four weeks after the initial one, with menstruation usually occurring two weeks after the second shot. Now the patient is back on a four-week cycle, Archer notes.
"The data from the WHO studies imply that there is good cycle control without any irregularity, without a lot of breakthrough bleeding," he says. "It is thought that it is due to the fact that Cyclo-Provera is both an estrogen and a progestin and that the estrogen helps to maintain the endometrium."
Providers will need to counsel women to expect that first initial bleeding two weeks after the first shot, Archer says. The grace period for combined injectable contraceptives is officially three days, so providers will need to underscore the need for on-time return in their counseling sessions.3
Will injections be a problem?
In other countries where women have ready access to clinics, getting a monthly shot is not seen as an inconvenience. In Mexico, women can even receive injections of Mesigyna at their local pharmacy, Archer says. But for women in the United States, getting to a health care provider each month may be a problem, says Robert Hatcher, MD, MPH, professor of gynecology and obstetrics at the School of Medicine at Emory University in Atlanta and senior author of Contraceptive Technology.
"The major advantage I see to Cyclo-Provera is more regular bleeding," Hatcher says. "The clear disadvantage I see is monthly injections. Maybe what this injectable will do is lead us on to the next stage, which is to provide women their own injections to take home and give to themselves."
Such convenience would be a significant patient benefit, Archer agrees. It would call for thorough patient education and training, though, since Cyclo-Provera’s solution must be thoroughly mixed then delivered through a deep intramuscular injection.
References
1. Technical Guidance/Competence Working Group and World Health Organization/Family Planning and Population Unit. Family planning methods: New guidance. Population Reports Series J, No. 44. Baltimore: Johns Hopkins School of Public Health, Population Information Program; October 1996, p. 12.
2. Program for Appropriate Technology in Health. WHO eligibility criteria for contraceptive use: combined injectables and sterilization. Outlook 1996; May:2-3.
3. Technical Guidance/Competence Working Group and World Health Organization/Family Planning and Population Unit. Family planning methods: New guidance. Population Reports Series J, No. 44. Baltimore: Johns Hopkins School of Public Health, Population Information Program; October 1996, p. 13.
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