Medroxyprogesterone Acetate

MEDROXYPROGESTERONE ACETATE- medroxyprogesterone acetate injection, suspension
Bryant Ranch Prepack

Figure 1Structural FormulaPPi Chart

1 INDICATIONS AND USAGE

Medroxyprogesterone Acetate Injectable Suspension is indicated for use by females of reproductive potential to prevent pregnancy.

Limitations of Use:

The use of Medroxyprogesterone Acetate Injectable Suspension is not recommended as a long-term (i.e., longer than 2 years) birth control method unless other options are considered inadequate [see Dosage and Administration (2.1) and Warnings and Precautions (5.1)].

2 DOSAGE AND ADMINISTRATION

2.1 Prevention of Pregnancy

The 1 mL vial of medroxyprogesterone acetate injectable suspension should be vigorously shaken just before use to ensure that the dose being administered represents a uniform suspension.

The recommended dose is 150 mg of medroxyprogesterone acetate injectable suspension every 3 months (13 weeks) administered by deep intramuscular (IM) injection using strict aseptic technique in the gluteal or deltoid muscle, rotating the sites with every injection. As with any IM injection, to avoid an inadvertent subcutaneous injection, body habitus should be assessed prior to each injection to determine if a longer needle is necessary particularly for gluteal IM injection.

Use for longer than 2 years is not recommended (unless other birth control methods are considered inadequate) due to the impact of long-term medroxyprogesterone acetate injectable suspension treatment on bone mineral density (BMD) [see Warnings and Precautions (5.1)]. Dosage does not need to be adjusted for body weight [see Clinical Studies (14.1)].

To ensure the patient is not pregnant at the time of the first injection, the first injection should be given ONLY during the first 5 days of a normal menstrual period; ONLY within the first 5-days postpartum if not breast-feeding; and if exclusively breast-feeding, ONLY at the sixth postpartum week. If the time interval between injections is greater than 13 weeks, the physician should determine that the patient is not pregnant before administering the drug. The efficacy of medroxyprogesterone acetate injectable suspension depends on adherence to the dosage schedule of administration.

2.2 Switching From Other Methods of Contraception

When switching from other contraceptive methods, medroxyprogesterone acetate injectable suspension should be given in a manner that ensures continuous contraceptive coverage based upon the mechanism of action of both methods, (e.g., patients switching from oral contraceptives should have their first injection of medroxyprogesterone acetate injectable suspension on the day after the last active tablet or at the latest, on the day following the final inactive tablet).

3 DOSAGE FORMS AND STRENGTHS

Sterile Aqueous suspension: 150 mg/mL

4 CONTRAINDICATIONS

The use of medroxyprogesterone acetate injectable suspension is contraindicated in the following conditions:

• Known or suspected pregnancy or as a diagnostic test for pregnancy.
• Active thrombophlebitis, or current or past history of thromboembolic disorders, or cerebral vascular disease [see Warnings and Precautions (5.2)].
• Known or suspected malignancy of breast [see Warnings and Precautions (5.3)].
• Known hypersensitivity to medroxyprogesterone acetate injectable suspension or any of its other ingredients [see Warnings and Precautions (5.5)].
• Significant liver disease [see Warnings and Precautions (5.7)].
• Undiagnosed vaginal bleeding [see Warnings and Precautions (5.10)].

5 WARNINGS AND PRECAUTIONS

5.1 Loss of Bone Mineral Density

Use of medroxyprogesterone acetate injectable suspension reduces serum estrogen levels and is associated with significant loss of BMD. This loss of BMD is of particular concern during adolescence and early adulthood, a critical period of bone accretion. It is unknown if use of medroxyprogesterone acetate injectable suspension by younger women will reduce peak bone mass and increase the risk for osteoporotic fracture in later life.

A study to assess the reversibility of loss of BMD in adolescents was conducted with medroxyprogesterone acetate injectable suspension. After discontinuing medroxyprogesterone acetate injectable suspension in these adolescents, mean BMD loss at the total hip and femoral neck did not fully recover by 5 years (60 months) post-treatment in the sub-group of adolescents who were treated for more than 2 years [see Clinical Studies (14.3)]. Similarly, in adults, there was only partial recovery of mean BMD at the total hip, femoral neck, and lumbar spine towards baseline by 2 years post-treatment [see Clinical Studies (14.2)].

The use of medroxyprogesterone acetate injectable suspension is not recommended as a long-term (i.e., longer than 2 years) birth control method unless other options are considered inadequate. BMD should be evaluated when a woman needs to continue to use medroxyprogesterone acetate injectable suspension long-term. In adolescents, interpretation of BMD results should take into account patient age and skeletal maturity.

Other birth control methods should be considered in the risk/benefit analysis for the use of medroxyprogesterone acetate injectable suspension in women with osteoporosis risk factors. Medroxyprogesterone acetate injectable suspension can pose an additional risk in patients with risk factors for osteoporosis (e.g., metabolic bone disease, chronic alcohol and/or tobacco use, anorexia nervosa, strong family history of osteoporosis or chronic use of drugs that can reduce bone mass such as anticonvulsants or corticosteroids).

5.2 Thromboembolic Disorders

There have been reports of serious thrombotic events in women using medroxyprogesterone acetate injectable suspension (150 mg). However, medroxyprogesterone acetate injectable suspension has not been causally associated with the induction of thrombotic or thromboembolic disorders. Any patient who develops thrombosis while undergoing therapy with medroxyprogesterone acetate injectable suspension should discontinue treatment unless she has no other acceptable options for birth control.

Do not re-administer medroxyprogesterone acetate injectable suspension pending examination if there is a sudden partial or complete loss of vision or if there is a sudden onset of proptosis, diplopia, or migraine. Do not re-administer if examination reveals papilledema or retinal vascular lesions.

5.3 Cancer Risks

Breast Cancer

Women who have or have had a history of breast cancer should not use hormonal contraceptives, including medroxyprogesterone acetate injectable suspension, because breast cancer may be hormonally sensitive [see Contraindications (4)]. Women with a strong family history of breast cancer should be monitored with particular care.

The results of five large case-control studies^{1, 2} assessing the association between depo-medroxyprogesterone acetate (DMPA) use and the risk of breast cancer are summarized in Figure 1. Three of the studies suggest a slightly increased risk of breast cancer in the overall population of users; these increased risks were statistically significant in one study. One recent US study¹ evaluated the recency and duration of use and found a statistically significantly increased risk of breast cancer in recent users (defined as last use within the past five years) who used DMPA for 12 months or longer; this is consistent with results of a previous study.

Figure 1. Risk estimates for breast cancer in DMPA users

Odds ratio estimates were adjusted for the following covariates:

Lee et al. (1987): age, parity, and socioeconomic status.

Paul et al. (1989): age, parity, ethnic group, and year of interview.

WHO (1991): age, center, and age at first live birth.

Shapiro et al. (2000): age, ethnic group, socioeconomic status, and any combined estrogen/progestogen oral contraceptive use.

Li et al. (2012): age, year, BMI, duration of OC use, number of full-term pregnancies, family history of breast cancer, and history of screening mammography.

Based on the published SEER-18 2011 incidence rate (age-adjusted to the 2000 US Standard Population) of breast cancer for US women, all races, age 20 to 49 years, a doubling of risk would increase the incidence of breast cancer in women who use medroxyprogesterone acetate injectable suspension from about 72 to about 144 cases per 100,000 women.

Cervical Cancer

A statistically nonsignificant increase in RR estimates of invasive squamous-cell cervical cancer has been associated with the use of medroxyprogesterone acetate injectable suspension in women who were first exposed before the age of 35 years (RR 1.22 to 1.28 and 95% CI 0.93 to 1.70). The overall, nonsignificant relative rate of invasive squamous-cell cervical cancer in women who ever used medroxyprogesterone acetate injectable suspension was estimated to be 1.11 (95% CI 0.96 to 1.29). No trends in risk with duration of use or times since initial or most recent exposure were observed.

Other Cancers

Long-term case-controlled surveillance of users of medroxyprogesterone acetate injectable suspension found no overall increased risk of ovarian or liver cancer.