U.S. flag An official website of the United States government
  1. Home
  2. Drug Databases
  3. Drug Safety-related Labeling Changes

Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

DEPO-SUBQ PROVERA 104 (NDA-021583)

(MEDROXYPROGESTERONE ACETATE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

Expand all

12/16/2024 (SUPPL-43)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.10 Injection Site Reactions

Additions and/or revisions underlined:

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.

6 Adverse Reactions

6.1 Clinical Trials Experience

Changes to Table 1. Frequently Reported Adverse Reactions in the Contraception Studies (>1%); please refer to label for complete information

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Injection Site Reactions

Counsel patients that injection site reactions including site dimpling, scarring or discoloration may occur [see Warnings and Precautions (5.10)].

PATIENT INFORMATION

Additions and/or revisions underlined:

WHAT ARE COMMON SIDE EFFECTS OF depo-subQ provera 104?

The most common side effects are:

  • 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.

07/11/2024 (SUPPL-40)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.2 Lactation

PLLR conversion

Additions and revisions underlined:

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.

8.3 Females and Males of Reproductive Potential

PLLR conversion

Newly added subsection:

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 (5.8)].

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

8.1 Pregnancy

PLLR conversion

Additions and revisions underlined:

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.

12/04/2020 (SUPPL-33)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Loss of Bone Mineral Density

(Additions and/or revisions underlined)

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)].

12/04/2020 (SUPPL-34)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Loss of Bone Mineral Density

(Additions and/or revisions underlined)

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)].

12/23/2019 (SUPPL-29)

Approved Drug Label (PDF)

Boxed Warning

(PLR conversion; please refer to label)

4 Contraindications

(PLR conversion; please refer to label)

5 Warnings and Precautions

(PLR conversion; please refer to label)

6 Adverse Reactions

(PLR conversion; please refer to label)

7 Drug Interactions

(PLR conversion; please refer to label)

8 Use in Specific Populations

(PLR conversion; please refer to label)

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

(PLR conversion; please refer to label)

Other

(PLR conversion; please refer to label)

01/31/2017 (SUPPL-23)

Approved Drug Label (PDF)

5 Warnings and Precautions

PRECAUTIONS

1. Physical Examination

Additions and/or revisions underlined:

… Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care.

WARNINGS

Additions and/or revisions underlined:

3. Cancer Risks

The results of Long-term, case-controlled surveillance of users of depot medroxyprogesterone acetate IM 150 mg (Depo-Provera CI, 150 mg) found slight or no increased overall risk of breast cancer  and no overall increased risk of ovarian, liver, or cervical cancer, and a prolonged, protective effect of reducing the risk of endometrial cancer.

A pooled analysis (ii superscript) from two case-control studies(iii and  iv superscript) reported the relative risk (RR) of breast cancer for women who had ever used Depo-Provera CI (150 mg) as 1.1 (95% confidence interval [CI] 0.97 to 1.4). Overall, there was no increase in risk with increasing duration of use of Depo-Provera CI (150 mg). The RR of breast cancer for women of all ages who had initiated use of Depo-Provera CI (150 mg) within the previous 5 years was estimated to be 2.0 (95% CI 1.5 to 2.8). A component of the pooled analysis (iii superscript) described above, showed an increased RR of 2.19 (95% CI 1.23 to 3.89) of breast cancer associated with use of Depo-Provera CI (150 mg) in women whose first exposure to drug was within the previous 4 years and who were under 35 years of age. However, the overall RR for ever-users of Depo-Provera CI (150 mg) was only 1.21 (95% CI 0.96 to 1.52).

[NOTE: The value of 2.19 means that women whose first exposure to drug was within the previous 4 years and who were under 35 years of age had a 2.19-fold (95% CI 1.23 to 3.89-fold) increased risk of breast cancer relative to nonusers. The National Cancer Institute reports an average annual incidence rate for breast cancer for US women, all races, age 30 to 34 years ing of 26.7 per 100,000. A RR of 2.19, thus, increases the possible risk from 26.7 to 58.5 cases per 100,000 women. The attributable risk, thus, is 31.8 per 100,000 women per year.]

7. Anaphylaxis and Anaphylactoid Reaction

Serious anaphylactic reactions have been infrequently reported in women using Depo-Provera CI (150 mg). 

6 Adverse Reactions

Postmarketing Experience

Addition of the following:

… In addition, infrequent voluntary reports of anaphylaxis and anaphylactoid reaction have been received associated with use of Depo-Provera CI (150 mg).

The following additional reactions have been reported with Depo-Provera Contraceptive Injection and may occur with use of depo-subQ provera 104:

Addition of the following:

Immune system disorders: allergic reaction

Skin disorders: angioedema …

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT INFORMATION

Newly added section; please refer to label for full information.

12/16/2016 (SUPPL-31)

Approved Drug Label (PDF)

5 Warnings and Precautions

PRECAUTIONS

 

 

6. Injection Site Reactions

(additions underlined)

 

In 5 clinical studies of depo-subQ provera 104 involving 2,325 women (282 treated for up to 6 months, 1,780 treated for up to 1 year and 263 women treated for up to 2 years), 5% of women reported injection site reactions, and 1% had persistent skin changes, typically described as small areas of induration or atrophy.

In post-marketing experience, injection site reactions such as persistent atrophy of the injection site, dimpling/indentation and injection site lump/nodule have been reported.

 

 

 

6 Adverse Reactions

Postmarketing Experience

(additions  underlined)

 

General disorders: asthenia, axillary swelling, chills, chest pain, fever, excessive thirst, injection site nodule/lump, injection site pain/tenderness, injection site persistent atrophy/indentation/dimpling, injection site reactions.

10/14/2016 (SUPPL-32)

Approved Drug Label (PDF)

6 Adverse Reactions

Postmarketing Experience (addition underlined)

Anaphylactic reaction, anaphylactoid reaction, angioedema, and drug hypersensitivity have been reported with depo-subQ provera 104. There have been rare cases of osteoporosis including osteoporotic fractures reported postmarketing in patients taking DEPO-PROVERA Contraceptive Injection.