Approved on.
Date of revision.
Mifepristone Tablets Instructions
Please read the instructions carefully and use under the guidance of your physician
[Drug Name].
Generic Name: Mifepristone Tablets
English name: Mifepristone Tablets
Hanyu Pinyin: Mifeisitong Pian
[Ingredients
The active ingredient of this product is mifepristone. Its chemical name is: 11β-[4-(N,N-dimethylamino)-1-phenyl]-17β-hydroxy-17α-(1-propargyl)-estra-4,9-dien-3-one.
Chemical structure formula.
Molecular formula: C29H35NO2
Molecular weight: 429.61
[Properties
This product is a slightly yellow biconvex round tablet.
[Indications
Mifepristone tablets are used in combination with prostaglandin drugs in sequence to terminate pregnancy within 49 days of menopause. .
[Specifications].
0.2g
[Dosage].
After fasting or eating for 2 hours, take 0.2g (1 tablet) of mifepristone tablets orally followed by a 2-hour fast, and then take misoprostol 0.6mg (0.2mg/tablet x 3 tablets) orally early in the morning on day 3 or 4 or place one carboprost suppository (1mg) in the posterior vaginal vault. Bed rest for 1 to 2 hours and outpatient observation for 6 hours. Pay attention to bleeding after drug administration, any pregnancy product excretion and side effects. .
[Adverse effects].
The frequency of adverse reactions was categorized as follows.
Very common (≥1/10)
Common (1/100~ 1/10 inclusive)
Occasional (1/1000 to 1/100 with 1/1000)
Rare (1/10000~1/1000 inclusive1/10,000)
Very rare (<1/10,000)
unknown (cannot be estimated from available data)
Nervous system
Rare.
Headache
Vascular and lymphatic vessels
Sometimes.
Low blood pressure (0.25%)
Gastrointestinal system
Very common.
nausea, vomiting, diarrhea (gastrointestinal effects related to prostaglandins are frequently reported)
Common.
Mild to moderate spasticity
Skin and subcutaneous tissue
Sometimes.
hypersensitivity reactions: rash (0.2%)
Rare.
Urticaria, erythroderma, erythema nodosum, and toxic epidermal necrolysis relaxation were reported in 1 case
Very rare.
Angioedema
Genital system and breast
Very common.
very common uterine contractions or spasms within hours of prostaglandin ingestion (10 to 45%)
Common.
Higher bleeding occurs in about 5% of cases and may require hemostatic curettage in up to 1.4% of cases.
Rare.
Uterine rupture after prostaglandin ingestion during induction of labor in mid-trimester or induction of intrauterine fetal death in late pregnancy has been reported rarely. Most of these reports occurred in women with multiple births or in women with cesarean scarring.
Systemic and administration site reactions.
Rare.
discomfort, vagal symptoms (hot flashes, dizziness, chills), fever
Post-marketing adverse reactions.
Gastrointestinal system: nausea, vomiting, abdominal pain, anal cramping sensation, dyspepsia
Heart: tachycardia (including rapid pulse, palpitations, rapid heart rate)
Respiratory, chest and mediastinum: shortness of breath
Neuropsychiatric system: dizziness, vertigo, syncope, loss of consciousness, anxiety
Vascular and lymphatic vessels: hypotension (including upright hypotension)
Blood and lymphatic system: anemia
Immune system: allergic reactions (including tachyphylaxis, angioedema, urticaria, rash, pruritus)
Musculoskeletal and connective tissue: back pain, leg pain
Reproductive system and breast: uterine rupture, ectopic pregnancy rupture, blood accumulation in the uterus, leukorrhea
Systemic and administration site reactions: malaise, pain
*Abdominal pain may occur with prostaglandins, and vomiting and diarrhea may occur in some subjects. A few have flushing and tingling. See the appropriate instructions for specific post-prostaglandin adverse reactions. .
[Contraindicated].
Intrauterine pregnancy not confirmed by ultrasound or biopsy.
Hypersensitivity to the product.
Patients with cardiac, hepatic or renal disease and adrenal cortical insufficiency.
Patients with contraindications to the use of prostaglandins: e.g. glaucoma, asthma and allergy to prostaglandins.
Pregnancy with an IUD and suspected ectopic pregnancy, and women over 35 years of age who smoke.
Severe asthma that is not controlled by treatment.
Bleeding disorders or combined anticoagulation therapy.
Persons with hereditary porphyria.
[Precautions
In those diagnosed with early intrauterine pregnancy, the number of days of menopause should not exceed 49 days, and the shorter the gestation period, the better the results. The effectiveness of the method decreases with the number of pregnancies and with the age of the woman.
Mifepristone Tablets must be used under conditions of emergency care, curettage procedures, and infusions and transfusions. This medication must not be sold over the counter by itself.
The person taking the medication must be informed in detail of the effects of treatment and possible side effects before taking the medication. If heavy bleeding or other abnormalities occur during treatment or follow-up, promptly seek medical attention.
After taking the medication, a small amount of vaginal bleeding usually occurs earlier, and some women bleed for a longer period of time after an abortion. A small number of women with early pregnancy can spontaneously abort after taking mifepristone tablets. About 80% of pregnant women expel the chorionic sac within 6 hours after using prostaglandin-based drugs, and about 10% expel the pregnancy within a week after taking the drug.
A follow-up visit to the original treatment unit should be made 8 to 15 days after taking the medication to determine the effect of abortion. If necessary, a B-type ultrasound or blood HCG measurement should be performed. If the diagnosis of incomplete abortion or continued pregnancy is confirmed, it should be treated promptly.
If termination of early pregnancy with this product fails, abortion must be performed to terminate the pregnancy.
Because pregnancy can occur between the time the embryo is expelled and the return of menstruation. Therefore, contraception should be recommended to be started immediately after termination of pregnancy by a medical procedure.
For suspected acute adrenal failure, dexamethasone administration is recommended, with dexamethasone (1 mg) antagonizing mifepristone (0.4 g). The effectiveness of long-term corticosteroid therapy (including inhaled glucocorticoids in asthmatics) may be reduced within 3-4 days of its use due to mifepristone’s anti-glucocorticoid activity. Treatment regimens should be changed.
Rare but serious cardiovascular accidents have been reported after vaginal and intramuscular administration of high doses of prostaglandin analogs (myocardial infarction and/or coronary artery spasm and severe hypotension). Oral misoprostol may also constitute a potential risk factor for acute cardiovascular events. Therefore, caution should be exercised in women at risk for cardiovascular disease (e.g., age over 35 years with chronic smoking, hyperlipidemia, diabetes mellitus), or with diagnosed cardiovascular disease.
Patients may have a combination of post-abortion infections (including endometritis, endomyometritis, paramyometritis, pelvic infection, pelvic inflammatory disease, and pelvic inflammatory disease). pelvic infection, pelvic inflammatory disease, and tubal infection).
Toxic shock and atypical pathogenic infectious shock (Clostridium perfringens and Escherichia coli) have been reported following the use of mifepristone (0.2 g) + misoprostol ) in severe cases (including fatal cases) with or without fever or other obvious signs of infection, clinicians should be aware of this potentially fatal complication.
Follow the precautions for prostaglandin-based medications.
[For pregnant and lactating women
In clinical practice, terminal fetal lower limb malformations (prolapse, clubfoot) have been reported rarely with mifepristone alone or in combination with prostaglandins. If the pregnancy fails at follow-up diagnosis and the patient’s consent is obtained, other methods of pregnancy termination may be used; if the patient wishes to continue the pregnancy, careful ultrasound examination should be performed at a specialized medical facility, with special attention to the embryonic extremities.
Mifepristone is secreted in small amounts in breast milk. Therefore, mifepristone should be avoided during breastfeeding.
This product does not affect fertility. Once a pregnancy is terminated, another pregnancy can occur, so contraception should be used immediately after a doctor confirms termination.
[For Children
There are limited data on the use of this product in minors.
[Geriatric Use
There are limited data on the use of this product in the elderly.
[Drug Interactions].
This product is metabolized by CYP3A4, which may be inhibited by ketoconazole, itraconazole, erythromycin, and grapefruit juice (elevated mifepristone serum levels). In addition, rifampin, dexamethasone, St. John’s wort, and certain anticonvulsants (phenytoin sodium, phenobarbital, carbamazepine) may induce mifepristone metabolism (decreased mifepristone serum levels).
Based on in vitro inhibition information, co-administration of mifepristone may lead to increased serum levels of CYP3A4 substrate drugs. Due to the slow clearance of mifepristone in vivo, this interaction may persist for a long time after administration. Therefore, caution should be exercised when mifepristone is used with drugs that are CYP3A4 substrates and have a narrow therapeutic window, including some drugs used for general anesthesia.
Because nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin (acetylsalicylic acid), have antiprostaglandin effects, theoretically the effectiveness of the approach decreases with the combination. However, there is evidence that the combination of NSAIDs on the day of prostaglandin administration does not affect the effect of mifepristone or prostaglandins on cervical maturation or uterine contractility, nor does it reduce the clinical efficacy of the drug for pregnancy termination.
[Drug overdose].
No drug overdose has been reported.
If large amounts of this product are ingested accidentally, signs of adrenal failure may occur. Acute toxic reactions may require specialized treatment, including administration of dexamethasone therapy.
[Pharmacologic Toxicology].
Mifepristone is a synthetic steroid that has an antiprogestational effect by competing with progesterone in the progesterone receptor.
Oral administration of 3-10 mg/kg of mifepristone inhibits endogenous or exogenous progesterone action in different species (rats, mice, rabbits, and monkeys). It manifests as termination of pregnancy in rodents.
At doses greater than or equal to 1 mg/kg, mifepristone antagonizes the effects of progesterone on the endometrium and myometrium. During pregnancy, it sensitizes the myometrium to the contraction-inducing effects of prostaglandins. In the early stages of pregnancy (first trimester), mifepristone pretreatment facilitates cervical softening and dilation. Although clinical trial data have demonstrated that mifepristone contributes to cervical dilation, there are no data to suggest that the cervical dilation effect of mifepristone decreases the incidence of complications during dilation (early or late).
Mifepristone produced relevant anti-hormonal (anti-progestin, anti-glucocorticoid, and anti-androgen) activity in a 6-month-long toxicology study in rats and monkeys.
Mifepristone is a potent abortifacient in reproductive toxicology studies. Mifepristone was not teratogenic to fetuses in rats and mice. However, fetal malformations (cranial vault, brain and spinal cord) were observed in rabbit fetuses exposed in a dose-dependent manner. The number of monkey fetuses that survived the abortive effects of mifepristone was insufficient for a conclusive assessment. There was no evidence of teratogenic effects of mifepristone on post-transplant embryos in rats and monkeys under in vitro conditions. .
[Pharmacokinetics].
Absorption
A single dose of mifepristone (600 mg) was rapidly absorbed after oral administration. 1.30 h reached a maximum peak concentration of 1.98 mg/L (mean of 10 subjects).
The absolute bioavailability of a small oral dose of mifepristone (20 mg) was 69%.
Distribution
In plasma, mifepristone is 98% bound to plasma proteins: including albumin and alpha-1-acid glycoprotein (AAG), where mifepristone is primarily bound to AAG and its binding can reach saturation. Because of this specific affinity, the volume of distribution and plasma clearance of mifepristone are inversely proportional to the plasma AAG concentration.
Metabolism
Metabolism is mainly via hepatic oxidation, with N-demethylation and terminal hydroxylation of the 17-propynyl chain being the major metabolic pathways of mifepristone.
Elimination
The elimination of mifepristone is a nonlinear dose-response. After the distribution phase, elimination is initially slow, with blood concentrations decreasing by approximately half at 12-72 h and then decreasing rapidly, with an elimination half-life of 18 h. Radioreceptor analysis studies have shown terminal elimination half-lives of up to 90 h, including all metabolites of mifepristone that bind to the progesterone receptor.
Mifepristone is primarily excreted in the feces. When mifepristone 600 mg is given, 10% is excreted in the urine and 90% is excreted in the feces.
[Storage].
Store under shade and seal.
[Packaging
Aluminium-plastic packaging, 1 tablet per plate, 1 plate per box.
Aluminum-plastic packaging, 3 tablets per plate, 1 plate per box.
[Expiration date
24 months
[Executive Standard
[Approval Number].
State Pharmacopoeia H10950004
[Drug Marketing Licensee
China Resources Zizhu Pharmaceutical Co.
Registered Address: No. 2 Jiuxianqiao Road, Chaoyang District, Beijing
[Manufacturer
Company name: China Resources Zizhu Pharmaceutical Co.
Manufacturing Address: No. 27 Chaoyang North Road, Chaoyang District, Beijing
Postal Code: 100024
Phone number: 400-6508-662 (after-sales service)
010-62262389 (after-sales service)
010-62250419 (after-sales service)
010-65483355-2221 (production)
Fax number: 010-62219316
Website: http://www.zizhu-pharm.com.cn