Pharmacology Update Medroxyprogesterone Acetate Injection (depo-subQ provera 104)
By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Associate Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationships to this field of study.
The FDA has approved a new formulation of medroxyprogesterone acetate (MPA). This lower-dose formulation permits subcutaneous injection rather than intramuscular (IM) injection and provides the same efficacy as Depo Provera with a 30% lower dose. This new formulation (DMPA-SC) is marketed by Pharmacia and Upjohn Co as depo-subQ provera 104.
Indications
DMPA-SC is indicated for the prevention of pregnancy and for the management of endometriosis-associated
pain.1
Dosage
The dose is given by subcutaneous injection once every 3 months. Injection should be given into the anterior thigh or abdomen. Dosage adjustment is not required for difference in body weight. For endometriosis, treatment for longer than 2 years is not
recommended.1 DMPA-SC is supplied as a pre-filled syringe containing 104 mg of MPA per 0.65
mL.
Potential Advantages
DMPA-SC formulation provides a more convenient injection and same efficacy with a 30% lower dose than
the intramuscular injection.1,2 For the treatment of endometriosis, patients experience a lower frequency of
hot flashes than with leuprolide and less loss of bone mineral density.1
Potential Disadvantages
DMPA-SC may be less effective than leuprolide in reduction of symptoms of
endometriosis.1 While no dosage adjustment for body weight is recommended,
mean MPA levels are significantly lower in obese women with BMI > 38 kg/m2.1 MPA is associated with
the loss of bone mineral density. This effect may not be completely reversible. The effect on BMD between the
subcutaneous and the intramuscular formulations appears to be the same.1 DMPA-SC may increase the
risk of acquiring sexually transmitted chlamydial and gonorrheal infections.3
Comments
The subcutaneous formulation provides a slower absorption of MPA resulting in a lower peak concentration, longer duration of action, and maintenance of the minimum effective concentration with a lower dose. In 2 large, 1-year, open-label phase 3 studies, DMPA-SC was found to be safe and efficacious in preventing pregnancy. With 16,023 woman-cycles of exposure, DMPA-SC was 99.9% effective.2 No pregnancies were observed, irrespective of BMI. Treatment emergent adverse events included headache, weight increase, intermenstrual bleeding, amenorrhea, decreased libido, and injection site reactions. Amenorrhea occurred in 55% of women at 1 year, similar to the rate with DMPA-IM.2 Primary reasons for discontinuation of therapy were uterine bleeding irregularities (35%), increased weight (18%), decreased libido (11%), acne (10%), and injection site reactions (6%).1 Decline in BMD was most significant during the first 2 years (-4.11% at year 2 in the lumbar spine) and with smaller declines thereafter (-5.38% at 5 years).1 Reversibility appears to be related to the duration of treatment, as full recovery may be more likely after 3 years of use than 5.1,4 In 2 comparative studies in patients with endometriosis (n = 573), DMPA-SC (104 mg every 3 months) was compared to leuprolide microspheres (11.25 mg every 3 months). Reduction of symptoms was similar or slightly better with leuprolide.1 Moderate or severe hot flushes were more common with leuprolide (74.2% vs 36.2% at 3 months, 68.5% vs 26.7% at 6 months) and greater loss of BMD was noted with leuprolide (-4.10 vs -1.20% in the lumbar spine).1 Patients who were younger than 35 years of age at first exposure (within the previous 4 years) to DMPA-IM had a relative risk of 2.19 (95% CI, 1.23- 3.89) of breast cancer compared to nonusers.1 However, the overall relative risk for ever-users was 1.21 (95% CI, 0.96-1.52). The wholesale cost of DMPA-SC is $68.40 for 3 months compared to $49.51 for DMPA-IM.
Clinical Implications
DMPA-SC provides a lower dose alternative to DMPA-IM. This form of contraceptive is a reasonable choice for women in whom estrogen is contraindicated and adherence to oral tablets is problematic. Delay in the return of fertility, which may take 4-31 months, is a drawback to therapy. For pain associated with endometriosis, gonadotropin-releasing hormone (GnRH) analogs are the standard of care. The side effects associated with GnRH are generally related to hypoestrogenism that could be corrected with "adding back" small amounts of estrogen, progestin, or both. In contrast, adverse events associated with DMPA may require discontinuation of therapy.
References
1. depo-subQ provera 104 product information. Pharmacia and Upjohn Co. March, 2005.
2. Jain J, et al. Contraceptive efficacy and safety of DMPA-SC. Contraception. 2004;70:269-275.
3. NIH News. www.nichd.nih.gov/new/releases/depo-provera-risk.cfm. Accessed 7/22/05.
4. Scholes D, et al. Injectable hormone contraception and bone density: results from a prospective study. Epidemiology. 2002;13:581-587.
By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Associate Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationships to this field of study.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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