Date of approval: Date of modification.
Misoprostol Tablets Instructions
Please read the instructions carefully and use under the guidance of a physician
Drug Name]
Generic name: Misoprostol Tablets
English name: Misoprostol Tablets
Hanyu Pinyin: Misuoqianliechun Pian
Ingredients
The main ingredient of this product is Misoprostol, whose chemical name is (±)-methyl-(1R,2R,3R)-3-hydroxy-2-[(E)-(4RS)-4-hydroxy-4-methyl-1-octenyl]-5-oxocyclopentylheptanoyl ester.
Chemical structure formula.
Molecular formula: C22H38O5
Molecular weight: 382.54
【Properties】.
This product is white or off-white tablet.
Indications】
Mifepristone tablets can be used in combination with misoprostol tablets in sequence to terminate intrauterine pregnancy up to 16 weeks (112 days), including: ① for termination of pregnancy up to 7 weeks (49 days); ② for termination of pregnancy from 8 to 16 weeks (50 to 112 days).
Specification
0.2mg
Dosage and Administration
1. For termination of pregnancy within 7 weeks (49 days): 25mg to 50mg (1 to 2 tablets) of mifepristone tablets to be taken orally twice a day for 2 to 3 days on an empty stomach or 2 hours after eating, for a total of 150mg (6 tablets), with 2 hours of fasting after each dose, and 600μg of misoprostol (200μg/tablet x 3 tablets) to be taken orally in the morning of the 3rd to 4th day, or place carboprost in the posterior vaginal fornix. 1 (1mg) of carboprost suppository in the posterior vaginal vault. Bed rest for 1 to 2 hours and outpatient observation for 6 hours. Pay attention to bleeding after administration, any pregnancy product excretion and side effects.
2. For termination of pregnancy within 8-16 weeks (50-112 days): on the first and second days, respectively, 100mg (4 tablets) of mifepristone on an empty stomach or 2 hours after eating, for a total of 200mg (8 tablets), with 2 hours of fasting after each dose, and on the third day, 36-48 hours after the first oral dose of mifepristone, 400μg (2 tablets) of misoprostol should be given orally, with repeat doses of misoprostol after 3 hours, depending on the clinical situation. Repeat misoprostol 400mg (2 tablets) once after an interval of 3 hours, with a maximum of 4 doses.
Adverse reactions
Digestive system: nausea, vomiting, abdominal pain, diarrhea, abdominal distension, etc.
Nervous system: headache, dizziness, vertigo, numbness, etc.
Skin reactions: rash, itching, flushing, etc.
Reproductive system: breast tenderness.
Immune system: allergic reactions, even anaphylaxis.
Systemic reactions: chills, chills, chills, fever, weakness, lumbago.
[Contraindicated].
1. patients with heart, liver and kidney diseases and adrenal cortical insufficiency.
2. patients with contraindications to the use of prostaglandin-based drugs, such as glaucoma, asthma and allergic to prostaglandin-based drugs.
3. early pregnancy with intrauterine device and suspected ectopic pregnancy.
Precautions]
1. For termination of pregnancy within 16 weeks (112 days), mifepristone tablets should be used in combination with misoprostol tablets and not alone.
2. Mifepristone tablets combined with prostaglandins in sequence should be used for termination of pregnancy up to 16 weeks (112 days) in medical institutions with emergency care, curettage, infusion and blood transfusion conditions.
(1) Termination of pregnancy up to 9 weeks (63 days) of menopause can be used in outpatient observation.
(2) Termination of pregnancy at 10 to 16 weeks (64 to 112 days) of menopause must be followed by inpatient abortion or induction of labor.
(3) Misoprostol tablets are used orally at intervals of 3 to 4 hours to maintain better contractions and achieve better abortion results. The drug itself should be taken into account in the clinical judgment of whether the infection is present.
The doctor must inform the patient in detail about the effects of treatment and possible side effects before taking the medication.
(1) Patients with menopause less than 7 weeks (49 days) must be observed in hospital for 4-6 hours or hospitalized when taking this product.
(2) Patients with 8 to 9 weeks of menopause (50 to 63 days) must be observed for 24 hours after termination of pregnancy before leaving the hospital if they are not hospitalized.
(3) Patients with 10 weeks (64 days) or more of menopause must be hospitalized. If heavy bleeding or other abnormalities occur during treatment or follow-up, prompt medical attention should be sought for appropriate management.
5. After taking the drug, a small amount of vaginal bleeding usually occurs. Very rarely, miscarriage occurs in pregnant women after taking mifepristone without prior administration of prostaglandins. A follow-up visit to the original treatment unit should be made 8 to 21 days after taking the drug to determine the effect of abortion. If necessary, ultrasound or blood HCG measurement should be done. If incomplete abortion or continued pregnancy is confirmed, it should be treated promptly.
6. If the pregnancy is not completely expelled within 24 hours after the use of this product, the pregnancy must be promptly terminated by other methods. If one of the following conditions occurs, symptomatic treatment must be given promptly, and if necessary, scraping may be considered.
(1) The embryo or fetus or placenta is not expelled after the drug is administered, and the amount of vaginal bleeding is >100ml (2) The amount of vaginal bleeding is >100ml after the fetus is expelled or there is active bleeding (3) The placenta is not expelled one hour after the fetus is expelled (4) The amount of vaginal bleeding after the embryo or fetus or placenta is expelled> 100ml (5) The placenta is obviously defective
Pregnant women and nursing mothers use]
Pregnancy
Since this product can cause uterine contractions and has been associated with miscarriage, preterm delivery, fetal death, and fetal malformations. The risk of teratogenicity is increased approximately threefold after exposure to misoprostol during early pregnancy. In particular, prenatal exposure to misoprostol causes Moebius syndrome (congenital facial nerve palsy resulting in expression deficits, sucking and swallowing and eye movement difficulties with or without limb defects), amniotic band syndrome (limb malformations/limb amputations, especially malformed feet, ankylosis, oligodactyly, and cleft palate) and central nervous system anomalies (cranial anomalies such as anencephaly, hydrocephalus, cerebellar hypoplasia, neural tube defects). Other observed defects include joint contractures.
Lactation
In the mother, misoprostol is rapidly metabolized to the biologically active misoprostol acid, which can be secreted via breast milk. Misoprostol should not be used in women who are breastfeeding because misoprostol acid secreted via breast milk can cause adverse reactions such as causing diarrhea in breastfed infants.
[Pediatric Use].
The use of misoprostol in children has not been evaluated.
Geriatric Use]
There is no significant difference in the safety profile of misoprostol in patients 65 years of age or older compared to younger patients.
Drug Interactions]
Concomitant use of NSAIDs with misoprostol has rarely resulted in cases of elevated aminotransferase levels and peripheral edema.
It is mainly metabolized by the fatty acid oxidation system and has no adverse effects on the hepatic P450 enzyme system. No clinically significant pharmacokinetic interactions have been observed when combined with antipyrine or diazepam. A moderate increase in propranolol concentrations (mean increase in AUC of approximately 20 % and mean increase in Cmax of approximately 30 %) was observed with multiple administrations of misoprostol. No drug-drug interactions caused by this product have been identified in large clinical studies. Studies of misoprostol interactions with several NSAIDs have shown no clinically significant effects of misoprostol on the pharmacokinetics of ibuprofen, diclofenac, piroxicam, aspirin, naproxen, or indomethacin.
Concomitant use of antacids containing magnesium should be avoided during misoprostol treatment as this may aggravate misoprostol-induced diarrhea.
Overdose]
Signs and Symptoms of Overdose
Clinical signs and symptoms suggestive of overdose include sedation, tremors, convulsions, dyspnea, abdominal pain, diarrhea, fever, palpitations, hypotension, or bradycardia.
Management of overdose
Because misoprostol is metabolized like fatty acids, dialysis is not an appropriate treatment for drug overdose. When an overdose occurs, standard supportive therapy should be used as needed.
[Clinical Trials].
A multicenter randomized controlled clinical trial included 629 women at 8 to 16 weeks (50 to 112 days) gestation, divided into 2 groups: 419 cases in the misoprostol oral group (hereafter referred to as the “oral group”) and 210 cases in the misoprostol vaginal group (hereafter referred to as the “vaginal group”). On the third day, misoprostol was administered to 400μg (2 tablets) in the oral group and 600μg (3 tablets) in the vaginal group, and then repeated at intervals of 3 hours (oral) or 6 hours (vaginal). The maximum number of doses should not exceed 4.
The clinical effectiveness includes both complete and incomplete miscarriage rates. The results showed that (1) complete abortion rate: 76.50% in the oral group and 76.44% in the vaginal group, with no statistical difference between the two groups (P=0.870). Incomplete abortion rate: 15.11% in the oral group and 16.83% in the vaginal group. (2) Complete abortion rate at 8 to 9 weeks (50-63 days): 83.84% in the oral group and 87.88% in the vaginal group; incomplete abortion rate: 10.10% in the oral group and 5.05% in the vaginal group. (3) Complete abortion rate at 10-16 weeks (64-112 days): 69.86% in the oral group and 66.06% in the vaginal group; incomplete abortion rate: 19.63% in the oral group and 27.52% in the vaginal group.
Pharmacology and Toxicology
It is a pregnancy termination drug, with cervical softening, enhancing uterine tone and intrauterine pressure. It can significantly increase or induce the frequency and amplitude of spontaneous uterine contractions when combined with mifepristone in a sequential manner. Also, as a natural analogue of prostaglandin E1, it can promote healing or relieve symptoms of peptic ulcers. The protective effect on the gastric and duodenal mucosa is achieved by inhibiting basal, irritant and nocturnal gastric acid secretion, reducing the amount of gastric acid secretion, decreasing the protein hydrolase activity of gastric juice, and increasing the secretion of bicarbonate and mucus.
Toxicological findings in animal (dog, rat, mouse) tests at several times the clinically recommended therapeutic dose for single and multiple dosing are consistent with the known pharmacological effects of prostaglandin E. The main symptoms were diarrhea, vomiting, dilated pupils, tremors and high fever. It was also found to cause hyperplasia of the gastric mucosa in dogs, rats, and mice. In rats and dogs, the hyperplasia was reversible when the drug was discontinued after 1 year of administration. Histological biopsies of the stomach were performed on patients 1 year after dosing and no adverse tissue changes were found. Toxicological studies on reproduction, teratogenicity and pre- and post-perinatal period in rats and rabbits showed no significant findings. When the dose exceeded 100 times the human dose, a reduced rate of implantation and delayed development of the pups were found. It can be concluded that misoprostol has no significant effect on reproduction, is not teratogenic or embryotoxic, and does not affect the development of rat pups before and after the perinatal period.
In a set of six in vitro analyses and one in vivo assay to assess mutagenic potential, the results obtained with misoprostol were negative. Carcinogenicity studies in rats and mice showed no carcinogenic risk.
Pharmacokinetics]
The product is rapidly absorbed after oral administration, and the blood concentration of the active metabolite (misoprostol acid) reaches its peak after 30 minutes. The plasma clearance half-life of misoprostolinic acid is 20-40 minutes. Repeated administration of 0.4 mg twice daily did not reveal accumulation of the active metabolite in plasma.
Storage
Store in a dry place below 30℃.
Package
Double aluminum packaging, 3 tablets per plate, 1 plate per box
Package: 3 tablets per plate, 4 plates per box
Double aluminum packaging, 4 tablets per plate, 1 plate per box
[Expiration date
36 months
Approval number
State Drug Authentication H20000668
Execution Standard
[Drug Marketing Licensee
Company Name: China Resources Zizhu Pharmaceutical Co.
Registered Address: No. 2 Jiuxianqiao Road, Chaoyang District, Beijing
Manufacturer
Company Name: China Resources Zizhu Pharmaceutical Co.
Address: No. 27 Chaoyang North Road, Chaoyang District, Beijing
Postal Code: 100024
Telephone number: 400-6508-662 (after-sales service)
010-62262389 010-62250419 (after-sales service)
010-65483355-2221 (production)
Fax number: 010-62219316
Web address: http://www.zizhu-pharm.com.cn