Usage
Medroxyprogesterone acetate is a synthetic progestin, a class of medications similar to the naturally occurring female hormone progesterone. It is prescribed for various conditions, including:
- Abnormal uterine bleeding: Due to hormonal imbalance without an underlying structural abnormality.
- Amenorrhea (absence of menstruation): When not caused by pregnancy.
- Endometrial hyperplasia: To prevent thickening of the uterine lining in postmenopausal women taking estrogen therapy.
- Endometriosis: To manage associated pain (limited duration).
- Certain hormone-dependent cancers: Such as endometrial, renal cell, and breast cancer (in postmenopausal women).
- Contraception: To prevent pregnancy.
Its pharmacological classifications include:
- Progestin
- Antineoplastic (in the context of cancer treatment)
- Contraceptive
Mechanism of Action: Medroxyprogesterone acetate primarily works by binding to progesterone receptors in the uterus, ovaries, and other tissues. This action transforms the proliferative endometrium into a secretory endometrium, suppressing endometrial growth and reducing the risk of hyperplasia. In the context of contraception, it inhibits gonadotropin release, preventing ovulation and thickening cervical mucus.
Alternate Names
Brand Names:
- Provera
- Depo-Provera
- Depo-subQ Provera 104
How It Works
Pharmacodynamics: Medroxyprogesterone acetate binds to progesterone receptors, exerting effects on the endometrium (transformation from proliferative to secretory phase), hypothalamus (suppression of gonadotropin-releasing hormone), and pituitary gland (inhibition of gonadotropin release). It also has some androgenic and anabolic activity but no estrogenic effects.
Pharmacokinetics:
- Absorption: Well-absorbed orally and from intramuscular (IM) or subcutaneous (SC) injection sites.
- Metabolism: Primarily hepatic, involving CYP3A4 enzymes.
- Elimination: Excreted mainly in urine and feces, with a half-life varying depending on the route of administration (oral: 24-48 hours, IM: several weeks).
Mode of Action: Binds to progesterone receptors, leading to downstream effects via genomic and non-genomic pathways, impacting gene transcription related to endometrial growth, hormonal regulation, and other functions.
Dosage
Standard Dosage
Adults:
Dosage varies widely depending on the indication and route of administration, ranging from 2.5 mg to 1500 mg daily for oral administration and up to 150 mg IM every three months for contraception.
Children:
Use is generally not recommended for pre-pubertal children, although it is utilized for some pediatric conditions such as precocious puberty under careful specialist supervision. Dosing is individualized based on age, weight and specific medical needs.
Special Cases:
- Elderly Patients: Close monitoring for adverse effects is advised, but dose adjustments may not be necessary.
- Patients with Renal Impairment: Dose modifications may be necessary depending on the degree of impairment.
- Patients with Hepatic Dysfunction: Contraindicated in severe liver disease. Caution is required in mild to moderate impairment, with possible dose reductions.
- Patients with Comorbid Conditions: Careful consideration of potential drug interactions and disease-specific risks is essential.
Clinical Use Cases Dosage recommendations for these settings vary significantly. Specific protocols should be consulted. For contraception, the IM injection of 150 mg every three months is commonly employed.
Dosage Adjustments
Dose modifications are often needed for renal/hepatic impairment, drug interactions, and other patient-specific factors. Consulting specialized resources and drug interaction databases is crucial.
Side Effects
Common Side Effects
- Breakthrough bleeding or spotting
- Menstrual changes
- Breast tenderness
- Headache
- Weight changes
- Mood swings
- Nausea, bloating
- Acne, hair growth or loss
Rare but Serious Side Effects
- Allergic reactions (anaphylaxis, angioedema)
- Thromboembolic events (stroke, pulmonary embolism, deep vein thrombosis)
- Jaundice
- Severe mental/mood changes
Long-Term Effects
- Decreased bone mineral density (with prolonged use, especially of injectable formulations)
- Increased risk of breast cancer (with long-term, high-dose use)
Adverse Drug Reactions (ADR)
Severe allergic reactions, thromboembolic events, significant liver dysfunction, and severe mood changes require immediate medical attention.
Contraindications
- Undiagnosed vaginal bleeding
- Known or suspected pregnancy
- History of or active thromboembolic disorders (stroke, DVT, PE)
- Breast cancer (current or past)
- Estrogen- or progesterone-dependent neoplasia
- Severe liver disease
Drug Interactions
Numerous drug interactions exist. Some notable ones include:
- Rifampin, St. John’s wort, anticonvulsants (carbamazepine, phenobarbital, phenytoin): May decrease medroxyprogesterone levels.
- Ketoconazole, itraconazole: May increase medroxyprogesterone levels.
- Aminoglutethimide: May decrease efficacy.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: X (Contraindicated)
- Medroxyprogesterone is contraindicated in pregnancy due to the risk of fetal harm.
- While small amounts are excreted in breast milk, it is generally considered safe to use while breastfeeding, especially six weeks postpartum. Individualized risk-benefit assessments should be conducted.
Drug Profile Summary
- Mechanism of Action: Binds to progesterone receptors, modulating various reproductive functions.
- Side Effects: Breakthrough bleeding, breast tenderness, headache, mood changes, weight changes, nausea.
- Contraindications: Pregnancy, undiagnosed vaginal bleeding, breast cancer, thromboembolic disorders, severe liver disease.
- Drug Interactions: Rifampin, St. John’s wort, anticonvulsants, azole antifungals.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; generally safe during breastfeeding after six weeks postpartum.
- Dosage: Highly variable depending on indication and route.
- Monitoring Parameters: Liver function tests, bone mineral density (with long-term use), blood pressure, lipid profile.
Popular Combinations
Medroxyprogesterone is sometimes combined with estrogens for hormone replacement therapy in postmenopausal women.
Precautions
Standard precautions apply, including pre-screening for contraindications and allergies. Specific populations (pregnant/breastfeeding women, children, elderly) require individualized risk assessment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Medroxyprogesterone acetate?
A: The dosage varies widely depending on the indication. It ranges from 2.5mg to 1500mg daily for oral administration and up to 150 mg IM every three months for contraception. Always consult specific guidelines for each indication.
Q2: Can medroxyprogesterone acetate be used during pregnancy?
A: No, it is contraindicated during pregnancy due to potential fetal harm.
Q3: Is it safe to use medroxyprogesterone acetate while breastfeeding?
A: Generally, yes, but it’s best to wait until six weeks postpartum. Small amounts are excreted in breast milk, but significant adverse effects in infants are rare. Discuss with your doctor to weigh the risks and benefits.
Q4: What are the most common side effects of this medication?
A: Common side effects include breakthrough bleeding, breast tenderness, headache, weight changes, and mood changes.
Q5: What should I do if a patient experiences a severe allergic reaction?
A: Immediately discontinue the medication and provide emergency medical care.
Q6: Does medroxyprogesterone acetate interact with other drugs?
A: Yes, it interacts with many medications, including rifampin, St. John’s wort, anticonvulsants, and some antifungals. Consult a drug interaction database or pharmacist for detailed information.
Q7: Can medroxyprogesterone acetate affect bone density?
A: Long-term use, particularly of injectable formulations, can decrease bone mineral density. Monitor bone density in patients on prolonged therapy.
Q8: Are there any long-term risks associated with using medroxyprogesterone acetate?
A: Yes, long-term high-dose use may increase the risk of breast cancer and other adverse effects. Use the lowest effective dose for the shortest duration possible.
Q9: How is medroxyprogesterone acetate administered for contraception?
A: It is typically given as a 150 mg IM injection every three months.
