DEPO-PROVERA

What it is

DEPO-PROVERA is an injection suspension containing 150 mg medroxyprogesterone acetate (MPA) per mL. It is a progestational agent with prolonged progestational effects when administered by intramuscular injection.

Approved indications

— Palliative treatment of recurrent and/or metastatic breast or renal cell cancer and of inoperable recurrent or metastatic endometrial carcinoma. — Treatment of visually proven (laparoscopy) endometriosis where the required end-point of treatment is pregnancy, or for the control of symptoms when surgery is contraindicated or has been unsuccessful. — Long-term prevention of pregnancy in women when administered at 3-month intervals.

Dosing overview

Key safety warnings

Loss of bone mineral density (BMD) may occur in pre-menopausal women who use MPA long-term (greater than 2 years), and women should be assessed before starting treatment for contraception or endometriosis for the risk of osteoporosis. Women under the age of 18 years may be at risk of failing to achieve their predicted peak BMD. The physician should be alert to the earliest manifestations of thrombotic disorders including thrombophlebitis, cerebrovascular disorders, pulmonary embolism and retinal thrombosis. Should any of these occur or be suspected, the drug should be discontinued immediately. Meningiomas have been reported following long-term administration of progestins, including MPA. MPA should be discontinued if a meningioma is diagnosed. Caution is advised when recommending medroxyprogesterone to patients with a history of meningioma. Most women receiving DEPO-PROVERA for contraception experienced disruption of menstrual bleeding patterns with altered bleeding including irregular or unpredictable bleeding or spotting, or rarely, heavy or continuous bleeding. If abnormal bleeding persists or is severe, appropriate investigations should be instituted to rule out organic pathology. An increased relative risk of 2.19 has been associated with use of DEPO-PROVERA in women whose first exposure to the drug was within the previous 4 years and were under 35 years of age. The risk increases in women aged between 25 and 34 years and rises to 4.6 in women aged less than 25 years with more than 2 years exposure to DEPO-PROVERA. Because this drug may cause some degree of fluid retention, conditions which might be influenced by this factor, such as epilepsy, migraine, asthma, or cardiac or renal dysfunction, require careful observation.

Contraindications

DEPO-PROVERA is contraindicated in patients with: thrombophlebitis, thromboembolic disorders, cerebral apoplexy or patients with a past history of these conditions; markedly impaired liver function; undiagnosed vaginal bleeding; undiagnosed urinary tract bleeding; undiagnosed breast pathology; missed abortion; known sensitivity to MPA or any of the excipients in the injection; known or suspected pregnancy; severe uncontrolled hypertension; or known or suspected malignancy of the breast (excluding use in oncology indications).

PBS listing

The 150 mg in 1 mL pre-filled syringe injection is listed on the PBS with unrestricted access at an ex-manufacturer price of A$13.14.

Regulatory history

DEPO-PROVERA was first approved on 2 August 1991. An aqueous suspension injection vial formulation (ARTG 12300) was first listed in 1991, and a pre-filled syringe formulation (ARTG 401610) was first listed on 3 May 2023. In November 2017, the PBAC recommended an amendment to the PBS listing to allow medroxyprogesterone acetate injection to be used for contraception. In November 2023, the PBAC recommended listing of the 150 mg/mL pre-filled syringe under the same circumstances as the currently listed injection vial forms, with equi-effective doses established and considered equivalent for substitution.