(medroxyprogesterone acetate injectable suspension, for intramuscular use)
5 WARNINGS AND PRECAUTIONS
5 WARNINGS AND PRECAUTIONS
5.1 Loss of Bone Mineral Density
Use of Depo-Provera CI reduces serum estrogen levels and is associated with significant loss of bone mineral density (BMD). This loss of BMD is of particular concern during adolescence and early adulthood, a critical period of bone accretion. It is unknown if use of Depo-Provera CI by younger women will reduce peak bone mass and increase the risk for osteoporotic fracture in later life.
A study to assess the reversibility of loss of BMD in adolescents was conducted with Depo-Provera CI. After discontinuing Depo-Provera CI in these adolescents, mean BMD loss at the total hip and femoral neck did not fully recover by 5 years (60 months) post-treatment in the sub-group of adolescents who were treated for more than 2 years [see Clinical Studies (14.3)]. Similarly, in adults, there was only partial recovery of mean BMD at the total hip, femoral neck, and lumbar spine towards baseline by 2 years post-treatment [see Clinical Studies (14.2)].
The use of Depo-Provera CI is not recommended as a long-term (i.e., longer than 2 years) birth control method unless other options are considered inadequate. BMD should be evaluated when a woman needs to continue to use Depo-Provera CI long-term. In adolescents, interpretation of BMD results should take into account patient age and skeletal maturity.
Other birth control methods should be considered in the risk/benefit analysis for the use of Depo-Provera CI in women with osteoporosis risk factors. Depo-Provera CI can pose an additional risk in patients with risk factors for osteoporosis (e.g., metabolic bone disease, chronic alcohol and/or tobacco use, anorexia nervosa, strong family history of osteoporosis or chronic use of drugs that can reduce bone mass such as anticonvulsants or corticosteroids).
5.2 Thromboembolic Disorders
There have been reports of serious thrombotic events in women using Depo-Provera CI (150 mg). However, Depo-Provera CI has not been causally associated with the induction of thrombotic or thromboembolic disorders. Any patient who develops thrombosis while undergoing therapy with Depo-Provera CI should discontinue treatment unless she has no other acceptable options for birth control.
Do not re-administer Depo-Provera CI pending examination if there is a sudden partial or complete loss of vision or if there is a sudden onset of proptosis, diplopia, or migraine. Do not re-administer if examination reveals papilledema or retinal vascular lesions.
5.3 Cancer Risks
Breast Cancer
Women who have or have had a history of breast cancer should not use hormonal contraceptives, including Depo-Provera CI, because breast cancer may be hormonally sensitive [see Contraindications (4)]. Women with a strong family history of breast cancer should be monitored with particular care.
The results of five large case-control studies assessing the association between depo-medroxyprogesterone acetate (DMPA) use and the risk of breast cancer are summarized in Figure 1. Three of the studies suggest a slightly increased risk of breast cancer in the overall population of users; these increased risks were statistically significant in one study. One recent US study1 evaluated the recency and duration of use and found a statistically significantly increased risk of breast cancer in recent users (defined as last use within the past five years) who used DMPA for 12 months or longer; this is consistent with results of a previous study2.
Figure 1. Risk estimates for breast cancer in DMPA users
Based on the published SEER-18 2011 incidence rate (age-adjusted to the 2000 US Standard Population) of breast cancer for US women, all races, age 20 to 49 years, a doubling of risk would increase the incidence of breast cancer in women who use Depo-Provera CI from about 72 to about 144 cases per 100,000 women.
Cervical Cancer
A statistically nonsignificant increase in relative risk (RR) estimates of invasive squamous-cell cervical cancer has been associated with the use of Depo-Provera CI in women who were first exposed before the age of 35 years (RR 1.22 to 1.28 and 95% CI 0.93 to 1.70). The overall, nonsignificant RR of invasive squamous-cell cervical cancer in women who ever used Depo-Provera CI was estimated to be 1.11 (95% CI 0.96 to 1.29). No trends in risk with duration of use or times since initial or most recent exposure were observed.
5.4 Meningioma
Cases of meningiomas have been reported following repeated administration of medroxyprogesterone acetate, primarily with long term use. Monitor patients on Depo-Provera CI for signs and symptoms of meningioma. Discontinue Depo-Provera CI if a meningioma is diagnosed.
5.5 Ectopic Pregnancy
Be alert to the possibility of an ectopic pregnancy among women using Depo-Provera CI who become pregnant or complain of severe abdominal pain.
5.6 Anaphylaxis and Anaphylactoid Reaction
Anaphylaxis and anaphylactoid reaction have been reported with the use of Depo-Provera CI. Institute emergency medical treatment if an anaphylactic reaction occurs.
5.7 Injection Site Reactions
Injection site reactions have been reported with use of Depo-Provera CI [see Adverse Reactions (6.2)]. Persistent injection site reactions may occur after administration of Depo-Provera CI due to inadvertent subcutaneous administration or release of the drug into the subcutaneous space while removing the needle [see Dosage and Administration (2.1)].
5.8 Liver Function
Discontinue Depo-Provera CI use if jaundice or acute or chronic disturbances of liver function develop. Do not resume use until markers of liver function return to normal and Depo-Provera CI causation has been excluded.
5.9 Convulsions
There have been a few reported cases of convulsions in patients who were treated with Depo-Provera CI. Association with drug use or pre-existing conditions is not clear.
5.10 Depression
Monitor patients who have a history of depression and do not re-administer Depo-Provera CI if depression recurs.
5.11 Bleeding Irregularities
Most women using Depo-Provera CI experience disruption of menstrual bleeding patterns. Altered menstrual bleeding patterns include amenorrhea, irregular or unpredictable bleeding or spotting, prolonged spotting or bleeding, and heavy bleeding. Rule out the possibility of organic pathology if abnormal bleeding persists or is severe, and institute appropriate treatment.
As women continue using Depo-Provera CI, fewer experience irregular bleeding and more experience amenorrhea. In clinical studies of Depo-Provera CI, by month 12 amenorrhea was reported by 55% of women, and by month 24, amenorrhea was reported by 68% of women using Depo-Provera CI.
5.12 Weight Gain
Women tend to gain weight while on therapy with Depo-Provera CI. From an initial average body weight of 136 lb, women who completed 1 year of therapy with Depo-Provera CI gained an average of 5.4 lb. Women who completed 2 years of therapy gained an average of 8.1 lb. Women who completed 4 years gained an average of 13.8 lb. Women who completed 6 years gained an average of 16.5 lb. Two percent of women withdrew from a large-scale clinical trial because of excessive weight gain.
5.13 Carbohydrate Metabolism
A decrease in glucose tolerance has been observed in some patients on Depo-Provera CI treatment. Monitor diabetic patients carefully while receiving Depo-Provera CI.
5.14 Fluid Retention
Because progestational drugs including Depo-Provera CI may cause some degree of fluid retention, monitor patients with conditions that might be influenced by this condition, such as epilepsy, migraine, asthma, and cardiac or renal dysfunction.
5.15 Return of Fertility
Return to ovulation and fertility is likely to be delayed after stopping Depo-Provera CI. In a large US study of women who discontinued use of Depo-Provera CI to become pregnant, data are available for 61% of them. Of the 188 women who discontinued the study to become pregnant, 114 became pregnant. Based on Life-Table analysis of these data, it is expected that 68% of women who do become pregnant may conceive within 12 months, 83% may conceive within 15 months, and 93% may conceive within 18 months from the last injection. The median time to conception for those who do conceive is 10 months following the last injection with a range of 4 to 31 months, and is unrelated to the duration of use. No data are available for 39% of the patients who discontinued Depo-Provera CI to become pregnant and who were lost to follow-up or changed their mind.
5.16 Sexually Transmitted Infections
Patients should be counseled that Depo-Provera CI does not protect against HIV infection (AIDS) and other sexually transmitted infections.
5.17 Monitoring
A woman who is taking hormonal contraceptive should have a yearly visit with her healthcare professional for a blood pressure check and for other indicated healthcare.
5.18 Interference with Laboratory Tests
The use of Depo-Provera CI may change the results of some laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins [see Drug Interactions (7.2)].
PATIENT INFORMATION
Patient Information
Depo-Provera® (DEP-po pro-VAIR-ah) CI
(medroxyprogesterone acetate injectable suspension)
Contraceptive Injection
Read this Patient Information carefully before you decide if Depo-Provera CI is right for you. This information does not take the place of talking with your gynecologist or other healthcare professional who specializes in women's health. If you have any questions about Depo-Provera CI, ask your healthcare professional. You should also learn about other birth control methods to choose the one that is best for you.
What is the most important information I should know about Depo-Provera CI?
Depo-Provera CI can cause serious side effects, including:
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- Use of Depo-Provera CI may cause you to lose calcium stored in your bone and decrease your bone mass. The longer you use Depo-Provera CI, the greater your loss of calcium from your bones. Your bones may not recover completely when you stop using Depo-Provera CI.
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- If you use Depo-Provera CI continuously for a long time (for more than 2 years), it may increase the risk of weak, porous bones (osteoporosis) that could increase the risk of broken bones, especially after menopause.
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- You should not use Depo-Provera CI for more than two years unless you cannot use other birth control methods.
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- It is not known if your risk of developing osteoporosis is greater if you are a teenager or young adult when you start to use Depo-Provera CI (see "What are the possible side effects of Depo-Provera CI?").
Depo-Provera CI is intended to prevent pregnancy. Depo-Provera CI does not protect against HIV infection (AIDS) and other sexually transmitted infections (STIs).
What is Depo-Provera CI?
Depo-Provera CI is a progestin hormone birth control method that is given by injection (a shot) to prevent pregnancy.
How well does Depo-Provera CI work?
Your chance of getting pregnant depends on how well you follow the directions for taking your Depo-Provera CI. The more carefully you follow the directions (such as returning every 3 months for your next injection), the less chance you have of getting pregnant.
In clinical studies, about 1 out of 100 women got pregnant during the first year that they used Depo-Provera CI.
The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant.
How should I take Depo-Provera CI?
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- Depo-Provera CI is given by your healthcare professional as a shot into your muscle (intramuscular injection). The shot is given in your buttock or upper arm 1 time every 3 months. At the end of the 3 months, you will need to return to your healthcare professional for your next injection in order to continue your protection against pregnancy.
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- To make sure that you are not pregnant before you take Depo-Provera CI, the first injection should be given only:
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- during the first 5 days of a normal menstrual period, or
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- within the first 5 days after giving birth, if you are not breastfeeding, or
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- at the 6th week after giving birth, if you are feeding your baby only breastmilk.
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- Depo-Provera CI may be given at other times than those listed above, but you will likely need to have a pregnancy test first to show that you are not pregnant.
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- During treatment with Depo-Provera CI, you should see your healthcare professional every year for a blood pressure check and other healthcare needs.
Who Should Not Use Depo-Provera CI?
Do not use Depo-Provera CI if you:
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- have bleeding from your vagina that has not been explained
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- have breast cancer now or in the past, or think you have breast cancer
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- have had a stroke
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- ever had blood clots in your arms, legs or lungs
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- have problems with your liver or liver disease
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- are allergic to medroxyprogesterone acetate or any of the other ingredients in Depo-Provera CI. See the end of this leaflet for a complete list of ingredients in Depo-Provera CI.
What should I tell my healthcare professional before taking Depo-Provera CI?
Before taking Depo-Provera CI, tell your healthcare professional if you have:
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- risk factors for weak bones (osteoporosis) such as bone disease, use alcohol or smoke regularly, anorexia nervosa, or a strong family history of osteoporosis
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- irregular or lighter than usual menstrual periods
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- breast cancer now or in the past, or think you have breast cancer
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- a family history of breast cancer
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- an abnormal mammogram (breast X-ray), lumps in your breasts, or bleeding from your nipples
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- have or have ever had a type of usually benign brain tumor called a meningioma
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- kidney problems
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- high blood pressure
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- had a stroke
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- had blood clots in your arms, legs or lungs
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- migraine headaches
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- asthma
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- epilepsy (convulsions or seizures)
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- diabetes
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- depression or a history of depression
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- any other medical conditions
If you are breastfeeding or plan to breastfeed, Depo-Provera CI can pass into your breast milk. Talk to your healthcare professional about the best way to feed your baby if you take Depo-Provera CI.
Tell your healthcare professional about all of the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.
Depo-Provera CI and certain other medicines may affect each other, causing serious side effects. Sometimes the doses of other medicines may need to be changed while you are taking Depo-Provera CI.
Some medicines may make Depo-Provera CI less effective at preventing pregnancy, including those listed below.
Especially tell your healthcare professional if you take:
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- medicine to help you sleep
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- bosentan
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- medicine for seizures
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- griseofulvin
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- an antibiotic
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- medicine for HIV (AIDS)
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- St. John's wort
Know the medicines you take. Keep a list of your medicines with you to show your healthcare professional or pharmacist before you first start taking Depo-Provera CI or when you get a new medicine.
Follow your healthcare professional's instructions about using a back-up method of birth control if you are taking medicines that may make Depo-Provera CI less effective.
What are the possible side effects of Depo-Provera CI?
Depo-Provera CI can cause serious side effects, including:
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- Effect on the bones: See "What is the most important information I should know about Depo-Provera CI?".
Teenage years are the most important years to gain bone strength. The decrease in calcium in your bones is of most concern if you are a teenager or have the following problems:- •
- bone disease
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- an eating disorder (anorexia nervosa)
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- a strong family history of osteoporosis
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- you take a drug that can lower the amount of calcium in your bones (drugs for epilepsy or steroid drugs)
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- you drink a lot of alcohol (more than 2 drinks a day)
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- you smoke
- If you need a birth control method for more than 2 years, your healthcare professional may switch you to another birth control method instead of using Depo-Provera CI. If you continue using Depo-Provera CI, your healthcare professional may ask you to have a bone test, especially if you have other risks for weak bones.
- When Depo-Provera CI is stopped, your bones may start to regain calcium. However, in a study of teenage girls who used Depo-Provera CI for more than 2 years, their hip bones did not completely recover by 5 years after they stopped using Depo-Provera CI. Taking calcium and Vitamin D and exercising daily may lessen the loss of calcium from your bones.
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- possible increased risk of breast cancer. Women who use Depo-Provera CI may have a slightly increased risk of breast cancer compared to non-users.
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- blood clots in your arms, legs, lungs, and eyes
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- stroke
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- a pregnancy outside of your uterus (ectopic pregnancy). Ectopic pregnancy is a medical emergency that often requires surgery. Ectopic pregnancy can cause internal bleeding, infertility, and even death.
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- allergic reactions. Severe allergic reactions have been reported in some women using Depo-Provera CI.
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- loss of vision or other eye problems
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- migraine headaches
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- possible increased risk for growth of a meningioma (a usually benign brain tumor), primarily when the product is used for a long time.
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- depression
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- convulsions or seizures
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- liver problems
Call your healthcare professional right away if you have:
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- sharp chest pain, coughing up blood, or sudden shortness of breath (indicating a possible clot in the lung)
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- sudden severe headache or vomiting, dizziness or fainting, problems with your eyesight or speech, weakness, or numbness in an arm or leg (indicating a possible stroke)
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- severe pain or swelling in the calf (indicating a possible clot in the leg)
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- sudden blindness, partial or complete (indicating a possible clot in the blood vessels of the eye)
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- unusually heavy vaginal bleeding
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- severe pain or tenderness in the lower abdominal area
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- persistent pain, pus, or bleeding at the injection site
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- yellowing of the eyes or skin
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- hives
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- difficulty breathing
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- swelling of the face, mouth, tongue or neck
The most common side effects of Depo-Provera CI include:
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- irregular vaginal bleeding, such as lighter or heavier menstrual bleeding, or continued spotting
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- weight gain. You may experience weight gain while you are using Depo-Provera CI. About two-thirds of the women who used Depo-Provera CI in the clinical trials reported a weight gain of about 5 pounds during the first year of use. You may continue to gain weight after the first year. Women who used Depo-Provera CI for 2 years gained an average of 8 pounds over those 2 years.
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- abdominal pain
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- headache
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- weakness
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- tiredness
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- nervousness
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- dizziness
Tell your healthcare professional if you have any side effect that bothers you or does not go away.
These are not all the possible side effects of Depo-Provera CI. For more information, ask your healthcare professional or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1- 800-FDA-1088.
What other information should I know before choosing Depo-Provera CI?
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- Pregnancy. When you take Depo-Provera CI every 3 months, your chance of getting pregnant is very low. You could miss a period or have a light period and not be pregnant. If you miss 1 or 2 periods and think you might be pregnant, see your healthcare professional as soon as possible. You should not use Depo-Provera CI if you are pregnant. However, Depo-Provera CI taken by accident during pregnancy does not seem to cause birth defects.
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- Nursing Mothers. Although Depo-Provera CI can be passed to the nursing baby in the breast milk, no harmful effects on babies have been found. Depo-Provera CI does not stop the breasts from producing milk, so it can be used by nursing mothers. However, to minimize the amount of Depo-Provera CI that is passed to the baby in the first weeks after birth, you should wait until your baby is 6 weeks old before you start using Depo-Provera CI for birth control.
How will Depo-Provera CI change my periods?
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- Change in normal menstrual cycle. The side effect reported most frequently by women who use Depo-Provera CI for birth controls is a change in their normal menstrual cycle. During the first year of using Depo-Provera CI, you might have one or more of the following changes:
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- irregular or unpredictable bleeding or spotting
- o
- an increase or decrease in menstrual bleeding
- o
- no bleeding at all. In clinical studies of Depo-Provera CI, 55% of women reported no menstrual bleeding (amenorrhea) after one year of use and 68% of women reported no menstrual bleeding after two years of use.
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- Missed period. During the time you are using Depo-Provera CI for birth controls, you may skip a period, or your periods may stop completely. If you have been receiving your shot of Depo-Provera CI regularly every 3 months, then you are probably not pregnant. However, if you think that you may be pregnant, see your healthcare professional.
Unusually heavy or continuous bleeding is not a usual effect of Depo-Provera CI and if this happens you should see your healthcare professional right away.
With continued use of Depo-Provera CI, bleeding usually decreases and many women stop having periods completely. When you stop using Depo-Provera CI your menstrual period will usually, in time, return to its normal cycle.
What if I want to become pregnant?
Because Depo-Provera CI is a long-acting birth control method, it takes some time after your last shot for its effect to wear off. Most women who try to get pregnant after using Depo-Provera CI get pregnant within 18 months after their last shot. The length of time you use Depo-Provera CI has no effect on how long it takes you to become pregnant after you stop using it.
General Information about Depo-Provera CI
Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. This leaflet summarizes the most important information about Depo-Provera CI. If you would like more information, talk with your healthcare professional. You can ask your healthcare professional for information about Depo-Provera CI that is written for healthcare professionals.
What are the ingredients in Depo-Provera CI?
Active ingredient: medroxyprogesterone acetate
Inactive ingredients: polyethylene glycol 3350, polysorbate 80, sodium chloride, methylparaben, propylparaben, and water for injection. When necessary, pH is adjusted with sodium hydroxide or hydrochloric acid, or both.
This Patient Information has been approved by the U.S. Food and Drug Administration.
This product's labeling may have been updated. For the most recent prescribing information, please visit www.pfizer.com.
LAB-0148-15.0
Revised December 2025
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