Lower-dose injectable contraceptive moves through research pipeline

Self-administration eyed, may give women new option

As you check the chart of your next patient, you note she is scheduled for her quarterly injection of depot medroxyprogesterone acetate (DMPA, Depo-Provera; Pfizer, New York City). While she is on time for this shot, she was late for two such appointments in the previous year.

What if there was a contraceptive injection that your patients could be instructed to use in self-injection? Initial research on a new lower-dose form of DMPA indicates that women can obtain safe, effective contraception in this convenient form.1

The low-dose subcutaneous contraceptive injection, DMPA-SC, is not yet approved by the Food and Drug Administration (FDA) or in any other country. The drug is in Phase 3 testing in the clinical research pipeline, reports Rebecca Hamm, spokeswoman for Pfizer, the manufacturer of the drug. The company offers no information as to its potential cost.

The new drug differs from DMPA’s current intramuscular (IM) formulation in that it contains two new buffering ingredients and one anti-flocculation agent, states Anita Nelson, MD, professor in the obstetrics and gynecology department at the University of California in Los Angeles and an investigator in the clinical trials. It is designed to be administered subcutaneously, not intramuscularly, as with the conventional 150 mg quarterly injection of DMPA.

The open-label, multinational, multicenter studies have been designed to assess the efficacy, safety, and participant satisfaction with DMPA-SC. Women who participated in the studies had to be between the ages of 18 and 49, sexually active, and could not have used hormonal contraception for at least two months prior to enrollment. Participants were injected once every three months over a 12-month period with a 104 mg dose of DMPA-SC to determine the safety and efficacy of the low-dose contraceptive injection.1

In the studies, about 31% of the participants self-administered the contraceptive after first receiving a health care professional-administered injection and instructions. The other participants had the injection administered by a health care professional throughout the course of the study.

No pregnancies were reported after 20,607 menstrual cycles of exposure to the contraceptive. The injection was well tolerated and had a safety profile similar to the IM formulation of Depo-Provera.1

"Not only were no clinically evident pregnancies detected, but in this study design, so-called chemical pregnancies would have been reported, since every woman underwent routine urine pregnancy testing prior to each injection," states Nelson.

The first study, conducted in North, Central, and South America, evaluated 720 women with an average age of 28.2 years. Changes in menstrual bleeding patterns included irregular bleeding decreasing over time and amenorrhea increasing. By the end of 12 months, 45.9% of women had become amenorrheic. The most common adverse effects reported were headache (11.8%), weight increase (8.5%), intermenstrual bleeding (6.4%), amenorrhea (5.8%), and decreased libido (5.1%).1

The second study, which was conducted in Europe and Asia, evaluated 1,059 women with an average age of 32.2 years. Changes in menstrual bleeding patterns included irregular bleeding decreasing over time and amenorrhea increasing. By the end of 12 months, 35.3% of women had become amenorrheic. The most common adverse effects reported were amenorrhea not otherwise specified (NOS) (8.0%), intermenstrual bleeding (7.9%), and headache NOS (5%). Overall, the mean weight gain by month 12 was 1.7 kg. Body mass index and body weight did not affect the efficacy of the dosage in either study.1

Will women use it?

"Subcutaneous DMPA should offer women the efficacy and safety of traditional’ DMPA with the advantages of subcutaneous administration: finer, shorter needle and possibility of self-administration," observes Andrew Kaunitz, MD, professor and assistant chair in the obstetrics and gynecology department at the University of Florida Health Science Center/Jacksonville. He also served as a clinical investigator for the DMPA-SC trials.

Results of patient satisfaction questionnaires from the studies indicate that women would use the new method if it were available on the commercial market.2 DMPA-SC was preferred by 84% of respondents when compared with other contraceptive methods; women reported a low incidence of injection-site pain and a significant decrease in anxiety about subsequent injections.

The home self-injection experience was rated highly convenient: 74% of women who had self-administered preferred to continue doing so. These data show the new lower-dose formulation, like the original formulation of DMPA, may provide an optimal contraceptive fit for a wide range of women.2

Using DMPA-SC will provide freedom for women to consider self-injection and may improve success rates as well, says Sharon Schnare, RN, FNP, CNM, MSN, clinician at South Kitsap Family Care Clinic in Port Orchard, WA. Women already self-inject several drugs, such as insulin, pergonal, and sumatriptan, she notes.

Find the right option

For some patients, a significant disadvantage to any injectable agent is that it requires monthly or quarterly administration by a health care professional, including the time and expense of scheduled office visits; nonetheless, DMPA contraceptive injections offer a reliable form of birth control for those who have problems with daily pill taking.3

More than 30 years of clinical experience show that DMPA is an effective contraceptive with an excellent safety profile and few short-term side effects.3 Results of the clinical trials indicate that the new formulation rapidly achieves target plasma MPA levels and provides immediate and sustained contraceptive effects.4

As with any long-term contraceptive, careful identification of those women who actually desire such long-acting birth control is an important step toward improving continuation rates.5

As with other progestin-only methods, women who are considering DMPA use need to be carefully counseled about initial increases in spotting and bleeding and eventual oligomenorrhea or amenorrhea.6 Other issues, such as potential impacts on weight and bone mineral density, need to be individualized. It appears from some studies that DMPA users may have a two- to five-pound weight gain the first year; how much of that gain is attributable to the injection is not clear.7

The continuation rate with DMPA has been lower in clinical practice (20-30% at one year) than was observed in initial trials.6 However, teens often return to DMPA use after switching to other methods because they had initially had side effects with DMPA.8

Remind women who choose DMPA that it does not protect against sexually transmitted diseases, including HIV/AIDS. Women who have multiple sexual partners or use intravenous drugs, or whose sexual partners have other partners or use intravenous drugs, should use condoms even if they rely on DMPA for family planning.9

References

1. Nelson A. The latest advance in nondaily contraception. Presented at the XVII International Federation of Gynecology and Obstetrics (FIGO) World Congress of Gynecology and Obstetrics. Santiago, Chile; November 2003.

2. Arias R. Strategies for optimizing contraceptive care. Presented at the XVII FIGO World Congress of Gynecology and Obstetrics. Santiago, Chile; November 2003.

3. Davidson MR. Contraception update: The latest hormonal options. Clinician Reviews 2003; 13:52-59.

4. Petta C. Thirty years of Depo-Provera use worldwide. Presented at the XVII FIGO World Congress of Gynecology and Obstetrics. Santiago, Chile; November 2003.

5. Westfall JM, Main DS, Barnard L. Continuation rates among injectable contraceptive users. Fam Plann Perspect 1996; 28:275-277.

6. Nelson A. Contraceptive Update Y2K: Need for contraception and new contraceptive options. Clin Cornerstone 2000; 3:48-62.

7. Moore LL, Valuck R, McDougall C, et al. A comparative study of one-year weight gain among users of medroxy-progesterone acetate, levonorgestrel implants, and oral contraceptives. Contraception 1995; 52:215-220.

8. Polaneczky M, Liblanc M. Long-term depot-medroxy-progesterone acetate (Depo-Provera) use in inner-city adolescents. J Adolesc Health 1998; 23:81-88.

9. Lande RE. New era for injectables. Population Reports, Series K, No. 5. Baltimore: Johns Hopkins School of Public Health, Population Information Program; August 1995.