Elagolix is used in the treatment of moderate to severe pain associated with endometriosis in premenopausal women.[1] Endometriosis is a condition in which the endometrium, the inner lining of the uterus, grows outside of the uterus into surrounding tissues and causes symptoms such as pelvic pain and infertility.[13] Around 10% of women may be affected by endometriosis.[13] Elagolix significantly decreases symptoms of dysmenorrhea (menstrual pelvic pain), non-menstrualpelvic pain, and dyspareunia (pain during sexual intercourse) in women with endometriosis.[1][14][15][16] The medication is used at a lower dosage of 150mg once per day or at a higher dosage of 200mg twice per day, depending on the severity of symptoms.[1][14]
The effectiveness of elagolix in the treatment of symptoms of endometriosis was demonstrated in the 6-month Elaris Endometriosis I and II (EM-I and EM-II) phase IIIclinical trials.[8][1] In Elaris EM-I, the percentage of women who had a clinical response with respect to dysmenorrhea was 46.4% in the lower-dose elagolix group and 75.8% in the higher-dose elagolix group, as compared with 19.6% in the placebo group; in Elaris EM-II, the corresponding percentages were 43.4% and 72.4%, as compared with 22.7% (P < 0.001 for all comparisons).[15] In Elaris EM-I, the percentage of women who had a clinical response with respect to non-menstrual pelvic pain was 50.4% in the lower-dose elagolix group and 54.5% in the higher-dose elagolix group, as compared with 36.5% in the placebo group (P < 0.001 for all comparisons); in Elaris EM-II, the corresponding percentages were 49.8% and 57.8%, as compared with 36.5% (P = 0.003 and P < 0.001, respectively).[15] The reductions in symptoms of endometriosis with elagolix resulted in an improved quality of life.[8][16]
The duration of use of elagolix in the treatment of endometriosis should be limited due to a progressive risk of bone loss, and the lowest effective dosage should be used.[1] Elagolix can be used for up to 24months at the 150mg once per day dosage and for up to 6months at the 200mg twice per day dosage.[1]
Because of its relatively short duration, elagolix should be taken at approximately the same time each day.[1] In the case of twice-daily administration, elagolix should be taken at approximate 12-hour intervals, for instance once in the morning and once at night.[1] It can be taken with or without food.[1]
Contraindications of elagolix include pregnancy, known osteoporosis, severe hepatic impairment, and concomitant use with strong organic anion-transporting polypeptide (OATP) 1B1inhibitors such as ciclosporin and gemfibrozil.[1] Elagolix may increase the risk of miscarriage in early pregnancy.[1] Women should avoid pregnancy while taking elagolix, for instance by using birth control, and should discontinue the medication if they become or wish to become pregnant.[1] Elagolix should not be used in women with osteoporosis because it may increase the risk of further bone loss.[1] Severe hepatic impairment is associated with 7-fold increased exposure to elagolix, which may increase the risk of bone loss.[1] In women with moderate hepatic impairment, which is associated with 3-fold increased exposure to elagolix, the medication at 200mg twice per day should not be used, while 150mg once per day should be used for no more than 6months.[1] OATP1B1 inhibitors are likely to greatly increase exposure to elagolix similarly to moderate to severe hepatic impairment.[1]
Combined birth control is not contraindicated with elagolix, but because of the estrogen component, is expected to decrease the effectiveness of elagolix in the treatment of endometriosis, and hence is not recommended.[1] Other forms of birth control, such as non-hormonal birth control, can be used instead.[1] Elagolix is not contraindicated in women who are breastfeeding, but it is unknown whether the medication is excreted in breast milk or if it has adverse effects on milk production or the breastfed child.[1] The use of elagolix in women who are breastfeeding should be considered carefully, weighing both benefits and risks.[1]
Side effects
Side effects of elagolix in clinical trials (mostly ≥5% incidence)[1][19][20]
Elagolix dose- and duration-dependently decreases BMD in premenopausal women with long-term therapy.[1] After 6months of treatment with elagolix, lumbar spine BMD was decreased by 0.3 to 1.3% with 150mg once per day and by 2.5 to 3.1% with 200mg twice per day.[1] The decrease in BMD during elagolix therapy may not be fully reversible with discontinuation, as only partial recovery was observed 12months after discontinuation of therapy.[1] The cause of the decrease in BMD with elagolix is estrogen deficiency, and is analogous to that associated with postmenopause.[1] The consequences of the effects of elagolix on BMD are unknown, but may be an increase in the risk of bone loss and fractures.[1] This is why the duration of use of elagolix should be limited.[1] In women with risk factors for bone loss and osteoporosis, such as a history of low-trauma fracture, assessment of BMD may be considered.[1] Elagolix should not be used in premenopausal women with known osteoporosis.[1] Supplementation with calcium and/or vitamin D during treatment with elagolix has not been studied, but may be beneficial for helping to maintain bone health.[1]
Elagolix decreases the amount, intensity, and duration of menstrual bleeding.[1] Amenorrhea, the cessation of menstruation, was observed in 4 to 17% of women with 150mg once per day and in 7 to 57% of women with 200mg twice per day, compared to less than 1% of women given placebo.[1] The decreased menstrual bleeding caused by elagolix may impede the ability to recognize pregnancy in a timely manner.[1] Based on its mechanism of action, elagolix may increase the risk of miscarriage in early pregnancy, and so should be discontinued if pregnancy occurs.[1][21] If pregnancy is suspected, pregnancy testing can be performed.[1] Elagolix decreases the rate of ovulation and thereby decreases the likelihood of pregnancy, but has not been shown to be a fully effective contraceptive and should not be relied on to prevent pregnancy.[1]
The incidence of depression and mood changes in clinical trials with elagolix was increased in premenopausal women taking elagolix relative to placebo.[1] Mood- and depression-type side effects such as altered mood, mood swings, depressed mood, depression, depressive symptoms, and tearfulness occurred in 3 to 6% of women with 150mg per day and in 5 to 6% of women with 200mg twice per day, compared to 2 to 3% in women given placebo.[1]Suicidal ideation and behavior occurred in a few women (0.2–0.4%), with one suicide observed.[1] People taking elagolix with new or existing depressive symptoms should be promptly evaluated to determine whether the benefits of treatment outweigh the risks.[1] In those with new or existing depressive symptoms, referral to a mental health professional, as appropriate, may be warranted.[1] Immediate medical attention should be sought for those with suicidal ideation and behavior.[1]
Elagolix dose-dependently produced elevated liver enzymes, including elevations of serumalanine aminotransferase of at least 3-fold the upper limit, in clinical trials.[1] This was observed in one woman (0.2%) with 150mg once per day and in five women (1.1%) with 200mg twice per day, compared to one woman (0.1%) given placebo.[1] Medical attention should be sought if signs or symptoms of liver injury, such as jaundice, are noticed.[1] The lowest effective dosage of elagolix may be used to minimize the risk of liver problems, and in those who develop elevated liver enzymes during elagolix therapy, prompt evaluation should be done to determine whether the benefits of treatment outweigh the risks.[1]
Overdose
In the event of an overdose of elagolix, the person should be monitored for any signs or symptoms of adverse reactions and should be treated on a symptomatic basis as needed.[1] Elagolix has been assessed in clinical studies at a dose as high as a single administration of 1,200mg, which resulted in concentrations of the medication that were 17times higher than with the typical high clinical dosage of 200mg twice per day.[1] No adverse effects were mentioned.[1] Chronic overdosage of elagolix may result in greater suppression of estradiol levels and a consequent increased risk of bone loss with long-term therapy.[1]
Interactions
Elagolix has a number of potential drug interactions with other medications.[1] Elagolix is a substrate of the cytochrome P450 (CYP450) enzymeCYP3A, and inhibitors and inducers of CYP3A4 may alter the metabolism of elagolix and increase or decrease its circulating levels.[1] The strong CYP3A4 inhibitor ketoconazole has been found to increase peak levels of and total exposure to a single 150mg dose of elagolix by about 2-fold.[1] Paradoxically, rifampin, a strong inducer of CYP3A4 and other CYP450 enzymes, increased peak levels of and total exposure to a single 150mg dose of elagolix as well.[1] A single dose of rifampin increased peak levels of elagolix by 4.4-fold and total exposure by 5.6-fold, whereas continuous rifampin therapy increased peak levels of elagolix by 2-fold and total exposure by 1.7-fold.[1] The use of elagolix at 200mg twice per day concomitantly with rifampin is not recommended, whereas the concomitant use of elagolix at 150mg once per day with rifampin should be limited to 6months.[1] No significant changes in exposure to elagolix were observed with concomitant administration of rosuvastatin (a substrate of OATP1B1, OATP1B3, and BCRP), sertraline (a moderate inhibitor of CYP2D6 and CYP2B6), or fluconazole (a strong inhibitor of CYP2C19 and a moderate inhibitor of CYP2C9 and CYP3A4).[1][22]
Elagolix is a substrate of the hepatic OATP1B1 transporter.[1] Levels of elagolix have been found to be increased by 78% in people with a genotype characterized by reduced OATP1B1 transporter function.[1] The concomitant use of elagolix with medications that inhibit OATP1B1 may increase elagolix levels, and the use of elagolix with strong OATP1B1 inhibitors like ciclosporin and gemfibrozil, which may markedly increase elagolix exposure, is contraindicated.[1]
Elagolix is a weak to moderate inducer of CYP3A, and may decrease levels of medications that are substrates of CYP3A4.[1] In addition, elagolix is an inhibitor of P-glycoprotein, and may increase levels of medications that are substrates of P-glycoprotein, such as digoxin.[1] Elagolix has been found to increase exposure to digoxin and ethinylestradiol, whereas it has been found to decrease exposure to rosuvastatin, midazolam, norethisterone, norelgestromin, and norgestrel.[1]
Because combined birth control pills and other forms of combined birth control contain an estrogen, and because elagolix treats endometriosis by decreasing estrogen levels in the endometrium, these form of hormonal birth control are likely and expected to decrease the effectiveness of elagolix in the treatment of this condition.[1] The effect of progestogen-only birth control on the effectiveness of elagolix in endometriosis is unknown.[1] However, progestogens are antiestrogenic in the uterus, and high-dose progestin therapy is known to be effective in the treatment of endometriosis similarly to GnRH antagonists.[23][24] On the basis of limited clinical research, combined birth control pills have also been found to be effective in the treatment of endometriosis, but are likely not as effective as GnRH modulator monotherapy.[23] It is advised that women use non-hormonal methods of birth control during elagolix therapy and for one week following discontinuation of elagolix.[1]
Estrogens like estradiol stimulate the growth of the endometrium, and thereby aggravate symptoms of endometriosis.[8] By suppressing estrogen production and levels, elagolix decreases the growth of the endometrium and decreases endometriosis symptoms such as pelvic pain.[8][1]
Elagolix is a short-acting GnRH antagonist, with a terminal half-life of typically about 4 to 6hours.[1][26][8] Because of the short duration of elagolix in the body, the activation of the GnRHR by GnRH is not fully blocked throughout the day with once-daily administration of elagolix.[6][5] As a result, gonadotropin and sex hormone levels are only partially suppressed when elagolix is taken once per day.[1][6][5] In addition, the degree of suppression can be dose-dependently adjusted as needed, for instance with higher-dose twice-daily administration to achieve greater hormonal suppression.[1][6][5] Because of its short duration in the body, the effects of elagolix are rapidly reversible upon discontinuation.[6][5] In addition, due to its partial and incomplete suppression of estradiol levels, the side effects of elagolix, such as hot flashes and decreased BMD, are lower than with first-generation GnRH modulators.[6][5][28][29]
In clinical trials, elagolix produced dose-dependent decreases in gonadotropin, estradiol, and progesterone levels in women.[1][26][5] Median levels of estradiol were partially suppressed to 42pg/mL (follicular phase levels) with 150mg once daily and were fully or near-fully suppressed to 12pg/mL (postmenopausal levels) with 200mg twice daily.[1] In a 21-day study in premenopausal women, the effects of elagolix on FSH levels were found to be maximal at a dosage of 300mg twice per day or above, whereas its effects on LH and estradiol levels were maximal at a dosage of 200mg twice per day or above.[26] Levels of progesterone were maintained at anovulatory levels (<2ng/mL) across the 21-day study period at dosages of elagolix of 100mg twice per day and above.[26] A dosage of elagolix of 400mg twice per day appears to produce no greater suppression in gonadotropin or estradiol levels than a dosage of 300mg twice per day in premenopausal women.[26] Suppression of gonadotropin and sex hormone levels with elagolix occurs rapidly, within hours, and upon discontinuation of elagolix, gonadotropin and sex hormone levels remain suppressed for at least 12hours, but show recovery within 24 to 48hours.[26] As a consequence of its suppression of gonadotropin and sex hormone levels, elagolix inhibits ovulation in women.[1] Over the course of three menstrual cycles, the ovulation rate with elagolix was 50% at 150mg once daily and 32% at 200mg twice daily.[1] Because ovulation is triggered by a surge in estradiol levels at mid-cycle, estrogen exposure during elagolix therapy might be greater around this time in some women.[30]
Elagolix is taken by the oralroute of administration, in contrast to other GnRH modulators.[1][26][8][6] The oral bioavailability of elagolix in humans is not described in the Food and Drug Administration (FDA) label for the medication, but in animal research elagolix showed a low oral bioavailability of 5.8% in rats and 11% in monkeys.[4] Following administration, elagolix is rapidly absorbed, with peak concentrations occurring after 0.5 to 1.5hours.[1][26] The drug accumulation ratio of elagolix at 150mg once per day is 0.98 and at 200mg twice per day is 0.89, indicating that it is not accumulated in the body with continuous administration.[1][26][5] At steady state, peak levels of elagolix at 150mg once per day are 574ng/mL and at 200mg twice per day are 774ng/mL while area-under-the-curve levels of elagolix at 150mg once per day are 1,292ng•hour/mL and at 200mg twice per day are 1,725ng•hour/mL.[1] A toxicology study found that levels of elagolix in women after a single dose of 1,200mg were 17times higher than in women taking 200mg twice daily.[1] Taking elagolix with a high-fatmeal has been found to decrease its peak levels by 36% and its area-under-the-curve levels by 24%.[1] In terms of distribution, the plasma protein binding of elagolix is 80% and its blood-to-plasma ratio is 0.6.[1] The volume of distribution at steady state is 1,674L at 150mg once per day and 881L at 200mg twice per day.[1]
Elagolix is metabolized in the liver, with the major pathway being by CYP3A and minor pathways including by CYP2D6, CYP2C8, and UDP-glucuronosyltransferases.[1] The terminal half-life of elagolix is typically about 4 to 6hours.[1][26] A study found that its half-life was 2.4 to 6.3hours with a single dose and was 2.2 to 10.8hours with continuous administration.[5][6] The oral clearance of elagolix is 123L/hour at 150mg once per day and 144L/hour at 200mg twice per day.[1] The major pathway of elimination of elagolix is hepatic metabolism.[1] Elagolix is taken up from the circulation into the liver by the hepatic OATP1B1 carrier.[1] In people with two reduced function alleles of the gene that encodes OATP1B1 (SLCO1B1 521T>C; SLCO1B1 521 C/C genotype), plasma levels of elagolix have been found to be increased by 78% relative to in people with normal OATP1B1 function (SLCO1B1 521T/T genotype).[1] The frequency of this reduced function OATP1B1 genotype is generally less than 5% in most racial and ethnic groups.[1] Elagolix is excreted less than 3% in urine and 90% in feces.[1]
Exposure to elagolix is not affected by renal impairment or mild hepatic impairment, but is increased by approximately 3-fold in women with moderate hepatic impairment and by approximately 7-fold in women with severe hepatic impairment.[1] There were no differences in the pharmacokinetics of elagolix between individuals of different racial and ethnic groups.[1] Similarly, the pharmacokinetics of elagolix were unaffected by body weight and body mass index.[1] Peak and area-under-the-curve levels of elagolix have been shown to be altered by CYP3A4inhibitors like ketoconazole and CYP3A4 inducers like rifampin.[1] Inhibitors of OATP1B1 may increase circulating levels of elagolix, and elagolix is considered to be contraindicated in combination with strong OATP1B1 inhibitors.[1] Elagolix is a substrate of P-glycoprotein, but the effect of inhibitors and inducers of P-glycoprotein on the pharmacokinetics of elagolix is unknown.[1] Elagolix itself is an inhibitor of P-glycoprotein.[1]
Elagolix is used as elagolix sodium, the sodiumsalt of elagolix.[1] It is a white to off white to light yellow powder.[1] The compound is freely soluble in water.[1] The chemical name of elagolix sodium is sodium 4-({(1R)-2-[5-(2-fluoro-3-methoxyphenyl)-3-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl}-4-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl]-1-phenylethyl}amino)butanoate.[1] It has a molecular formula of C32H29F5N3O5Na and a molecular weight of 653.58g/mol.[1] The free acid form of elagolix has a molecular formula of C32H29F5N3O5 and a molecular weight of 631.60g/mol.[1]
History
Elagolix was first described in the literature in 2005.[33][34][10] It was originally developed by the pharmaceutical companyNeurocrine Biosciences, and was later developed together by Neurocrine Biosciences and AbbVie (previously Abbott Laboratories).[9][10][25] In June 2010, Neurocrine Biosciences and Abbott announced a global agreement to develop and commercialize elagolix for the treatment of endometriosis.[35] The medication completed phase IIIclinical trials for endometriosis in November 2016.[4] Two phase III clinical trials, the Elaris Endometriosis I and II (EM-I and EM-II) studies, were conducted.[8][1] The studies included almost 1,700women, about 950 of whom were treated with elagolix.[8][1][14] In September 2017, AbbVie filed a New Drug Application (NDA) for elagolix for the treatment of pain associated with endometriosis in the United States.[4] The medication was approved by the FDA for the treatment of endometriosis-associated pain in the United States on 23 July 2018.[9][36] It was the first new medication to be approved by the FDA for the treatment of endometriosis in more than a decade.[37][38] Elagolix was the first member of a new class of GnRH modulators described as "second-generation" due to their non-peptide and small-molecule nature and oral activity to be marketed.[4][6] A second member of this group, relugolix (brand name Relumina), was introduced in Japan in January 2019.[11] In addition to endometriosis, elagolix is under development for the treatment of uterine fibroids and menorrhagia.[9] It is in phase III clinical trials for these indications.[9]
Society and culture
Generic names
Elagolix is the generic name of the drug and its INNTooltip International Nonproprietary Name and USANTooltip United States Adopted Name.[31] It is also known by its former developmental code names NBI-56418 and ABT-620.[9][31]
Brand names
Elagolix is marketed under the brand name Orilissa.[1]
Availability
Elagolix is available in the United States and Canada.[1][2][3] A similar medication, relugolix, is available in Japan.[11]
Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candidiasis, pityriasis versicolor, dandruff, and seborrheic dermatitis. Taken by mouth it is a less preferred option and only recommended for severe infections when other agents cannot be used. Other uses include treatment of excessive male-patterned hair growth in women and Cushing's syndrome.
Buserelin, sold under the brand name Suprefact among others, is a medication which is used primarily in the treatment of prostate cancer and endometriosis. It is also used for other indications such as the treatment of premenopausal breast cancer, uterine fibroids, and early puberty, in assisted reproduction for female infertility, and as a part of transgender hormone therapy. In addition, buserelin is used in veterinary medicine. The medication is typically used as a nasal spray three times per day, but is also available for use as a solution or implant for injection into fat.
Norethisterone acetate (NETA), also known as norethindrone acetate and sold under the brand name Primolut-Nor among others, is a progestin medication which is used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication available in low-dose and high-dose formulations and is used alone or in combination with an estrogen. It is ingested orally.
Polyestradiol phosphate (PEP), sold under the brand name Estradurin, is an estrogen medication which is used primarily in the treatment of prostate cancer in men. It is also used in women to treat breast cancer, as a component of hormone therapy to treat low estrogen levels and menopausal symptoms, and as a component of feminizing hormone therapy for transgender women. It is given by injection into muscle once every four weeks.
Danazol, sold as Danocrine and other brand names, is a medication used in the treatment of endometriosis, fibrocystic breast disease, hereditary angioedema and other conditions. It is taken by mouth.
Gonadotropin-releasing hormone antagonists are a class of medications that antagonize the gonadotropin-releasing hormone receptor and thus the action of gonadotropin-releasing hormone (GnRH). They are used in the treatment of prostate cancer, endometriosis, uterine fibroids, female infertility in assisted reproduction, and for other indications.
Cetrorelix, or cetrorelix acetate, sold under the brand name Cetrotide, is an injectable gonadotropin-releasing hormone (GnRH) antagonist. A synthetic decapeptide, it is used in assisted reproduction to inhibit premature luteinizing hormone surges The drug works by blocking the action of GnRH upon the pituitary, thus rapidly suppressing the production and action of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In addition, cetrorelix can be used to treat hormone-sensitive cancers of the prostate and breast and some benign gynaecological disorders. It is administered as either multiple 0.25 mg daily subcutaneous injections or as a single-dose 3 mg subcutaneous injection. The duration of the 3 mg single dose is four days; if human chorionic gonadotropin (hCG) is not administered within four days, a daily 0.25 mg dose is started and continued until hCG is administered.
Controlled ovarian hyperstimulation is a technique used in assisted reproduction involving the use of fertility medications to induce ovulation by multiple ovarian follicles. These multiple follicles can be taken out by oocyte retrieval for use in in vitro fertilisation (IVF), or be given time to ovulate, resulting in superovulation which is the ovulation of a larger-than-normal number of eggs, generally in the sense of at least two. When ovulated follicles are fertilised in vivo, whether by natural or artificial insemination, there is a very high risk of a multiple pregnancy.
Feminizing hormone therapy, also known as transfeminine hormone therapy, is hormone therapy and sex reassignment therapy to change the secondary sex characteristics of transgender people from masculine or androgynous to feminine. It is a common type of transgender hormone therapy and is used to treat transgender women and non-binary transfeminine individuals. Some, in particular intersex people, but also some non-transgender people, take this form of therapy according to their personal needs and preferences.
Dienogest, sold under the brand name Visanne among others, is a progestin medication which is used in birth control pills and in the treatment of endometriosis. It is also used in menopausal hormone therapy and to treat heavy periods. Dienogest is available both alone and in combination with estrogens. It is taken by mouth.
Darolutamide, sold under the brand name Nubeqa, is an antiandrogen medication which is used in the treatment of non-metastatic castration-resistant prostate cancer in men. It is specifically approved to treat non-metastatic castration-resistant prostate cancer (nmCRPC) in conjunction with surgical or medical castration. The medication is taken by mouth twice per day with food.
Relugolix, sold under the brand names Orgovyx and Relumina among others, is a gonadotropin-releasing hormone antagonist medication which is used in the treatment of prostate cancer in men and uterine fibroids in women. It is taken by mouth.
A GnRH modulator, or GnRH receptor modulator, also known as an LHRH modulator or LHRH receptor modulator, is a type of medication which modulates the GnRH receptor, the biological target of the hypothalamic hormone gonadotropin-releasing hormone. They include GnRH agonists and GnRH antagonists. These medications may be GnRH analogues like leuprorelin and cetrorelix – peptides that are structurally related to GnRH – or small-molecules like elagolix and relugolix, which are structurally distinct from and unrelated to GnRH analogues.
High-dose estrogen therapy (HDE) is a type of hormone therapy in which high doses of estrogens are given. When given in combination with a high dose of progestogen, it has been referred to as pseudopregnancy. It is called this because the estrogen and progestogen levels achieved are in the range of the very high levels of these hormones that occur during pregnancy. HDE and pseudopregnancy have been used in medicine for a number of hormone-dependent indications, such as breast cancer, prostate cancer, and endometriosis, among others. Both natural or bioidentical estrogens and synthetic estrogens have been used and both oral and parenteral routes may be used.
The medical uses of bicalutamide, a nonsteroidal antiandrogen (NSAA), include the treatment of androgen-dependent conditions and hormone therapy to block the effects of androgens. Indications for bicalutamide include the treatment of prostate cancer in men, skin and hair conditions such as acne, seborrhea, hirsutism, and pattern hair loss in women, high testosterone levels in women, hormone therapy in transgender women, as a puberty blocker to prevent puberty in transgender girls and to treat early puberty in boys, and the treatment of long-lasting erections in men. It may also have some value in the treatment of paraphilias and hypersexuality in men.
Linzagolix, sold under the brand name Yselty, is a medication used in the treatment of uterine fibroids. Linzagolix is a small-molecule, non-peptide, orally active gonadotropin-releasing hormone antagonist developed by Kissei Pharmaceutical and ObsEva.
The pharmacodynamics of spironolactone, an antimineralocorticoid and antiandrogen medication, concern its mechanisms of action, including its biological targets and activities, as well as its physiological effects. The pharmacodynamics of spironolactone are characterized by high antimineralocorticoid activity, moderate antiandrogenic activity, and weak steroidogenesis inhibition. In addition, spironolactone has sometimes been found to increase estradiol and cortisol levels and hence could have slight indirect estrogenic and glucocorticoid effects. The medication has also been found to interact very weakly with the estrogen and progesterone receptors, and to act as an agonist of the pregnane X receptor. Likely due to increased activation of the estrogen and/or progesterone receptors, spironolactone has very weak but significant antigonadotropic effects.
The pharmacology of cyproterone acetate (CPA) concerns the pharmacology of the steroidal antiandrogen and progestin medication cyproterone acetate.
Elagolix/estradiol/norethisterone acetate, sold under the brand name Oriahnn, is a fixed-dose combination medication used to treat heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women. It contains elagolix, a gonadotropin-releasing hormone (GnRH) receptor antagonist, estradiol, an estrogen, and norethisterone acetate, a progestin. It is taken by mouth. Oriahnn is co-packaged as a combination of elagolix/estradiol/norethisterone acetate capsules with elagolix capsules.
Relugolix/estradiol/norethisterone acetate, sold under the brand names Myfembree and Ryeqo, is a fixed-dose combination hormonal medication which is used for the treatment of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) and for moderate to severe pain associated with endometriosis. It contains relugolix, an orally active gonadotropin-releasing hormone antagonist, estradiol, an estrogen, and norethisterone acetate, a progestin. The medication is taken by mouth.
1 2 3 4 5 6 7 8 9 10 11 12 Clemenza S, Sorbi F, Noci I, Capezzuoli T, Turrini I, Carriero C, Buffi N, Fambrini M, Petraglia F (February 2018). "From pathogenesis to clinical practice: Emerging medical treatments for endometriosis". Best Pract Res Clin Obstet Gynaecol. 51: 92–101. doi:10.1016/j.bpobgyn.2018.01.021. PMID29559388. S2CID3952054.
↑ Tan O, Carr BR, Beshay VE, Bukulmez O (January 2013). "The extrapituitary effects of GnRH antagonists and their potential clinical implications: a narrated review". Reprod Sci. 20 (1): 16–25. doi:10.1177/1933719112459244. PMID23012318. S2CID21376889.
1 2 Becker KL (2001). "Endometriosis". Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. pp.975–. ISBN978-0-7817-1750-2. Archived from the original on 2022-06-10. Retrieved 2018-07-26.
1 2 Lemke TL, Williams DA (24 January 2012). "Womens Health". Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp.1411–. ISBN978-1-60913-345-0. Archived from the original on 21 December 2016. Retrieved 24 October 2016.
↑ Matsumoto AM, Bremmer WJ (1 January 2016). "Testicular Disorders". In Melmed S (ed.). Williams Textbook of Endocrinology. Elsevier Health Sciences. pp.752–. ISBN978-0-323-29738-7. Archived from the original on 27 July 2020. Retrieved 26 July 2018.
↑ Diamond MP, Carr B, Dmowski WP, Koltun W, O'Brien C, Jiang P, Burke J, Jimenez R, Garner E, Chwalisz K (2014). "Elagolix treatment for endometriosis-associated pain: results from a phase 2, randomized, double-blind, placebo-controlled study". Reprod Sci. 21 (3): 363–71. doi:10.1177/1933719113497292. PMID23885105. S2CID9607500.
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External links
"Elagolix". Drug Information Portal. U.S. National Library of Medicine.
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