It is good medical practice for all women to have annual
history and physical examinations, including women using DEPO-PROVERA Sterile
Aqueous Suspension. The physical examination, however, may be deferred until
after initiation of DEPO
PROVERA 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
Women who have or have had a history of breast cancer
should be advised against the use of DEPO-PROVERA, as breast cancer may be
hormonally sensitive. Women with a strong family history of breast cancer
should be monitored with particular care.
Because progestational drugs may cause some degree of
fluid retention, conditions which might be influenced by this condition, such
as epilepsy, migraine, asthma, cardiac or renal dysfunction, require careful
In cases of breakthrough bleeding, as in all cases of
irregular bleeding per vaginum, nonfunctional causes should be borne in mind
and adequate diagnostic measures undertaken.
Patients who have a history of psychic depression should
be carefully observed and the drug discontinued if the depression recurs to a
Masking Of Climacteric
The age of the patient constitutes no absolute limiting
factor although treatment with progestin may mask the onset of the climacteric.
Use With Estrogen
Studies of the addition of a progestin product to an
estrogen replacement regimen for seven or more days of a cycle of estrogen
administration have reported a lowered incidence of endometrial hyperplasia.
Morphological and biochemical studies of endometrial suggest that 10-13 days of
a progestin are needed to provide maximal maturation of the endometrium and to
eliminate any hyperplastic changes. Whether this will provide protection from
endometrial carcinoma has not been clearly established.
There are possible risks which may be associated with the
inclusion of progestin in estrogen replacement regimen, including adverse
effects on carbohydrate and lipid metabolism. The dosage used may be important
in minimizing these adverse effects.
A decrease in glucose tolerance has been observed in a
small percentage of patients on estrogen-progestin combination treatment. The
mechanism of this decrease is obscure. For this reason, diabetic patients
should be carefully observed while receiving such therapy.
Monitor patients for hepatic dysfunction periodically and
temporarily interrupt DEPOPROVERA Sterile Aqueous Suspension use if the patient
develops hepatic dysfunction. Do not resume use until markers of liver function
return to normal.
Decrease In Bone Mineral Density
Studies in pre-menopausal women show that
medroxyprogesterone acetate given as 150 mg intramuscularly every three months
reduces serum estrogen levels and is associated with loss of bone mineral density
(BMD). It is unknown if use of Depo-Provera during adolescence and early
adulthood, a critical period of bone accretion, will reduce peak bone mass. An
evaluation of BMD may be appropriate in some patients who use higher doses of
medroxyprogesterone acetate for long-term treatment of endometrial or renal
Effects On The Hypothalmic-Pituitary-Adrenal Axis
Some patients receiving medroxyprogesterone acetate may
exhibit suppressed adrenal function. Medroxyprogesterone acetate may have cortisol-like
glucocorticoid activity and provide negative feedback to the hypothalamus or
pituitary. This may result in decreased plasma cortisol levels, decreased
cortisol secretion, and low plasma ACTH levels.
The use of DEPO-PROVERA Sterile Aqueous Suspension may,
due to its cortisol-like glucocorticoid activity, also produce Cushingoid
symptoms such as weight gain, edema/fluid retention, and facial swelling.
The effect of prolonged use of DEPO-PROVERA Sterile
Aqueous Suspension at the recommended doses on pituitary, ovarian, adrenal,
hepatic, and uterine function is not known.
Interference With Laboratory Tests
The use of DEPO-PROVERA Sterile Aqueous Suspension may
change the results of some laboratory tests, such as coagulation factors,
lipids, glucose tolerance, and binding proteins. [See Laboratory Test
When multi-dose vials are used, special care to prevent
contamination of the contents is essential. There is some evidence that
benzalkonium chloride is not an adequate antiseptic for sterilizing
DEPO-PROVERA Sterile Aqueous Suspension multi-dose vials. A povidone-iodine
solution or similar product is recommended to cleanse the vial top prior to
aspiration of contents. [See WARNINGS].
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term intramuscular administration of
Medroxyprogesterone acetate (MPA) has been shown to produce mammary tumors in
beagle dogs. There is no evidence of a carcinogenic effect associated with the
oral administration of MPA to rats and mice.
Medroxyprogesterone acetate was not mutagenic in a
battery of in vitro or in vivo genetic toxicity assays.
Medroxyprogesterone acetate at high doses is an
anti-fertility drug and return to ovulation and fertility may be delayed after
It is not known whether medroxyprogesterone acetate can
cause fetal harm when administered to a pregnant woman. Medroxyprogesterone
acetate should be given to a pregnant woman only if clearly needed.
Published studies report the presence of
medroxyprogesterone acetate in human milk. Caution should be exercised when
medroxyprogesterone acetate is administered to a nursing woman.
Safety and efficacy of DEPO-PROVERA for endometrial and
renal carcinoma have not been established in pediatric patients.
Studies in pre-menopausal women show that Depo-Provera is
associated with loss of BMD. It is unknown if use of Depo-Provera during
adolescence and early adulthood, a critical period of bone accretion, will
reduce peak bone mass. (See PRECAUTIONS: Decrease in Bone Mineral