(medroxyprogesterone acetate)
PRECAUTIONS
PRECAUTIONS
A. General
1. Addition of a progestin when a woman has not had a hysterectomy
Studies of the addition of a progestin for 10 or more days of a cycle of estrogen administration, or daily with estrogen in a continuous regimen, have reported a lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone. Endometrial hyperplasia may be a precursor to endometrial cancer.
There are, however, possible risks that may be associated with the use of progestins with estrogens compared to estrogen-alone regimens. These include an increased risk of breast cancer.
2. Unexpected abnormal vaginal bleeding
In cases of unexpected abnormal vaginal bleeding, adequate diagnostic measures are indicated.
3. Elevated blood pressure
Blood pressure should be monitored at regular intervals with estrogen plus progestin therapy.
4. Hypertriglyceridemia
In women with pre-existing hypertriglyceridemia, estrogen plus progestin therapy may be associated with elevations of plasma triglycerides leading to pancreatitis. Consider discontinuation of treatment if pancreatitis occurs.
5. Hepatic Impairment and/or past history of cholestatic jaundice
Estrogens plus progestins may be poorly metabolized in women with impaired liver function. For women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, caution should be exercised, and in the case of recurrence, medication should be discontinued.
6. Fluid Retention
Progestins may cause some degree of fluid retention. Women who have conditions which might be influenced by this factor, such as cardiac or renal impairment, warrant careful observation when estrogen plus progestin are prescribed.
B. Patient Information
Physicians are advised to discuss the Patient Information leaflet with women for whom they prescribe PROVERA.
There may be an increased risk of minor birth defects in children whose mothers are exposed to progestins during the first trimester of pregnancy. The possible risk to the male baby is hypospadias, a condition in which the opening of the penis is on the underside rather than the tip of the penis. This condition occurs naturally in approximately 5 to 8 per 1000 male births. The risk may be increased with exposure to PROVERA. Enlargement of the clitoris and fusion of the labia may occur in female babies. However, a clear association between hypospadias, clitoral enlargement and labial fusion with use of PROVERA has not been established.
Inform the patient of the importance of reporting exposure to PROVERA in early pregnancy.
C. Drug-Laboratory Test Interactions
The following laboratory results may be altered by the use of estrogen plus progestin therapy:
- 1.
- Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of anti-factor Xa and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity.
- 2.
- Increased thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels as measured by protein-bound iodine (PBI), T4 levels (by column or by radioimmunoassay) or T3 levels by radioimmunoassay, T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Women on thyroid replacement therapy may require higher doses of thyroid hormone.
- 3.
- Other binding proteins may be elevated in serum, for example, corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG) leading to increased circulating corticosteroid and sex steroids, respectively. Free hormone concentrations, such as testosterone and estradiol, may be decreased. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).
- 4.
- Increased plasma high-density lipoprotein (HDL) and HDL2 cholesterol subfraction concentrations, reduced low-density lipoprotein (LDL) cholesterol concentration, increased triglycerides levels.
- 5.
- Impaired glucose tolerance.
D. Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity
Long-term intramuscular administration of medroxyprogesterone acetate has been shown to produce mammary tumors in beagle dogs. There was no evidence of a carcinogenic effect associated with the oral administration of medroxyprogesterone acetate to rats and mice.
Long-term continuous administration of estrogen plus progestin therapy has shown an increased risk of breast cancer and ovarian cancer. (See WARNINGS and PRECAUTIONS.)
E. Pregnancy
PROVERA should not be used during pregnancy. (See CONTRAINDICATIONS.)
There may be increased risks for hypospadias, clitoral enlargement and labial fusion in children whose mothers are exposed to PROVERA during the first trimester of pregnancy. However, a clear association between these conditions with use of PROVERA has not been established.
F. Nursing Mothers
PROVERA should not be used during lactation. Detectable amounts of progestin have been identified in the breast milk of nursing mothers receiving progestins.
G. Pediatric Use
PROVERA tablets are not indicated in children. Clinical studies have not been conducted in the pediatric population.
H. Geriatric Use
There have not been sufficient numbers of geriatric women involved in clinical studies utilizing PROVERA alone to determine whether those over 65 years of age differ from younger subjects in their response to PROVERA alone.
The Women's Health Initiative Studies
In the WHI estrogen plus progestin substudy (daily CE [0.625 mg] plus MPA [2.5 mg] versus placebo), there was a higher relative risk of nonfatal stroke and invasive breast cancer in women greater than 65 years of age. (See CLINICAL STUDIES.)
The Women's Health Initiative Memory Study
In the WHIMS ancillary studies of postmenopausal women 65 to 79 years of age, there was an increased risk of developing probable dementia in women receiving estrogen-alone or estrogen plus progestin when compared to placebo. (See WARNINGS, Probable Dementia.)
Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women. (See WARNINGS, Probable Dementia.)
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).
- •
- Using estrogens with progestins may increase your chance of getting heart attacks, strokes, breast cancer, and blood clots.
- •
- Using estrogens with progestins may increase your chance of getting dementia, based on a study of women age 65 years or older.
- •
- 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:
- •
- 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:
- •
- 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
- •
- currently have or have had liver problems
- •
- 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:
- •
- breast tenderness
- •
- breast milk secretion
- •
- breakthrough bleeding
- •
- spotting (minor vaginal bleeding)
- •
- irregular periods
- •
- amenorrhea (absence of menstrual periods)
- •
- vaginal secretions
- •
- headaches
- •
- nervousness
- •
- dizziness
- •
- depression
- •
- insomnia, sleepiness, fatigue
- •
- premenstrual syndrome-like symptoms
- •
- thrombophlebitis (inflamed veins)
- •
- blood clot
- •
- itching, hives, skin rash
- •
- acne
- •
- hair loss, hair growth
- •
- abdominal discomfort
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- nausea
- •
- bloating
- •
- fever
- •
- increase in weight
- •
- swelling
- •
- 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:
- •
- heart attack
- •
- stroke
- •
- blood clots
- •
- dementia
- •
- breast cancer
- •
- cancer of the uterus
- •
- cancer of the ovary
- •
- high blood pressure
- •
- high blood sugar
- •
- gallbladder disease
- •
- liver problems
- •
- changes in your thyroid hormone levels
- •
- 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:
- •
- new breast lumps
- •
- unusual vaginal bleeding
- •
- changes in vision and speech
- •
- sudden new severe headaches
- •
- severe pains in your chest or legs with or without shortness of breath, weakness and fatigue
- •
- memory loss or confusion
Less serious, but common side effects include:
- •
- headache
- •
- breast pain
- •
- irregular vaginal bleeding or spotting
- •
- stomach or abdominal cramps, bloating
- •
- nausea and vomiting
- •
- hair loss
- •
- fluid retention
- •
- 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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