Ulipristal 5mg tablets

Objective: A systematic review and meta-analysis to determine the effectiveness of various emergency contraceptive methods to prevent pregnancy.Method: This study followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) protocol. Data search used four databases, namely Pubmed, Google Scholar, Science Direct, and Wiley. Data that met the inclusion criteria were subjected to meta-analysis to analyze the combined proportion of data using MedCalc 20.012 software, calculation of a percentage of 95% Confidence Intervals (CI) and P<0.05, and heterogeneity test between studies.Results: There were 6 journals that met the criteria. Some of the contraceptives used as emergency contraception are: the copper IUD (CuIUD) with effectiveness reaching 100% in preventing pregnancy, levonorgestrel (LNG) 52-mg IUS with effectiveness reaching 99.95%, the levonorgestrel (LNG) 52-mg IUD with effectiveness reaching 99.7%, mifepristone 10 mg with effectiveness reaching 99.3%, mifepristone 5 mg with effectiveness reaching 98.8%, ulipristal acetate (UPA) 30 mg in pre-ovulatory women with effectiveness reaching 98.6%, levonorgestrel (LNG) 0.75 mg with effectiveness reaching 98.3%, yuzpe regimen with effectiveness reaching 98.2%, and ulipristal acetate (UPA) 30 mg in post-ovulatory women with effectiveness reaching 97.9%. The results of the proportion meta-analysis showed the proportion of pregnancies after the use of emergency contraceptive, which was 0.231% (95% CI 0.116–0.384) from 4,927 samples in 6 studies, and the results of the heterogeneity test between studies were found to be not meaningful (I2 = 0%). Conclusion: The emergency contraception used to prevent pregnancy is very effective with the results of a meta-analysis of the proportion of 0.231% (95% CI 0.116–0.384). This suggests that the percentage of pregnancies after emergency contraceptive use is quite low.Efektivitas Kontrasepsi Darurat untuk Mencegah Kehamilan: Tinjauan Sistematis dan Meta-AnalisisAbstrakTujuan: Tinjauan sistematis dan meta-analisis untuk mengetahui efektivitas berbagai metode kontrasepsi darurat untuk mencegah kehamilan.Metode: Penelitian ini mengikuti protokol Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA). Pencarian data menggunakan empat database yaitu Pubmed, Google Scholar, Science Direct, dan Wiley. Data yang memenuhi kriteria inklusi dilakukan meta analisis dengan analisis proporsi gabungan data menggunakan software MeldCalc 20.012, dilakukan perhitungan persentase 95% CI dan P<0.05, serta dilakukan uji heterogenitas antar studi.Hasil: Terdapat 6 jurnal yang memenuhi kriteria. Beberapa alat kontrasepsi yang digunakan sebagai kontrasepsi darurat yaitu: AKDR tembaga (CuIUD) dengan efektivitas mencapai 100% dalam mencegah kehamilan, levonorgestrel (LNG) 52-mg IUS dengan efektivitas mencapai 99,95%, levonorgestrel (LNG) 52-mg IUD dengan efektivitas mencapai 99,7%, mifepristone 10 mg dengan efektivitas mencapai 99,3%, mifepristone 5 mg dengan efektivitas mencapai 98,8%, ulipristal asetat (UPA) 30 mg pada wanita pre-ovulasi dengan efektivitas mencapai 98,6%, levonorgestrel (LNG) 0,75 mg dengan efektivitas mencapai 98,3%, yuzpe regimen dengan efektivitas mencapai 98,2%, dan ulipristal asetat (UPA) 30 mg pada wanita post-ovulasi dengan efektivitas mencapai 97,9%. Hasil meta analisis proporsi menunjukkan proporsi kehamilan setelah penggunaan kontrasepsi darurat yaitu 0,231% (95% CI 0,116–0,384) dari 4.927 sampel, serta hasil uji heterogenitas antar studi ditemukan tidak bermakna (I2 = 0%).Kesimpulan: Penggunaan kontrasepsi darurat sangat efektif dalam mencegah kehamilan dengan hasil meta analisis proporsi yaitu 0,231% (95%CI 0,116–0,384). Hasil tersebut menunjukkan bahwa persentase kehamilan setelah penggunaan kontrasepsi darurat cukup rendah.Kata kunci: Efektivitas, Kontrasepsi Darurat

Abstract licence: CC BY-SA

Background: Heavy menstrual bleeding affects one in four women and negatively impacts quality of life. Ulipristal acetate is prescribed to treat symptoms associated with uterine fibroids. We compared the effectiveness of ulipristal acetate and the levonorgestrel-releasing intrauterine system at reducing the burden of heavy menstrual bleeding, irrespective of the presence of fibroids. Methods: This randomised, open-label, parallel group phase III trial enrolled women over 18 years with heavy menstrual bleeding from 10 UK hospitals. Participants were centrally randomised, in a 1:1 ratio, to either three, 12-week treatment cycles of 5 mg ulipristal acetate daily, separated by 4-week treatment-free intervals, or a levonorgestrel-releasing intrauterine system. The primary outcome, analysed by intention-to-treat, was quality of life measured by the Menorrhagia Multi-Attribute Scale at 12 months. Secondary outcomes included menstrual bleeding and liver function. The trial is registered with ISRCTN, 20426843. Findings: Between June 5th, 2015 and February 26th, 2020, 236 women were randomised, either side of a recruitment suspension due to concerns of ulipristal acetate hepatoxicity. Subsequent withdrawal of ulipristal acetate led to early cessation of recruitment but the trial continued in follow-up. The primary outcome substantially improved in both groups, and was 89, (interquartile range [IQR] 65 to 100, n = 53) and 94, (IQR 70 to 100, n = 50; adjusted odds ratio 0.55, 95% confidence interval [CI] 0.26-1.17; p = 0.12) in the ulipristal and levonorgestrel-releasing intrauterine system groups. Rates of amenorrhoea at 12 months were higher in those allocated ulipristal acetate compared to levonorgestrel-releasing intrauterine system (64% versus 25%, adjusted odds ratio 7.12, 95% CI 2.29-22.2). Other outcomes were similar between the two groups and there were no cases of endometrial malignancy or hepatotoxicity due to ulipristal acetate use. Interpretation: Our findings suggested that both treatments improved quality of life. Ulipristal was more effective at inducing amenorrhoea. Ulipristal has been demonstrated to be an effective medical therapeutic option but currently its use has restrictions and requires liver function monitoring. Funding: UK Medical Research Council and National Institute of Health Research EME Programme (12/206/52).

Abstract licence: CC BY

Objective To determine whether increasing the dose of ulipristal acetate (UPA)-containing emergency contraception (EC) improves pharmacodynamic outcomes in individuals with obesity. Study design We enrolled healthy, regularly-cycling, confirmed ovulatory, reproductive-age individuals with body mass index (BMI) >30 kg/m 2 and weight >80 kg in a randomised crossover study. We monitored participants with transvaginal ultrasound and blood sampling for progesterone, luteinising hormone (LH), and estradiol every other day until a dominant follicle measuring >15 mm was visualised. At that point, participants received either oral UPA EC 30 mg or 60 mg and returned for daily monitoring up to 7 days. After a no treatment washout cycle, participants returned for a second monitored cycle and received the other UPA dose. Our primary outcome was the proportion of subjects with no follicle rupture 5 days post-dosing (yes/no). For reference, we also enrolled a control group with BMI <25 kg/m 2 and weight <80 kg who received UPA EC 30 mg during a single cycle. We also obtained blood samples for pharmacokinetic parameters for UPA and its active metabolite, N -monodemethyl-UPA (NDM-UPA) as an optional substudy. Results We enrolled a total of 52 participants with BMI >30 kg/m 2 and 12 controls, with the following cycles completed: 12 controls, 49 UPA 30 mg, and 46 UPA 60 mg. The entire cohort demographics were a mean (SD) age of 29.8 (3.4) years and BMI by group: controls 22.5 (1.4) kg/m 2 , group 1 37.9 (6.7) kg/m 2 , and group 2 39.3 (5.4) kg/m 2 . All 12 (100%) of controls had a delay of at least 5 days for follicle rupture. Among the high BMI group, dosing groups (UPA EC 30 mg vs 60 mg) were similar in the proportion of cycles without follicle rupture over 5 days post-UPA dosing (UPA 30 mg: 47/49 (96%), UPA 60 mg: 42/46 (91%), Fisher’s exact test p=0.43). However, after excluding cycles where dosing occurred too late (after LH surge), a delay of at least 5 days occurred in all participants at both doses. The 60 mg UPA dose resulted in a twofold increase in maximum observed concentration and the area under the curve of both UPA and NDM-UPA levels compared with 30 mg. Conclusion A standard 30 mg dose of UPA is sufficient to delay ovulation regardless of BMI or weight. Results of our study do not support dose adjustment for body size.

Abstract licence: CC BY-NC

Introduction: Ulipristal acetate (UPA, 5 mg) demonstrated efficacy in symptom reduction for patients with symptomatic fibroids. While registration and post-marketing trials assessing UPA identified few hepatic concerns, post-marketing concerns about potential drug-induced liver injury (DILI) led to significant restrictions, including indication restriction, warning labels and mandatory liver function monitoring. These measures, along with two marketing suspensions, resulted in a decline in UPA use, ultimately leading to the withdrawal of its marketing authorization previously in Canada, Australia, as well as Singapore and in 2024, at the request of the marketing authorization holder for commercial reasons, also for the European Union. Methods: This narrative review critically evaluates the hepatic safety considerations associated with UPA. Results: On reassessment, the risk of severe DILI with UPA is low at 13.5:100.000, with an incidence of 1 in 200,000 for liver transplantation. These numbers are lower than with many other widely prescribed medications, where no regular liver monitoring is recommended. UPA was subjected to strict liver test monitoring although proof of effectiveness of these measures in preventing serious DILI was lacking. While the risk of severe hepatotoxic events is important to consider, a balanced approach to safety measures is needed, particularly in light of the higher risks associated with alternative treatment options such as surgical intervention. Conclusion: While UPA had a unique place in the treatment of uterine fibroids, overly cautious regulatory measures due to exceedingly rare DILI incidences led to the withdrawal of its marketing authorization in most parts of the world. There is a need for an improved understanding of DILI mechanisms and causality assessments to aid in the development of more proportional regulatory responses, balancing patient safety and sustained access to effective innovative treatment.

Abstract licence: CC BY-NC-ND

OBJECTIVES: Ulipristal acetate (UPA) is a selective progesterone receptor modulator and the most effective oral emergency contraceptive (EC) method available in the United States. The aim of this review is to identify and describe uses of UPA beyond EC and to further discuss the concerns regarding the possible off-target liver effects. STUDY DESIGN: We conducted a literature search in August 2024, using Embase, Medline (PubMed), and Cochrane, utilizing a combination of MeSH and keywords for UPA, excluding animal studies, and limiting to English language publications. After excluding duplicates using covidence, two authors reviewed the remaining 610 results and identified 340 studies. We further excluded case reports and case series. RESULTS: UPA has shown significant promise for indications outside of EC, most notably treatment of uterine leiomyomas, but also ongoing contraception, prevention and treatment of breast cancer, and abnormal uterine bleeding. While UPA has extensive potential for use both within and beyond reproductive health, unfortunately any ongoing development is at a standstill due to concerns regarding its possible role in causing serious liver injury. The role of UPA in causing drug-induced liver injury is not confirmed and preclinical studies during development did not demonstrate a concern that UPA causes drug-induced liver injury. CONCLUSIONS: Access to UPA is crucial not only for EC but for the treatment of many other gynecological and nongynecological conditions. IMPLICATIONS: Ulipristal acetate (UPA) has shown significant promise for indications outside of EC, including uterine leiomyomas, prevention and treatment of breast cancer, and abnormal uterine bleeding. Access to UPA is crucial not only for EC but for the treatment of many other gynecologic and non-gynecologic conditions.

Abstract licence: CC BY-NC-ND