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1. Physical Examination

It is good medical practice for all women to have annual history and physical examinations, including women using depo-subQ provera 104^™. The physical examination, however, may be deferred until after initiation of depo-subQ provera 104^™ if requested by the woman and judged appropriate by the clinician. The physical examination should include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology and relevant laboratory tests. In case of undiagnosed, persistent or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care.

2. Fluid Retention

Because progestational drugs may cause some degree of fluid retention, conditions that might be influenced by this condition, such as epilepsy, migraine, asthma, and cardiac or renal dysfunction, require careful observation.

3. Weight Gain

Weight gain is a common occurrence in women using depo-subQ provera 104^™. In three large clinical trials using depo-subQ provera 104^™, the mean weight gain was 3.5 lb in the first year of use. In a small, two-year study comparing depo-subQ provera 104^™ to Depo-Provera CI (150 mg), the mean weight gain observed for women using depo-subQ provera 104^™ (7.5 lb) was similar to the mean weight gain for women using Depo-Provera CI, 150 mg (7.6 lb).

Although there are no data related to weight gain beyond 2 years for depo-subQ provera 104^™, the data on Depo-Provera CI (150 mg) 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, while 114 women using non-hormonal contraception had a mean weight gain of 6.4 lb.

4. Return to Ovulation and Fertility

Return to ovulation is likely to be delayed after stopping therapy. Among 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^™, and therefore it is important to follow the recommended dosing schedule.

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, 1 became pregnant within 1 year of her last injection. A second woman became pregnant 443 days after her last injection. Seven women were lost to follow-up.

5. Depression

Patients with a history of treatment for clinical depression should be carefully monitored while receiving depo-subQ provera 104^™.

6. Injection Site Reactions

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.

7. Carbohydrate/Metabolism

Some patients receiving progestins may exhibit a decrease in glucose tolerance. Diabetic patients should be carefully observed while receiving such therapy.

8. Liver Function

If jaundice or any other liver abnormality develops in any woman receiving depo-subQ provera 104^™, treatment should be stopped while the cause is determined. Treatment may be resumed when liver function is acceptable and when the healthcare provider has determined that depo-subQ provera 104^™ did not cause the abnormality.

9. Drug Interactions

No drug-drug interaction studies have been conducted with depo-subQ provera 104^™. Aminoglutethimide administered concomitantly with depo-subQ provera 104^™ may significantly decrease the serum concentrations of MPA.

10. Laboratory Tests

The pathologist should be advised of progestin therapy when relevant specimens are submitted. The physician should be informed that certain endocrine and liver function tests, and blood components may be affected by progestin therapy:

(a)	Plasma and urinary steroid levels are decreased (e.g., progesterone, estradiol, pregnanediol, testosterone, cortisol).
(b)	Plasma and urinary gonadotropin levels are decreased (e.g., LH, FSH).
(c)	SHBG concentrations are decreased.
(d)	T3-uptake values may decrease.
(e)	There may be small changes in coagulation factors.
(f)	Sulfobromophthalein and other liver function test values may be increased slightly.
(g)	There may be small changes in lipid profiles.

11. Carcinogenesis, Mutagenesis, Impairment of Fertility

See WARNINGS, section 3 and PRECAUTIONS, section 4.

12. Pregnancy

Although depo-subQ provera 104^™ should not be used during pregnancy, there appears to be little or no increased risk of birth defects in women who have inadvertently been exposed to medroxyprogesterone acetate injections in early pregnancy. Neonates exposed to medroxyprogesterone acetate in-utero and followed to adolescence showed no evidence of any adverse effects on their health including their physical, intellectual, sexual or social development.

13. Nursing Mothers

Although the drug is detectable in the milk of mothers receiving Depo-Provera CI (150 mg), milk composition, quality, and amount are not adversely affected. Neonates and infants exposed to medroxyprogesterone acetate from breast milk have been studied for developmental and behavioral effects through puberty, and no adverse effects have been noted..

14. Pediatric Use

depo-subQ provera 104^™ is not indicated before menarche. 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 and early adulthood, a critical period of bone accretion. In adolescents, interpretation of BMD results should take into account patient age and skeletal maturity. It is unknown if use of depo-subQ provera 104^™ by younger women will reduce peak bone mass and increase the risk for osteoporotic fractures in later life. Other than concerns about loss of BMD, the safety and effectiveness are expected to be the same for postmenarchal adolescents and adult women.

15. Geriatric Use

depo-subQ provera 104^™ is intended for use in women with childbearing potential. Studies with depo-subQ provera 104^™ in geriatric women have not been conducted.

INFORMATION FOR THE PATIENT

See PATIENT LABELING.