May 25, 2017
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Depo-SubQ Provera

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Depo-SubQ Provera


depo-subQ provera 104 (medroxyprogesterone acetate injectable suspension), when administered at 104 mg/0.65 mL to women every 3 months (12 to 14 weeks), inhibits the secretion of gonadotropins, which prevents follicular maturation and ovulation and causes endometrial thinning. These actions produce its contraceptive effect.

Supression of serum estradiol concentrations and a possible direct action of depo-subQ provera (medroxyprogesterone acetate) 104 on the lesions of endometriosis are likely to be responsible for the therapeutic effect on endometriosis-associated pain.


The pharmacokinetic parameters of medroxyprogesterone acetate (MPA) following a single SC injection of depo-subQ provera (medroxyprogesterone acetate) 104 are shown in Table 1 and Figure 1.

Table 1 : Pharmacokinetic Parameters of MPA after a Single SC Injection of depo-subQ provera (medroxyprogesterone acetate) 104 in Healthy Women (n = 42)


Mean 1.56 8.8 0.402 66.98 92.84 43
Min 0.53 2.0 0.133 20.63 31.36 16
Max 3.08 80.0 0.733 139.79 162.29 114
Cmax = peak serum concentration; Tmax = time when Cmax is observed; C91 = serum concentration at 91 days; AUC0–91 and AUC0–∞ = area under the concentration-time curve over 91 days or infinity, respectively; t½ = terminal half-life


Following a single SC injection of depo-subQ provera (medroxyprogesterone acetate) 104, serum MPA concentrations reach ≥ 0.2 ng/mL within 24 hours. The mean Tmax is attained approximately 1 week after injection.

Figure 1 : Mean (SD) Serum Concentration-Time Profile of MPA after a Single Injection of depo-subQ provera (medroxyprogesterone acetate) 104 to Healthy Women

Mean (SD) Serum Concentration-Time Profile of MPA after a Single Injection of depo-subQ provera 104 to Healthy Women  - Illustration

In a study to assess accumulation and the achievement of steady state following multiple SC administrations, trough concentrations of MPA were determined after 6, 12, and 24 months, and in a subset of 8 subjects, bi-weekly concentrations were determined within one dosing interval in the second year of administration. The mean (SD) MPA trough concentrations were 0.67 (0.36) ng/mL (n=157), 0.79 (0.36) ng/mL (n=144), and 0.87 (0.33) ng/mL (n=106) at 6, 12 and 24 months, respectively.

Effect of Injection Site

depo-subQ provera (medroxyprogesterone acetate) 104 was administered into the anterior thigh or the abdomen to evaluate effects on the MPA concentration-time profile. MPA trough concentrations (Cmin; Day 91) were similar for the two injection locations.


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).


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.


Residual MPA concentrations at the end of the first dosing interval (12 to 14 weeks) of depo-subQ provera (medroxyprogesterone acetate) 104 are generally below 0.5 ng/mL, consistent with its apparent terminal half-life of ~40 days after SC administration. Most MPA metabolites are excreted in the urine as glucuronide conjugates with only small amounts excreted as sulfates.


Following a single SC administration of doses ranging from 50 to 150 mg, the AUC and Cmin (Day 91) increased with higher doses of depo-subQ provera (medroxyprogesterone acetate) 104, but there was considerable overlap across dose levels. Serum MPA concentrations at Day 91 increased in a dose proportional manner but Cmax did not appear to increase proportionally with increasing dose. The AUC data were suggestive of dose linearity.

Special Populations


There were no significant differences in the pharmacokinetics and/or pharmacodynamics of MPA after SC administration of depo-subQ provera (medroxyprogesterone acetate) 104 in African-American and Caucasian women. The pharmacokinetics/pharmacodynamics of depo-subQ provera (medroxyprogesterone acetate) 104 were evaluated in Asian women in a separate study and also found to be similar to African-American and Caucasian women.

Effect of Body Weight

Although total MPA exposure was lower in obese women, no dosage adjustment of depo-subQ provera (medroxyprogesterone acetate) 104 is necessary based on body weight. The effect of body weight on the pharmacokinetics of MPA following a single dose was assessed in a subset of women (n = 42, body mass index [BMI] ranged from 18.2 to 46.7 kg/m²). The AUC0–91 values for MPA were 71.6, 67.9, and 46.3 ng·day/mL in women with BMI categories of ≤ 28 kg/m², > 28–38 kg/m², and > 38 kg/m², respectively. The mean MPA Cmax was 1.74 ng/mL in women with BMI ≤ 28 kg/m², 1.53 ng/mL in women with BMI > 28–38 kg/m², and 1.02 ng/mL in women with BMI > 38 kg/m², respectively. The MPA trough (Cmin) concentrations had a tendency to be lower in women with BMI > 38 kg/m².

Hepatic Insufficiency

No clinical studies have evaluated the effect of hepatic disease on the disposition of depo-subQ provera (medroxyprogesterone acetate) 104. However, steroid hormones may be poorly metabolized in patients with severe liver dysfunction (see CONTRAINDICATIONS).

Renal Insufficiency

No clinical studies have evaluated the effect of renal disease on the pharmacokinetics of depo-subQ provera (medroxyprogesterone acetate) 104.

Drug-Drug Interactions


Last reviewed on RxList: 7/27/2009
This monograph has been modified to include the generic and brand name in many instances.

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