Medication Overview

Provera (medroxyprogesterone acetate) is a synthetic form of the hormone progesterone. It is commonly prescribed for various medical conditions related to hormone imbalances, including menstrual disorders, abnormal uterine bleeding, and to support the endometrial lining in hormone replacement therapy.

Active Ingredient

The active ingredient in Provera is medroxyprogesterone acetate. It is a derivative of progesterone, a hormone naturally produced in the body. Medroxyprogesterone acetate mimics the actions of natural progesterone, playing a critical role in the menstrual cycle and pregnancy.

Mechanism of Action

Medroxyprogesterone acetate works by binding to progesterone receptors in the body. This binding alters the expression of certain genes, leading to changes in the endometrium. As a result, it induces secretory changes in the endometrium, stabilizes uterine lining, and regulates menstrual cycles.

Indications

Menstrual Disorders

Provera is commonly used to treat secondary amenorrhea, a condition where menstruation stops for several months in a woman who previously had normal periods. It helps initiate and maintain regular menstrual cycles by providing the necessary hormonal support.

Abnormal Uterine Bleeding

Provera is prescribed to manage abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology. It helps stabilize the endometrium, reducing heavy or prolonged menstrual bleeding.

Hormone Replacement Therapy

In postmenopausal women, Provera is used in combination with estrogen therapy to reduce the risk of endometrial hyperplasia and carcinoma. Provera counteracts the effects of estrogen on the endometrium, promoting a healthier uterine lining.

Dosage and Administration

General Dosage Information

The dosage of Provera varies based on the condition being treated and individual patient factors. It is essential to follow the prescribed dosage regimen by a healthcare professional to ensure efficacy and safety.

Menstrual Disorders Dosage

For treating secondary amenorrhea, the typical dosage is 5 to 10 mg of Provera daily for 5 to 10 days, starting on day 16 or 21 of the menstrual cycle. Menstruation usually occurs within three to seven days after discontinuing the therapy.

Abnormal Uterine Bleeding Dosage

When used to manage abnormal uterine bleeding, the dosage generally ranges from 5 to 10 mg daily for 5 to 10 days, starting on day 16 or 21 of the menstrual cycle. The bleeding should subside within this period.

Hormone Replacement Dosage

In hormone replacement therapy, Provera is administered at a dose of 2.5 mg to 10 mg daily, typically during the last 10 to 14 days of a 28-day estrogen therapy cycle. This regimen helps mitigate the risk of estrogen-induced endometrial hyperplasia.

Pharmacokinetics

Absorption and Distribution

Medroxyprogesterone acetate is rapidly absorbed in the gastrointestinal tract after oral administration. It exhibits a high bioavailability and achieves peak plasma concentrations within 2 to 4 hours. The drug is widely distributed throughout the body tissues, particularly in fatty tissues.

Metabolism and Elimination

Provera is extensively metabolized in the liver, primarily by hydroxylation and conjugation pathways. The metabolites are eliminated via urine and feces. The half-life of medroxyprogesterone acetate ranges from 12 to 17 hours, which supports its once-daily dosing regimen.

Drug Interactions

Anticoagulants Interaction

Provera may reduce the effectiveness of anticoagulants such as warfarin, leading to a decreased anticoagulant effect. Monitoring of INR levels is recommended during concurrent use.

Enzyme Inducers Interaction

Medroxyprogesterone acetate metabolism can be accelerated by enzyme inducers like phenytoin, carbamazepine, and rifampicin, leading to reduced therapeutic effects of Provera. Dose adjustments may be necessary.

Contraceptives Interaction

When used with other hormonal contraceptives, there could be an increased risk of side effects or reduced efficacy of the contraceptive methods. It is vital to consult a healthcare provider for appropriate contraceptive advice.

Adverse Effects

Common Side Effects

Commonly reported side effects of Provera include headache, nausea, breast tenderness, and mood changes. Patients should be aware of these potential adverse effects and report persistent symptoms to their healthcare provider.

Serious Side Effects

Serious side effects may include thromboembolic disorders, stroke, and severe hypertension. The incidence of these effects increases with long-term use and in patients with pre-existing risk factors.

Endometrial Changes

Provera can cause changes in the endometrial tissue, including endometrial atrophy and hyperplasia. These changes necessitate regular monitoring through pelvic examinations and possibly endometrial biopsies.

Patient Monitoring

Regular Examinations

Patients on Provera should have regular follow-up appointments with their healthcare provider to monitor the drug’s effectiveness and detect any adverse effects early. This includes periodic pelvic examinations and assessments of liver function.

Hormonal Levels Monitoring

Hormonal levels may need to be monitored periodically to ensure therapeutic efficacy and adjust the dosage if necessary. This is particularly important for patients using Provera as part of hormone replacement therapy.

Bone Density Monitoring

Long-term use of Provera can affect bone density, particularly in postmenopausal women. Regular bone density scans may be recommended to detect any adverse impact early and take appropriate preventive measures.

Special Populations

Geriatric Use

The use of Provera in elderly patients should be approached cautiously. Older adults may have an increased risk of thromboembolic events and other serious side effects. Individual risk assessment and dose adjustments are necessary.

Renal Impairment

Patients with renal impairment may require dosage adjustments, as their ability to clear the drug may be reduced. Renal function should be assessed before starting therapy and monitored periodically.

Hepatic Impairment

Provera is extensively metabolized in the liver, so patients with hepatic impairment may experience altered drug metabolism. Dose reductions or alternative therapies may be necessary, and liver function tests should be performed regularly.

Contraindications

Active Thromboembolism

Provera is contraindicated in patients with active or recent thromboembolic disorders, such as deep vein thrombosis, pulmonary embolism, or stroke. The drug can exacerbate these conditions, leading to life-threatening complications.

Undiagnosed Vaginal Bleeding

Provera should not be used in patients with undiagnosed vaginal bleeding, as the cause of the bleeding must be determined before starting hormonal therapy. This helps to rule out malignancies and other serious underlying conditions.

Hypersensitivity Reactions

Patients who have known hypersensitivity to medroxyprogesterone acetate or any of its components should not use Provera. Hypersensitivity reactions can range from mild skin rashes to severe anaphylactic reactions.