PROVERA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROVERA (PROVERA).
Provera (medroxyprogesterone acetate) is a progestin that binds to progesterone receptors, suppressing gonadotropin secretion, inhibiting endometrial growth, and inducing secretory changes in the endometrium. It also has antigonadotropic effects by reducing LH and FSH release from the pituitary.
| Metabolism | Primarily hepatic metabolism via reduction and hydroxylation (CYP3A4 and other CYP450 enzymes). Conjugation with glucuronide and sulfate. Metabolites are excreted in urine. |
| Excretion | Renal (50-60% as metabolites), biliary/fecal (30-40%). Less than 1% excreted unchanged. |
| Half-life | Terminal elimination half-life is approximately 12-17 hours for medroxyprogesterone acetate (oral). With depot intramuscular injection, the half-life is extended to approximately 50 days due to slow absorption from the injection site. |
| Protein binding | Highly protein bound (90-95%), primarily to albumin and to a lesser extent to corticosteroid-binding globulin (CBG). |
| Volume of Distribution | Approximately 8-12 L/kg (20-30 L total), indicating extensive tissue distribution. Clinical meaning: high Vd suggests sequestration in adipose tissue and slow release. |
| Bioavailability | Oral: approximately 100% (well absorbed, but first-pass metabolism reduces systemic bioavailability to about 10-15% due to extensive hepatic metabolism). Intramuscular depot: 100% bioavailability as it bypasses first-pass metabolism. |
| Onset of Action | Oral: clinical effects (e.g., endometrial shedding) occur within 24-48 hours. Intramuscular depot: onset of contraceptive effect within 24 hours if given within first 5 days of menstrual cycle; for endometrial cancer, effects may take weeks. |
| Duration of Action | Oral: duration of action for single dose is about 24-48 hours. Intramuscular depot: contraceptive effect lasts for at least 14 weeks (FDA labeling supports 13 weeks). For high-dose therapy in endometrial cancer, duration depends on regimen. |
| Action Class | Progestins (First generation) |
| Brand Substitutes | Medona 10mg Tablet, Empeea 10mg Tablet, Regeeva 10mg Tablet, Medrigest Tablet, Medace 10mg Tablet, Farlutal 5mg Tablet, Meprate 5mg Tablet, Pantoride 40 Tablet, Topp 40 Tablet, Panplus 40 Tablet, Pancare 40mg Tablet, Aciban 40 Tablet, Panfirst 40mg Injection, Troypanto 40mg Injection, Zepoxin 40mg Injection, P-Ppi Injection, Pantodac IV Injection |
Oral: 5-10 mg daily for 5-10 days for secondary amenorrhea; 5-10 mg daily for 12-14 days per cycle in combination with estrogen for endometrial hyperplasia; 400-1000 mg/day IM monthly for endometriosis.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment required; use with caution in severe renal impairment. |
| Liver impairment | Contraindicated in severe hepatic dysfunction (Child-Pugh C). In mild to moderate impairment (Child-Pugh A or B), use with caution and consider dose reduction based on response and tolerability. |
| Pediatric use | Weight-based dosing: 2.5-10 mg/day orally for 5-10 days for functional uterine bleeding; dosing per body weight not well established; adjust based on clinical response. |
| Geriatric use | Elderly patients: Use lowest effective dose; monitor for fluid retention, thromboembolic events, and cognitive effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROVERA (PROVERA).
| Breastfeeding | Excreted in breast milk in small amounts. M/P ratio not established. Use with caution; avoid if possible. Consider alternative agents. |
| Teratogenic Risk | Pregnancy category X. Contraindicated in pregnant women. First trimester: Major congenital anomalies (including genital abnormalities, neural tube defects) and fetal loss. Second/third trimester: Possible masculinization of female fetuses (in utero exposure to progestins). |
| Fetal Monitoring |
■ FDA Black Box Warning
There is an increased risk of dementia (including Alzheimer's disease) in postmenopausal women aged 65 years or older who use Provera combined with conjugated estrogens. This warning is based on the Women's Health Initiative Memory Study (WHIMS).
| Serious Effects |
["Known or suspected pregnancy","Undiagnosed abnormal genital bleeding","Known or suspected breast cancer (except palliative use)","Active thromboembolic disorders (e.g., DVT, PE) or history of these conditions","Liver dysfunction or disease","Hypersensitivity to medroxyprogesterone acetate or any component"]
| Precautions | ["Cardiovascular disorders: Increased risk of thromboembolic events (stroke, DVT, PE), MI, and breast cancer","Dementia risk in women ≥65 years when used with estrogens","Visual disturbances (e.g., retinal thrombosis) – discontinue if papilledema or retinal vascular lesions occur","Fluid retention – use with caution in conditions affected by edema (e.g., cardiac/renal disease, asthma, migraine, epilepsy)","Depression history – monitor and discontinue if severe depression recurs","Uterine bleeding irregularities – rule out malignancy if persistent abnormal bleeding"] |
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| Monitor for signs of thromboembolism, fluid retention, and pregnancy status. If inadvertent pregnancy, discontinue immediately. |
| Fertility Effects | May inhibit ovulation (high-dose). Low-dose may not consistently suppress ovulation. Indicated for secondary amenorrhea, abnormal uterine bleeding; off-label for luteal phase support. Contraceptive effect reversible within one menstrual cycle. |