DEPO-PROVERA (medroxyprogesterone acetate injectable suspension, USP) 10 Clinical Pharmacology

Medical Information

In order to provide you with relevant and meaningful content we need to know more about you.

Please choose the category that best describes you.

This content is intended for Canadian Healthcare Professionals. Would you like to proceed?

10.2 Pharmacodynamics

DEPO-PROVERA (medroxyprogesterone acetate) is a long-acting progestational steroid (progestogen) derived from a natural source (soybeans). Its long duration of action is a result of slow absorption from the injection site. DEPO-PROVERA does not contain estrogen.

For conception control, DEPO-PROVERA inhibits the secretion of gonadotropins which, in turn, prevents follicular maturation and ovulation, and results in endometrial thinning. Additional progestational effects that may contribute to the contraceptive effectiveness of DEPO-PROVERA include the transformation and maintenance of an endometrium hostile to implantation, and thickening of cervical mucus making sperm penetration of the cervix more difficult.

DEPO-PROVERA administered parenterally to women with adequate endogenous estrogen transforms proliferative endometrium into secretory endometrium.

Endometriosis is an estrogen-dependent disorder in women of reproductive age that is characterized by the presence of endometrial-like tissue (glands and stoma) outside the uterine lining. The putative mechanism of action of DEPO-PROVERA in the treatment of endometriosis is by inhibition of gonadotropin production, induction of decidualization followed by atrophy of endometriotic implants, prevention of follicular maturation and ovulation and decrease in circulating estrogen levels.

10.3 Pharmacokinetics

Table 7 - Summary of medroxyprogesterone acetate suspension for injection’s Pharmacokinetic Parameters in adult women population




t½ (h)




Single dose mean

150 mg I.M.

1-7 ng/mL


≈ 1000


1600-4000 litres/day

20 ± 3 litres

* not available


Following intramuscular administration, medroxyprogesterone acetate is slowly released from the injection site, resulting in low, but persistent levels of drug and drug-related materials in the circulation. On average, the time required to obtain a maximum concentration of medroxyprogesterone acetate in the circulation is between 4 and 20 days. Following a single 150 mg IM dose of DEPO-PROVERA, 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.

Circulating levels of medroxyprogesterone acetate can be detected for as long as 7 to 9 months. Increasing the injection volume of medroxyprogesterone acetate produces an increased rate of absorption and higher serum levels; however, extent of absorption is not affected.


Medroxyprogesterone acetate is approximately 90 to 95 percent protein bound. Volume of distribution is reported as 20 ± 3 litres. It crosses the blood-brain barrier and is secreted in breast milk.

Medroxyprogesterone acetate binding occurs primarily to serum albumin; no binding of medroxyprogesterone acetate occurs with sex hormone-binding globulin (SHBG).


The principal metabolite of medroxyprogesterone acetate that has been identified is a 6α-methyl-6β, 17α, 21-trihydroxy-4-pregnene-3, 20-dione-17-acetate, which is excreted in the urine. Numerous other metabolites of medroxyprogesterone acetate have been reported; however, these have not been well quantified. Metabolism may be influenced by the route of administration as well as the physical state of the drug.


The terminal half-life of medroxyprogesterone acetate is approximately 30 to 60 hours.  The elimination half-life following intramuscular administration is approximately 6 weeks, reflecting the prolonged absorption of the drug from the intramuscular injection site.  The levels then decrease exponentially until they become undetectable (<100 pg/mL) between 120 to 200 days following injection.  Plasma clearance is reported as approximately 1600-4000 litres per day. Medroxyprogesterone acetate (as the glucuronide conjugate) is primarily excreted in the feces, via biliary secretion. 

Special Populations and Conditions

  • Hepatic Insufficiency

The effect of hepatic disease on the pharmacokinetics of DEPO-PROVERA is unknown. However, medroxyprogesterone acetate is almost exclusively eliminated by hepatic metabolism and steroid hormones may be poorly metabolized in patients with severe liver insufficiency, (see 2 CONTRAINDICATIONS).

  • Renal Insufficiency

The effect of renal disease on the pharmacokinetics of DEPO-PROVERA is unknown.