Mifepristone

429.59

429.59

1806241-263-5

320T6RNW1F

DTXSID5023322

C655

Yellow powder

G03XB01|G - Genito urinary system and sex hormones

29372900

40.5

4.5

1

1.2±0.1 g/cm3

150 °C

628.6±55.0 °C at 760 mmHg

334.0±31.5 °C

1.623

Poorly soluble

2-8°C

8.0X10-14 mm Hg at 25 deg C /Estimated/

D20 +138.5° (c = 0.5 in chloroform)

Henry's Law constant = 5.0X10-13 atm-cu m/mole at 25 °C /Estimated/

Hydroxyl radical reaction rate constant = 5.1X10-10 cu cm/molec-sec at 25 °C /Estimated/|Ozone reaction rate constant = 1.4X10-14 cu cm/molec-sec at 25 °C /Estimated/

NONH for all modes of transport

3

60-61

53-22-36/37/39-45

KG2955000

T

Stable at normal temperatures and pressures.

P201-P280-P308 + P313

H360

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).|The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl mifepristone, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Danger|H302 (28.81%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P261, P263, P264, P270, P271, P280, P281, P301+P312, P302+P352, P304+P312, P304+P340, P308+P313, P312, P322, P330, P363, P405, and P501|Aggregated GHS information provided by 59 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Nearly all of the women who receive mifepristone will report adverse reactions, and many can be expected to report more than one such reaction. About 90% of patients report adverse reactions following administration of misoprostol on day three of the treatment procedure. Side effects include more heavy bleeding than a heavy menstrual period, abdominal pain, uterine cramping, nausea, vomiting, and diarrhea.

In large prelicensure clinical trials, medical abortion with mifepristone/misoprostol was safe and not accompanied by abnormalities in laboratory tests or cases of hepatitis or jaundice. Since its licensure and more widescale use, there have been no published reports of liver injury attributed to mifepristone and misoprostol used to induce medical abortion.

Excessive bleeding may occur with concomitant use of anticoagulant therapy and mifepristone.

98% (bound to plasma proteins, albumin and a 1-acid glycoprotein)

Mifepristone's production and use as an abortifacient(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 89,000(SRC), determined from a structure estimation method(2), indicates that mifepristone is expected to be immobile in soil(SRC). Volatilization of mifepristone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.0X10-13 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Mifepristone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.0X10-14 mm. Biodegradation data were not available(SRC, 2005).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 89,000(SRC), determined from a structure estimation method(2), indicates that mifepristone is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 5.0X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 2,800(SRC), from an estimated log Kow of 89,000(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is very high(SRC). Biodegradation data were not available(SRC, 2005).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), mifepristone, which has an estimated vapor pressure of 8.0X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase mifepristone may be removed from the air by wet and dry deposition(SRC). Mifepristone does not contain chromophores that absorb light at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of mifepristone with ozone has been estimated as 1.5X10-14 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1.1 min at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(2). Mifepristone is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(3). Mifepristone does not contain chromophores that absorb light at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 2,800 was calculated for mifepristone(SRC), using an estimated log Kow of 5.39(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not altered physically or chemically once released into the environment(SRP).

Using a structure estimation method based on molecular connectivity indices(1), the Koc for mifepristone can be estimated to be 89,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that mifepristone is expected to be immobile in soil.

The Henry's Law constant for mifepristone is estimated as 5.0X10-5 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that mifepristone is expected to be essentially nonvolatile. Mifepristone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.0X10-14 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to mifepristone may occur through inhalation dermal contact with this compound at workplaces where mifepristone is produced or used. Exposure to the drug among the general population may be limited to those being administered the drug mifepristone, (an abortifacient). (SRC)

For the medical termination of intrauterine pregnancy through 49 days' pregnancy. Also indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and are not candidates for surgery or have had unsuccessful surgery.|FDA Label|Treatment of endometriosis|Treatment of hypercortisolism (Cushing's syndrome) of endogenous origin|Treatment of leiomyoma of uterus|Medical Abortion

Mifepristone, also known as RU-486, is a potent synthetic steroidal antiprogesterone which is used as a single dose in combination with misoprostol, a prostaglandin analogue, to induce medical abortion. Mifepristone with misoprostol have not been associated with serum enzyme elevations or with clinically apparent liver injury.

Pregnancy Termination Agents

Abortifacient Agents, Steroidal; Contraceptives, Oral, Synthetic; Contraceptives, Postcoital, Synthetic; Hormone Antagonists; Luteolytic Agents; Menstruation-Inducing Agents|Mifepristone is indicated in combination with misoprostol for the medical termination of intrauterine pregnancy of 49 days duration or less. /Included in US product labeling/

Confirmed or suspected ectopic pregnancy, undiagnosed adnexal mass, or IUD currently in place. Chronic adrenal failure or concurrent long-term corticosteroid therapy. Known hypersensitivity to mifepristone, misoprostol, or other prostaglandins. Hemorrhagic disorders, inherited porphyrias, or concurrent anticoagulant therapy.|Vaginal bleeding that is heavier than associated with a normal menses occurs in almost all women receiving mifepristone and misoprostol. Based on clinical studies, bleeding or spotting should be expected for an average of 9-16 days. ... Excessive bleeding may require treatment with vasoconstrictors, saline infusions, and/or blood transfusions or curettage.|Severe vaginal bleeding may occur following spontaneous, surgical, or medical abortion (including following mifepristone administration). Prolonged heavy vaginal bleeding (i.e. soaking through 2 thick full-size sanitary pads per hour for 2 consecutive hours) may be a sign of incomplete abortion or other complications, and prompt medical or surgical intervention maybe required to prevent the development of hypovolemic shock. Patients should be advised to seek immediate medical attention if prolonged heavy vaginal bleeding or syncope occurs following mifepristone administration.|Serious bacterial infections (including very rare cases of fatal septic shock) have been reported following mifepristone administration; a causal relationship to the mifepristone-misoprostol regimen has not been established. Clinicians should consider the possibility of infection if sustained fever (temperature of 38 degrees C or higher persisting for more than 4 hours), severe abdominal pain, or pelvic tenderness occurs within several days of medical abortion. Atypical presentations of serious infection and sepsis (i.e., presence of significant leukocytosis, tachycardia, or hemoconcentration without fever, severe abdominal pain, pelvic tenderness) may also occur.|For more Drug Warnings (Complete) data for MIFEPRISTONE (14 total), please visit the HSDB record page.

Mifepristone is a synthetic steroid with antiprogestational effects indicated for the medical termination of intrauterine pregnancy through 49 days' pregnancy. Doses of 1 mg/kg or greater of mifepristone have been shown to antagonize the endometrial and myometrial effects of progesterone in women. During pregnancy, the compound sensitizes the myometrium to the contraction-inducing activity of prostaglandins. Mifepristone also exhibits antiglucocorticoid and weak antiandrogenic activity. The activity of the glucocorticoid dexamethasone in rats was inhibited following doses of 10 to 25 mg/kg of mifepristone. Doses of 4.5 mg/kg or greater in human beings resulted in a compensatory elevation of adrenocorticotropic hormone (ACTH) and cortisol.

Steroidal compounds with abortifacient activity. (See all compounds classified as Abortifacient Agents, Steroidal.)|Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites. (See all compounds classified as Hormone Antagonists.)|Postcoital contraceptives which owe their effectiveness to synthetic preparations. (See all compounds classified as Contraceptives, Postcoital, Synthetic.)|Chemical compounds that induce menstruation either through direct action on the reproductive organs or through indirect action by relieving another condition of which amenorrhea is a secondary result. (From Dorland, 27th ed) (See all compounds classified as Menstruation-Inducing Agents.)|Chemical compounds that cause LUTEOLYSIS or degeneration of the CORPUS LUTEUM. (See all compounds classified as Luteolytic Agents.)|Oral contraceptives which owe their effectiveness to synthetic preparations. (See all compounds classified as Contraceptives, Oral, Synthetic.)

The absolute bioavailability of a 20 mg oral dose is 69%|Fecal: 83%; Renal: 9%.|The absolute bioavailability of oral mifepristone is 69%.|Protein binding: Very high (98%); predominantly to albumin and alpha1- acid glycoprotein.|Time to peak concentration: 90 minutes after a 600 mg oral dose.|Peak plasma concentration: 1.98 mg/L following a single 600 mg oral dose.|Fecal; 83% of a 600 mg dose over 11 days. Renal; 9% of a 600 mg dose over 11 days.

Hepatic. Hepatic, by Cytochrome P450 3A4 isoenzyme to the N-monodemethylated metabolite (RU 42 633); RU 42 698, which results from the loss of two methyl groups from position 11 beta; and RU 42 698, which results from terminal hydroxylation of the 17–propynyl chain.|Hepatic, by Cytochrome P450 3A4 isoenzyme to the N-monodemethylated metabolite (RU 42 633); RU 42 698, which results from terminal hydroxylation of the 17-propynyl chain.|Mifepristone has known human metabolites that include 17alpha-hydroxymifepristone and Monodemethylated mifepristone.

18 hours|Terminal: 18 hours; begins slowly and becomes more rapid with time.

The anti-progestational activity of mifepristone results from competitive interaction with progesterone at progesterone-receptor sites. Based on studies with various oral doses in several animal species (mouse, rat, rabbit and monkey), the compound inhibits the activity of endogenous or exogenous progesterone. The termination of pregnancy results. In the treatment of Cushing's syndrome, Mifepristone blocks the binding of cortisol to its receptor. It does not decrease cortisol production but reduces the effects of excess cortisol, such as high blood sugar levels.|Mifepristone competitively inhibits the actions of progesterone at progesterone-receptor sites, resulting in termination of pregnancy.The combination of mifepristone and misoprostol causes expulsion of the products of conception through decidual necrosis, myometrial contractions, and cervical softening.|When administered in the early stages of pregnancy, mifepristone causes decidual breakdown by blockade of uterine progesterone receptors. This leads to detachment of the blastocyte, which decreases hCG production. This in turn causes a decrease in progesterone secretion from the corpus luteum, which further accentuates decidual breakdown. Decreased endogenous progesterone coupled with blockade of progesterone receptors in the uterus increases prostaglandin levels and sensitizes the myometrium to the contractile actions of prostaglandins.|In addition, mifepristone promotes uterine contractions and softening of the cervix and sensitizes the myometrium to effects of prostaglandins (e.g., misoprostol) that stimulate uterine contraction and expulsion of the products of conception. In the absence of progesterone, mifepristone acts as a partial progestin agonist. At dosages higher than those used for termination of pregnancy, mifepristone also exhibits antiglucocorticoid activity. The drug also has been shown to have weak antiandrogenic activity.

There is no known specific antidote to mifepristone. Treatment is generally symptomatic and supportive. Patients ingesting a massive overdose should be closely observed for signs of adrenal failure.|Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/SIGNS AND SYMPTOMS/ Vaginal bleeding that is heavier than associated with a normal menses occurs in almost all women receiving mifepristone and misoprostol. Based on clinical studies, bleeding or spotting should be expected for an average of 9-16 days. ... Excessive bleeding may require treatment with vasoconstrictors, saline infusions, and/or blood transfusions or curettage.|/SIGNS AND SYMPTOMS/ Serious bacterial infections) including very rare cases of fatal septic shock) have been reported following mifepristone administration; a causal relationship to the mifepristone-misoprostol regimen has not been established. Clinicians should consider the possibility of infection if sustained fever (temperature of 38 degrees C or higher persisting for more than 4 hours), severe abdominal pain, or pelvic tenderness occurs within several days of medical abortion. Atypical presentations of serious infection and sepsis (i.e., presence of significant leukocytosis, tachycardia, or hemoconcentration without fever, severe abdominal pain, pelvic tenderness) may also occur.|/HUMAN EXPOSURE STUDIES/ Myocardial infarction occurred in at least one patient 3 days following use of mifepristone and vaginal misoprostol; a causal relationship to the regimen has not been established.

Mifégyne

Oral: Tablets 200 mg Mifeprex (Danco Laboratories)

Commercially available mifepristone must be obtained through a restricted distribution program. Clinicians in institutions must sign a prescriber's agreement form before ordering the drug from the distributor or prescribing the drug; the drug is not available through pharmacies.|Progesterone receptor antagonist with partial agonist activity.|Information available in 2005 indicated that Mifepristone was used in the manufacture of pharmaceutical preparations in the following countries: Denmark, Finland, France, Germany, India, Indonesia, Israel, Norway, Russian Federation, Spain, Sweden, Switzerland, United Kingdom, United States (1,2)

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