Talk:Mifepristone
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Cite this page: Hill, M.A. (2024, April 26) Embryology Mifepristone. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Mifepristone |
http://embryology.med.unsw.edu.au/wwwhuman/MCycle/RU486.htm
2011
Medical methods for first trimester abortion
Cochrane Database Syst Rev. 2011 Nov 9;11:CD002855.
Kulier R, Kapp N, Gülmezoglu AM, Hofmeyr GJ, Cheng L, Campana A. Source
World Health Organization, Avenue Via Appia 20, Geneva, Switzerland, CH-1202.
Abstract
BACKGROUND: Surgical abortion by vacuum aspiration or dilatation and curettage has been the method of choice for early pregnancy termination since the 1960s. Medical abortion became an alternative method of first trimester pregnancy termination with the availability of prostaglandins in the early 1970s and anti-progesterones in the 1980s. The most widely researched drugs are prostaglandins (PGs) alone, mifepristone alone, methotrexate alone, mifepristone with prostaglandins and methotrexate with prostaglandins. OBJECTIVES: To compare different medical methods for first trimester abortion. SEARCH STRATEGY: The Cochrane Controlled Trials Register, MEDLINE and Popline were systematically searched. Reference lists of retrieved papers were also searched. Experts in WHO/HRP were contacted. SELECTION CRITERIA: Types of studies Randomised controlled trials comparing different medical methods for abortion during first trimester (e.g. single drug, combination) were considered. Trials were assessed and included if they had adequate concealment of allocation, randomisation procedure and follow-up. Women, pregnant during the first trimester, undergoing medical abortion were the participants. The outcomes were mortality, failure to achieve complete abortion, surgical evacuation, ongoing pregnancy at follow-up, time until passing of conceptus, blood transfusion, side effects and women's dissatisfaction with the procedure. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion from the results of the search strategy described previously.The selection of trials for inclusion in the review was performed independently by two reviewers after employing the search strategy described previously. Trials under consideration were evaluated for appropriateness for inclusion and methodological quality without consideration of their results. Data were processed using Revman software. MAIN RESULTS: Fifty-eight trials were included in the review. The effectiveness outcomes below refer to 'failure to achieve complete abortion' with the intended method unless otherwise stated. 1) Combined regimen mifepristone/prostaglandin: Mifepristone 600 mg compared to 200 mg shows similar effectiveness in achieving complete abortion (4 trials, RR 1.07, 95% CI 0.87 to 1.32). Misoprostol administered orally is less effective (more failures) than the vaginal route (RR 3.00, 95% CI 1.44 to 6.24) and may be associated with more frequent side effects such as nausea and diarrhoea. Sublingual and buccal routes were similarly effective compared to the vaginal route, but had higher rates of side effects. 2) Mifepristone alone is less effective when compared to the combined regimen mifepristone/prostaglandin (RR 3.76 95% CI 2.30 to 6.15). 3) Five trials compared prostaglandin alone to the combined regimen (mifepristone/prostaglandin). All but one reported higher effectiveness with the combined regimen. The results of these studies could not be combined but the RR of failure with prostaglandin alone is reportedly between 1.4 to 3.75 with the 95% confidence intervals indicating statistical significance. 4) In one trial comparing gemeprost 0.5 mg with misoprostol 800 mcg, misoprostol was more effective (failure with gemeprost: RR 2.86, 95% CI 1.14 to 7.18). 5) There was no difference in effectiveness with use of a divided dose compared to a single dose of prostaglandin. 6) Combined regimen methotrexate/prostaglandin demonstrates similar rates of failure to complete abortion when comparing intramuscular to oral methotrexate administration (RR 2.04, 95% CI 0.51 to 8.07). Similarly, day 3 vs. day 5 administration of prostaglandin following methotrexate administration showed no significant differences (RR 0.72, 95% CI 0.36 to 1.43). One trial compared the effect of tamoxifen vs. methotrexate and no statistically significant differences were observed in effectiveness between the groups.
AUTHORS' CONCLUSIONS: Safe and effective medical abortion methods are available. Combined regimens are more effective than single agents. In the combined regimen, the dose of mifepristone can be lowered to 200 mg without significantly decreasing the method effectiveness. Vaginal misoprostol is more effective than oral administration, and has less side effects than sublingual or buccal. Some results are limited by the small numbers of participants on which they are based. Almost all trials were conducted in settings with good access to emergency services, which may limit the generalizability of these results.
PMID 22071804
Effect of bacterial vaginosis on the pharmacokinetics of misoprostol in early pregnancy
Hum Reprod. 2011 Nov 28. [Epub ahead of print]
Sioutas A, Sandström A, Fiala C, Watzer B, Schweer H, Gemzell-Danielsson K. Source Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet/Karolinska University Hospital, 17176 Stockholm, Sweden.
Abstract
BACKGROUND Misoprostol has been shown to be an effective agent for cervical ripening and termination of early pregnancy especially when administered vaginally. Our objective was to evaluate whether bacterial vaginosis (BV) affected the pharmacokinetics of vaginally administered misoprostol during early pregnancy.
METHODS Ten women with BV and 10 healthy women requesting medical abortion up to 9 weeks of pregnancy were administered 200 mg mifepristone followed 24-48 h later by a single dose of 800 µg misoprostol vaginally. Blood samples were taken before (0 h) and 0.5, 1, 2, 3 and 4 h after misoprostol administration. Misoprostol acid was determined in serum samples using liquid chromatography/tandem mass spectrometry.
RESULTS All women with BV had a vaginal pH > 4.7. The mean bioavailability measured as the area under the curve (AUC) and maximum concentration (C(max)) appeared higher in the control than in the BV group (1458.7 versus 878.1 pg h/ml) and (630.7 versus 342.5 pg/ml), respectively, but did not achieve statistical significance and there was no other significant difference in the pharmacokinetics between the two groups. However, if two women with vaginal pH > 4.7 were excluded from the control group the difference in AUC(240) (1359 versus 878.1 pgh/ml) reached statistical significance (P = 0.048).
CONCLUSIONS BV had an effect on pharmacokinetics of vaginally administered misoprostol in early pregnancy. However, the results should be interpreted with caution due to the small sample size and marked individual variations.
PMID 22128294
Mifepristone Prevents Stress-Induced Apoptosis in Newborn Neurons and Increases AMPA Receptor Expression in the Dentate Gyrus of C57/BL6 Mice
PLoS One. 2011;6(11):e28376. Epub 2011 Nov 30.
Llorens-Martín M, Trejo JL. Source CSIC, Madrid, Spain.
Abstract
Chronic stress produces sustained elevation of corticosteroid levels, which is why it is considered one of the most potent negative regulators of adult hippocampal neurogenesis (AHN). Several mood disorders are accompanied by elevated glucocorticoid levels and have been linked to alterations in AHN, such as major depression (MD). Nevertheless, the mechanism by which acute stress affects the maturation of neural precursors in the dentate gyrus is poorly understood. We analyzed the survival and differentiation of 1 to 8 week-old cells in the dentate gyrus of female C57/BL6 mice following exposure to an acute stressor (the Porsolt or forced swimming test). Furthermore, we evaluated the effects of the glucocorticoid receptor (GR) antagonist mifepristone on the cell death induced by the Porsolt test. Forced swimming induced selective apoptotic cell death in 1 week-old cells, an effect that was abolished by pretreatment with mifepristone. Independent of its antagonism of GR, mifepristone also induced an increase in the percentage of 1 week-old cells that were AMPA(+). We propose that the induction of AMPA receptor expression in immature cells may mediate the neuroprotective effects of mifepristone, in line with the proposed antidepressant effects of AMPA receptor potentiators.
PMID 22140582
Immunopharmacology of ulipristal as an emergency contraceptive
Int J Womens Health. 2011;3:391-7. Epub 2011 Nov 22.
Miech RP. Source Department of Molecular Pharmacology, Physiology and Biotechnology, Warren Alpert School of Medicine, Brown University, Providence, RI, USA.
Abstract
A new progesterone antagonist, ulipristal has been made available as an emergency contraceptive. Ulipristal's major mechanism of action as an emergency contraceptive has been ascribed to its ability to delay ovulation beyond the life span of the sperm. This paper analyzes the potential action of ulipristal (1) when unprotected intercourse and administration of ulipristal occur outside the fertility window and (2) when unprotected intercourse and administration of ulipristal occur at or within 24 hours of ovulation. When unprotected intercourse and the use of a single low dose of ulipristal occur outside of the fertility window, ulipristal behaves like a placebo. When unprotected intercourse and the use of a single low dose of ulipristal occur within the fertility window but before ovulation, ulipristal behaves like an emergency contraceptive by delaying ovulation and thereby preventing fertilization. When unprotected intercourse and the administration of ulipristal occur at or within 24 hours of ovulation, then ulipristal has an abortifacient action. It is proposed that the abortifacient mechanism of a low dose of ulipristal taken after fertilization but before implantation is due to the ability of ulipristal to block the maternal innate immune system to become immunotolerant to the paternal allogenic embryo. Progesterone's critical immunotolerant actions involving early pregnancy factor, progesterone-induced blocking factor, and uterine natural killer cells are compromised by ulipristal.
PMID 22140327
Ulipristal acetate for emergency contraception
Ann Pharmacother. 2011 Jun;45(6):780-6. Epub 2011 Jun 10.
Snow SE, Melillo SN, Jarvis CI. Source Biogen Idec/Massachusetts College of Pharmacy and Health Sciences, School of Pharmacy, Worcester, Manchester, MA, USA. sarasnow23@gmail.com
Abstract
OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of data of ulipristal acetate, a new emergency contraceptive approved for use up to 120 hours after unprotected intercourse. DATA SOURCES: Articles pertaining to the topic were identified and reviewed through searches of PubMed (1994-March 2011) and clinicaltrials.gov, using the key terms ulipristal and CDB-2914. Ella approval documents were obtained and reviewed from Drugs@FDA on the Food and Drug Administration (FDA) Web site. STUDY SELECTION AND DATA EXTRACTION: All published data and FDA approval documents examining pharmacologic, pharmacokinetic, and clinical studies related to ulipristal acetate as an emergency contraceptive were evaluated. Selected studies included 3 randomized trials and 1 meta-analysis. DATA SYNTHESIS: Ulipristal acetate is a progesterone agonist/antagonist emergency contraceptive approved for the prevention of pregnancy to be taken as soon as possible, within 120 hours after unprotected intercourse or a known or suspected contraceptive failure. Based upon results of the Phase 3 clinical trials used to obtain approval, ulipristal acetate administration was at least as effective as levonorgestrel in the reduction of pregnancy rate when studied alone after unprotected intercourse and when taken up to 120 hours after unprotected intercourse. Commonly reported adverse effects associated with ulipristal acetate in trials included headache, breast tenderness, nausea, and abdominal pain. CONCLUSIONS: Ulipristal acetate is effective as an emergency contraceptive for up to 120 hours after unprotected intercourse. Because ulipristal is available only via prescription, it may be covered by insurance. However, the additional factors of travel expenses and time to make and attend a physician appointment must be taken into account when considering use of ulipristal as an emergency contraceptive. Due to the similarity of its structure to mifepristone, controversy regarding ulipristal's mechanism of action has arisen. Comment in Ann Pharmacother. 2011 Jun;45(6):813-5.
PMID 21666089
Medical methods for mid-trimester termination of pregnancy
Cochrane Database Syst Rev. 2011 Jan 19;(1):CD005216.
Wildschut H, Both MI, Medema S, Thomee E, Wildhagen MF, Kapp N.
Department of Obstetrics and Gynaecology, Erasmus Medical Center, PO Box 2040, Rotterdam, Netherlands, 3000 CA. Abstract BACKGROUND: With the improvement of ultrasound technology, the likelihood of detection of major fetal structural anomalies in mid-pregnancy has increased considerably. Upon the detection of serious anomalies, women typically are offered the option of pregnancy termination. Additionally, there are still many reasons other than fetal anomalies why women seek abortion in the mid-trimester.
OBJECTIVES: To compare different methods of second trimester medical termination of pregnancy for their efficacy and side-effects.
SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, Popline and reference lists of retrieved papers and other sources.
SELECTION CRITERIA: All randomised controlled trials (RCTs) examining medical regimens for termination of pregnancy of a singleton living fetus between 12-28 weeks' gestation were analysed. The outcome measures were the induction to abortion interval, abortion rate within 24 hours, need for surgical evacuation, blood loss, uterine rupture, pain, and side-effects.Trials including >20% fetal death, multiple pregnancies, previous uterine scars and regimens which involved cervical preparation were excluded.
DATA COLLECTION AND ANALYSIS: Two authors selected the trials and three authors extracted data.
MAIN RESULTS: Fourty RCTs were included, addressing various agents for pregnancy termination and methods of administration. When used alone, misoprostol was an effective inductive agent, though it appeared to be more effective in combination with mifepristone. However, the evidence from RCTs is limited.Misoprostol was preferably administered vaginally, although among multiparous women sublingual administration appeared equally effective. A range of doses of vaginally administered misoprostol has been used. No randomised trials comparing doses of misoprostol were identified; however low doses of misoprostol appear to be associated with fewer side-effects while moderate doses appear to be more efficient in completing abortion. Four RCTs showed that the induction to abortion interval with 3-hourly vaginal administration of prostaglandins is shorter than 6-hourly administration without an increase in side-effects.Many studies reported the need for surgical evacuation. Indications for surgical evacuation include retained products of the placenta and heavy vaginal bleeding. Fewer women required surgical evacuation when misoprostol was administrated vaginally compared with women receiving intra-amniotical PGF(2a) . Mild, self-limiting diarrhoea was more common among women who received misoprostol compared to other agents.
AUTHORS' CONCLUSIONS: Medical abortion in the second trimester using the combination of mifepristone and misoprostol appeared to have the highest efficacy and shortest abortion time interval. Where mifepristone is not available, misoprostol alone is a reasonable alternative. The optimal route for administering misoprostol is vaginally, preferably using tablets at 3-hourly intervals. Apart from pain, the side-effects of vaginal misoprostol are usually mild and self limiting. Conclusions from this review are limited by the gestational age ranges and variable medical regimens, including dosing, administrative routes and intervals of medication, of the included trials.
PMID: 21249669 http://www.ncbi.nlm.nih.gov/pubmed/21249669
2000
Mifepristone for induction of labour
Cochrane Database Syst Rev. 2009 Jul 8;(3):CD002865. Hapangama D, Neilson JP.
School of Reproductive and Developmental Medicine, Division of Perinatal and Reproductive Medicine, The University of Liverpool, First Floor, Liverpool Women's NHS Foundation Trust, Crown Street, Liverpool, UK, L8 7SS. Update of:
Cochrane Database Syst Rev. 2000;(4):CD002865. Abstract BACKGROUND: The steroid hormone, progesterone, inhibits contractions of the pregnant uterus at all gestations. Antiprogestins (including mifepristone) have been developed to antagonise the action of progesterone, and have a recognised role in medical termination of early or mid-trimester pregnancy. Animal studies have suggested that mifepristone may also have a role in inducing labour in late pregnancy.
OBJECTIVES: To determine the effects of mifepristone for third trimester cervical ripening or induction of labour.
SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and reference lists of relevant papers (May 2009).
SELECTION CRITERIA: Clinical trials comparing mifepristone used for third trimester cervical ripening or labour induction with placebo/no treatment or other labour induction methods.
DATA COLLECTION AND ANALYSIS: A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. For this update, two review authors independently assessed trial quality and extracted data.
MAIN RESULTS: Ten trials (1108 women) are included. Compared to placebo, mifepristone treated women were more likely to be in labour or to have a favourable cervix at 48 hours (risk ratio (RR) 2.41, 95% confidence intervals (CI) 1.70 to 3.42) and this effect persisted at 96 hours (RR 3.40, 95% CI 1.96 to 5.92). They were less likely to need augmentation with oxytocin (RR 0.80, 95% CI 0.66 to 0.97). Mifepristone treated women were less likely to undergo caesarean section (RR 0.74, 95% CI 0.60 to 0.92) but more likely to have an instrumental delivery (RR 1.43, 95% CI 1.04 to 1.96). Women receiving mifepristone were less likely to undergo a caesarean section as a result of failure to induce labour (RR 0.40, 95% CI 0.20 to 0.80). There is insufficient evidence to support a particular dose but a single dose of 200 mg mifepristone appears to be the lowest effective dose for cervical ripening (increased likelihood of cervical ripening at 72 hours (RR 2.13, 95% CI 1.15 to 3.97). Abnormal fetal heart rate patterns were more common after mifepristone treatment (RR 1.85, 95% CI 1.17 to 2.93), but there was no evidence of differences in other neonatal outcomes. There is insufficient information on the occurrence of uterine rupture/dehiscence in the reviewed studies.
AUTHORS' CONCLUSIONS: There is insufficient information available from clinical trials to support the use of mifepristone to induce labour. However, the studies suggest that mifepristone is better than placebo in reducing the likelihood of caesarean sections being performed for failed induction of labour; therefore, this may justify future trials comparing mifepristone with the routine cervical ripening agents currently in use. There is little information on effects on the baby.
PMID: 19588336
