DEPO-PROVERA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DEPO-PROVERA (DEPO-PROVERA).
Progestin that suppresses gonadotropin secretion, inhibiting ovulation and causing endometrial thinning.
| Metabolism | Hepatic via CYP3A4; metabolites are glucuronidated and excreted in feces and urine. |
| Excretion | Primarily metabolized in the liver via hydroxylation and conjugation; metabolites are excreted in urine (60-70%) and feces (20-30%). Less than 1% excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is approximately 12-17 hours after single dose, but after multiple doses or depot administration, the half-life extends to about 40-60 hours due to slow release from injection site. |
| Protein binding | 96-99% bound to albumin; also binds to sex hormone-binding globulin (SHBG) to a lesser extent. |
| Volume of Distribution | Approximately 20 L/kg (range 17-25 L/kg), indicating extensive tissue distribution including adipose tissue and breast milk. |
| Bioavailability | Oral: <10% due to extensive first-pass metabolism. Intramuscular depot: 100% bioavailability. Subcutaneous: 100% bioavailability. |
| Onset of Action | Intramuscular depot: Onset of contraceptive effect occurs within 24 hours if given within first 5 days of menstrual cycle; full effect by 72 hours. Subcutaneous: similar onset. |
| Duration of Action | Contraceptive effect lasts at least 14 weeks after a single IM injection; clinically, doses are repeated every 3 months (12-14 weeks). Return to fertility may be delayed up to 18 months after last dose. |
| Action Class | Progestins (First generation) |
| Brand Substitutes | Freedom Inject Contraceptive Injection |
150 mg intramuscularly every 3 months (13 weeks) for contraception; for endometriosis, 50 mg subcutaneously once weekly or 150 mg intramuscularly every 90 days.
| Dosage form | INJECTABLE |
| Renal impairment | No dosage adjustment required for renal impairment; minimal renal elimination. |
| Liver impairment | Contraindicated in severe hepatic disease (Child-Pugh class C). In mild to moderate impairment (Child-Pugh class A or B), use with caution; no specific dose adjustment guidelines. |
| Pediatric use | Not approved for use before menarche; for adolescent contraception, same adult dose: 150 mg IM every 3 months. |
| Geriatric use | No specific dose adjustments; use with caution due to potential decreased bone density and risk of thromboembolic events; consider lower bone mass and cardiovascular risk. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DEPO-PROVERA (DEPO-PROVERA).
| Breastfeeding | Depot medroxyprogesterone acetate (DMPA) is excreted into breast milk in small amounts; reported milk-to-plasma ratio approximately 0.5. No adverse effects reported in breastfed infants. Considered compatible with breastfeeding; minimal risk. |
| Teratogenic Risk | First trimester: No significant increase in major malformations noted; potential association with genital ambiguity in female fetuses (androgenic effects). Second and third trimesters: No documented teratogenicity; possible effects on fetal bone density and immune function with prolonged exposure. |
■ FDA Black Box Warning
Loss of bone mineral density (BMD) is significant with long-term use; use beyond 2 years is not recommended unless other methods are inadequate.
| Serious Effects |
Known or suspected pregnancy; undiagnosed vaginal bleeding; breast cancer; active liver disease; hypersensitivity to medroxyprogesterone acetate; known or suspected history of thromboembolic disorders.
| Precautions | Monitor for bone mineral density loss; increased risk of breast cancer; thromboembolic disorders; ectopic pregnancy risk; delayed return to fertility; irregular bleeding; depression; fluid retention; hepatic disease; migraine or headache. |
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| Fetal Monitoring |
| Maternal: Periodic weight, blood pressure, and glucose monitoring; assess for thromboembolic symptoms. Fetal: Routine prenatal ultrasound for growth and anatomy; no specific additional monitoring required beyond standard obstetric care. |
| Fertility Effects | DMPA results in reversible infertility; median return to ovulation 10 months after last injection (range 4-31 months). Long-term use may be associated with delayed return to fertility but no permanent damage. No effect on future pregnancy outcomes. |