PROVERA

What it is

PROVERA contains medroxyprogesterone acetate (MPA) as the active ingredient and is available in tablet strengths of 2.5 mg, 5 mg, 10 mg, 100 mg, 200 mg, 250 mg or 500 mg. MPA is a progestational agent. MPA is rapidly absorbed after oral administration. PROVERA is an orally active progestational steroid having an apparent half-life of about 30 hours.

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. — Secondary amenorrhoea proven not due to pregnancy, in amenorrhoea associated with a poorly developed proliferative endometrium, with conventional estrogen therapy. — Abnormal uterine bleeding in the absence of organic pathology. — Combination hormone replacement therapy (menopausal hormone therapy) in non-hysterectomised women.

Dosing overview

Combined estrogen-progestogen therapy in post-menopausal women should be prescribed at the lowest effective doses and limited to the shortest duration consistent with treatment goals and risks for the individual woman, and should be periodically evaluated. Menopausal hormone therapy in post-menopausal women is not generally appropriate for long-term use and should not be prescribed for longer than 6 months without re-examining the patient.

Key safety warnings

Physicians should be alert to the earliest manifestations of thrombotic disorders (thrombophlebitis, cerebrovascular disorders, pulmonary embolism, and retinal thrombosis). Should any of these occur, 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. Observational and randomised, prospective trials on the long-term effects of combined estrogen-progestogen regimen in post-menopausal women have reported an increased risk of several disorders including cardiovascular diseases (such as coronary heart disease and stroke), breast cancer, and venous thromboembolism. Mortality can be increased in those who are diagnosed with incident breast cancers. The possible effect of menopausal hormone therapy on mammographic density and on the sensitivity and specificity of breast cancer screening should also be considered. In current users the increased risk of breast cancer in women taking combined estrogen-progestin for menopausal hormone therapy becomes apparent after about 1–4 years. Current use of estrogen-alone or estrogen-plus-progestogen products in post-menopausal women for 5 or more years has been associated with an increased risk of ovarian cancer. A higher incidence of probable dementia in women aged 65 years and older has been reported during treatment with a menopausal hormone therapy regimen of conjugated estrogens and MPA. Eighty-five percent of cases of probable dementia occurred in the subgroup of women (54%) that were older than 70 years of age. Use of menopausal hormone therapy to prevent dementia or mild cognitive impairment in women 65 years or older is not recommended.

Contraindications

PROVERA is contraindicated in patients with thrombophlebitis, thrombotic or 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 to any of the excipients in the tablet; known or suspected pregnancy; severe uncontrolled hypertension; and known or suspected malignancy of the breast (excluding use in oncology indications).

PBS listing

PROVERA is listed on the PBS in tablet strengths of 100 mg, 200 mg and 250 mg, with restricted access (requiring authority approval). The ex-manufacturer price is A$67.83 for the 100 mg tablet, A$77.36 for the 200 mg tablet, and A$79.71 for the 250 mg tablet.

Regulatory history

PROVERA 100 mg, 200 mg, 250 mg and 500 mg tablets were first approved on 2 August 1991. The 2.5 mg, 5 mg and 10 mg tablets were first approved on 7 January 1993.