Medroxyprogesterone Acetate (Page 4 of 7)

11 DESCRIPTION

Medroxyprogesterone acetate injectable suspension, USP a contraceptive injection, contains medroxyprogesterone acetate, USP a derivative of progesterone, as its active ingredient. Medroxyprogesterone acetate is active by the parenteral and oral routes of administration. It is a white to off-white, odorless, fine powder that is stable in air and that melts between 200°C and 210°C. It is freely soluble in chloroform, soluble in acetone and dioxane, sparingly soluble in alcohol and methanol, slightly soluble in ether, and insoluble in water.

The chemical name for medroxyprogesterone acetate, USP is pregn-4-ene-3, 20-dione, 17-(acetyloxy)-6-methyl-, (6α)-. The structural formula is as follows:

Structural Formula

Molecular Formula C24 H34 O4 Molecular Weight 386.52

Medroxyprogesterone acetate injectable suspension, USP for IM injection is available in vials containing 1 mL of medroxyprogesterone acetate sterile aqueous suspension 150 mg/mL.

Each mL of sterile aqueous suspension contains:

Medroxyprogesterone acetate, USP

150 mg

Polyethylene glycol 3350

28.9 mg

Polysorbate 80

2.41 mg

Sodium chloride

8.68 mg

Methylparaben

1.37 mg

Propylparaben

0.150 mg

Water for injection

quantity sufficient

When necessary, pH is adjusted with sodium hydroxide or hydrochloric acid, or both.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Medroxyprogesterone acetate injectable suspension [MPA] inhibits the secretion of gonadotropins which primarily prevents follicular maturation and ovulation and causes thickening of cervical mucus. These actions contribute to its contraceptive effect.

12.2 Pharmacodynamics

No specific pharmacodynamic studies were conducted with medroxyprogesterone acetate injectable suspension.

12.3 Pharmacokinetics

Absorption

Following a single 150 mg IM dose of medroxyprogesterone acetate injectable suspension in eight women between the ages of 28 and 36 years old, medroxyprogesterone acetate concentrations, measured by an extracted radioimmunoassay procedure, increase for approximately 3 weeks to reach peak plasma concentrations of 1 to 7 ng/mL.

Distribution

Plasma protein binding of MPA averages 86%. MPA binding occurs primarily to serum albumin. No binding of MPA occurs with sex-hormone-binding globulin (SHBG).

Metabolism

MPA is extensively metabolized in the liver by P450 enzymes. Its metabolism primarily involves ring A and/or side-chain reduction, loss of the acetyl group, hydroxylation in the 2-, 6-, and 21-positions or a combination of these positions, resulting in more than 10 metabolites.

Excretion

The concentrations of medroxyprogesterone acetate decrease exponentially until they become undetectable (<100 pg/mL) between 120 to 200 days following injection. Using an unextracted radioimmunoassay procedure for the assay of medroxyprogesterone acetate in serum, the apparent half-life for medroxyprogesterone acetate following IM administration of medroxyprogesterone acetate injectable suspension is approximately 50 days. Most medroxyprogesterone acetate metabolites are excreted in the urine as glucuronide conjugates with only minor amounts excreted as sulfates.

Specific Populations

The effect of hepatic and/or renal impairment on the pharmacokinetics of medroxyprogesterone acetate injectable suspension is unknown.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

[See Warnings and Precautions, (5.3, 5.15, and 5.17)].

14 CLINICAL STUDIES

14.1 Contraception

In five clinical studies using medroxyprogesterone acetate injectable suspension, the 12-month failure rate for the group of women treated with medroxyprogesterone acetate injectable suspension was zero (no pregnancies reported) to 0.7 by Life-Table method. The effectiveness of medroxyprogesterone acetate injectable suspension is dependent on the patient returning every 3 months (13 weeks) for reinjection.

14.2 Bone Mineral Density Changes in Adult Women Treated with Medroxyprogesterone Acetate Injectable Suspension

In a controlled, clinical study, adult women using medroxyprogesterone acetate injectable suspension (150 mg) for up to 5 years showed spine and hip bone mineral density (BMD) mean decreases of 5 to 6%, compared to no significant change in BMD in the control group. The decline in BMD was more pronounced during the first two years of use, with smaller declines in subsequent years. Mean changes in lumbar spine BMD of -2.86%, -4.11%, -4.89%, -4.93% and -5.38% after 1, 2, 3, 4, and 5 years, respectively, were observed. Mean decreases in BMD of the total hip and femoral neck were similar.

After stopping use of medroxyprogesterone acetate injectable suspension, there was partial recovery of BMD toward baseline values during the 2-year post-therapy period. Longer duration of treatment was associated with less complete recovery during this 2-year period following the last injection. Table 4 shows the change in BMD in women after 5 years of treatment with medroxyprogesterone acetate injectable suspension and in women in a control group, as well as the extent of recovery of BMD for the subset of the women for whom 2-year post treatment data were available.

Table 4. Mean Percent Change from Baseline in BMD in Adults by Skeletal Site and Cohort (5 Years of Treatment and 2 Years of Follow-Up)

Spine

Total Hip

Femoral Neck

Time in Study

Medroxyprogesterone acetate injectable suspension *

Control **

Medroxyprogesterone acetate injectable suspension *

Control **

Medroxyprogesterone acetate injectable suspension *

Control **

5 years

-5.38%

n = 33

0.43%

n = 105

-5.16%

n = 21

0.19%

n = 65

-6.12%

n = 34

-0.27%

n = 106

7 years

-3.13%

n = 12

0.53%

n = 60

-1.34%

n = 7

0.94%

n = 39

-5.38%

n = 13

-0.11%

n = 63

* The treatment group consisted of women who received medroxyprogesterone acetate injectable suspension for 5 years and were then followed for 2 years post-use (total time in study of 7 years).

** The control group consisted of women who did not use hormonal contraception and were followed for 7 years.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2022. All Rights Reserved.