elagolix

Estrogens play a critical role in the pathogenesis of endometriosis and it is logical to assume that lowering estradiol levels with oral gonadotropin-releasing hormone (GnRH) antagonists may prove effective, especially in women who fail to respond to progestogens. Indeed, due to progesterone resistance, oral contraceptives and progestogens work well in two-thirds of women suffering from endometriosis, but are ineffective in 33% of women. Oral GnRH antagonists have therefore been evaluated for management of premenopausal women with endometriosis-associated pelvic pain...

BACKGROUND: Elagolix is a gonadotropin-releasing hormone (GnRH) modulator and used for pain relief from endometriosis. OBJECTIVE: The present research was performed to develop and validate a simple, novel, fast, sensitive, and cost-effective LC-MS-compatible chromatographic method for quantification of all prominent organic impurities of elagolix sodium in tablet formulation with identification of major degradation products. METHODS: The optimum separation of the organic impurities of elagolix sodium was achieved on an ACE C18-PFP (250 mm × 4...

BACKGROUND: Current practice in health technology assessment (HTA) of pharmaceuticals conducts cost-effectiveness analyses (CEAs) based on a static price or the estimated price at market launch. Recent publications suggest incorporating dynamic pricing. To test the feasibility and importance of including dynamic pricing, we compared the standard static approach to four dynamic scenarios by replicating US-based HTA evaluations with dynamic pricing inputs. METHODS: The four case examples included omalizumab (Xolair® ) for the treatment of allergic asthma, elagolix (Orilissa® ) for the treatment of endometriosis, ocrelizumab (Ocrevus® ) for the treatment of primary progressive multiple sclerosis (PPMS), and dupilumab (Dupixent® ) for the treatment of atopic dermatitis (AD)...

PURPOSE: The aim of this NMA is to comprehensively analyze evidence of oral GnRH antagonist in the treatment of moderate-to-severe endometriosis-associated pain. METHODS: Literature searching was performed to select eligible studies published prior to April 2022 in PubMed, Cochrane, Embase and Web of Science. Randomized controlled trials involving patients who suffered from moderate-to-severe endometriosis-associated pain and treated with oral nonpeptide GnRH antagonists or placebo were included...

Elagolix sodium (ELS) is a marketed product using to release moderate to severe endometriosis-associated pain. It contains functional groups such as carboxyl group, secondary amino group, 2,4-dioxo pyrimidinyl and several benzyl or benzyl-like position hydrogen atom that are susceptive to occur stress degradation. Forced degradation studies of ELS reveal different degradation profiles of the drug substance which are conducted under photo, thermal, acidic, neutral, alkaline and hydrogen peroxide oxidative conditions in the direction of the ICH guidances...

OBJECTIVE: This review aimed to assess the efficacy and safety of GnRH antagonists in patients with symptomatic uterine fibroids. DATA SOURCES: A literature search was performed on PubMed, Web of Science, Embase, Cochrane, and clinicaltrials.gov using the MeSH and Emtree terms "Leiomyoma" and "Gonadotropin-Releasing Hormone." STUDY SELECTION: All clinical trials that provided efficacy and safety data in clinical terms (i.e., reduction in menstrual bleeding and discomfort, changes in the size of leiomyoma and uterine volume, etc...

OBJECTIVE: To review the use of oral gonadotropin-releasing hormone (GnRH) antagonists and synthesize their efficacy and safety parameters for the treatment of endometriosis-associated pain. DESIGN: Systematic review and network meta-analysis. SETTING: Not applicable. PATIENT(S): Premenopausal women with endometriosis who had experienced moderate or severe pain. INTERVENTION(S): The Web of Science, Embase, Scopus, and MEDLINE were searched until April 10, 2022...

Elagolix is an FDA-approved treatment for moderate-to-severe pain associated with endometriosis but has been associated with increased acute porphyric attacks in women with the acute hepatic porphyrias (AHPs). A fluorescence-based screening assay for drug porphyrogenicity in LMH cells indicates that elagolix is porphyrogenic; thus, elagolix should be avoided or used with caution in patients with the AHPs.

INTRODUCTION: Endometriosis is a chronic, estrogen-dependent, inflammatory disease associated with pelvic pain, infertility, impaired sexual function, and psychological suffering. Therefore, tailored patient management appears of primary importance to address specific issues and identify the appropriate treatment for each woman. Over the years, abundant research has been carried out with the objective to find new therapeutic approaches for this multifaceted disease. AREAS COVERED: This narrative review aims to present the latest advances in the pharmacological management of endometriosis...

OBJECTIVE: To determine the effect relugolix and elagolix have on the production of extracellular matrix (ECM) proteins in human leiomyoma cells. DESIGN: Laboratory study. SETTING: University hospital. PATIENT(S) OR ANIMALS: None. January 5, 2022 Cell culture, protein analysis, immunohistochemistry. MAIN OUTCOME MEASURE(S): Production of GnRHR, COL1A1, FN1, VCAN, p-ERK, & ERK in treated/untreated leiomyoma cells...

OBJECTIVE: The aim of this systematic review is to summarize the data obtained from randomized controlled trials looking at new pharmacologic treatments for endometriosis published over the last decade with a focus on hormonal therapeutic options for endometriosis-associated pelvic pain (EAPP), excluding studies focusing on fertility. METHODS: We identified relevant original studies in the English language through a search of the MEDLINE, Scopus, and EMBASE (2012 to present) databases using the appropriate MeSH terms and applying the article type filter 'randomized controlled trials'...

INTRODUCTION: Uterine fibroids are the most common benign gynecological tumors affecting women of reproductive ages. Although surgery is the definitive treatment choice, several medical approaches have been investigated to control their symptoms. The main issue of currently employed drugs for uterine fibroids is the long-term safety and tolerability profile. Today, new emerging options represent hopeful alternatives that could potentially overcome these limitations. AREAS COVERED: This manuscript aims to give an updated overview of the pharmacodynamic and pharmacokinetic properties of current and new investigational medical drugs for the treatment of symptomatic uterine fibroids...

Elagolix (ELX) is an orally administered non-peptidic GnRH antagonist that has been approved by the Food and Drug Administration in 2018 for the treatment of endometriosis pain. A sensitive and selective method for estimating elagolix (ELX) in human plasma and content uniformity was developed and validated. The spectrofluorimetric technique was used to investigate ELX utilizing boron-doped carbon quantum dots (B@CQDs). After gradually adding ELX, the quantum dots fluorescence was enhanced with LOQ of 1.74 ng mL-1 , the calibration curve between ELX and corresponding fluorescence intensity was found over a range of 4-100 ng mL-1 ...

INTRODUCTION: Infertility is a common complication of endometriosis. While in vitro fertilisation-embryo transfer (IVF) successfully treats endometriosis-associated infertility, there is some evidence that pregnancy rates may be diminished in women seeing fertility treatment for endometriosis-associated infertility compared with other etiologies of infertility. The use of gonadotropin releasing hormone (GnRH) agonist prior to IVF has been suggested to improve success, however studies have been small and rarely reported live birth rates...

AIM: Elagolix, a gonadotropin-releasing hormone receptor antagonist, was recently approved for heavy menstrual bleeding associated with uterine fibroids (UF, Oriahnn) at a dose of 300 mg twice daily (BID) in combination with add-back therapy (oestradiol 1 mg/norethindrone acetate 0.5 mg [E2/NETA] once daily) for 24 months use. The limited duration of treatment is related to elagolix dose- and duration-dependent decrease in oestrogen that is mechanistically linked to changes in bone mineral density (BMD)...

INTRODUCTION: The aim of this analysis was to use a physiologically based pharmacokinetic (PBPK) model to predict the impact of changes in dissolution rates on elagolix exposures and define clinically relevant acceptance criteria for dissolution. METHODS: Varying in vitro dissolution profiles were utilized in a PBPK model to describe the absorption profiles of elagolix formulations used in Phase 3 clinical trials and for the to be marketed commercial formulations...

INTRODUCTION: Not too long ago, Lupron Depot® (leuprolide acetate), an injectable gonadotropin-releasing hormone (GnRH) agonist, was the only Food and Drug Administration (FDA) approved GnRH analog used to clinically treat abnormal uterine bleeding associated with uterine leiomyoma (AUB-L) when second-line medical management was warranted; however, the FDA has now approved elagolix and relugolix, GnRH antagonists, to be treatment options as well. This is a review of GnRH antagonists for the management of uterine fibroids reviewing their treatment efficacy, side effect profile, and current use in military medicine...

This study evaluated the effect of repeated doses of elagolix on the pharmacokinetics of omeprazole and its metabolites in healthy premenopausal female subjects. Adult premenopausal female subjects (N = 20) received a single oral dose of omeprazole (40 mg) on Day 1 and Day 11 and oral doses of elagolix (300 mg) twice-daily on Days 3 to 11. Serial blood samples for assay of omeprazole and its metabolites were collected for 24 hours after dosing on Days 1 and 11. Pharmacokinetic parameters were calculated for omeprazole, 5-hydroxyomeprazole and omeprazole sulfone; and were compared between Day 1 and Day 11...

BACKGROUND: Elagolix is effective and safe for treating menorrhagia in women with uterine fibroid. However, it is reported to be associated with hypoestrogenism that can be alleviated by adding estradiol/norethindrone acetate. This systematic review and meta-analysis aimed to determine the effectiveness of elagolix treatment in women with heavy menstrual bleeding associated with uterine fibroid by comparing: elagolix versus placebo and elagolix versus estradiol/norethindrone acetate. METHODOLOGY: The Cochrane Central Register of Controlled Trials (CENTRAL 2021, Issue 3 of 12), MEDLINE databases (1980 to December week 1, 2020), and trial registries for relevant randomized clinical trials were used...

OBJECTIVE: The aim of this systematic review is to gather and synthesize evidence regarding the use of oral gonadotrophin-releasing hormone (GnRH) antagonist for the treatment of bleeding associated with uterine myomas. DATA SOURCES: Web of Science, and MEDLINE databases were searched electronically on March 5, 2021, using combinations of the relevant Medical Subject Headings terms and keywords. The search was restricted to the English language and to human studies...