Injectable update: Subcutaneous form of Depo-Provera is approved
Injectable update: Subcutaneous form of Depo-Provera is approved
Injectable will be packaged in single-use subcutaneous injection device
Get ready to add a new form of Depo-Provera [depot medroxyprogesterone acetate (DMPA), Pfizer, New York City] to your formulary: Depo-SubQ Provera 104 (DMPA-SC).
The drug, approved by the Food and Drug Administration (FDA) in December, should be available on retail pharmacy shelves in mid-May, says An Phan, Pfizer corporate spokeswoman. Pricing has not been set yet on the drug, she adds.
The new formulation is designed to be administered subcutaneously, not intramuscularly, as with the conventional quarterly injection of DMPA. The 104 refers to the 104 mg of its active ingredient, medroxyprogesterone acetate. It, too, is administered every three months to achieve contraceptive efficacy.
DMPA-SC continues the benefits of highly effective injectable contraception with the additional advantage of a smaller injection volume and a smaller needle size, says Andrew Kaunitz, MD, professor and assistant chair in the obstetrics and gynecology department at the University of Florida Health Science Center/Jacksonville. The subcutaneous route of administration opens the door to self-administration at home, an approach that would increase access to this approach to birth control, says Kaunitz, who served as one of the clinical investigators in studies of the injectable.
While the drug will be packaged in a single-shot subcutaneous injection device with a passive needle safety unit, it can be administered only by a health care professional, Phan says.
The major advantage of the subcutaneous form of DMPA is the potential for eventual approval of the consumer to self-administer the medication, observes David Archer, MD, professor of obstetrics and gynecology and director of the Clinical Research Center at the Eastern Virginia Medical Center in Norfolk. "This is also possible with the IM [intramuscular] formulation but is potentially more painful," he adds.
Review research on drug
Two large, open-label, Phase III studies assessed the one-year contraceptive efficacy, safety, and patient satisfaction with DMPA-SC administered every three months.1 Zero pregnancies were reported in both studies, which included a total of 16,023 woman-cycles of exposure to DMPA-SC and substantial numbers of overweight or obese women.1
In a prospective, randomized, single-dose trial designed to evaluate the pharmacokinetics of DMPA-SC in comparison to original formulation, researchers found the lower-dose formulation of Depo-Provera suppressed ovulation for more than 13 weeks in all subjects and was not affected by body mass index or race.2 Median time for return to ovulation was 30 weeks, with a 97.4% cumulative rate of return to ovulation at 12 months.2
In the clinical trials, most women using DMPA-SC experienced changes in menstrual bleeding patterns, such as amenorrhea, irregular spotting or bleeding, prolonged spotting or bleeding, and heavy bleeding. As women continued using the drug, fewer experienced irregular bleeding and more experienced amenorrhea.
In the trials, 39% of women experienced amenorrhea during month six, and 56.5% experienced amenorrhea during month 12.
In the clinical trials, 10% of women discontinued treatment for adverse reactions. Among these women, the most common reasons for discontinuation were uterine bleeding irregularities, increased weight, decreased libido, acne, and injection site reactions.
"The subcutaneous dosage is smaller — 104 mg — than the standard IM and has a similar duration of action and bleeding profile," Archer points out. "I would hope that this route would be more acceptable to physicians and health care providers."
What about bone issues?
As with Depo-Provera, clinicians will need to be prepared to counsel patients on the drug’s impact on bone health. Research published in 2004 indicated that women using DMPA for two years recorded a decline in bone mineral density (BMD) of roughly 6%, compared with a loss of 2.6% among women on oral contraceptives.3
As with DMPA, DMPA-SC’s labeling states that bone loss in women who use Depo-Provera is greater with increased duration of use and may not be completely reversible. The labeling states that it is "unknown if use of Depo-SubQ Provera 104 during adolescence or early adulthood, a critical period of bone accretion, will reduce peak bone mass and increase the risk for osteoporotic fracture in later life."
The contraceptive injection should be used as a long-term birth control method (longer than two years) only if other birth control methods are inadequate, the label advises. Women who continue to use DMPA-SC past the two-year mark should have their BMD evaluated, according to the labeling.
Although there are no studies addressing whether calcium and vitamin D lessen BMD loss in women using DMPA-SC, all patients should be advised to have adequate calcium and vitamin D intake, according to the package insert.
Who can use the drug?
What are the contraindications to DMPA-SC? According to the labeling, they include:
- known or suspected pregnancy;
- undiagnosed vaginal bleeding;
- known or suspected breast malignancy;
- active thrombophlebitis, or current or past history of thromboembolic disorders, or cerebral vascular disease;
- significant liver disease;
- known hypersensitivity to medroxyprogesterone acetate or any of its other ingredients.
Follow these precautions
Before initiating the method, ensure the patient is not pregnant at the time of the first injection. For women who are sexually active and having regular menses, the first shot should be given only during the first five days of a normal menstrual period. Women who are breast-feeding may have their first injection during or after their sixth postpartum week. Remind all patients that the method does not protect against sexually transmitted diseases, including HIV.
DMPA-SC must be given by subcutaneous injection into the anterior thigh or abdomen once every three months (12-14 weeks). If more than 14 weeks elapse between injections, pregnancy should be ruled out before the next injection. The pre-filled syringe must be vigorously shaken just before use to create a uniform suspension.
Patients who are switching from combined hormonal contraceptives should have their first injection of DMPA-SC within seven days after the last day of using that method, state the package instructions. If patients are switching from DMPA use, contraceptive coverage will be maintained if the next injection is given within the prescribed dosing period for DMPA.
Pfizer plans to provide patient education on the drug through its patient package insert, a web site, and consumer hotline, says Phan. Provider education will be available via a video, which will be available this fall, she adds. (Look for ordering information in CTU when the video is released.)
References
- Jain J, Jakimiuk AJ, Bode FR, et al. Contraceptive efficacy and safety of DMPA-SC. Contraception 2004; 70:269-275.
- Jain J, Dutton C, Nicosia A, et al. Pharmacokinetics, ovulation suppression, and return to ovulation following a lower dose subcutaneous formulation of Depo-Provera. Contraception 2004; 70:11-18.
- Berenson AB, Breitkopf CR, Grady JJ, et al. Effects of hormonal contraception on bone mineral density after 24 months of use. Obstet Gynecol 2004; 103:899-906.
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