Depo-Provera 500 mg

/ Pfizer

Recurrent and/or Metastatic Breast Cancer
Injectable DMPA initial dose 500 to 1000 mg intramuscularly per day for 28 days. The patient should then be placed on a maintenance schedule of 500 mg twice weekly as long as she responds to treatment.
Recurrent and/or Metastatic Endometrial or Renal Cancer
Injectable DMPA 400 to 1000 mg intramuscularly per week is recommended initially. If improvement is noted within a few weeks or months and the disease appears stabilized, it may be possible to maintain improvement with as little as 400 mg per month.
Long-Term Use
Since loss of bone mineral density (BMD) may occur in pre-menopausal women who use DMPA injection long-term, a risk/benefit assessment, which also takes into consideration the decrease in BMD that occurs during pregnancy and/or lactation, should be considered.
Use in Children
DMPA IM is not indicated before menarche. Data are available in adolescent females (12-18 years). Other than concerns about loss of BMD, the safety and effectiveness of DMPA IM are expected to be the same as for postmenarcheal adolescent and adult females.
Hepatic Insufficiency
No clinical studies have evaluated the effect of hepatic disease on the pharmacokinetics of MPA. However, MPA is almost exclusively eliminated by hepatic metabolism and steroid hormones may be poorly metabolized in patients with severe liver insufficiency.
Renal Insufficiency
No clinical studies have evaluated the effect of renal disease on the pharmacokinetics of MPA. However, since MPA is almost exclusively eliminated by hepatic metabolism, no dosage adjustment should be necessary in women with renal insufficiency.

Palliation of inoperable recurrent or metastatic carcinoma of endometrium, breast, ovary and kidney.

Hypersensitivity to medroxyprogesterone acetate or to any of excipients.
Suspected or confirmed pregnancy.
Undiagnosed vaginal bleeding.
Severe liver impairment.

Any unexpected vaginal bleeding that takes place during treatment should be investigated.
The drug can cause fluid retention, and as a result, precaution is necessary in patients whose pre-existing clinical situation may be negatively affected by the retention of liquids.
Patients with a history of clinical treatment for mental depression should be carefully monitored when undergoing therapy.
Reduced glucose tolerance has been observed in some patients receiving Depo-Provera. For this reason, diabetics should be kept under careful observation during treatment.
When pathology examinations of endometrium or endocervix tissues are carried out, the pathologist should be advised that the patient is under treatment.
The doctor and the laboratory should be aware that treatment can reduce the levels of the following endocrine biomarkers:
– steroids in plasma and urine (e.g. cortisol, oestrogen, pregnanediol, progesterone, testosterone)
– gonadotrophins in plasma and urine [e.g. Luteinising Hormone (LH) and Follicle Stimulating Hormone (FSH)]
– female sex hormone binding globulins
Treatment should not be resumed until the patient has been examined for unexpected occurrence of partial or complete loss of vision, proptosis, diplopia or migraines. If the examination reveals the existence of papilloedema or vascular lesions of the retina, the treatment should not be resumed.
Depo-Provera has not been associated with the induction of thrombotic or thromboembolic disorders, but its use in patients with a prior history of venous thromboembolism (VTE) is not recommended. Discontinuation is also advised for patients who develop VTE during treatment.
Loss of bone mineral density:
There are no studies on the effect caused by medroxyprogesterone, administered parenterally, on bone mineral density in oncological treatment.
It could be necessary to make an assessment of bone mineral density in patients who are undergoing prolonged treatment with Depo-Provera.
Treatment with Depo-Provera reduces serum levels of oestrogen and is associated with a statistically significant loss of bone mineral density, resulting from an adaptation of the bone metabolism to a lower level of oestrogen. Bone loss increases with prolonged treatment duration, and may be not completely reversible in some women. It is not known whether treatment of young women with Depo-Provera during adolescence and early adulthood, a critical period of bone accretion, will reduce peak bone mass and increase the risk for fractures in later life, i.e. after menopause.
A study to assess the BMD effects of Depo-Provera in adolescent females showed that its use was associated with a statistically significant decline in BMD from baseline.
After discontinuing depot medroxyprogesterone acetate intramuscular (DMPA-IM) in adolescents, full recovery of mean BMD required 1.2 years at the lumbar spine, 4.6 years at the total hip, and 4.6 years at the femoral neck. However, in some participants, BMD did not fully return to baseline during follow-up and the long-term outcome is not known in this group.
A large observational study of predominantly adult female contraceptive users showed that use of DMPA-IM did not increase risk for bone fractures. It should be noted that this study could not determine whether use of medroxyprogesterone acetate has an effect on fracture rate later in life.
It is recommended that all patients should have adequate ingestion of calcium and vitamin D.
Breast cancer
After various epidemiological studies, no increase in the risk of breast cancer was found in users of injectable prolonged-release progestogen, when compared to non-users. However, an increase was found in the relative risk (for example 2.0 in one study) in women who used prolonged-release injectable progestogen or had used it in previous years. From these data it is not possible to infer whether the increased rate of diagnoses of breast cancer in women who were users is due to an increase of vigilance, to the biological effects of injectable progestogen or to a combination of both reasons.
Special warnings and precautions for use of Depo-Provera in oncology:
Prolonged anovulation, with amenorrhoea and/or an irregular menstrual pattern, can occur after the administration of a single dose or multiple administration of Depo-Provera.
Depo-Provera can give rise to Cushingoid symptoms.
Some patients in treatment with Depo-Provera may present suppressed adrenal function. Depo-Provera® may reduce blood levels of corticotropin (ACTH) and hydrocortisone.
The doctor and the laboratory should be informed that in addition to the biomarkers referred to above, the use of Depo-Provera in oncological indications can also cause partial adrenal insufficiency (reduction of the response of the adrenal– pituitary axis) during the metyrapone test. Therefore, capacity of the adrenal cortex to respond to corticotropin (ACTH) should be demonstrated before the administration of metyrapone.
This medicine contains methyl parahydroxybenzoate (Methylparaben) and propyl parahydroxybenzoate (Propylparaben). It can cause allergic reactions (possibly delayed), and, exceptionally, bronchial spasm.
See prescribing information for full details.

Common: Weight fluctuation, Increased appetite, Insomnia, Headache, Dizziness, Tremors, Vomiting, Constipation, Nausea, Hyperhidrosis, Erectile dysfunction, Oedema /fluid retention, Fatigue Injection site reaction.
See prescribing information for full details.

Aminoglutethimide, when administered concomitantly with high doses of Depo-Provera, can significantly reduce serum levels of medroxyprogesterone acetate. The possibility of reducing the efficacy of high doses of Depo-Provera should be taken into consideration when using aminoglutethimide simultaneously.
Medroxyprogesterone acetate (MPA) is metabolized in-vitro primarily by hydroxylation via the CYP3A4. Specific drug-drug interaction studies evaluating the clinical effects of CYP3A4 inducers or inhibitors on MPA have not been conducted and therefore the clinical effects of CYP3A4 inducers or inhibitors are unknown.
See prescribing information for full details.

Pregnancy
Depo-Provera is contraindicated during pregnancy.
Notifications suggest, in certain circumstances, an association between intrauterine exposure to progestogen medications during the first three months of pregnancy and the occurrence of genital anomalies in the foetus.
Children resulting from unintentional pregnancies that took place 1 to 2 months after administration of Depo-Provera can present an increased risk of being born with low weight, which in turn is associated with an increased risk of neonatal death. The risk attributed is low since pregnancy during treatment with Depo-Provera is infrequent. There is no definitive information on the other formulations of medroxyprogesterone acetate. If the pregnancy occurs during the therapy, the patient should be informed about the potential risks for the foetus.
Breastfeeding
Medroxyprogesterone acetate and its metabolites are excreted in breast milk. There is no evidence that this fact represents a risk to the infant.
Fertility
Depo-Provera has a prolonged contraceptive effect. In the event of conception, the average time for this to occur is after 10 months (ranging from 4-31 months) after the last administration, but there is no relation to the duration of the treatment.

No positive action is required other than cessation of therapy.

Injectable suspensions should be shaken well before use.
May cause headaches and dizziness. Patients should be advised not to drive or operate machinery if affected.
This medicine contains sodium. It contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially ‘sodium free’.