The wait for a monthly combined hormonal injectable may be over soon
Clinical trial complete — Lunelle awaits federal regulatory approval
Pending approval by the federal Food and Drug Administration (FDA), American providers may have access to Lunelle, a monthly combined hormonal injectable for contraceptive use, as early as the end of this year.
"We are still looking at mid-fall approval, dependent on FDA approval, which is not under our control," states Kristin Elliott, public relations director for Bridgewater, NJ-based Pharmacia & Upjohn’s diversified products division. "Once approval is received, we hope to have product available later in the calendar year."
If FDA approval is acquired this year, it will end a three-year wait for the drug. The Upjohn Co. (predecessor of Pharmacia & Upjohn) received marketing rights in 1996 to the injectable from The Concept Foundation in Thailand and an affiliated company, Program for Appro priate Technol ogy, a nonprofit foundation in Seattle. (Read more about the history of the drug in Contraceptive Technology Update, June 1996, p. 71.) Family planners also may recognize this drug as Cyclofem, the name under which it is marketed outside the United States, or Cyclo-Provera, the original name slotted for the U.S. brand.
Results of the 40-center Phase III clinical trial were presented earlier this year at the annual meeting of the American College of Obstetricians and Gynecologists in Philadelphia.1 The study enrolled women who chose Lunelle (25 mg medroxyprogesterone acetate /5 mg estradiol cypionate monthly contraceptive injections) or Ortho Novum 7/7/7 oral contraceptives (OCs), manufactured by Ortho-McNeil Pharmaceuticals in Raritan, NJ.
Participants included 782 subjects who chose Lunelle and 321 who chose OCs, according to Andrew Kaunitz, MD, professor and assistant chair of the OB/GYN department at the Univer sity of Florida Health Science Center in Jackson ville, who was a co-presenter of the paper. Some 44% of women in the Lunelle group had recently used hormonal contraception vs. 65% of those in the OC group. Overall, some 55% of the Lunelle users and 68% of the OC users completed the 60-week trial.
Zero pregnancies in Lunelle group
During the 60 weeks, there were no pregnan -cies in the Lunelle group and two in the OC group, Kaunitz says. After the first cycle, women in both treatment groups experienced regular menstrual cycles with average cycle length of 28 days in Lunelle and 27 days in OC users. No serious adverse events resulted in discontinuation of Lunelle or OC use, says Kaunitz.
Although the U.S. trial was not designed to assess return to fertility after discontinuing Lunelle, a large Latin American trial found that two months from the last injection, return to fertility is comparable to women discontinuing OCs, intrauterine devices, or barrier methods.2
"Results of this first large clinical trial of monthly combination injectable contraception in the U.S. suggest that Lunelle should represent a welcome new, convenient, safe, and effective contraceptive choice for U.S. women," he says.
According to Managing Contraception, candidates for monthly injectable use include women who can use combined pills, want a highly effective reversible method, desire to have a child in one to two years, or don’t want to take a daily pill.3
Advantages of monthly combined injectable contraception include the following:
• single dose for one month of contraception (no interference at time of sexual intercourse);
• more regular bleeding than with DMPA (depot medroxyprogesterone or Depo-Provera);
• discreet and private;
• rapid return to fertility.3
Disadvantages include:
• menstrual irregularity in some women;
• breast tenderness;
• need for return to clinic every 30 days for injections;
• patients may fear injections;
• injections cannot be removed once given;
• not ideal for breast-feeding women.3
Women who participated in the U.S. trial at the Jacksonville, FL, site were pleased with the advantages offered by the injectable method, says Kim Bartley, ARNP, MSN, Jacksonville Lunelle study coordinator. Most of the women who were enrolled at the Florida site had used contraceptives in the past and found Lunelle a good fit in their contraceptive plans, she notes.
"Some of them had used Norplant, Depo-Provera, birth control pills, diaphragms — they had used the gamut, and they were successful Lunelle users," says Bartley. "They weren’t people who had contraceptive failures on those methods, but of all the methods, they found this one to be particularly convenient."
Women liked the idea that the injectable was given every month, so if they wanted to make a change in their fertility plans, they could easily do so, unlike other methods such as DMPA, which have a longer-acting effect, says Bartley.
"They were just really pleased and continue to be pleased with it," says Bartley, whose site is running a continued study of the drug. "I believe it is a wonderful option for women."
With the advent of two injectables, family planning clinicians will need to be meticulous about how they distinguish between DMPA and Lunelle in their contraceptive counseling sessions, because they are two very different methods, says Kaunitz. Both methods are highly effective and are given by intramuscular injection, but the similarities end there, he notes.
Lunelle relies on a monthly injection of an estrogen and progestin for its contraceptive efficacy, while DMPA is a progestin-only injectable administered every three months. Return to fertility is rapid with Lunelle and delayed with DMPA, says Kaunitz.
According to Managing Contraception, women experience more regular bleeding patterns while receiving Lunelle than DMPA, and they maintain regular estrogen levels.3
Talking about Lunelle and DMPA will be easier with Pharmacia & Upjohn’s decision to name the drug something other than Cyclo-Provera, says Bartley. The two distinct names help providers talk about the drugs, both of which represent "birth control in a shot" for patients.
Monthly visit no problem
Women at the Jacksonville site did not find the monthly shot requirement a problem to work into their normal routines, reports Bartley. Many patients came to the clinic in the morning before work or during their lunch hours.
Providers will need to work out office scheduling to accommodate the monthly shot schedules, but Bartley says the visits are uncomplicated and not time-consuming.
Lunelle likely will appeal to women who might otherwise be interested in OC use but would prefer the convenience and contraceptive security of monthly injections, says Kaunitz. "To the extent that injections can be made available away from traditional clinical sites [i.e. employee health nurses, pharmacies], the appeal of Lunelle will be that much increased."
The contraceptive privacy afforded by Lunelle has made it a popular choice for women in South ern California, who vote with their feet as they go to Mexico once a month for the shot, notes Willa Brown, MD, director of the Personal Health Bureau at the Howard County Health Department in Columbia, MD. She sees the shot’s chief advantage in its combination of estrogen and progestin with few side effects. Its chief disadvantage lies in determining whether it can be self-administered and, if not, what level of professional can give the shots.
Robert Hatcher, MD, MPH, professor of OB/ GYN at Emory University School of Medicine in Atlanta, concurs, saying: "The success of monthly injections will depend on the development of systems which will permit women to give injections to themselves at home. Returning each month for injections will be a great burden for the average woman."
References
1. Kaunitz AM, Garceau RJ, Cromie MA. Comparative safety, efficacy and cycle control of Lunelle monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension) and Ortho-Novum 7/7/7 oral contraceptive (norethindrone/ethinyl estradiol triphasic). Presented at the Clinical Meeting of the American College of Obstetricians and Gynecologists. Philadelphia; May 18, 1999.
2. Bahamondes L, Lavin P, Ojeda G, et al. Return of fer tility after discontinuation of the once-a-month injectable contraceptive Cyclofem. Contraception 1997; 55:307-310.
3. Hatcher RA, Zieman M, Watt A, et al. Managing Contraception. Tiger, GA: Bridging the Gap Foundation; 1999.
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