Single Oral Dose Of Mifepristone Research Articles

EFFICACY OF MIFEPRISTONE FOLLOWED BY MISOPROSTOL VERSUSMISOPROSTOL ALONE IN MEDICAL MANAGEMENT OF EARLY PREGNANCY FAILURE

Purpose of the study- To study the efcacy of mifepristone followed by misoprostol over misoprostol alone in early pregnancy failure in terms of complete evacuation of uterus. METHODS: In a randomized comparative study at the Department of Obstetrics and Gynaecology of Kasturba Hospital, 100 women with early pregnancy failure and gestational age ≤12 weeks between January 2017 and December 2017 were recruited. Of these, 50 women were given a single oral dose of mifepristone (200 mg) followed by 800 mcg misoprostol vaginally (if required) after 24 hours and the other 50 women were treated with 800 mcg misoprostol vaginally alone. RESULTS: Complete evacuation of uterus was achieved in 96% women treated with a sequential combination of mifepristone and misoprostol versus 84% women treated with misoprostol alone. The difference in the rate of complete expulsion was 12% (p <0.05, 95% CI). Also, pre-treatment with mifepristone resulted in statistically signicant reduction in induction to abortion interval (2.40 ± 1.774 vs 3.30 ± 1.951 hr), amount of bleeding (402.2 ± 111.84 vs 535.0 ± 114.84 ml) and duration of bleeding (10.7 ± 2.30 vs 12.4 ± 3.38 days). CONCLUSION Medical treatment of early pregnancy failure with a sequential combination of mifepristone and misoprostol was more effective than misoprostol alone. Hence, women with early pregnancy failure may be offered mifepristone pretreatment before misoprostol to increase the chance of successful management, while reducing the need for surgery.

Medical management of unruptured interstitial pregnancy with mifepristone and methotrexate

Ectopic pregnancy is a serious complication of pregnancy in which embryo gets implanted any where other than the uterine cavity. In interstitial pregnancy, the pregnancy is located in that part of the fallopian tube that penetrates the muscular layer of the uterus. Overall incidence of ectopic pregnancy is one to two percent among which the incidence of interstitial pregnancy is only two percent. Interstitial pregnancy being the hazardous type requires immediate management. Though surgical treatment is the management of choice, its association with decreased fertility rate and increased rate of uterine rupture in future pregnancy cannot be ignored. We hereby report of medical management of interstitial ectopic pregnancy with single oral dose of Mifepristone 200mg along with single dose of Methotrexate 50miligram intramuscularly.Journal of Kathmandu Medical College, Vol. 4(1) 2015, 34-36

Pharmacokinetics of 10 mg of mifepristone

The results of several randomized studies have verified the efficacy of 10 mg mifepristone in emergency contraception. In the present study we characterized the pharmacokinetics of 10 mg mifepristone. Eight healthy female volunteers received a single oral dose of mifepristone on the day 10 or 11 of their menstrual cycle. Blood samples were collected at 0, 1, 2, 4 and 8 h, daily for the next 6 days and on day 10 after mifepristone. Mifepristone concentrations were determined by radioimmunoassay preceded by column chromatography. A peak level of 1.41 ± 0.31 μmol/L (mean ± SD) was measured at 1 h. Individual elimination phase half-lives varied from 15.3 to 26.8 h, the mean (± SD) value being 19.6 ± 4.50 h. Serum mifepristone concentrations exceeded 10 nmol/L in all volunteers for an average of 4.9 days. The pharmacokinetic data on 10 mg mifepristone are in line with previous pharmacokinetic and clinical data, and encourage further development of the 10-mg dose in emergency contraception.

Medical management of early fetal demise using a combination of mifepristone and misoprostol.

This study aims to assess the efficacy of a combination of mifepristone and misoprostol in the management of missed miscarriage and anembryonic pregnancy. Data of 220 consecutive women with miscarriage, undergoing medical evacuation of the uterus were collected prospectively at an early pregnancy assessment unit in a tertiary referral hospital. Each woman received a single oral dose of mifepristone 200 mg and 36-48 h later vaginal misoprostol 800 microg. Three hours following the first dose, two further doses of misoprostol, 400 microg each, were administered vaginally or orally at 3 h intervals. Women who failed to pass products of conception were offered repeat medical regime with misoprostol. Success was defined as complete uterine evacuation within 3 days, without the need for surgical evacuation. The overall success rate of medical management was 84.1%. Mifepristone alone induced natural expulsion of products of conception in 18.1% of women. The median dose of misoprostol required was 1600 microg and the median induction miscarriage interval after first prostaglandin administration was 8.04 h (range: 0.58-50.54 h). Of the 142 women who were symptomatic at presentation the medical regime failed in 30 (21.1%), compared with five (6.4%) failures of the 78 who were asymptomatic (P = 0.007). Of the 35 women who had surgical evacuation, eight required an emergency curettage for bleeding. The combination of oral mifepristone 200 mg with vaginal or oral misoprostol is an alternative to surgical management of early fetal demise, although it is not as effective as surgery.

Medical abortion at 57 to 63 days’ gestation with a lower dose of mifepristone and gemeprost

Objective. To compare the abortifacient efficacy and side‐effects of 200 mg and 600 mg of mifepristone, followed by gemeprost 1 mg vaginally, at 57 to 63 days’ gestation.Design. Double‐blind, randomized controlled trial.Setting. Ten international centers.Subjects. Eight hundred and ninety‐six healthy women requesting medical abortion.Interventions. Participants were randomly assigned to receive a single oral dose of mifepristone of either 200 mg or 600 mg followed in 48 h by gemeprost 1 mg vaginally. The allocation sequence was concealed by using a central pharmacy, and double masking was maintained throughout the study.Main outcome measures. Complete abortion rate was the principal outcome measure. We also evaluated the incidence of side‐effects and time to abort.Results. The complete abortion rate with the lower dose of mifepristone was similar to that with the higher dose (92.4% vs. 91.7%). The relative risk of failure to achieve a complete abortion with the 200 mg dose compared to 600 mg dose was 0.9 (95% CI 0.6–1.4). The timing of the abortion and the incidence of side‐effects were comparable in both groups, with the exception of reported nausea at one‐week follow‐up which was reported more frequently by women in the higher‐dose group.Conclusions. The 200 mg dose of mifepristone is equally as effective as the 600 mg dose in the antiprogestogen‐prostaglandin regimen for pregnancy termination. With vaginal gemeprost, the abortifacient efficacy of the regimen remains high at 57–63 days’ gestation.

Medical abortion at 57 to 63 days' gestation with a lower dose of mifepristone and gemeprost. A randomized controlled trial

To compare the abortifacient efficacy and side-effects of 200 mg and 600 mg of mifepristone, followed by gemeprost 1 mg vaginally, at 57 to 63 days' gestation. Double-blind, randomized controlled trial. Ten international centers. Eight hundred and ninety-six healthy women requesting medical abortion. Participants were randomly assigned to receive a single oral dose of mifepristone of either 200 mg or 600 mg followed in 48 h by gemeprost 1 mg vaginally. The allocation sequence was concealed by using a central pharmacy, and double masking was maintained throughout the study. Complete abortion rate was the principal outcome measure. We also evaluated the incidence of side-effects and time to abort. The complete abortion rate with the lower dose of mifepristone was similar to that with the higher dose (92.4% vs. 91.7%). The relative risk of failure to achieve a complete abortion with the 200 mg dose compared to 600 mg dose was 0.9 (95% CI 0.6-1.4). The timing of the abortion and the incidence of side-effects were comparable in both groups, with the exception of reported nausea at one-week follow-up which was reported more frequently by women in the higher-dose group. The 200 mg dose of mifepristone is equally as effective as the 600 mg dose in the antiprogestogen-prostaglandin regimen for pregnancy termination. With vaginal gemeprost, the abortifacient efficacy of the regimen remains high at 57-63 days' gestation.

Medical abortion at 57 to 63 days' gestation with a lower dose of mifepristone and gemeprost: A randomized controlled trial

OBJECTIVE: To compare the abortifacient efficacy and side-effects of 200 mg and 600 mg of mifepristone, followed by gemeprost 1 mg vaginally, at 57 to 63 days' gestation. DESIGN: Double-blind, randomized controlled trial. SETTING: Ten international centers. SUBJECTS: Eight hundred and ninety-six healthy women requesting medical abortion. INTERVENTIONS: Participants were randomly assigned to receive a single oral dose of mifepristone of either 200 mg or 600 mg followed in 48 h by gemeprost 1 mg vaginally. The allocation sequence was concealed by using a central pharmacy, and double masking was maintained throughout the study. MAIN OUTCOME MEASURES: Complete abortion rate was the principal outcome measure. We also evaluated the incidence of side-effects and time to abort. RESULTS: The complete abortion rate with the lower dose of mifepristone was similar to that with the higher dose (92.4% vs. 91.7%). The relative risk of failure to achieve a complete abortion with the 200 mg dose compared to 600 mg dose was 0.9 (95% CI 0.6-1.4). The timing of the abortion and the incidence of side-effects were comparable in both groups, with the exception of reported nausea at one-week follow-up which was reported more frequently by women in the higher-dose group. CONCLUSIONS: The 200 mg dose of mifepristone is equally as effective as the 600 mg dose in the antiprogestogen-prostaglandin regimen for pregnancy termination. With vaginal gemeprost, the abortifacient efficacy of the regimen remains high at 57-63 days' gestation.

Nonsurgical mid-trimester termination of pregnancy: a review of 500 consecutive cases.

To assess the effectiveness of a regimen comprising mifepristone followed by a combination of the vaginal and oral administration of misoprostol for mid-trimester medical termination of pregnancy. Retrospective analysis of prospectively collected data in women undergoing mid-trimester medical termination of pregnancy. Aberdeen Royal Infirmary, Scotland. A consecutive series of 500 women with pregnancies of 13-21 weeks of amenorrhea undergoing legally induced abortion in one Scottish NHS hospital. Each woman received a single oral dose of mifepristone 200 mg and 36-48 h later vaginal misoprostol 800 microg. Three hours following the first dose of misoprostol, 400 microg doses were administered orally at three hourly intervals, to a maximum of four doses. Success was defined as abortion occurring with five doses of prostaglandin, or within 15 h of administration of the first dose of prostaglandin. Ninety-seven percent aborted successfully. The median dose of misoprostol required was 1200 microg and the median induction-to-abortion interval after first prostaglandin administration was 6.5 h. The median number of doses of misoprostol required to induce abortion, and the induction-to-abortion interval, was statistically significantly higher among women at gestations 17-21 weeks than among those at 13-16 weeks (P = 0.0001). A total of 9.4% required surgical evacuation of the uterus under general anaesthesia and 66.4% of the women were managed as day cases. The combination of oral mifepristone 200 mg followed by vaginally and orally administered misoprostol provides a noninvasive and effective regimen for second trimester termination of pregnancy.

Medical management of missed abortion and anembryonic pregnancy.

Mifepristone (an antiprogesterone) and misoprostol (a synthetic analogue of prostaglandin E1) were administered to 60 women diagnosed with missed abortion or anembryonic pregnancy (gestation sac present but no developing embryo) equivalent to 13 weeks' gestation or less who were recruited after counselling. The median age was 227 (range 15-44), and the median duration of amenorrhoea was 71 (42-110) days. 25 of the women had been referred for ultrasound scanning because of bleeding in early pregnancy, while the rest were diagnosed by routine scanning. 29 patients had anembryonic pregnancies, and 31 had a missed abortion. Each patient received a 600 mg single oral dose of mifepristone, and 36-48 hours later misoprostol 600 mcg was given orally (400 mcg and, 2 hours later, 200 mcg). If the products of conception were not expelled within 4 hours, vaginal ultrasonography was performed. 8 patients aborted with mifepristone alone, 43 aborted after taking 600 mcg of misoprostol, and 5 more aborted after receiving a 2nd divided dose of 600 mcg misoprostol. In 3 patients the treatment failed, and they underwent evacuation of the uterus under general anaesthesia. Exploratory curettage was performed in 2 other patients at 14 and 22 days after treatment with misoprostol, but no products of conception were obtained. The median time from administration of misoprostol to abortion was 4 (1-11) hours. The median duration of bleeding after abortion was 10 (2-22) days. Side effects included nausea, vomiting (5 patients received antiemetic drugs), and diarrhoea (7 patients) from misoprostol treatment. 39 women did not want any pain relief, 13 asked for oral analgesia, and 7 obtained parenteral analgesia.

Mifepristone (RU 486) for cervical priming prior to surgically induced abortion in the late first trimester

Mifepristone (RU) 486; Roussel-Uclaf, Paris, France) is an antiprogesterone agent, which has been used successfully in combination with prostaglandin for early pregnancy medical abortion. Forty primigravidae were studied from 10–13 weeks of gestation. Women were randomly allocated to receive either placebo or a 600 mg single oral dose of Mifepristone 48 hours prior to vacuum aspiration under general anaesthesia. An objective mechanical method was used to assess the dilatation of the cervix at surgery. In 35% of the treated patients, there was no need for further dilatation prior to evacuation of the uterus. All patients in the placebo group required further dilatation (p < 0.001). In those patients receiving Mifepristone who did require further dilatation, the initial dilatation of the cervix was significantly greater (p < 0.01) and significantly less force was required to dilate the cervix to 9 mm (p < 0.001). Perioperative blood loss was reduced. There were no serious complications or side effects. Mifepristone for cervical priming is safe and effective and has advantages over prostaglandins and hydrophilic cervical dilators.

Histological and clinical features of menstruation induced by the antiprogestin mifepristone (RU486) compared to menstruation occurring spontaneously.

The clinical and histological features of menstruation induced by a single oral dose of mifepristone were compared to those in normal spontaneous menstruation to aid understanding of the mechanism of endometrial shedding. 30 healthy volunteers, sterilized or seeking sterilization, were given a single oral dose, ranging from 5-200 mg mifepristone (RU-486) in the 1st half of the luteal phase, timed by the LH surge. Endometrial biopsies were taken on that day or the day after the 1st episode of bleeding for histological examination. Quantitative histological features on a 15 item scale were compared to those seen in women having spontaneous menses. 7 of 15 features differed between the 2 groups. Bleeding induced by mifepristone was associated with the following endometrial characteristics: increased gland cell height, reduced secretion in gland lumen, increased volume fraction of gland occupied by cells and nuclei, increased pseudostratification of gland cells, reduced stromal predecidual reaction, as judged by glycogen and fat content, and reduced leukocyte infiltration in the stroma. Thus there was less gland activity and an appearance of more cell packing, taller and more pseudostratified cells. The features in common with normal menses were mitotic activity in both glands and stroma, secretory vacuoles, edema and extravasation. Clinically the amount and duration of menstrual flow induced by mifepristone was similar to normal menses, suggestive of a similar hemostatic process.

Blood loss following induction of early abortion using mifepristone (RU 486) and a prostaglandin analogue (gemeprost)

The pattern and amount of blood loss following induction of therapeutic abortion using mifepristone (RU 486) and a prostaglandin E analogue (gemeprost) was studied in 222 women of less than 63 days amenorrhoea. A single oral dose of mifepristone (400, 500 or 600 mg) was followed 48 hours later by a half or 1 mg gemeprost vaginal pessary. Complete abortion occurred in 218 (98%) women without necessity for surgical evacuation of the uterus. Bleeding commonly occurred following administration of mifepristone and prior to prostaglandin administration. The median duration of bleeding following abortion was 13 days with a range of from 1 to 44 days. There was a wide individual variation in measured blood loss between women, from 14 to 512 ml, with a median loss of 74 ml. The amount of blood loss was independent of the dose of mifepristone or prostaglandin but was significantly correlated with gestation. These results confirm that the combination of mifepristone and gemeprost is a highly effective and safe method of inducing therapeutic abortion medically. As the amount of blood loss increases with increasing gestation, it is suggested that its use should be restricted to women with amenorrhoea ≤ 56 days.