What Is Medroxyprogesterone?

Medroxyprogesterone is a white or off-white crystalline powder and is odorless. Insoluble in water, easily soluble in chloroform, slightly soluble in absolute ethanol. Melting point 202 ~ 208 ° C. Regardless of the rapid increase in plasma concentration after oral or intramuscular injection, the peak blood plasma level during intramuscular injection is lower than oral, but it lasts longer than 1 week. It is mainly used to treat kidney cancer, breast cancer, endometrial cancer, prostate cancer and enhance appetite of patients with advanced cancer, improve general condition and gain weight.

Chinese name: Medroxyprogesterone
Foreign name: MedroxyProgesterone

Alias: Megestrol, progesterone
Dosage form: tablet

Introduction to medroxyprogesterone compounds

Medroxyprogesterone Basic Information

Chinese name: medroxyprogesterone

Chinese alias: 6Alpha-methyl-17Alpha-hydroxyprogesterone; medroxyprogesterone; 17-Hydroxy-6-methyl-4-pregnene-3,20-dione; 6-methyl-17-hydroxyprogesterone; Angong progesterone Ketone; Deproxil; Dibo-Provira; Maplean; Faluda; Medroxyprogesterone; Medroxyprogesterone acetate

English name: medroxyprogesterone

English alias: Medroxyprogesteron; Medroxyprogesteronum; Hydroxymethylprogesterone; 17alpha-Hydroxy-6alpha-methylprogesterone; (6S, 8R, 9S, 10R, 13S, 14S, 17R) -17-acetyl-17-hydroxy-6,10,13-trimethyl-2 , 6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta [a] phenanthren-3-one; Farlutal; Provera; Deporone; Depo-Provera

CAS number: 520-85-4

Molecular formula: C ₂₂ H ₃₂ O ₃

Molecular weight: 344.48800

Exact mass: 344.23500

PSA: 54.37000

LogP: 4.08440

Physicochemical properties of medroxyprogesterone

Density: 1.13g / cm

Melting point: 220-223.5ºC

Boiling point: 488ºC at 760mmHg

Flash point: 263ºC

Refractive index: 1.538

Storage conditions: Refrigerator

Medroxyprogesterone Safety Information

Symbol: GHS08

Signal Word: Warning

Hazard statement: H361

Cautionary Statement: P281

Danger category code: R48; R63; R68

Dangerous goods mark: Xn ^[1]

Medroxyprogesterone drug description

Classification of medroxyprogesterone

Endocrine System Drugs> Gonad Diseases

Medroxyprogesterone dosage form

1. Tablet: 2mg, 4mg, 10mg, 500mg;

2. Injection: 150mg;

3. Long-acting injection (powder): 150mg;

4. Cycloprogesterone oil injection: containing 25mg medroxyprogesterone and 5mg cyclopentaestrol;

5. Medroxyprogesterone silicone rubber vaginal ring: Contains 100 ~ 200mg of medroxyprogesterone.

Medroxyprogesterone pharmacological action

Medroxyprogesterone is a potent progestogen and has no estrogen activity. After oral administration or injection, based on an appropriate amount of endogenous estrogen in the body, the endometrium of the proliferative phase can be transformed into the membrane of the secretory phase to prepare for the implantation of fertilized eggs. Its progestogen activity is 20 to 30 times that of progesterone when injected subcutaneously, and 10 to 15 times that of ethinyl progesterone when taken orally. The main function is to promote the endometrial proliferation and secretion, complete the preparation for conception, and protect the safe growth of the fetus. It also has the effects of changing the menstrual cycle, enhancing cervical mucus consistency and inhibiting ovulation. Large doses of medroxyprogesterone have anti-tumor effects, but also have a significant effect on improving appetite and relieving pain in patients. Medroxyprogesterone has an anti-estrogen effect, but it does not oppose the benign effects of estrogen on lipoproteins, and has no obvious androgenic effect. It is the closest to natural progesterone. It can mainly increase the viscosity of cervical mucus. Large doses can inhibit pituitary gonadotropin and inhibit ovulation. It has a long-lasting antifertility effect. When medroxyprogesterone is used as an anti-tumor hormone, through years of experimental and clinical research, it has been proven that this class of preparations can have dual effects and are dose-dependent.

1. Inhibit the anterior pituitary gland by negative feedback, so as to inhibit the production of luteinizing hormone (LH), adrenocorticotropic hormone (ACTH) and other growth factors.

2. High-dose irradiation has a direct cytotoxic effect on sensitive cells. Medroxyprogesterone mainly counteracts the effect of estrogen on promoting the growth of tumor cells by making the estrogen receptor (ER) in the cells unrenewable, but it has no effect on drug-resistant cells. Pathological examination of endometrial cancer can reveal chromosomal damage. Medroxyprogesterone can also reduce the level of estrogen in cells by enhancing the activity of E2-deoxygenase, and induce liver 5-reductase to prevent androgen from being converted to estrogen ^[2] .

Medroxyprogesterone pharmacokinetics

The average oral absorption rate is 5.7%. The bioavailability of intraperitoneal injection is better than oral and intramuscular injection, and it is well tolerated. Plasma half-life is 4 to 5 hours. After intramuscular injection, it is slowly released in local tissues and produces a long-lasting effect. It can be maintained for more than 2 to 4 weeks, and it can reach 3 months when the dose is large. Orally metabolized by the liver, excreted mainly from urine in the form of sulfate and glucuronide within 1 to 2 days. It is secreted in breast milk. Individual differences in drug metabolism are large ^[2] .

Medroxyprogesterone indications

1. Large doses can be used as long-acting contraception. Clinically used for dysmenorrhea, functional amenorrhea, dysfunctional uterine bleeding, threatened abortion or habitual abortion, endometriosis and so on.

2. Large doses can also be used to treat renal cell carcinoma, breast cancer, endometrial cancer, prostate cancer, and enhance appetite in patients with advanced cancer, improve general conditions and gain weight.

Medroxyprogesterone contraindications

Thrombovenous thrombophlebitis, thromboembolism, stroke, severe liver and kidney dysfunction, known or suspected breast or genital malignancies, hypercalcemia, late abortion, uterine bleeding, pregnancy, coagulopathy or parathyroid Patients with progesterone allergy are contraindicated ^[2] .

Medroxyprogesterone precautions

1. Use with caution in those with mental depression.

2. A comprehensive physical examination (especially breast and pelvic examination) should be performed before treatment. For long-term medication, pay attention to check liver function and pay special attention to breast examination.

3. Progesterone can cause fluid retention to some extent, and epilepsy, migraine, and asthma should be closely observed.

4. During the application, there are signs of thrombosis, such as sudden visual impairment, diplopia, migraine, should be checked immediately. If there is optic disc edema or retinal vascular disease, the drug should be discontinued immediately.

5. Long-term administration of medroxyprogesterone should be calculated on a 28-day cycle.

6. Women who use medroxyprogesterone for a long time should not smoke.

7. When taking large doses (over 500mg), take a seated or upright position and drink plenty of water. If necessary, the tablets can be taken in two halves.

8. Injections should not be mixed with other drugs and shake well before use.

9. For those who apply estrogen replacement therapy after menopause, the addition of progestin for more than 7 days can reduce the incidence of endometrial hyperplasia. Using progestins for 12 to 14 days can provide optimal endometrial maturation and eliminate proliferative changes.

10. Store at room temperature.

11. Intramuscular injection Use long thick needles for deep injection, which can reduce local aseptic abscess or inflammatory infiltration. When used in patients with cancer, it must be used under the guidance of an experienced tumor chemist and discontinued when thromboembolism, migraine or eye disease occurs. Large doses of long-term medication will produce adrenocortical hormone response, especially pay attention to patients with diabetes and high blood pressure and hypertension. Medroxyprogesterone may cause vaginal bleeding, but care should be taken to rule out more serious causes. The use of medroxyprogesterone in early pregnancy can cause congenital heart dysplasia in the fetus. Breast nodules have been caused by long-term medication in animals (beagles). These small nodules are malignant, but the same has not been reported in humans ^[2] .

Medroxyprogesterone adverse reactions

1. Breakout bleeding, spotting bleeding, menstrual changes, amenorrhea, edema, weight changes (increased or decreased), cholestasis jaundice, allergic reactions, rash, mental depression, insomnia, nausea. If breakthrough bleeding occurs, detailed examination should be made to rule out organic diseases, and 0.05 to 0.1 mg of ethinyl estradiol can be added according to the amount of bleeding, even for 3 days to stop bleeding.

2. Large doses can be used for tumors that can cause progesterone reactions such as breast pain, galactorrhea, vaginal bleeding, amenorrhea, irregular menstruation, abnormal cervical secretion, uterine erosion, etc .; long-term application also has symptoms of hyperadrenal function such as full moon face, reservoir Hin syndrome, weight gain, etc. Can also produce effects similar to corticosteroids, such as can cause weight gain, abdominal pain, headache, mood changes, hand tremor, sweating, nocturnal calf spasm and other similar reactions. There have also been reports of obstructive jaundice.

3. Medroxyprogesterone can cause abnormal blood coagulation ^[2] .

Medroxyprogesterone dosage

1. Long-acting medroxyprogesterone powder injection is formulated as an aqueous suspension for injection, 150 mg intramuscularly every 3 months, and is administered in 2-7 days of menstruation. Cycloprogesterone oil injection is 1 injection per month. Maternal use should be resumed 4 weeks after delivery. The medroxyprogesterone vaginal ring is a medroxyprogesterone sustained-release system. It can be taken out during menstruation and can be used continuously for 3 to 6 months.

2. Threatened abortion: 4 to 8 mg each time, 2 to 3 times a day.

3. Habitual abortion: Take 10mg daily for the first 3 months, 20mg daily for the 4th to 4.5th months, and finally reduce the dose.

4. Dysmenorrhea: starting on the 6th day of the menstrual cycle, 2 to 4mg daily for 20 days; or starting on the 1st day of menstruation, 3 times a day for 3 days.

5. Functional amenorrhea: 4 to 8 mg daily for 5 to 10 days.

6. Endometriosis: It can start from 6 to 8 mg per day and gradually increase to a total of 20 to 30 mg per day for 6 to 8 weeks.

7. For tumors: 500 to 1,000 mg orally daily. Take 1 or 2 times for 10 days. Later, depending on the condition, it can be changed to 250 ~ 500mg per day, which can be taken for a long time. Intramuscular injection begins with 500 mg each time, once a day. Up to 4 weeks, later changed to 3 times a week.

8. For endometrial cancer and prostate cancer: 0.2 ~ 0.5g per day;

9. For renal adenocarcinoma: 0.2 ~ 0.5g per day.

10. Intramuscular injection: (1) for breast cancer: 0.5-1.0g per day for 4 weeks, and then intramuscular injection of 0.5g every 2 weeks, maintenance treatment or oral 1.0-1.5g per day; (2) for uterus Endometrial cancer and prostate cancer: intramuscular injection of 0.5 g each time, twice a week, and then changed to a maintenance dose of 0.5 g intramuscular injection or 0.2 to 0.5 g per day orally ^[2] .

Medroxyprogesterone drug interactions

Used together with Aminutam, it can reduce the bioavailability of Aminutam.

Clinical condition of medroxyprogesterone

It is mainly used to treat kidney cancer, breast cancer, endometrial cancer, prostate cancer and enhance appetite of patients with advanced cancer, improve general condition and gain weight. Clinically used for dysmenorrhea, functional amenorrhea, functional uterine bleeding, threatened abortion or habitual abortion, endometriosis, etc. A large dose can be used as a long-acting contraceptive, and an intramuscular injection of 150 mg can be used for 3 months.

1. The clinical manifestations of kidney cancer are various and can vary depending on the number of occurrences, tumor origin, pathological type, location of occurrence, and duration of disease. Without any symptoms, sometimes the tumor has developed extensively in the body. There are even signs of metastases in the lungs and bones. However, hematuria, low back pain and lumps are still the three typical symptoms of renal malignancies, and there are also many extrarenal manifestations of the non-essential urinary system.

2. Breast cancer is one of the most common malignant tumors in women. According to statistics, the incidence rate is 7-10% of various malignant tumors in the whole body, second only to uterine cancer in women. Its incidence is often related to heredity, and between 40 and 60 years old, the incidence is higher in women before and after menopause. Only about 1-2% of breast patients are male. Malignant tumors that usually occur in the epithelial tissue of the breast glands. It is one of the most common malignant tumors that seriously affect women's physical and mental health and even endanger life. Men with breast cancer are rare.

Breast cancer is a mutation in the genes of mammary gland epithelial cells under the action of a variety of carcinogens, which leads to uncontrolled cell proliferation. Due to the change in the biological behavior of cancer cells, disordered and unrestricted malignant hyperplasia appears. Its histological manifestation is that a large number of immature cancer cells proliferate indefinitely and are crowded into disorderly clusters, squeezing and eroding the surrounding normal tissue and destroying the normal tissue structure of the breast.

Breast cells have lost the characteristics of normal cells after being mutated. The tissue structure is disordered, the cells are loosely connected, and the cancer cells are easily detached. They spread throughout the body with blood or lymph fluid, forming an early distant metastasis, which will give breast cancer Healing adds a lot of difficulty. The transfer of vital organs throughout the body, such as lung metastases, brain metastases, and bone metastases, will directly threaten human life. Therefore, breast cancer is a malignant disease that seriously threatens human life.

3. Prostate cancer is a malignant tumor of the prostate. Common tumors in men. Occurs more than 50 years of age, the incidence increases with age. The development of prostate cancer is affected by sex hormones, androgen promotes its growth, elevated serum acid phosphatase and estrogen inhibit it. Prostate cancer is divided into 7 stages: A1, A2, B1, B2, C, D1, D2. The clinical manifestations are mainly symptoms of urination obstruction, such as slow onset of urination, fine urine flow and nocturia. Those without concurrent benign prostatic hyperplasia may not have symptoms of urination obstruction. About 5% of patients are mainly complained of metastatic cancer, such as local pain caused by bone metastases, upper abdominal masses can be found in liver metastases, and left supraclavicular lymphadenopathy, cough, chest pain, etc. can be found in advanced stages.

Medroxyprogesterone Expert Reviews

Group A (20 patients) received chemotherapy plus medroxyprogesterone in the first cycle, chemotherapy alone in cycles 2 and 3; group B (20 patients) received chemotherapy alone in the first cycle, and chemotherapy plus medroxyprogesterone in the second cycle Ketone, chemotherapy alone in the third cycle; group C (20 patients) were treated with chemotherapy plus medroxyprogesterone in the third cycle. The dosage of medroxyprogesterone is 500 mg each time, twice a day for 3 to 9 weeks. Results Most of the patients in the three groups increased their eating, accounting for 75.0%, 80%, and 90.0%, respectively. The patients who gained weight in the three groups were 85.0%, 80.0%, and 95.0%, respectively. According to WHO's bone marrow suppression toxicity standard, those who achieved or higher in the single chemotherapy group were 52.8%; 19.0% of medroxyprogesterone in the chemotherapy medroxyprogesterone group could significantly improve the toxicities and side effects of the chemotherapy drugs, and increase appetite and The role of weight and protection of bone marrow function is a useful protective agent for chemotherapy ^[2] .

Medroxyprogesterone tablets

Drug Name

Common name: Medroxyprogesterone acetate dispersible tablets

English name: Medroxyprogesterone Acetate Dispersible Tablets

Chinese Pinyin: Cusuan Jiaqiangyuntong Fensanpian

The main ingredients of this product and its chemical name are:

The main ingredient of this product is medroxyprogesterone acetate. Its chemical name is 6-methyl-17-hydroxypregn-4-ene-3,20-dione acetate.

Its structural formula is:

Molecular formula: C ₂₄ H ₃₄ O ₄

Molecular weight: 386.53

[Character]

This product is a white dispersion tablet.

[Pharmacology and Toxicology]

Animal tests show that this product has a certain inhibitory effect on transplanted tumors, such as breast cancer tumor lines. Its antitumor effect is related to its progestin activity. Prolonged or overdose can produce symptoms of the corresponding hormonal drugs.

Pharmacokinetics

For healthy people, after 0.5g administration of this product, the blood concentration reached 2.58 ± 0.5 hours, and its peak value was 30.3 ± 10.8mg / L. The metabolism of this product is mainly carried out in the liver. The half-life of medroxyprogesterone acetate elimination phase in plasma is 14.0 ± 2.12 hours.

[Indications]

For palliative or adjuvant treatment of inoperable, recurrent or metastatic hormone-dependent tumors, such as endometrial cancer, kidney cancer, breast cancer, etc.

Dosage

This product must be prescribed by a doctor.

Endometrial and renal cancer: 0.2 to 0.4 g daily; breast cancer: 0.4 to 0.8 g daily, or even as high as 1 g daily. Sex hormone therapy requires at least 8 to 10 weeks of treatment before responding.

Palliative treatment of cachexia and pain of various cancer patients: 0.5 1g per day.

Bone marrow protection during chemotherapy for various cancers: 0.5 to 1 g per day (from one week before chemotherapy to one week after a course of treatment).

Adverse reactions

Similar to other progesterone drugs, breast pain, galactorrhea, amenorrhea, cervical erosion or changes in cervical secretion and feminization of male breasts may occur.

Mental aspects: nervousness, insomnia, lethargy, tiredness, dizziness.

Skin and mucous membranes: Allergic reactions including pruritus, measles, angioedema to systemic rash, and non-defensive reactions have been reported. A few cases have reported acne, baldness, or hairiness.

Gastrointestinal tract: Nausea and indigestion, especially at higher doses.

Adrenocortical and hypercalcemia-like reactions may also occur, with occasional reports of obstructive jaundice.

[Taboo]

Allergic to medroxyprogesterone acetate and any other ingredients of this product, various thromboembolic diseases (thrombophlebitis, pulmonary embolism, etc.), severe liver damage, hypercalcemia due to tumor bone metastasis, Many, pregnant or lactating women are prohibited.

Precautions

1. This medicine must be used under the guidance of an experienced clinician, and should be discontinued as soon as symptoms of thromboembolism such as migraine, vision loss, and double vision occur due to the drug's enhanced coagulation mechanism.

2. During continuous large-dose MPA treatment, attention should be paid to the presence of hypertension, water and sodium retention, and hypercalcemia. If these symptoms occur, the medication should be adjusted.

3 This product may cause some fluid retention. Patients with epilepsy, migraine, asthma, cardiac insufficiency or renal insufficiency should be carefully observed when using this product.

4 Patients with a history of depression need to be carefully observed, and patients with severe relapsed depression should stop taking the drug. Some patients with progestogens have reduced tolerance to glucose and should be used with caution in patients with diabetes.

[Medication for pregnant and lactating women]

Progesterone drugs are potentially harmful to the fetus, so this product is not recommended during pregnancy. Breastfeeding women should stop breastfeeding. Women of childbearing age who are about to take this product should avoid pregnancy.

Disabled during pregnancy or lactation.

medicine interactions

still uncertain.

Storage

Shaded and sealed.

package

Packed in plastic bottles, 30 tablets / bottle ^[3] .