Drug Safety-related Labeling Changes (SrLC)

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DEPO-SUBQ PROVERA 104 (NDA-021583)

(MEDROXYPROGESTERONE ACETATE)

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

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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.

Questions related to the drug data in these files should be directed to the Center for Drug Evaluation and Research, Division of Drug Information
druginfo@fda.hhs.gov.

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