(medroxyprogesterone acetate)
CLINICAL STUDIES
CLINICAL STUDIES
Effects on the Endometrium
In a 3-year, double-blind, placebo-controlled study of 356 nonhysterectomized, postmenopausal women between 45 and 64 years of age randomized to receive placebo (n=119), 0.625 mg conjugated estrogen only (n=119), or 0.625 mg conjugated estrogen plus cyclic PROVERA (n=118), results showed a reduced risk of endometrial hyperplasia in the treatment group receiving 10 mg PROVERA plus 0.625 mg conjugated estrogens compared to the group receiving 0.625 mg conjugated estrogens only. See Table 2.
| Histological Results | Placebo (n=119) | CEE † (n=119) | PROVERA ‡ + CEE (n=118) |
|---|---|---|---|
Normal/No hyperplasia (%) | 116 (97) | 45 (38) | 112 (95) |
Simple (cystic) hyperplasia (%) | 1 (1) | 33 (28) | 4 (3) |
Complex (adenomatous) hyperplasia (%) | 1 (1) | 27 (22) | 2 (2) |
Atypia (%) | 0 | 14 (12) | 0 |
Adenocarcinoma (%) | 1 (1) | 0 | 0 |
In a second 1-year study, 832 postmenopausal women between 45 and 65 years of age were treated with daily 0.625 mg conjugated estrogen (days 1–28), plus either 5 mg cyclic PROVERA or 10 mg cyclic PROVERA (days 15–28), or daily 0.625 mg conjugated estrogen only. The treatment groups receiving 5 or 10 mg cyclic PROVERA (days 15–28) plus daily conjugated estrogens showed a significantly lower rate of hyperplasia as compared to the conjugated estrogens only group. See Table 3.
| CEE * | MPA † + CEE * | ||
|---|---|---|---|
| (n=283) | MPA 5 mg (n=277) | MPA 10 mg (n=272) | |
Cystic hyperplasia (%) | 55 (19) | 3 (1) | 0 |
Adenomatous hyperplasia without atypia | 2 (1) | 0 | 0 |
Women's Health Initiative Studies
The WHI enrolled approximately 27,000 predominantly healthy postmenopausal women in two substudies to assess the risks and benefits of daily oral CE (0.625 mg)-alone or in combination with MPA (2.5 mg) compared to placebo in the prevention of certain chronic diseases. The primary endpoint was the incidence of coronary heart disease (CHD) (defined as nonfatal MI, silent MI and CHD death), with invasive breast cancer as the primary adverse outcome. A "global index" included the earliest occurrence of CHD, invasive breast cancer, stroke, PE, endometrial cancer (only in the CE plus MPA substudy), colorectal cancer, hip fracture, or death due to other cause. These substudies did not evaluate the effects of CE-alone or CE plus MPA on menopausal symptoms.
WHI Estrogen Plus Progestin Substudy
The WHI estrogen plus progestin substudy was stopped early. According to the predefined stopping rule, after an average follow-up of 5.6 years of treatment, the increased risk of invasive breast cancer and cardiovascular events exceeded the specified benefits included in the "global index." The absolute excess risk of events included in the "global index" was 19 per 10,000 women-years.
For those outcomes included in the WHI "global index" that reached statistical significance after 5.6 years of follow-up, the absolute excess risks per 10,000 women-years in the group treated with CE plus MPA were 7 more CHD events, 8 more strokes, 10 more PEs, and 8 more invasive breast cancers, while the absolute risk reduction per 10,000 women-years were 6 fewer colorectal cancers and 5 fewer hip fractures.
Results of the CE plus MPA substudy, which included 16,608 women (average 63 years of age, range 50 to 79; 83.9 percent White, 6.8 percent Black, 5.4 percent Hispanic, 3.9 percent Other) are presented in Table 4. These results reflect centrally adjudicated data after an average follow-up of 5.6 years.
| Event | Relative Risk CE/MPA vs placebo (95%nCI ‡) | CE/MPA n = 8,506 | Placebo n = 8,102 |
|---|---|---|---|
| Absolute Risk per 10,000 Women-Years | |||
| |||
CHD events | 1.23 (0.99–1.53) | 41 | 34 |
Non-fatal MI | 1.28 (1.00–1.63) | 31 | 25 |
CHD death | 1.10 (0.70–1.75) | 8 | 8 |
All strokes | 1.31 (1.03–1.68) | 33 | 25 |
Ischemic stroke | 1.44 (1.09–1.90) | 26 | 18 |
Deep vein thrombosis§ | 1.95 (1.43–2.67) | 26 | 13 |
Pulmonary embolism | 2.13 (1.45–3.11) | 18 | 8 |
Invasive breast cancer¶ | 1.24 (1.01–1.54) | 41 | 33 |
Colorectal cancer | 0.61 (0.42–0.87) | 10 | 16 |
Endometrial cancer§ | 0.81 (0.48–1.36) | 6 | 7 |
Cervical cancer§ | 1.44 (0.47–4.42) | 2 | 1 |
Hip fracture | 0.67 (0.47–0.96) | 11 | 16 |
Vertebral fractures§ | 0.65 (0.46–0.92) | 11 | 17 |
Lower arm/wrist fractures§ | 0.71 (0.59–0.85) | 44 | 62 |
Total fractures§ | 0.76 (0.69–0.83) | 152 | 199 |
Overall mortality# | 1.00 (0.83–1.19) | 52 | 52 |
Global IndexÞ | 1.13 (1.02–1.25) | 184 | 165 |
Timing of the initiation of estrogen plus progestin therapy relative to the start of menopause may affect the overall risk benefit profile. The WHI estrogen plus progestin substudy stratified by age showed in women 50 to 59 years of age a nonsignificant trend toward reduced risk in overall mortality [hazard ration (HR) 0.69 (95 percent CI, 0.44–1.07)].
Women's Health Initiative Memory Study
The WHIMS estrogen plus progestin ancillary study of WHI enrolled 4,532 predominantly healthy postmenopausal women 65 years of age and older (47 percent were aged 65 to 69 years of age, 35 percent were 70 to 74 years of age, and 18 percent were 75 years of age and older) to evaluate the effects of daily CE (0.625 mg) plus MPA (2.5 mg) on the incidence of probable dementia (primary outcome) compared to placebo.
After an average follow-up of 4 years, the relative risk of probable dementia for CE plus MPA versus placebo was 2.05 (95 percent CI, 1.21–3.48). The absolute risk of probable dementia for CE plus MPA versus placebo was 45 versus 33 per 10,000 women-years. Probable dementia as defined in this study included Alzheimer's disease (AD), vascular dementia (VaD) and mixed type (having features of both AD and VaD). The most common classification of probable dementia in the treatment group and the placebo group was AD. Since the ancillary study was conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women. (See WARNINGS, Probable Dementia and PRECAUTIONS, Geriatric Use).
PATIENT INFORMATION
PATIENT INFORMATION
PROVERA
(pro-VE-rah)
(medroxyprogesterone acetate tablets, USP)
Read this Patient Information before you start taking PROVERA and read what you get each time you refill your PROVERA prescription. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
What is the most important information I should know about PROVERA (a progestin hormone)?
- •
- Do not use estrogens with progestins to prevent heart disease, heart attacks, strokes, or dementia (decline in brain function).
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- Using estrogens with progestins may increase your chance of getting heart attacks, strokes, breast cancer, and blood clots.
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- Using estrogens with progestins may increase your chance of getting dementia, based on a study of women age 65 years or older.
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- You and your healthcare provider should talk regularly about whether you still need treatment with PROVERA.
What is PROVERA?
PROVERA is a medicine that contains medroxyprogesterone acetate, a progestin hormone.
What is PROVERA used for?
PROVERA is used to:
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- Treat menstrual periods that have stopped or to treat abnormal uterine bleeding. Women with a uterus who are not pregnant, who stop having regular menstrual periods or who begin to have irregular menstrual periods may have a drop in their progesterone level. Talk with your healthcare provider about whether PROVERA is right for you.
- •
- Reduce your chances of getting cancer of the uterus (womb). In postmenopausal women with a uterus who use estrogens, taking progestin in combination with estrogen will reduce your chance of getting cancer of the uterus (womb).
Who should not take PROVERA?
Do not start taking PROVERA if you:
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- have unusual vaginal bleeding
- •
- currently have or have had certain cancers
Estrogen plus progestin may increase your chance of getting certain types of cancers, including cancer of the breast. If you have or have had cancer, talk with your healthcare provider about whether you should use PROVERA. - •
- had a stroke or heart attack
- •
- currently have or have had blood clots
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- currently have or have had liver problems
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- are allergic to PROVERA or any of its ingredients
See the list of ingredients in PROVERA at the end of this leaflet. - •
- think you may be pregnant
PROVERA is not for pregnant women. If you think you may be pregnant, you should have a pregnancy test and know the results. Do not use PROVERA if the test is positive and talk to your healthcare provider. There may be an increased risk of minor birth defects in children whose mothers take PROVERA during the first 4 months of pregnancy.
PROVERA should not be used as a test for pregnancy.
What should I tell my healthcare provider before taking PROVERA? Before you take PROVERA, tell your healthcare provider if you:
- •
- have any other medical problems
Your healthcare provider may need to check you more carefully if you have certain conditions such as asthma (wheezing), epilepsy (seizures), diabetes, migraine, endometriosis (severe pelvic pain), lupus, or problems with your heart, liver, thyroid, kidneys, or have high calcium in your blood. - •
- are going to have surgery or will be on bed rest
Your healthcare provider will let you know if you need to stop taking PROVERA. - •
- are breast feeding
The hormone in PROVERA can pass into your breast milk.
Tell your healthcare provider about all the medicines you take including prescription and nonprescription medicines, vitamins, and herbal supplements. Some medicines may affect how PROVERA works. PROVERA may also affect how other medicines work.
How should I take PROVERA?
Start at the lowest dose and talk to your healthcare provider about how well that dose is working for you. The lowest effective dose of PROVERA has not been determined. You and your healthcare provider should talk regularly (every 3 to 6 months) about the dose you are taking and whether you still need treatment with PROVERA.
- 1.
- Absence of menstrual period: PROVERA may be given in doses ranging from 5 to 10 mg daily for 5 to 10 days.
- 2.
- Abnormal Uterine Bleeding: PROVERA may be given in doses ranging from 5 to 10 mg daily for 5 to 10 days.
- 3.
- Overgrowth of the lining of the uterus: When used in combination with oral conjugated estrogens in postmenopausal women with a uterus, PROVERA may be given in doses ranging from 5 or 10 mg daily for 12 to 14 straight days per month.
What are the possible side effects of PROVERA?
The following side effects have been reported with the use of PROVERA alone:
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- breast tenderness
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- breast milk secretion
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- breakthrough bleeding
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- spotting (minor vaginal bleeding)
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- irregular periods
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- amenorrhea (absence of menstrual periods)
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- vaginal secretions
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- headaches
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- nervousness
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- dizziness
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- depression
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- insomnia, sleepiness, fatigue
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- premenstrual syndrome-like symptoms
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- thrombophlebitis (inflamed veins)
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- blood clot
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- itching, hives, skin rash
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- acne
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- hair loss, hair growth
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- abdominal discomfort
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- nausea
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- bloating
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- fever
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- increase in weight
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- swelling
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- changes in vision and sensitivity to contact lenses
Call your healthcare provider right away if you get hives, problems breathing, swelling of the face, mouth, tongue or neck
The following side effects have been reported with the use of PROVERA with an estrogen.
Side effects are grouped by how serious they are and how often they happen when you are treated.
Serious, but less common side effects include:
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- heart attack
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- stroke
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- blood clots
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- dementia
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- breast cancer
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- cancer of the uterus
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- cancer of the ovary
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- high blood pressure
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- high blood sugar
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- gallbladder disease
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- liver problems
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- changes in your thyroid hormone levels
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- enlargements of benign tumors ("fibroids")
Call your healthcare provider right away if you get any of the following warning signs or any other unusual symptoms that concern you:
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- new breast lumps
- •
- unusual vaginal bleeding
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- changes in vision and speech
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- sudden new severe headaches
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- severe pains in your chest or legs with or without shortness of breath, weakness and fatigue
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- memory loss or confusion
Less serious, but common side effects include:
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- headache
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- breast pain
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- irregular vaginal bleeding or spotting
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- stomach or abdominal cramps, bloating
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- nausea and vomiting
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- hair loss
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- fluid retention
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- vaginal yeast infection
These are not all the possible side effects of PROVERA with or without estrogen. For more information, ask your healthcare provider or pharmacist for advice about side effects. Tell your healthcare provider if you have side effect that bothers you or does not go away. You may report side effects to Pfizer at 1-800-438-1985 or FDA at 1-800-FDA-1088.
What can I do to lower my chances of a serious side effect with PROVERA?
- •
- Talk with your healthcare provider regularly about whether you should continue taking PROVERA. The addition of a progestin is generally recommended for women with a uterus to reduce the chance of getting cancer of the uterus (womb).
- •
- See your healthcare provider right away if you get vaginal bleeding while taking PROVERA.
- •
- Have a pelvic exam, breast exam and mammogram (breast X-ray) every year unless your healthcare provider tells you something else. If members of your family have had breast cancer or if you have ever had breast lumps or an abnormal mammogram, you may need to have breast exams more often.
- •
- If you have high blood pressure, high cholesterol (fat in the blood), diabetes, are overweight, or if you use tobacco, you may have a higher chance of getting heart disease. Ask your healthcare provider for ways to lower your chance of getting heart disease.
General information about safe and effective use of PROVERA
- •
- Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets.
- •
- Do not take PROVERA for conditions for which it was not prescribed.
- •
- Do not give PROVERA to other people, even if they have the same symptoms you have. It may harm them.
Keep PROVERA out of the reach of children.
This leaflet provides a summary of the most important information about PROVERA. If you would like more information, talk with your health care provider or pharmacist. You can ask for information about PROVERA that is written for health professionals. You can get more information by calling the toll-free number, 1-800-438-1985.
What are the ingredients in PROVERA?
Each PROVERA tablet for oral administration contains 2.5 mg, 5 mg or 10 mg of medroxyprogesterone acetate and the following inactive ingredients:
Calcium stearate, corn starch, lactose, mineral oil, sucrose and talc.
The 2.5 mg tablets also contain: FD&C Yellow No. 6.
The 5 mg tablets also contain: FD&C Blue No.2 – Aluminum Lake.
This product's labeling may have been updated. For the most recent prescribing information, please visit www.pfizer.com.
Rx only
LAB-0365-9.0
Revised March 2024
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