6 ADVERSE REACTIONS
The following important adverse reactions observed with the use of Depo-Provera CI are discussed in greater detail in the Warnings and Precautions section (5):
- Loss of Bone Mineral Density [see Warnings and Precautions (5.1)]
- Thromboembolic disease [see Warnings and Precautions (5.2)]
- Breast Cancer [see Warnings and Precautions (5.3)]
- Anaphylaxis and Anaphylactoid Reactions [see Warnings and Precautions (5.5)]
- Bleeding Irregularities[see Warnings and Precautions (5.10)]
- Weight Gain [see Warnings and Precautions (5.11)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies 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.
In the two clinical trials with Depo-Provera CI, over 3,900 women, who were treated for up to 7 years, reported the following adverse reactions, which may or may not be related to the use of Depo-Provera CI. The population studied ranges in age from 15 to 51 years, of which 46% were White, 50% Non-White, and 4.9% Unknown race. The patients received 150 mg Depo-Provera CI every 3-months (90 days). The median study duration was 13 months with a range of 1–84 months. Fifty eight percent of patients remained in the study after 13 months and 34% after 24 months.
| Body System* | Adverse Reactions [Incidence (%)] |
|---|---|
| |
| Body as a Whole | Headache (16.5%) Abdominal pain/discomfort (11.2%) |
| Metabolic/Nutritional | Increased weight> 10lbs at 24 months (37.7%) |
| Nervous | Nervousness (10.8%) Dizziness (5.6%) Libido decreased (5.5%) |
| Urogenital | Menstrual irregularities: (bleeding (57.3% at 12 months, 32.1% at 24 months) amenorrhea (55% at 12 months, 68% at 24 months) |
| Body System* | Adverse Reactions [Incidence (%)] |
|---|---|
| |
| Body as a Whole | Asthenia/fatigue (4.2%) Backache (2.2%) Dysmenorrhea (1.7%) Hot flashes (1.0%) |
| Digestive | Nausea (3.3%) Bloating (2.3%) |
| Metabolic/Nutritional | Edema (2.2%) |
| Musculoskeletal | Leg cramps (3.7%) Arthralgia (1.0%) |
| Nervous | Depression (1.5%) Insomnia (1.0%) |
| Skin and Appendages | Acne (1.2%) No hair growth/alopecia (1.1%) Rash (1.1%) |
| Urogenital | Leukorrhea (2.9%) Breast pain (2.8%) Vaginitis (1.2%) |
Adverse reactions leading to study discontinuation in ≥2% of subjects: bleeding (8.2%), amenorrhea (2.1%), weight gain (2.0%)
6.2 Post-Marketing Experience
The following adverse reactions have been identified during post approval use of Depo-Provera CI. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
There have been cases of osteoporosis including osteoporotic fractures reported post-marketing in patients taking Depo-Provera CI.
| Body System* | Adverse Reactions |
|---|---|
| |
| Body as a Whole | Chest pain, Allergic reactions including angioedema, Fever, Injection site abscess†, Injection site infection†, Injection site nodule/lump, Injection site pain/tenderness, Injection site persistent atrophy/indentation/dimpling, Injection-site reaction, Lipodystrophy acquired, Chills, Axillary swelling |
| Cardiovascular | Syncope, Tachycardia, Thrombophlebitis, Deep vein thrombosis, Pulmonary embolus, Varicose veins |
| Digestive | Changes in appetite, Gastrointestinal disturbances, Jaundice, Excessive thirst, Rectal bleeding |
| Hematologic and Lymphatic | Anemia, Blood dyscrasia |
| Musculoskeletal | Osteoporosis |
| Neoplasms | Cervical cancer, Breast cancer |
| Nervous | Paralysis, Facial palsy, Paresthesia, Drowsiness |
| Respiratory | Dyspnea and asthma, Hoarseness |
| Skin and Appendages | Hirsutism, Excessive sweating and body odor, Dry skin, Scleroderma |
| Urogenital | Lack of return to fertility, Unexpected pregnancy, Prevention of lactation, Changes in breast size, Breast lumps or nipple bleeding, Galactorrhea, Melasma, Chloasma, Increased libido, Uterine hyperplasia, Genitourinary infections, Vaginal cysts, Dyspareunia |