These Highlights Do Not Include All The Information Needed To Use Depo-subq Provera 104®

Limitations of Use:

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 [see Dosage and Administration (2.1) and Warnings and Precautions (5.1)].

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.

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…

• •
  Have any unexplained vaginal bleeding
• •
  Have or have ever had breast cancer or think you have breast cancer
• •
  Ever had serious blood clots, such as blood clots in your legs (deep venous thrombophlebitis), lungs (pulmonary embolism), heart (heart attack), or head (stroke)
• •
  Have liver disease
• •
  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
• •
  Have breast cancer in your family
• •
  Have an abnormal mammogram (breast X-ray), lumps in your breast, or bleeding from your nipples
• •
  Have or have ever had a type of usually benign brain tumor called a meningioma
• •
  Have irregular, light, or heavy menstrual periods
• •
  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:

• •
  Bosentan (used to treat pulmonary arterial hypertension)
• •
  Efavirenz, etravirine (HIV medicines)
• •
  Modafinil (used to improve wakefulness)
• •
  Mitotane (used to treat adrenal cortical carcinoma)
• •
  Phenytoin, carbamazepine, phenobarbital (used to treat seizures)
• •
  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.
• •
  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

Store at controlled room temperature 20° C to 25° C (68° F to 77°F) [see USP]. Do not refrigerate.

• 1.
  Li CI, Beaber EF, Tang MCT et al. Effect of Depo-Medroxyprogesterone Acetate on Breast Cancer Risk among Women 20 to 44 years of Age. Cancer Research 2012; 72:2028-2035.
• 2.
  Paul C, Skegg DCG, Spears GFS. Depot medroxyprogesterone (Depo-Provera) and risk of breast cancer. Br Med J 1989; 299:759-62.

Risk Summary

There is no use for contraception in pregnancy; therefore, depo-subQ provera 104 should be discontinued during pregnancy.

Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to progestins before conception or during early pregnancy.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15‑20%, respectively.

Risk Summary

Although medroxyprogesterone acetate is detectable in the milk of mothers receiving DMPA-IM, milk composition, quality, and amount do not appear to be adversely affected. Effects on milk production and lactation initiation/duration remain unclear when administered before 6 weeks after delivery, therefore, in mothers who exclusively breastfeed, initiate depo-subQ provera 104 during or after the sixth post-partum week [see Dosage and Administration (2.1)].

No adverse effects in breastfed infants would be expected with maternal use of progestins. Neonates and infants exposed to medroxyprogesterone acetate from breast milk have been studied and no adverse effects have been noted.

The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for depo-subQ provera 104 and any potential adverse effects on the breastfed child from depo-subQ provera 104 or from the underlying maternal condition.

Depo-subQ provera 104 contains medroxyprogesterone acetate (MPA), a derivative of progesterone, as its active ingredient. MPA is a white to off-white, odorless crystalline powder that is stable in air and that melts between 205°C and 209°C. It is freely soluble in chloroform, soluble in acetone and dioxane, sparingly soluble in alcohol and methanol, slightly soluble in ether, and insoluble in water.

The chemical name for MPA is 17-hydroxy-6α-methylpregn-4-ene-3,20-dione 17-acetate. The structural formula is as follows:

Depo-subQ provera 104 for subcutaneous use is available in pre-filled syringes, each containing 0.65 mL (104 mg) of sterile medroxyprogesterone acetate injectable suspension.

Each 0.65 mL contains the following inactive ingredients:

When necessary, the pH is adjusted with sodium hydroxide or hydrochloric acid, or both.

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.

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.

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.

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).

Depo-subQ provera 104 medroxyprogesterone acetate injectable suspension (104 mg/0.65 mL) is available in a single dose, disposable pre-filled syringe and is packaged with a 26-gauge × 3/8-inch Terumo SurGuard^® needle.

NDC 0009-4709-13

Depo-subQ provera 104 is indicated for the prevention of pregnancy and management of endometriosis-associated pain in females of reproductive age. Efficacy is expected to be the same for post-menarchal females under the age of 17 as for users 17 years and older.

Use of depo-subQ provera 104 is associated with significant loss of bone mineral density (BMD). This loss of BMD is of particular concern during adolescence, a critical period of bone accretion. It is unknown if use of depo-subQ provera 104 by female adolescents will reduce peak bone mass and increase the risk for osteoporotic fractures in later life. In a study of adolescent females (12–18 years of age) receiving DMPA-IM for contraception, mean BMD 2 years after starting DMPA-IM decreased 1.9% (spine), 4.3% (total hip), and 4.2% (femoral neck). In those adolescents who used DMPA-IM for more than 2 years, mean BMD at total hip and femoral neck did not return to baseline within 5 years.

Depo-subQ provera 104 is not indicated before menarche.

Depo-subQ provera 104 is not indicated in post-menopausal women.

The use of depo-subQ provera 104 is contraindicated in the following conditions:

• •
  Active thrombophlebitis, or current or history of thromboembolic disorders, or cerebral vascular disease [see Warnings and Precautions (5.2)].
• •
  Known, suspected, or past malignancy of the breast [see Warnings and Precautions (5.3)].
• •
  Significant liver disease [see Warnings and Precautions (5.14)].
• •
  Known hypersensitivity to medroxyprogesterone acetate or any of the ingredients in depo-subQ provera 104 [see Warnings and Precautions (5.6)].
• •
  Undiagnosed vaginal bleeding [see Warnings and Precautions (5.12)].

Because progestational drugs including depo-subQ provera 104 may cause fluid retention, monitor patients with conditions that might be affected by fluid retention.

The following important adverse reactions are described in more detail in other sections of the prescribing information:

• •
  Loss of bone mineral density [see Warnings and Precautions (5.1)]
• •
  Arterial and venous thromboembolic disorders [see Warnings and Precautions (5.2)]
• •
  Anaphylaxis [see Warnings and Precautions (5.6)]
• •
  Fluid retention [see Warnings and Precautions (5.7)]
• •
  Delayed return of ovulation or fertility [see Warnings and Precautions (5.9)]
• •
  Depression [see Warnings and Precautions (5.10)]
• •
  Injection site reactions [see Warnings and Precautions (5.11)]
• •
  Bleeding irregularities [see Warnings and Precautions (5.12)]

Strong CYP3A inhibitors and inducers: Avoid concomitant use. (7)

The following laboratory tests are expected to be affected by progestins including depo-subQ provera 104:

• •
  Plasma and urinary steroid levels are decreased (e.g., progesterone, estradiol, pregnanediol, testosterone, cortisol).
• •
  Gonadotropin levels are decreased.
• •
  Sex-hormone-binding-globulin concentrations are decreased.
• •
  Histology specimens may demonstrate changes consistent with progestin effects.

The following laboratory tests may be affected by depo-subQ provera 104, however the clinical significance is unknown:

• •
  Protein-bound iodine and butanol extractable protein-bound iodine may increase.
• •
  T₃-uptake values may decrease.
• •
  Coagulation test values for prothrombin (Factor II), and Factors VII, VIII, IX, and X may increase.
• •
  Sulfobromophthalein and other liver function test values may be increased.
• •
  The effects of medroxyprogesterone acetate on lipid metabolism are inconsistent. Both increases and decreases in total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol have been observed in studies.

The pharmacokinetic parameters of MPA following a single subcutaneous injection of depo-subQ provera 104 in healthy women (n=42) are shown in Table 2 and Figure P.

Following subcutaneous administration of single depo-subQ provera 104 doses ranging from 50 to 150 mg (0.48 and 1.4 times the recommended dose, respectively), the AUC and C_min (Day 91) increased with higher doses, but there was considerable overlap across dose levels. Serum MPA concentrations at Day 91 increased in a dose proportional manner but C_max did not appear to increase proportionally with increasing dose. The AUC data were suggestive of dose linearity.

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.

Depo-subQ provera 104 is indicated in females of reproductive age for:

• •
  Prevention of pregnancy and
• •
  Management of endometriosis-associated pain.

Depo-subQ provera 104 inhibits the secretion of gonadotropins, which primarily prevents follicular maturation and ovulation and causes thickening of cervical mucus. These actions contribute to its contraceptive effect.

Suppression of serum estradiol concentrations is likely to be responsible for the therapeutic effect on endometriosis-associated pain.

In three open label clinical studies, depo-SubQ provera 104 (104 mg given every three months subcutaneously), was administered to healthy, sexually-active, nonpregnant women 18 to 49 years of age who desired long-term contraception. In these three studies, no pregnancies were detected among 2042 women treated with depo-subQ provera 104 for up to 1 year. In women less than 36 years of age (at baseline), the Pearl Index pregnancy rate in cycles in which no other contraceptive methods were used, was 0 pregnancies per 100 women-years of use (upper 95% CI = 0.25).

The efficacy of depo-subQ provera 104 in the reduction of endometriosis-associated pain in women with the signs and symptoms of endometriosis was demonstrated in two active comparator-controlled studies in pre-menopausal women 18 to 49 years of age with laparoscopically diagnosed endometriosis and persistent endometriosis pain symptoms (i.e., Studies 268 and 270). Each study assessed endometriosis-associated pain over 6 months of treatment and recurrence of symptoms for 12-months post treatment.

Subjects were treated for six months with depo-subQ provera 104 [104 mg given subcutaneously every 3 months (2 injections)] or leuprolide [11.25 mg given subcutaneously every 3 months (2 injections) or 3.75 mg given subcutaneously every month (6 injections)]. Study 268 was conducted in the U.S. and Canada and enrolled 274 subjects (136 subjects received depo-subQ provera 104 and 138 subjects received leuprolide). Study 270 was conducted in South America, Europe, and Asia, and enrolled 299 subjects (153 subjects received depo-subQ provera 104 and 146 subjects received leuprolide).

Reduction in endometriosis pain was evaluated using a modified Biberoglu and Behrman scale that consisted of three patient-reported symptoms (i.e., dysmenorrhea, dyspareunia, and pelvic pain not related to menses) and two signs assessed during pelvic examination (i.e., pelvic tenderness and induration). For each category, a favorable response was defined as improvement of at least 1 unit (severity was assessed on a scale of 0 to 3) relative to baseline score (Figure Q).

Additionally, scores from each of the five categories were combined into a composite score that was considered a global measurement of overall disease improvement. For subjects with baseline scores for each of the 5 categories, a mean decrease of 4 points relative to baseline was considered a clinically meaningful improvement. Across both studies, the mean changes in the composite score met the protocol-defined criterion for improvement for the depo-subQ provera 104 and leuprolide treatment groups.

In the clinical trials, treatment with depo-subQ provera 104 was limited to six months. Data on the persistence of benefit with longer treatment are not available.

• •
  Thromboembolic disorders: Discontinue depo-subQ provera 104 in patients who develop arterial or venous thrombosis. (5.2)
• •
  Breast cancer risks: Monitor women with a family history of breast cancer or a significant risk of breast cancer carefully. (5.3)
• •
  Meningioma: Discontinue depo-subQ provera 104 if meningioma is diagnosed. Monitor patients for signs and symptoms of meningioma. (5.4)
• •
  Ectopic pregnancy: Consider ectopic pregnancy if a woman becomes pregnant or complains of severe abdominal pain. (5.5)
• •
  Anaphylaxis: Provide emergency medical treatment. (5.6)
• •
  Injection site reactions (e.g., persistent atrophy, dimpling/indentation, lump/nodule and discoloration) have been reported. (5.11)
• •
  Diabetics may be at greater risk of hyperglycemia. (5.13)
• •
  Jaundice and elevated transaminase: Discontinue depo-subQ provera 104 if jaundice or elevated transaminase levels develop. (5.14)

• •
  Only for healthcare professional administration. (2.1)
• •
  Prior to first injection, confirm the patient is not pregnant. (2.1)
• •
  Administer 104 mg of depo-subQ provera 104 by subcutaneous injection into the anterior thigh or abdomen, once every 12 to 14 weeks. (2.1)
• •
  See Full Prescribing Information for recommendations on switching from another contraceptive method to depo-subQ provera 104. (2.2)
• •
  See Full Prescribing Information for important preparation and administration instructions. (2.3)

Injectable suspension (104 mg/0.65 mL) in a single-dose pre-filled syringe, packaged with a 26-gauge × 3/8-inch Terumo SurGuard^® needle.

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.

The following adverse reactions have been identified during post-approval use of DMPA-IM. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

• •
  Immune system disorders: anaphylactic reaction, anaphylactoid reaction, angioedema
• •
  Vascular disorders: pulmonary embolism, deep vein thrombosis, thrombophlebitis
• •
  Musculoskeletal and connective tissue disorders: osteoporosis (including osteoporotic fractures)
• •
  Reproductive system and breast disorders: prolonged anovulation, unexpected pregnancy, uterine hyperplasia
• •
  Respiratory, thoracic and mediastinal disorders: hoarseness
• •
  Skin and subcutaneous tissue disorders: increased body odor
• •
  Gastrointestinal disorders: gastrointestinal disturbances
• •
  General disorders and administration site conditions: axillary swelling, chills, thirst

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.

• •
  Pregnancy: Discontinue if pregnancy occurs. (8.1)
• •
  Lactation: Detectable amounts of drug have been identified in the milk of mothers receiving depot-medroxyprogesterone acetate. (8.2)
• •
  Pediatric patients (after menarche): Bone loss is a particular concern. (8.4)

Clinical trials are conducted under widely varying conditions, therefore adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to depo-subQ provera 104 in five clinical trials involving 2325 women including 2043 women who received treatment for contraception (1780 treated up to 1 year and 263 treated for up to 2 years) and 282 women for endometriosis for up to 6 months. In these pooled trials, 9% of women discontinued treatment due to an adverse reaction and the most common reason for discontinuation was dysfunctional uterine bleeding (3%).

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).

Advise the patient to read the FDA-approved patient labeling (Patient Information).

• •
  Women who use depo-subQ provera 104 may lose significant bone mineral density. Bone loss is greater with increasing duration of use and may not be completely reversible [see Warnings and Precautions (5.1)].
• •
  It is unknown if use of depo-subQ provera 104 during adolescence or early adulthood, a critical period of bone accretion, will reduce peak bone mass and increase the risk for osteoporotic fracture in later life [see Warnings and Precautions (5.1)].
• •
  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 [see Indications and Usage (1) and Warnings and Precautions (5.1)].

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.

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:

• •
  Median time to ovulation was 10 months after the last injection.
• •
  Earliest return to ovulation was 6 months after the last injection.
• •
  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.

Prior to injection:

• •
  Ensure all the components in Figure A are available and that depo-subQ provera 104 is at room temperature.
• •
  Shake the pre-filled syringe vigorously prior to injection to ensure appropriate viscosity of the suspension.
• •
  Inspect depo-subQ provera 104 visually for particulate matter and discoloration.
  
  Figure A. Components in the Package

Depo-subQ provera 104 is indicated for the prevention of pregnancy and would therefore be expected to impair female fertility until cessation of treatment. Women may experience a delay in return to ovulation and fertility (conception) following discontinuation of depo-subQ provera 104 [see Warnings and Precautions (5.9)].

PAA229214

depo-subQ

provera 104^®

(medroxyprogesterone acetate) injectable

suspension (104 mg/0.65 mL for subcutaneous use)

104 mg/0.65 mL

0.65 mL Single Dose Syringe

Store at 20°C to 25°C (68°F to 77°F).

Do not refrigerate.

Shake vigorously before use.

Pharmacia & Upjohn Company LLC

LOT/EXP:

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.

NDC 0009-4709-13

Single Dose 0.65 mL Prefilled Syringe

depo-subQ provera 104^®

(medroxyprogesterone acetate) injectable suspension

(104 mg/0.65 mL for subcutaneous use)

104 mg/0.65 mL

Pfizer

Distributed by

Pharmacia & Upjohn Company LLC

A Subsidiary of Pfizer Inc.

New York, NY 10011

Rx only

When switching from another contraceptive method to depo-subQ provera 104, administer depo-subQ provera 104 in a manner that ensures continuous contraceptive coverage. Follow the respective recommendations when switching from the contraceptive methods listed below:

• •
  Combined hormonal contraceptives: administer the first injection of depo-subQ provera 104 within 7 days after the last day of using the combined hormonal contraceptive method (i.e., within 7 days after taking the last active pill).
• •
  An implant: administer the first injection of depo-subQ provera 104 on the day of implant removal.
• •
  A contraceptive vaginal ring or transdermal system: administer the first injection of depo-subQ provera 104 on the day the patient would have inserted the next ring or applied the next transdermal system.
• •
  An Intrauterine Device (IUD) or Intrauterine System (IUS): administer the first injection of depo-subQ provera 104 on the day of IUD/IUS removal. If the IUD/IUS is not removed on the first day of the patient's menstrual cycle, instruct patients to use a non-hormonal back-up method of birth control for the first 7 days after administration of depo-subQ provera 104.
• •
  Depot medroxyprogesterone acetate injectable suspension for intramuscular use (DMPA-IM): inject depo-subQ provera 104 12 to 14 weeks after the last dose of DMPA-IM.

Depo-subQ provera 104 is only for subcutaneous administration and is only to be administered by a healthcare professional.

Use for longer than 2 years is not recommended (unless other birth control methods or medical therapies for endometriosis-associated pain are considered inadequate) due to the impact of long-term depo-subQ provera 104 treatment on bone mineral density (BMD) [see Warnings and Precautions (5.1)].

Prior to the first injection confirm that the patient is not pregnant. For women who are sexually active and who have regular menses, administer the first injection only during the first 5 days of a normal menstrual period. For women who are breast-feeding, administer the first injection during or after the sixth post-partum week.

The recommended dosage of depo-subQ provera 104 is 104 mg given subcutaneously every 12 to 14 weeks. If more than 14 weeks elapse between injections, confirm that the patient is not pregnant before the next injection. Instruct the patient that if they are unable to receive an injection within 12–14 weeks, another contraceptive method should be used until the next depo-subQ provera 104 injection. The dosage does not need to be adjusted for body weight.

Inject the entire contents of the pre-filled syringe using strict aseptic technique into the upper anterior thigh or abdomen, rotating the sites with every injection [see Dosage and Administration (2.3)].

Some patients receiving progestins may exhibit a decrease in glucose tolerance; therefore, patients with diabetes may be at greater risk of hyperglycemia.

Patients should be counseled that this product does not protect against HIV infection (including AIDS) and other sexually transmitted infections.

[See Warnings and Precautions (5.3, 5.9)]

In two clinical studies of 573 adult women with endometriosis, the BMD effects of 6 months of depo-subQ provera 104 treatment (104 mg subcutaneously every 3 months) were compared to 6 months of leuprolide treatment (either 11.25 mg given subcutaneously every 3 months or 3.75 mg given subcutaneously every month). Subjects were then observed after treatment completion, for an additional 12 months. See Table 7 for the results.

In a study that compared changes in bone mineral density (BMD) in adult women using depo-subQ provera 104 or DMPA-IM for contraception, both treatments showed BMD reductions in the lumbar spine, total hip, and femoral neck. Mean percent changes in BMD in depo-subQ provera 104-treated women are shown in Table 3.

The effect of DMPA-IM on BMD in adolescents is described below, and the effect of depo-subQ provera 104 on BMD in adolescents is expected to be similar. The impact of DMPA-IM use for up to 240 weeks (4.6 years) was evaluated in an open-label non-randomized clinical study in 389 adolescent females (12 to 18 years of age). Use of DMPA-IM was associated with a significant decline from baseline in BMD.

Partway through the trial, DMPA-IM administration was stopped (at 120 weeks). The mean number of injections per DMPA-IM user was 9.3. Table 5 summarizes the study findings. The decline in BMD at total hip and femoral neck was greater with longer duration of use. The mean decrease in BMD at 240 weeks was more pronounced at total hip (-6.4%) and femoral neck (-5.4%) compared to lumbar spine (-2.1%).

Adolescents in the untreated cohort had an increase in BMD during the period of growth following menarche. However, the two cohorts were not matched at baseline for age, gynecologic age, race, BMD, and other factors that influence the rate of acquisition of BMD.

A retrospective cohort study to assess the association between DMPA-IM injection and the incidence of bone fractures was conducted in 312,395 female contraceptive users in the UK. The incidence rates of fracture were compared between DMPA-IM users and contraceptive users who had no recorded use of DMPA-IM. The Incident Rate Ratio (IRR) for any fracture during the follow-up period (mean=5.5 years) was 1.41 (95% CI 1.35, 1.47). It is not known if this is due to DMPA-IM use or to other related lifestyle factors that have a bearing on fracture rate.

In the study, when cumulative exposure to DMPA-IM was calculated, the fracture rate in users who received fewer than 8 injections was higher than that in women who received 8 or more injections. However, it is not clear that cumulative exposure, which may include periods of intermittent use separated by periods of non-use, is a useful measure of risk, as compared to exposure measures based on continuous use.

There were very few osteoporotic fractures (fracture sites known to be related to low BMD) in the study overall, and the incidence of osteoporotic fractures was not found to be higher in DMPA-IM users compared to non-users.

Importantly, this study could not determine whether use of DMPA-IM has an effect on fracture rate later in life. Given the similar effects on BMD from depo-subQ provera 104 and DMPA-IM described above, bone fracture incidence may also be expected to be similar.

Limitations of Use:

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 [see Dosage and Administration (2.1) and Warnings and Precautions (5.1)].

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.

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…

• •
  Have any unexplained vaginal bleeding
• •
  Have or have ever had breast cancer or think you have breast cancer
• •
  Ever had serious blood clots, such as blood clots in your legs (deep venous thrombophlebitis), lungs (pulmonary embolism), heart (heart attack), or head (stroke)
• •
  Have liver disease
• •
  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
• •
  Have breast cancer in your family
• •
  Have an abnormal mammogram (breast X-ray), lumps in your breast, or bleeding from your nipples
• •
  Have or have ever had a type of usually benign brain tumor called a meningioma
• •
  Have irregular, light, or heavy menstrual periods
• •
  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:

• •
  Bosentan (used to treat pulmonary arterial hypertension)
• •
  Efavirenz, etravirine (HIV medicines)
• •
  Modafinil (used to improve wakefulness)
• •
  Mitotane (used to treat adrenal cortical carcinoma)
• •
  Phenytoin, carbamazepine, phenobarbital (used to treat seizures)
• •
  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.
• •
  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

Store at controlled room temperature 20° C to 25° C (68° F to 77°F) [see USP]. Do not refrigerate.

• 1.
  Li CI, Beaber EF, Tang MCT et al. Effect of Depo-Medroxyprogesterone Acetate on Breast Cancer Risk among Women 20 to 44 years of Age. Cancer Research 2012; 72:2028-2035.
• 2.
  Paul C, Skegg DCG, Spears GFS. Depot medroxyprogesterone (Depo-Provera) and risk of breast cancer. Br Med J 1989; 299:759-62.

Risk Summary

There is no use for contraception in pregnancy; therefore, depo-subQ provera 104 should be discontinued during pregnancy.

Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to progestins before conception or during early pregnancy.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15‑20%, respectively.

Risk Summary

Although medroxyprogesterone acetate is detectable in the milk of mothers receiving DMPA-IM, milk composition, quality, and amount do not appear to be adversely affected. Effects on milk production and lactation initiation/duration remain unclear when administered before 6 weeks after delivery, therefore, in mothers who exclusively breastfeed, initiate depo-subQ provera 104 during or after the sixth post-partum week [see Dosage and Administration (2.1)].

No adverse effects in breastfed infants would be expected with maternal use of progestins. Neonates and infants exposed to medroxyprogesterone acetate from breast milk have been studied and no adverse effects have been noted.

The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for depo-subQ provera 104 and any potential adverse effects on the breastfed child from depo-subQ provera 104 or from the underlying maternal condition.

Depo-subQ provera 104 contains medroxyprogesterone acetate (MPA), a derivative of progesterone, as its active ingredient. MPA is a white to off-white, odorless crystalline powder that is stable in air and that melts between 205°C and 209°C. It is freely soluble in chloroform, soluble in acetone and dioxane, sparingly soluble in alcohol and methanol, slightly soluble in ether, and insoluble in water.

The chemical name for MPA is 17-hydroxy-6α-methylpregn-4-ene-3,20-dione 17-acetate. The structural formula is as follows:

Depo-subQ provera 104 for subcutaneous use is available in pre-filled syringes, each containing 0.65 mL (104 mg) of sterile medroxyprogesterone acetate injectable suspension.

Each 0.65 mL contains the following inactive ingredients:

When necessary, the pH is adjusted with sodium hydroxide or hydrochloric acid, or both.

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.

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.

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.

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).

Depo-subQ provera 104 medroxyprogesterone acetate injectable suspension (104 mg/0.65 mL) is available in a single dose, disposable pre-filled syringe and is packaged with a 26-gauge × 3/8-inch Terumo SurGuard^® needle.

NDC 0009-4709-13

Depo-subQ provera 104 is indicated for the prevention of pregnancy and management of endometriosis-associated pain in females of reproductive age. Efficacy is expected to be the same for post-menarchal females under the age of 17 as for users 17 years and older.

Use of depo-subQ provera 104 is associated with significant loss of bone mineral density (BMD). This loss of BMD is of particular concern during adolescence, a critical period of bone accretion. It is unknown if use of depo-subQ provera 104 by female adolescents will reduce peak bone mass and increase the risk for osteoporotic fractures in later life. In a study of adolescent females (12–18 years of age) receiving DMPA-IM for contraception, mean BMD 2 years after starting DMPA-IM decreased 1.9% (spine), 4.3% (total hip), and 4.2% (femoral neck). In those adolescents who used DMPA-IM for more than 2 years, mean BMD at total hip and femoral neck did not return to baseline within 5 years.

Depo-subQ provera 104 is not indicated before menarche.

Depo-subQ provera 104 is not indicated in post-menopausal women.

The use of depo-subQ provera 104 is contraindicated in the following conditions:

• •
  Active thrombophlebitis, or current or history of thromboembolic disorders, or cerebral vascular disease [see Warnings and Precautions (5.2)].
• •
  Known, suspected, or past malignancy of the breast [see Warnings and Precautions (5.3)].
• •
  Significant liver disease [see Warnings and Precautions (5.14)].
• •
  Known hypersensitivity to medroxyprogesterone acetate or any of the ingredients in depo-subQ provera 104 [see Warnings and Precautions (5.6)].
• •
  Undiagnosed vaginal bleeding [see Warnings and Precautions (5.12)].

Because progestational drugs including depo-subQ provera 104 may cause fluid retention, monitor patients with conditions that might be affected by fluid retention.

The following important adverse reactions are described in more detail in other sections of the prescribing information:

• •
  Loss of bone mineral density [see Warnings and Precautions (5.1)]
• •
  Arterial and venous thromboembolic disorders [see Warnings and Precautions (5.2)]
• •
  Anaphylaxis [see Warnings and Precautions (5.6)]
• •
  Fluid retention [see Warnings and Precautions (5.7)]
• •
  Delayed return of ovulation or fertility [see Warnings and Precautions (5.9)]
• •
  Depression [see Warnings and Precautions (5.10)]
• •
  Injection site reactions [see Warnings and Precautions (5.11)]
• •
  Bleeding irregularities [see Warnings and Precautions (5.12)]

Strong CYP3A inhibitors and inducers: Avoid concomitant use. (7)

The following laboratory tests are expected to be affected by progestins including depo-subQ provera 104:

• •
  Plasma and urinary steroid levels are decreased (e.g., progesterone, estradiol, pregnanediol, testosterone, cortisol).
• •
  Gonadotropin levels are decreased.
• •
  Sex-hormone-binding-globulin concentrations are decreased.
• •
  Histology specimens may demonstrate changes consistent with progestin effects.

The following laboratory tests may be affected by depo-subQ provera 104, however the clinical significance is unknown:

• •
  Protein-bound iodine and butanol extractable protein-bound iodine may increase.
• •
  T₃-uptake values may decrease.
• •
  Coagulation test values for prothrombin (Factor II), and Factors VII, VIII, IX, and X may increase.
• •
  Sulfobromophthalein and other liver function test values may be increased.
• •
  The effects of medroxyprogesterone acetate on lipid metabolism are inconsistent. Both increases and decreases in total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol have been observed in studies.

The pharmacokinetic parameters of MPA following a single subcutaneous injection of depo-subQ provera 104 in healthy women (n=42) are shown in Table 2 and Figure P.

Following subcutaneous administration of single depo-subQ provera 104 doses ranging from 50 to 150 mg (0.48 and 1.4 times the recommended dose, respectively), the AUC and C_min (Day 91) increased with higher doses, but there was considerable overlap across dose levels. Serum MPA concentrations at Day 91 increased in a dose proportional manner but C_max did not appear to increase proportionally with increasing dose. The AUC data were suggestive of dose linearity.

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.

Depo-subQ provera 104 is indicated in females of reproductive age for:

• •
  Prevention of pregnancy and
• •
  Management of endometriosis-associated pain.

Depo-subQ provera 104 inhibits the secretion of gonadotropins, which primarily prevents follicular maturation and ovulation and causes thickening of cervical mucus. These actions contribute to its contraceptive effect.

Suppression of serum estradiol concentrations is likely to be responsible for the therapeutic effect on endometriosis-associated pain.

In three open label clinical studies, depo-SubQ provera 104 (104 mg given every three months subcutaneously), was administered to healthy, sexually-active, nonpregnant women 18 to 49 years of age who desired long-term contraception. In these three studies, no pregnancies were detected among 2042 women treated with depo-subQ provera 104 for up to 1 year. In women less than 36 years of age (at baseline), the Pearl Index pregnancy rate in cycles in which no other contraceptive methods were used, was 0 pregnancies per 100 women-years of use (upper 95% CI = 0.25).

The efficacy of depo-subQ provera 104 in the reduction of endometriosis-associated pain in women with the signs and symptoms of endometriosis was demonstrated in two active comparator-controlled studies in pre-menopausal women 18 to 49 years of age with laparoscopically diagnosed endometriosis and persistent endometriosis pain symptoms (i.e., Studies 268 and 270). Each study assessed endometriosis-associated pain over 6 months of treatment and recurrence of symptoms for 12-months post treatment.

Subjects were treated for six months with depo-subQ provera 104 [104 mg given subcutaneously every 3 months (2 injections)] or leuprolide [11.25 mg given subcutaneously every 3 months (2 injections) or 3.75 mg given subcutaneously every month (6 injections)]. Study 268 was conducted in the U.S. and Canada and enrolled 274 subjects (136 subjects received depo-subQ provera 104 and 138 subjects received leuprolide). Study 270 was conducted in South America, Europe, and Asia, and enrolled 299 subjects (153 subjects received depo-subQ provera 104 and 146 subjects received leuprolide).

Reduction in endometriosis pain was evaluated using a modified Biberoglu and Behrman scale that consisted of three patient-reported symptoms (i.e., dysmenorrhea, dyspareunia, and pelvic pain not related to menses) and two signs assessed during pelvic examination (i.e., pelvic tenderness and induration). For each category, a favorable response was defined as improvement of at least 1 unit (severity was assessed on a scale of 0 to 3) relative to baseline score (Figure Q).

Additionally, scores from each of the five categories were combined into a composite score that was considered a global measurement of overall disease improvement. For subjects with baseline scores for each of the 5 categories, a mean decrease of 4 points relative to baseline was considered a clinically meaningful improvement. Across both studies, the mean changes in the composite score met the protocol-defined criterion for improvement for the depo-subQ provera 104 and leuprolide treatment groups.

In the clinical trials, treatment with depo-subQ provera 104 was limited to six months. Data on the persistence of benefit with longer treatment are not available.

• •
  Thromboembolic disorders: Discontinue depo-subQ provera 104 in patients who develop arterial or venous thrombosis. (5.2)
• •
  Breast cancer risks: Monitor women with a family history of breast cancer or a significant risk of breast cancer carefully. (5.3)
• •
  Meningioma: Discontinue depo-subQ provera 104 if meningioma is diagnosed. Monitor patients for signs and symptoms of meningioma. (5.4)
• •
  Ectopic pregnancy: Consider ectopic pregnancy if a woman becomes pregnant or complains of severe abdominal pain. (5.5)
• •
  Anaphylaxis: Provide emergency medical treatment. (5.6)
• •
  Injection site reactions (e.g., persistent atrophy, dimpling/indentation, lump/nodule and discoloration) have been reported. (5.11)
• •
  Diabetics may be at greater risk of hyperglycemia. (5.13)
• •
  Jaundice and elevated transaminase: Discontinue depo-subQ provera 104 if jaundice or elevated transaminase levels develop. (5.14)

• •
  Only for healthcare professional administration. (2.1)
• •
  Prior to first injection, confirm the patient is not pregnant. (2.1)
• •
  Administer 104 mg of depo-subQ provera 104 by subcutaneous injection into the anterior thigh or abdomen, once every 12 to 14 weeks. (2.1)
• •
  See Full Prescribing Information for recommendations on switching from another contraceptive method to depo-subQ provera 104. (2.2)
• •
  See Full Prescribing Information for important preparation and administration instructions. (2.3)

Injectable suspension (104 mg/0.65 mL) in a single-dose pre-filled syringe, packaged with a 26-gauge × 3/8-inch Terumo SurGuard^® needle.

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.

The following adverse reactions have been identified during post-approval use of DMPA-IM. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

• •
  Immune system disorders: anaphylactic reaction, anaphylactoid reaction, angioedema
• •
  Vascular disorders: pulmonary embolism, deep vein thrombosis, thrombophlebitis
• •
  Musculoskeletal and connective tissue disorders: osteoporosis (including osteoporotic fractures)
• •
  Reproductive system and breast disorders: prolonged anovulation, unexpected pregnancy, uterine hyperplasia
• •
  Respiratory, thoracic and mediastinal disorders: hoarseness
• •
  Skin and subcutaneous tissue disorders: increased body odor
• •
  Gastrointestinal disorders: gastrointestinal disturbances
• •
  General disorders and administration site conditions: axillary swelling, chills, thirst

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.

• •
  Pregnancy: Discontinue if pregnancy occurs. (8.1)
• •
  Lactation: Detectable amounts of drug have been identified in the milk of mothers receiving depot-medroxyprogesterone acetate. (8.2)
• •
  Pediatric patients (after menarche): Bone loss is a particular concern. (8.4)

Clinical trials are conducted under widely varying conditions, therefore adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to depo-subQ provera 104 in five clinical trials involving 2325 women including 2043 women who received treatment for contraception (1780 treated up to 1 year and 263 treated for up to 2 years) and 282 women for endometriosis for up to 6 months. In these pooled trials, 9% of women discontinued treatment due to an adverse reaction and the most common reason for discontinuation was dysfunctional uterine bleeding (3%).

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).

Advise the patient to read the FDA-approved patient labeling (Patient Information).

• •
  Women who use depo-subQ provera 104 may lose significant bone mineral density. Bone loss is greater with increasing duration of use and may not be completely reversible [see Warnings and Precautions (5.1)].
• •
  It is unknown if use of depo-subQ provera 104 during adolescence or early adulthood, a critical period of bone accretion, will reduce peak bone mass and increase the risk for osteoporotic fracture in later life [see Warnings and Precautions (5.1)].
• •
  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 [see Indications and Usage (1) and Warnings and Precautions (5.1)].

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.

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:

• •
  Median time to ovulation was 10 months after the last injection.
• •
  Earliest return to ovulation was 6 months after the last injection.
• •
  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.

Prior to injection:

• •
  Ensure all the components in Figure A are available and that depo-subQ provera 104 is at room temperature.
• •
  Shake the pre-filled syringe vigorously prior to injection to ensure appropriate viscosity of the suspension.
• •
  Inspect depo-subQ provera 104 visually for particulate matter and discoloration.
  
  Figure A. Components in the Package

Depo-subQ provera 104 is indicated for the prevention of pregnancy and would therefore be expected to impair female fertility until cessation of treatment. Women may experience a delay in return to ovulation and fertility (conception) following discontinuation of depo-subQ provera 104 [see Warnings and Precautions (5.9)].

PAA229214

depo-subQ

provera 104^®

(medroxyprogesterone acetate) injectable

suspension (104 mg/0.65 mL for subcutaneous use)

104 mg/0.65 mL

0.65 mL Single Dose Syringe

Store at 20°C to 25°C (68°F to 77°F).

Do not refrigerate.

Shake vigorously before use.

Pharmacia & Upjohn Company LLC

LOT/EXP:

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.

NDC 0009-4709-13

Single Dose 0.65 mL Prefilled Syringe

depo-subQ provera 104^®

(medroxyprogesterone acetate) injectable suspension

(104 mg/0.65 mL for subcutaneous use)

104 mg/0.65 mL

Pfizer

Distributed by

Pharmacia & Upjohn Company LLC

A Subsidiary of Pfizer Inc.

New York, NY 10011

Rx only

When switching from another contraceptive method to depo-subQ provera 104, administer depo-subQ provera 104 in a manner that ensures continuous contraceptive coverage. Follow the respective recommendations when switching from the contraceptive methods listed below:

• •
  Combined hormonal contraceptives: administer the first injection of depo-subQ provera 104 within 7 days after the last day of using the combined hormonal contraceptive method (i.e., within 7 days after taking the last active pill).
• •
  An implant: administer the first injection of depo-subQ provera 104 on the day of implant removal.
• •
  A contraceptive vaginal ring or transdermal system: administer the first injection of depo-subQ provera 104 on the day the patient would have inserted the next ring or applied the next transdermal system.
• •
  An Intrauterine Device (IUD) or Intrauterine System (IUS): administer the first injection of depo-subQ provera 104 on the day of IUD/IUS removal. If the IUD/IUS is not removed on the first day of the patient's menstrual cycle, instruct patients to use a non-hormonal back-up method of birth control for the first 7 days after administration of depo-subQ provera 104.
• •
  Depot medroxyprogesterone acetate injectable suspension for intramuscular use (DMPA-IM): inject depo-subQ provera 104 12 to 14 weeks after the last dose of DMPA-IM.

Depo-subQ provera 104 is only for subcutaneous administration and is only to be administered by a healthcare professional.

Use for longer than 2 years is not recommended (unless other birth control methods or medical therapies for endometriosis-associated pain are considered inadequate) due to the impact of long-term depo-subQ provera 104 treatment on bone mineral density (BMD) [see Warnings and Precautions (5.1)].

Prior to the first injection confirm that the patient is not pregnant. For women who are sexually active and who have regular menses, administer the first injection only during the first 5 days of a normal menstrual period. For women who are breast-feeding, administer the first injection during or after the sixth post-partum week.

The recommended dosage of depo-subQ provera 104 is 104 mg given subcutaneously every 12 to 14 weeks. If more than 14 weeks elapse between injections, confirm that the patient is not pregnant before the next injection. Instruct the patient that if they are unable to receive an injection within 12–14 weeks, another contraceptive method should be used until the next depo-subQ provera 104 injection. The dosage does not need to be adjusted for body weight.

Inject the entire contents of the pre-filled syringe using strict aseptic technique into the upper anterior thigh or abdomen, rotating the sites with every injection [see Dosage and Administration (2.3)].

Some patients receiving progestins may exhibit a decrease in glucose tolerance; therefore, patients with diabetes may be at greater risk of hyperglycemia.

Patients should be counseled that this product does not protect against HIV infection (including AIDS) and other sexually transmitted infections.

[See Warnings and Precautions (5.3, 5.9)]

In two clinical studies of 573 adult women with endometriosis, the BMD effects of 6 months of depo-subQ provera 104 treatment (104 mg subcutaneously every 3 months) were compared to 6 months of leuprolide treatment (either 11.25 mg given subcutaneously every 3 months or 3.75 mg given subcutaneously every month). Subjects were then observed after treatment completion, for an additional 12 months. See Table 7 for the results.

In a study that compared changes in bone mineral density (BMD) in adult women using depo-subQ provera 104 or DMPA-IM for contraception, both treatments showed BMD reductions in the lumbar spine, total hip, and femoral neck. Mean percent changes in BMD in depo-subQ provera 104-treated women are shown in Table 3.

The effect of DMPA-IM on BMD in adolescents is described below, and the effect of depo-subQ provera 104 on BMD in adolescents is expected to be similar. The impact of DMPA-IM use for up to 240 weeks (4.6 years) was evaluated in an open-label non-randomized clinical study in 389 adolescent females (12 to 18 years of age). Use of DMPA-IM was associated with a significant decline from baseline in BMD.

Partway through the trial, DMPA-IM administration was stopped (at 120 weeks). The mean number of injections per DMPA-IM user was 9.3. Table 5 summarizes the study findings. The decline in BMD at total hip and femoral neck was greater with longer duration of use. The mean decrease in BMD at 240 weeks was more pronounced at total hip (-6.4%) and femoral neck (-5.4%) compared to lumbar spine (-2.1%).

Adolescents in the untreated cohort had an increase in BMD during the period of growth following menarche. However, the two cohorts were not matched at baseline for age, gynecologic age, race, BMD, and other factors that influence the rate of acquisition of BMD.

A retrospective cohort study to assess the association between DMPA-IM injection and the incidence of bone fractures was conducted in 312,395 female contraceptive users in the UK. The incidence rates of fracture were compared between DMPA-IM users and contraceptive users who had no recorded use of DMPA-IM. The Incident Rate Ratio (IRR) for any fracture during the follow-up period (mean=5.5 years) was 1.41 (95% CI 1.35, 1.47). It is not known if this is due to DMPA-IM use or to other related lifestyle factors that have a bearing on fracture rate.

In the study, when cumulative exposure to DMPA-IM was calculated, the fracture rate in users who received fewer than 8 injections was higher than that in women who received 8 or more injections. However, it is not clear that cumulative exposure, which may include periods of intermittent use separated by periods of non-use, is a useful measure of risk, as compared to exposure measures based on continuous use.

There were very few osteoporotic fractures (fracture sites known to be related to low BMD) in the study overall, and the incidence of osteoporotic fractures was not found to be higher in DMPA-IM users compared to non-users.

Importantly, this study could not determine whether use of DMPA-IM has an effect on fracture rate later in life. Given the similar effects on BMD from depo-subQ provera 104 and DMPA-IM described above, bone fracture incidence may also be expected to be similar.