(medroxyprogesterone acetate)
CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY
Medroxyprogesterone acetate (MPA) administered orally or parenterally in the recommended doses to women with adequate endogenous estrogen, transforms proliferative into secretory endometrium. Androgenic and anabolic effects have been noted, but the drug is apparently devoid of significant estrogenic activity. While parenterally administered MPA inhibits gonadotropin production, which in turn prevents follicular maturation and ovulation, available data indicate that this does not occur when the usually recommended oral dosage is given as single daily doses.
Pharmacokinetics
The pharmacokinetics of MPA were determined in 20 postmenopausal women following a single-dose administration of eight PROVERA 2.5 mg tablets or a single administration of two PROVERA 10 mg tablets under fasting conditions. In another study, the steady-state pharmacokinetics of MPA were determined under fasting conditions in 30 postmenopausal women following daily administration of one PROVERA 10 mg tablet for 7 days. In both studies, MPA was quantified in serum using a validated gas chromatography-mass spectrometry (GC-MS) method. Estimates of the pharmacokinetic parameters of MPA after single and multiple doses of PROVERA tablets were highly variable and are summarized in Table 1.
| Tablet Strength | C max (ng/mL) | T max (h) | Auc 0–(∞) (ng∙h/mL) | t 1/2 (h) | Vd/f (L) | CL/f (mL/min) |
|---|---|---|---|---|---|---|
| ||||||
Single Dose | ||||||
2 × 10 mg | 1.01 (0.599) | 2.65 (1.41) | 6.95 (3.39) | 12.1 (3.49) | 78024 | 64110 |
8 × 2.5 mg | 0.805 (0.413) | 2.22 (1.39) | 5.62 (2.79) | 11.6 (2.81) | 62748 | 74123 |
Multiple Dose | ||||||
10 mg * | 0.71 (0.35) | 2.83 (1.83) | 6.01 (3.16) | 16.6 (15.0) | 40564 | 41963 |
A. Absorption:
No specific investigation on the absolute bioavailability of MPA in humans has been conducted. MPA is rapidly absorbed from the gastrointestinal tract, and maximum MPA concentrations are obtained between 2 to 4 hours after oral administration.
Administration of PROVERA with food increases the bioavailability of MPA. A 10 mg dose of PROVERA, taken immediately before or after a meal, increased MPA Cmax (50 to 70%) and AUC (18 to 33%). The half-life of MPA was not changed with food.
B. Distribution:
MPA is approximately 90% protein bound, primarily to albumin; no MPA binding occurs with sex hormone binding globulin.
C. Metabolism:
Following oral dosing, MPA is extensively metabolized in the liver via hydroxylation, with subsequent conjugation and elimination in the urine.
D. Excretion:
Most MPA metabolites are excreted in the urine as glucuronide conjugates with only minor amounts excreted as sulfates.
E. Specific Populations
Hepatic Insufficiency
MPA is almost exclusively eliminated via hepatic metabolism. In 14 patients with advanced liver disease, MPA disposition was significantly altered (reduced elimination). In patients with fatty liver, the mean percent dose excreted in the 24-hour urine as intact MPA after a 10 mg or 100 mg dose was 7.3% and 6.4%, respectively.
F. Drug Interactions
Medroxyprogesterone acetate (MPA) is metabolized in-vitro primarily by hydroxylation via the CYP3A4. Specific drug-drug interaction studies evaluating the clinical effects with CYP3A4 inducers or inhibitors on MPA have not been conducted. Inducers and/or inhibitors of CYP3A4 may affect the metabolism of MPA.
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)?
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- 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.
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- 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
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- 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
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- 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:
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- 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
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- 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?
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- 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.
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- 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.
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- 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
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- Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets.
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- Do not take PROVERA for conditions for which it was not prescribed.
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- 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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