(medroxyprogesterone acetate)
5 WARNINGS AND PRECAUTIONS
5 WARNINGS AND PRECAUTIONS
5.1 Loss of Bone Mineral Density
Use of depo-subQ provera 104 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-subQ provera 104 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 DMPA-IM. After discontinuing DMPA-IM 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 (14.4)]. 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 (14.3)].
The use of depo-subQ provera 104 is not recommended as a long-term (i.e., longer than 2 years) birth control method or medical therapy for endometriosis-associated pain unless other options are considered inadequate. BMD should be evaluated when a woman needs to continue to use depo-subQ provera 104 long-term. In adolescents, interpretation of BMD results should take into account patient age and skeletal maturity.
Other birth control methods or therapies for endometriosis-associated pain should be considered in the risk/benefit analysis for the use of depo-subQ provera 104 in women with osteoporosis risk factors. Depo-subQ provera 104 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 Arterial and Venous Thromboembolic Disorders
There have been reports of serious arterial and venous thrombotic events in women treated with DMPA-IM. Women with a history of thromboembolic disorders were not studied in clinical trials of depo-subQ provera 104. Although no causal relationship between the use of depo-subQ provera 104 and thrombotic events has been clearly established, patients who develop arterial or venous thrombosis while taking depo-subQ provera 104 should discontinue treatment.
Do not re-administer depo-subQ provera 104 pending examination if there is a sudden onset of a suspected vascular ocular event (e.g., partial or complete loss of vision, proptosis, or diplopia) or migraine. Do not re-administer depo-subQ provera 104 if examination reveals papilledema or retinal vascular lesions.
5.3 Cancer Risks
Breast Cancer
The use of hormonal contraceptives, including depo sub-Q provera 104, is contraindicated in women who have or have had breast cancer because breast cancer may be sensitive to hormones [see Contraindications (4)]. Women who have a family history of breast cancer or a significant risk of breast cancer should be monitored.
The results of five large case-control studies assessing the association between DMPA-IM use and the risk of breast cancer are summarized in Figure M. 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 US study1 evaluated the timing and duration of use and found a statistically significant increased risk of breast cancer in recent DMPA-IM users (defined as last use within the past five years) who used DMPA-IM for 12 months or longer; this is consistent with results of a previous study2.
Based on the published SEER-18 2015 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 DMPA-IM from about 73 to about 146 cases per 100,000 women.
Other Cancers
The relative rate of invasive squamous-cell cervical cancer in women who ever used DMPA-IM 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.
Long-term, case-controlled surveillance of users of DMPA-IM found no overall increased risk of ovarian or liver cancer.
5.4 Meningioma
Cases of meningiomas have been reported following repeated administration of medroxyprogesterone acetate, primarily with long term use. Monitor patients on depo-subQ provera 104 for signs and symptoms of meningioma. Discontinue depo-subQ provera 104 if a meningioma is diagnosed.
5.5 Ectopic Pregnancy
Healthcare professionals should be alert to the possibility of an ectopic pregnancy among women using depo-subQ provera 104 who become pregnant or complain of severe abdominal pain.
5.6 Anaphylaxis
Serious anaphylactic reactions have been reported in women using depo-subQ provera 104. If an anaphylactic reaction occurs, appropriate emergency medical treatment should be administered.
5.7 Fluid Retention
Because progestational drugs including depo-subQ provera 104 may cause fluid retention, monitor patients with conditions that might be affected by fluid retention.
5.8 Weight Gain
Weight gain is a common occurrence in women using depo-subQ provera 104. In three large clinical trials using depo-subQ provera 104, the mean weight gain was 3.5 lb (1.6 kg) in the first year of use. In a small, two-year study comparing depo-subQ provera 104 to DMPA-IM, the mean weight gain observed for women using depo-subQ provera 104 [7.5 lb (3.4 kg)] was similar to the mean weight gain for women using DMPA-IM [7.6 lb (3.5 kg)].
Although there are no data related to weight gain beyond 2 years for depo-subQ provera 104, the data on DMPA-IM may be relevant. In a clinical study, after five years, 41 women using Depo-Provera CI (150 mg) had a mean weight gain of 11.2 lb (5.1 kg), while 114 women using non-hormonal contraception had a mean weight gain of 6.4 lb (2.9 kg).
5.9 Delayed Return of Ovulation or Fertility
Return to ovulation is likely to be delayed after stopping depo-subQ provera 104, as demonstrated in a study of 15 women who received multiple doses of depo-subQ provera 104:
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- Median time to ovulation was 10 months after the last injection.
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- Earliest return to ovulation was 6 months after the last injection.
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- 12 women (80%) ovulated within 1 year of the last injection.
However, ovulation has occurred as early as 14 weeks after a single dose of depo-subQ provera 104; therefore, administer the next depo-subQ provera 104 12 to 14 weeks after the last injection.
Return to fertility also is likely to be delayed after stopping therapy. Among 28 women using depo-subQ provera 104 for contraception who stopped treatment to become pregnant, 7 women were lost to follow-up. One woman became pregnant within one year of her last injection and another woman became pregnant 443 days after her last injection. The remaining 19 women had not become pregnant; it is not known if these 19 women were still attempting to become pregnant or if they had started a new contraceptive method.
5.10 Depression
Depression (3% of depo-subQ provera 104-treated patients) and other mood disorders have been reported in clinical trials of depo-subQ provera 104 [see Adverse Reactions (6.1)]. Patients with a history of depression or who are on treatment for depression may be at increased risk for depression recurrence or exacerbation and for associated mood disorders while receiving depo-subQ provera 104. Therefore, patients should be monitored for symptoms of depression and mood changes.
5.11 Injection Site Reactions
In five clinical studies of depo-subQ provera 104 involving 2325 women (282 treated for up to 6 months, 1780 treated for up to 1 year, and 263 women treated for up to 2 years), 5% of women reported injection site reactions (such as pain/tenderness, nodule/lump, lipodystrophy, discoloration), and 1% had persistent atrophy/indentation/dimpling [see Adverse Reactions (6.1)]. These injection site reactions have also been reported in post-marketing experience.
5.12 Bleeding Irregularities
Most women using depo-subQ provera 104 experienced changes in menstrual bleeding patterns, such as amenorrhea, irregular unpredictable spotting or bleeding, prolonged spotting or bleeding, or heavy bleeding [see Adverse Reactions (6.1)]. Fewer women experienced irregular bleeding and more experienced amenorrhea with longer term use of depo‑subQ provera 104, consistent with expected endometrial thinning effects.
In three contraception trials, 39% of 2053 depo-subQ provera 104-treated women experienced amenorrhea during Month 6, and 57% experienced amenorrhea during Month 12. In two endometriosis trials using depo-subQ provera 104, 24% of 289 women experienced amenorrhea during Month 6 [see Adverse Reactions (6.1)].
If abnormal bleeding is persistent or severe, evaluate the patient for underlying pathology or pregnancy.
5.13 Risk of Hyperglycemia in Patients with Diabetes
Some patients receiving progestins may exhibit a decrease in glucose tolerance; therefore, patients with diabetes may be at greater risk of hyperglycemia.
5.14 Jaundice and Elevated Transaminase
Discontinue depo-subQ provera 104 if jaundice or elevated transaminase levels develop. Depo-subQ provera 104 may be resumed after both the jaundice and elevated transaminase levels resolve, and the healthcare professional determines that depo-subQ provera 104 did not cause the abnormalities.
MEDICATION GUIDE
PATIENT INFORMATION
DEPO-SUBQ PROVERA 104®
(deh-poh' sub-cue' pro-ver-ah' one-oh-four)
(medroxyprogesterone acetate injectable suspension)
for subcutaneous use
WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT depo-subQ provera 104?
Use of depo-subQ provera 104 may cause you to lose calcium stored in your bones. The longer you use depo-subQ provera 104 the more calcium you are likely to lose. The calcium may not return completely once you stop using depo-subQ provera 104.
Loss of calcium may cause weak, porous bones (osteoporosis) that could increase the risk that your bones might break, especially after menopause. It is not known whether your risk of developing osteoporosis may be greater if you are a teenager when you start to use depo-subQ provera 104.
You should use depo-subQ provera 104 long-term (for example, more than 2 years) only if other methods of birth control or other treatments for endometriosis pain are not right for you.
Depo-subQ provera 104 does not protect you from HIV (AIDS) and other sexually transmitted infections (STIs).
WHAT IS depo-subQ provera 104?
Depo-subQ provera 104 is a drug for birth control. It also helps relieve pain related to endometriosis (en-do-ME-tree-OH-sis). Symptoms of endometriosis arise when cells normally inside your uterus grow outside the uterus. The cells respond to menstrual cycle hormones, and may cause painful periods, pelvic pain, and painful sex.
Depo-subQ provera 104 contains a hormone called medroxyprogesterone acetate (MPA). It is given as a shot (injection) every 3 months. Three months is the same as 12 to 14 weeks.
HOW WELL DOES depo-subQ provera 104 WORK FOR PREVENTING PREGNANCY?
When you use depo-subQ provera 104 correctly, the chance of getting pregnant is very low. In studies, no women became pregnant during the year they used depo-subQ provera 104 injection.
The list below estimates the chances of getting pregnant using different types of birth control. The numbers are based on typical use. Typical use includes people who use the method correctly and people who use the method incorrectly. The list shows the number of women out of 100 women who will likely get pregnant if they use the method for 1 year.
| Method | Typical Chance of Getting Pregnant in 1 year (Number of pregnancies in 100 women) |
|---|---|
Shot | Less than 1 |
Pill | 5 |
Condom alone (male) | 14 |
Withdrawal | 19 |
Diaphragm with spermicides | 20 |
Condom alone (female) | 21 |
Periodic abstinence | 25 |
Spermicides alone | 26 |
Vaginal sponge or Cervical cap with spermicide | 20 to 40 |
HOW WILL I GET depo-subQ provera 104?
Depo-subQ provera 104 is given as a shot just under the skin on your thigh or belly. You get it once every 3 months.
For Birth Control
First shot:
Your healthcare professional will want to be sure that you are not pregnant before you get your first shot. Normally, you get the shot by the 5th day from the START of your menstrual period. You get it whether or not you are still bleeding.
If you are breast-feeding, you may have your first shot as early as 6 weeks after you deliver your baby.
After the first shot:
It is very important to keep getting depo-subQ provera 104 every 3 months. If you wait more than 14 weeks between shots, you could become pregnant. Your healthcare professional must make sure you are not pregnant before you get your next shot.
When you get your shot, make an appointment for your next shot. Mark it on your calendar.
If you need a birth control method for more than two years, your healthcare professional may ask you to have a test of your bones or ask you to switch to another birth control method before continuing depo-subQ provera 104, especially if you have other risks for weak bones.
For Endometriosis
If you have regular periods, you will get depo-subQ provera 104 the same way as described above for birth control. If your periods have stopped or are not regular, your healthcare professional must test to make sure you are not pregnant before you get your first shot.
It is not recommended that you receive depo-subQ provera 104 for treatment of endometriosis for longer than 2 years. If your painful symptoms return after stopping treatment, your healthcare professional should ask you to have a test of your bones before restarting treatment.
WHAT IF I MISS A SHOT?
If you miss a shot, or wait longer than 14 weeks between shots, you could get pregnant. The longer you wait, the greater the risk of getting pregnant.
Talk with your healthcare professional to find out when to restart depo-subQ provera 104. You should be tested to be sure you are not pregnant.
Use another kind of non-hormonal birth control, such as condoms, until you start depo-subQ provera 104 again.
DO NOT TAKE depo-subQ provera 104 IF YOU…
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- Have any unexplained vaginal bleeding
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- Have or have ever had breast cancer or think you have breast cancer
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- Ever had serious blood clots, such as blood clots in your legs (deep venous thrombophlebitis), lungs (pulmonary embolism), heart (heart attack), or head (stroke)
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- Have liver disease
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- Are allergic to anything in depo-subQ provera 104. There is a list of what is in depo-subQ provera 104 at the end of this leaflet.
BEFORE TAKING depo-subQ provera 104
Your healthcare professional may do a physical examination and check your blood and urine.
Tell your healthcare professional about all your medical conditions.
Most importantly, tell your healthcare professional if you:
- •
- Are pregnant or might be pregnant. You should not get depo-subQ provera 104 if you are pregnant.
- •
- Plan to become pregnant in the next year. After you stop getting depo-subQ provera 104, it takes time for your body to be able to get pregnant. It can be as early as 1 week after the last shot wears off. Most likely it will take up to 1 year or longer for you to get pregnant.
- •
- Have or have ever had breast cancer, or think you have breast cancer
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- Have breast cancer in your family
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- Have an abnormal mammogram (breast X-ray), lumps in your breast, 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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- Have irregular, light, or heavy menstrual periods
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- Have or had any of the following medical problems:
- o
- Kidney problems
- o
- High blood pressure
- o
- Migraine headaches
- o
- Asthma
- o
- Seizures
- o
- Diabetes, or if it runs in your family
- o
- Depression
- o
- Heart attack, stroke, or blood clots
- o
- Bone disease
- o
- Anorexia nervosa (an eating disorder)
- o
- A strong family history of osteoporosis
- o
- Use of a drug that can lower the amount of calcium in bones (drugs for epilepsy or steroids)
- o
- Drinking a lot of alcohol or smoking a lot
It is important to see your healthcare professional regularly if you have any of these conditions.
Some medicines may make depo-subQ provera 104 less effective at preventing pregnancy, including those listed below:
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- Bosentan (used to treat pulmonary arterial hypertension)
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- Efavirenz, etravirine (HIV medicines)
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- Modafinil (used to improve wakefulness)
- •
- Mitotane (used to treat adrenal cortical carcinoma)
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- Phenytoin, carbamazepine, phenobarbital (used to treat seizures)
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- Rifampin (an antibiotic)
- •
- St. John's Wort (herbal medicinal product)
Tell your healthcare professional about all the medicines you take. This includes prescription and over-the-counter medicines, vitamins, and herbal products.
WHAT ELSE SHOULD I KNOW ABOUT TAKING depo-subQ provera 104?
Other Birth Control. If you can't take birth control pills or can't use a birth control patch or ring, you may be able to use depo-subQ provera 104. Ask your healthcare professional.
Pregnancy. When you take depo-subQ provera 104 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-subQ provera 104 if you are pregnant. However, depo-subQ provera 104 taken by accident during pregnancy does not seem to cause birth defects.
Pregnancy in your fallopian tubes (Ectopic Pregnancy). If you have severe pain low in your belly, tell your healthcare professional right away. Infrequently, a baby may start to grow outside the uterus, most often in the tubes.
Nursing a baby. Wait at least 6 weeks after your baby is born to start depo-subQ provera 104. You can use depo-subQ provera 104 if you are nursing.
It does not lower the amount of milk you can make.
It can pass through breast milk into your baby, but it is not harmful.
Blood or urine tests. Depo-subQ provera 104 may affect blood or urine test results. Tell your healthcare professional you are taking depo-subQ provera 104 if you are going to have blood or urine tests.
Liver problems. Your healthcare professional may stop depo-subQ provera 104 if you have liver problems. Some signs of liver problems are yellow skin or eyes, feeling like you have the flu, feeling more tired than usual, and itching. Tell your healthcare professional if you have these symptoms.
WHAT ARE THE MOST SERIOUS RISKS OF depo-subQ provera 104?
Losing calcium from your bones. Depo-subQ provera 104 use may decrease the amount of calcium in your bones. The longer you use depo-subQ provera 104, the more calcium you are likely to lose. This increases the risk of your bones weakening if you use depo-subQ provera 104 continuously for a long time (for example, if you use depo-subQ provera 104 for more than 2 years). The loss of calcium may increase your risk of osteoporosis and broken bones, particularly after your menopause.
Calcium is generally added to the bones during teenage years. The decrease of calcium in your bones is of most concern if you are a teenager or have the following risk factors:
- •
- Bone disease
- •
- Anorexia nervosa (an eating disorder)
- •
- A strong family history of osteoporosis
- •
- Using a drug that can lower the amount of calcium in bones (drugs for epilepsy or steroids), or
- •
- Drinking a lot of alcohol or smoking a lot
If you need a birth control method for more than 2 years, your healthcare professional may ask you to have a test of your bones or ask you to switch to another birth control method before continuing depo-subQ provera 104, especially if you have other risks for weak bones. When depo-subQ provera 104 is stopped, the calcium in your bones begins to come back. The lost calcium may not return completely once you stop using depo-subQ provera 104.
Abnormal or very heavy bleeding. If you start having very heavy or very long periods, tell your healthcare professional.
Allergic reaction. Allergic reactions to depo-subQ provera 104 have been reported. If you have hives, problems breathing, swelling of the face, mouth, tongue, or neck, or just do not feel right after your shot, call your healthcare professional or go to the Emergency Room right away.
Serious blood clots. Call your healthcare professional immediately if you:
- •
- Have sharp chest pain, cough blood, or suddenly have trouble breathing
- •
- Have a sudden severe headache with vomiting, blindness or trouble talking, weakness, or numbness in an arm or leg, or get dizzy or faint
- •
- Have swelling or severe pain in your leg
Depression. If you suffer from depression or have a history of depression, inform your healthcare professional if you notice any worsening of your depression while taking depo-subQ provera 104.
Meningioma (a type of usually benign brain tumor). Possible increased risk for growth of a meningioma, primarily when the product is used for a long time.
WHAT ARE COMMON SIDE EFFECTS OF depo-subQ provera 104?
The most common side effects are:
- •
- Changes in your monthly periods. You may not know when you will bleed, your periods may not be regular, you may have heavy bleeding, or you may have spotting. You may have more days of bleeding during the first 2 or 3 months after you start depo-subQ provera 104. Over time, you may have less and less bleeding. Many women stop having periods by the end of 1 year. Your periods will come back eventually after you stop using depo-subQ provera 104.
- •
- Headache.
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- Weight gain. In studies, women gained an average of 3 to 4 pounds during the first year they used depo-subQ provera 104. After 2 years of using depo-subQ provera 104, women gained an average of 7 to 8 pounds. Some women gained more, some gained less, some lost, and some stayed the same. Weight changes beyond 2 years of use with depo-subQ provera 104 have not been studied. Women who used a similar birth control product for 5 years gained on average 5 pounds more than women who did not use a hormone contraceptive product.
- •
- Skin reaction where you got the shot. Lumps, skin dimpling, or pain may occur. Scarring and discoloration are uncommon, but may happen. If there is swelling or your skin gets hot, has pus or looks bruised 1 or more days after your shot, call your healthcare professional.
Women using depo-subQ provera 104 for birth control or endometriosis had these less common side effects: Vaginal inflammation, vaginal thrush, abdominal pain, urinary tract infections, acne, depression, less sex drive, nausea, back pain, breast pain/tenderness, fatigue, anxiety, being irritable, dizziness, hot flushes and fluid retention.
If you feel you are having other side effects, talk with your healthcare professional.
DOES depo-subQ provera 104 CAUSE CANCER?
There have been several studies of women who use birth control like depo-subQ provera 104.
- •
- Women who use depo-subQ provera 104 may have a slightly increased risk of breast cancer compared to non-users.
- •
- The risk of cancer of the ovary, liver, or cervix did not change.
WHAT IF I WANT TO BECOME PREGNANT?
Plan ahead. The effect of depo-subQ provera 104 can last for a long time after you stop getting shots. Although you may be able to get pregnant quickly, it is more likely to take a year or longer after your last shot before you get pregnant.
It's best to see your healthcare professional for a pre-pregnancy check-up. Your healthcare professional may also tell you to take a vitamin called folic acid every day if you are planning to become pregnant.
GENERAL ADVICE ABOUT depo-subQ provera 104
For more information about depo-subQ provera 104, ask your healthcare professional or pharmacist.
WHAT IS IN depo-subQ provera 104?
Active ingredient: medroxyprogesterone acetate.
Inactive ingredients: methylparaben, propylparaben, sodium chloride, polyethylene glycol, polysorbate 80, monobasic sodium phosphate∙H2O, dibasic sodium phosphate∙12H2O, methionine, povidone, water for shot. When necessary, the pH is adjusted with sodium hydroxide or hydrochloric acid, or both.
This product's labeling may have been updated. For the most recent prescribing information, please visit www.pfizer.com.
LAB-0298-12.0
Revised December 2025
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