Medroxyprogesterone acetate

386.52

386.52

200-757-9

C2QI4IOI2G

26386|21171

DTXSID0025527

C1155

29372390

60.4

3.5

Medroxyprogesterone acetate is an odorless white to off-white microcrystalline powder. (NTP, 1992)

1.1±0.1 g/cm3

207-209 °C

432.7°C (rough estimate)

213.2±28.8 °C

1.539

H2O: <0.1 g/100 mL at 23 ºC

Refrigerator

D +61° (in chloroform)

197.2 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]|200.27 Ų [M+H]+

This chemical is sensitive to prolonged exposure to air and light. Insoluble in water.

Esters, Sulfate Esters, Phosphate Esters, Thiophosphate Esters, and Borate Esters

Known Catalytic Activity

Flammable and/or toxic gases are generated by the combination of alcohols with alkali metals, nitrides, and strong reducing agents. They react with oxoacids and carboxylic acids to form esters plus water. Oxidizing agents convert them to aldehydes or ketones. Alcohols exhibit both weak acid and weak base behavior. They may initiate the polymerization of isocyanates and epoxides.

NONH for all modes of transport

3

40-48

22-36/37/39-45

TU5010000

Xn

Stable, but weakly air and light sensitive. Incompatible with strong oxidizing agents.

P281

H351

Flash point data for this chemical are not available; however, it is probably combustible. (NTP, 1992)

|Danger|H302 (13.84%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P261, P263, P264, P270, P271, P273, P280, P281, P301+P312, P302+P352, P304+P312, P304+P340, P308+P313, P312, P322, P330, P363, P405, and P501|Aggregated GHS information provided by 225 companies from 16 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should protect this chemical from exposure to light. Keep the container tightly closed under an inert atmosphere, and store under refrigerated temperatures. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

The oral LD50 in rats is >6400mg/kg and in mice is >16g/kg. The intraperitoneal LD50 in rats is >900mg/kg and in mice is >1500mg/kg. The subcutaneous LD50 in rats is >900mg/kg and in mice is>1500mg/kg. Patients experiencing and overdose or oral medroxyprogesterone acetate (MPA) may present with nausea, vomiting, breast tenderness, dizziness, abdominal pain, drowsiness, fatigue, and withdrawal bleeding. Treat patients by stopping MPA and beginning symptomatic treatment. Patients who have been given too much of a MPA depo injection should contact a healthcare professional, hospital emergency department, or local poison control immediately.

Medroxyprogesterone acetate is 86% protein bound in serum, mainly to albumin. No binding occurs with sex hormone binding globulin.

Medroxyprogesterone acetate (MPA) oral tablets are indicated to treat secondary amenorrhea, reduce the incidence of endometrial hyperplasia in postmenopausal women, and to treat abnormal uterine bleeding due to hormonal imbalance, not organic pathology. Oral tablets containing MPA and conjugated estrogens are indicated to prevent postmenopausal osteoporosis and to treat moderate to severe menopausal symptoms such as vasomotor symptoms, vulvar atrophy, and vaginal atrophy. Subcutaneous MPA is indicated to prevent pregnancy and manage pain associated with endometriosis. Intramuscular MPA is indicated to prevent pregnancy, and at higher concentrations for palliative treatment of endometrial or renal carcinoma.|FDA Label

Medroxyprogesterone acetate (MPA) inhibits gonadotropin production, reduces nuclear estrogen receptors and DNA synthesis in epithelial cells of the endometrium, and induces p53 dependant apoptosis in cancer cell lines. MPA oral tablets have a half life of 40-60 hours and other formulations can have half lives that are considerably longer, so the duration of action is long. The therapeutic window is wide as patients may take doses ranging from 5mg orally daily to 1000mg as a depo injection weekly. Long term use of MPA is associated with a reduction in bone density and patients who taking MPA during adolescence may have lower peak bone mass than untreated patients, which can also increase the risk of osteoporosis and fractures in the future.

Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079) (See all compounds classified as Antineoplastic Agents, Hormonal.)|Contraceptive agents that act on the ENDOCRINE SYSTEM. (See all compounds classified as Contraceptive Agents, Hormonal.)|Chemical substances or agents with contraceptive activity in females. Use for female contraceptive agents in general or for which there is no specific heading. (See all compounds classified as Contraceptive Agents, Female.)|Chemical substances or agents with contraceptive activity in males. Use for male contraceptive agents in general or for which there is no specific heading. (See all compounds classified as Contraceptive Agents, Male.)

Absorption of oral medroxyprogesterone acetate (MPA) varies considerably between formulations. A 1000mg oral dose reaches an average C_max of 145-315nmol/L while a 500mg oral dose reaches an average C_max of 33-178nmol/L with a T_max of 1-3 hours and a lag time of half an hour. The AUC of a 500mg oral dose of MPA was 543.4-1981.1nmol\*L/h depending on formulation. Intramuscular MPA reaches a C_max of 4.69±1.52nmol/L with a T_max of 4.75±2.09 days and an AUC of 81.58±27.64days\*nmol/L. Subcutaneous MPA reaches a C_max of 3.83±1.56nmol/L with a T±max of 6.52±2.07 days and an AUC of 72.26±38.73days\*nmol/L. However, the pharmacokinetics of MPA may also vary depending on injection site.|The majority of medroxyprogesterone acetate (MPA) is eliminated in the urine as glucuronide conjugates and a minority of sulphate conjugates. Glucuronide conjugates are also detected in the feces. Determining the exact ratio of metabolites and parent compound eliminated in the urine and feces is difficult as the metabolite profile in the urine is not significantly different and radio labelling studies are not readily available.|The volume of distribution of medroxyprogesterone acetate is 20±3L.|The mean clearance of medroxyprogesterone acetate (MPA) is 1668±146L/day or 21.9±4.3L/kg/day. Due to the high inter patient variability in MPA pharmacokinetics, clearance has been reported to be 1600-4000L/day.

Medroxyprogesterone acetate undergoes beta hydroxylation to form the metabolites 6-beta (M-2), 2-beta (M-4), and 1-beta-hydroxymedroxyprogesterone acetate (M-3). M-2 and M-4 are further metabolized to 2-beta,6-beta-dihydroxymedroxyprogesterone (M-1). M-3 is further metabolized to 1,2-dehydromedroxyprogesterone acetate (M-5).|Medroxyprogesterone Acetate has known human metabolites that include M-2, M-3, and Medroxyprogesterone Acetate.

Oral medroxyprogesterone acetate (MPA) has an absorption half life of 15-30min and a biological half life of 40-60 hours. Intramuscular MPA has an absorption half life of 0.86±0.30 days and an elimination half life of 24.03±21.74 days. Subcutaneous MPA has an absorption half life of 1.05±0.56 days and an elimination half life of 30.90±15.11 days.

Medroxyprogesterone acetate (MPA) inhibits the production of gonadotropin, preventing follicular maturation and ovulation, which is responsible for it’s ability to prevent pregnancy. This action also thins the endometrium. MPA reduces nuclear estrogen receptors and DNA synthesis in epithelial cells of the endometrium. MPA can also induce p53 dependant apoptosis in certain cancer cell lines, and inhibit GABA-A receptors.

SYMPTOMS: Symptoms of exposure to this compound include breast tenderness, galactorrhea, nervousness, insomnia, somnolence, fatigue, dizziness, thromboembolic phenomena such as thrombophlebitis, pulmonary embolism, pruritus, urticaria, angioneurotic edema, rash, anaphylaxis, alopecia, acne, hirsutism, nausea, jaundice, headache, hyperpyrexia, liver dysfunction, premenstrual-like syndrome, changes in libido, changes in appetite, cystitis-like syndrome, backache, loss of scalp hair, erythema multiforme, erythema nodosum, hemorrhagic eruption, itching, breakthrough bleeding, spotting, amenorrhea, changes in cervical erosion and secretions, melasma or chloasma, mental depression, clitoral hypertrophy, postpartum bleeding (prolonged), postabortal bleeding and missed abortion. Other symptoms include increased intraocular pressure, teratogenic effects such as developmental abnormalities of the urogenital system, and reproductive effects such as spermatogenesis changes, menstrual cycle changes or disorders, postpartum effects, female fertility effects and newborn behavior effects. Exposure may cause edema, candidiasis, cramps and ischemic colitis. ACUTE/CHRONIC HAZARDS: When heated to decomposition this compound emits acrid smoke and irritating fumes. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. OTHER: Since this chemical is a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health effects and potential recommendation for medical monitoring. Recommendations from the physician will depend upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and the route of exposure. (NTP, 1992)

(6 alpha)-17-(Acetoxy)-6-methylpregn-4-ene-3,20-dione

Pregn-4-ene-3,20-dione, 17-(acetyloxy)-6-methyl-, (6.alpha.)-: ACTIVE

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals -> Animal Drugs -> Approved in Taiwan