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Management of moderate to severe endometriosis-associated pain
Elagolix acts as a potent and selective competitive antagonist of the gonadotropin-releasing hormone receptor (GnRHR), the biological target of the hypothalamic peptide hormone gonadotropin-releasing hormone (GnRH).[1] As such, it is a GnRH antagonist. The affinity (KD) of elagolix for the GnRHR is 54 pM. By blocking the GnRHR in the pituitary gland, elagolix suppresses the GnRH-induced secretion of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary, and thereby decreases the production of sex hormones by the gonads. In women, elagolix dose-dependently suppresses the production of ovarian hormones including estradiol, progesterone, and testosterone, and thereby decreases the circulating levels of these hormones. In men, GnRH modulators suppress the testicular production of testosterone and estradiol, decreasing the circulating levels of these hormones similarly. Unlike previous GnRH agonists and antagonists, referred to collectively as GnRH analogues, elagolix is a non-peptide and small-molecule compound that can be taken orally
Oral Administration:
Administer orally once or twice daily (at approximately the same time every day) without regard to meals.
If dose is missed, take missed dose as soon as possible and resume regular dosing schedule with next dose. Do not exceed 1 or 2 tablets daily in patients receiving the drug in a once- or twice-daily regimen, respectively.
Elagolix has a number of potential drug interactions with other medications. Elagolix is a substrate of the cytochrome P450 (CYP450) enzyme CYP3A, and inhibitors and inducers of CYP3A4 may alter the metabolism of elagolix and increase or decrease its circulating levels. The strong CYP3A4 inhibitor ketoconazole has been found to increase peak levels of and total exposure to a single 150 mg dose of elagolix by about 2-fold. Paradoxically, rifampin, a strong inducer of CYP3A4 and other CYP450 enzymes, increased peak levels of and total exposure to a single 150 mg dose of elagolix as well. 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. The use of elagolix at 200 mg twice per day concomitantly with rifampin is not recommended, whereas the concomitant use of elagolix at 150 mg once per day with rifampin should be limited to 6 months. 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)
Contraindications
Pregnancy. (See Fetal/Neonatal Morbidity and Mortality and also see Pregnancy under Cautions.)
Known osteoporosis. (See Decreased Bone Mineral Density under Cautions.)
Severe hepatic impairment. (See Hepatic Effects under Cautions.)
Concomitant use with potent organic anion transporting polypeptide (OATP) 1B1 inhibitors.(See Drugs Transported by Organic Anion Transporting Polypeptide 1B1 under Interactions.)
Professionals
AHFS Monographs
Elagolix Sodium
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Elagolix Sodium
Class: Antigonadotropins
Chemical Name: sodium;4-[[(1R)-2-[5-(2-fluoro-3-methoxyphenyl)-3-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-4-methyl-2,6-dioxopyrimidin-1-yl]-1-phenylethyl]amino]butanoate
Molecular Formula: C32H29F5N3O5Na
CAS Number: 832720-36-2
Brands: Orilissa
Medically reviewed by Drugs.com. Last updated on May 18, 2020.
Overview
Side Effects
Dosage
FAQ
Professional
Interactions
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Introduction
Gonadotropin-releasing hormone (GnRH, luteinizing hormone-releasing hormone [LHRH], gonadorelin) receptor antagonist.1
Uses for Elagolix Sodium
Endometriosis
Management of moderate to severe endometriosis-associated pain.1 2 3
Elagolix Sodium Dosage and Administration
General
Exclude pregnancy prior to initiation of elagolix or begin therapy ≤7 days after onset of menses.1
Administration
Oral Administration
Administer orally once or twice daily (at approximately the same time every day) without regard to meals.1
If dose is missed, take missed dose as soon as possible and resume regular dosing schedule with next dose.1 Do not exceed 1 or 2 tablets daily in patients receiving the drug in a once- or twice-daily regimen, respectively.1
Dosage
Available as elagolix sodium; dosage expressed in terms of elagolix.1
Adults
Endometriosis
Moderate to Severe Pain
Oral
Use lowest effective dosage, taking into account severity of symptoms and goals of treatment.1 Limit duration of therapy because greater loss of bone mineral density (BMD) occurs with increasing duration of use.1 (See Decreased Bone Mineral Density under Cautions.)
Recommended dosage differs depending on presence or absence of endometriosis-associated dyspareunia.1 (See Table 1.)
Table 1. Recommended Dosage and Treatment Duration of Elagolix for Management of Pain in Patients with Endometriosis.1
Dosage
Maximum Treatment Duration
Patients without concomitant dyspareunia
Initiate treatment with elagolix 150 mg once daily
24 months
Patients with concomitant dyspareunia
Consider initiating treatment with elagolix 200 mg twice daily
6 months
Special Populations
Hepatic Impairment
For dosage recommendations in patients with hepatic impairment, see Table 2.1
Table 2. Recommended Dosage and Treatment Duration of Elagolix for Management of Pain in Patients with Hepatic Impairment.1
Hepatic Impairment
Dosage
Maximum Treatment Duration
Mild hepatic impairment (Child-Pugh class A)
Initiate treatment with elagolix 150 mg once daily
24 months
Moderate hepatic impairment (Child-Pugh class B)
Initiate treatment with elagolix 150 mg once daily; use of elagolix 200 mg twice daily not recommended.
6 months
Severe hepatic impairment (Child-Pugh class C)
Contraindicated
Renal Impairment
Mild, moderate, or severe renal impairment or end-stage renal disease, including patients receiving dialysis: Dosage adjustment not needed.1
Geriatric Patients
No specific dosage recommendations at this time.1
Cautions for Elagolix Sodium
Contraindications
Pregnancy.1 (See Fetal/Neonatal Morbidity and Mortality and also see Pregnancy under Cautions.)
Known osteoporosis.1 (See Decreased Bone Mineral Density under Cautions.)
Severe hepatic impairment.1 (See Hepatic Effects under Cautions.)
Concomitant use with potent organic anion transporting polypeptide (OATP) 1B1 inhibitors.1 (See Drugs Transported by Organic Anion Transporting Polypeptide 1B1 under Interactions.)
Warnings/Precautions
Decreased Bone Mineral Density
Elagolix causes dose- and duration-dependent decreases in BMD that may not be completely reversible after discontinuance of the drug.1 Impact of elagolix loss on long-term bone health and future fracture risk unknown.1
Limit duration of therapy to reduce extent of bone loss.1 (See Dosage under Dosage and Administration.) Consider assessment of BMD in patients with history of low-trauma fracture or other risk factors for osteoporosis or bone loss.1 Supplementation with calcium and vitamin D may be beneficial; however, effect of such supplements not studied in this patient population.1 Use of elagolix contraindicated in patients with known osteoporosis because of risk of further bone loss.1
Effects on Menstrual Bleeding Pattern
Elagolix causes a dose-dependent reduction in mean number days of menstrual bleeding and spotting and bleeding intensity.1 Amenorrhea reported in clinical studies; menses resumed in most patients ≤6 months after discontinuance of elagolix.1
Elagolix-associated changes in menstrual bleeding may impair timely recognition of a pregnancy.1 Perform pregnancy testing if pregnancy suspected; discontinue if pregnancy confirmed.1 (See Pregnancy under Cautions.)
Suicidal Ideation/Behavior and Exacerbation of Mood Disorders
Elagolix associated with an increased incidence of adverse mood changes (e.g., altered mood, mood swings, depressed mood, depression, depressive symptoms, tearfulness), particularly in patients with a history of depression.1 Suicidal ideation and behavior, including one completed suicide, occurred in patients receiving elagolix in clinical studies.1
Advise patients to seek medical attention immediately for suicidal ideation or behavior.1 Evaluate patients experiencing depressive symptoms promptly to determine whether risks of continued therapy outweigh benefits.1 Refer patients with new or worsening depression, anxiety, or other mood changes to a mental health clinician, as appropriate.1 Reevaluate benefits and risks of continued elagolix therapy if such events occur.1
Hepatic Effects
Asymptomatic, dose-dependent increases in ALT concentrations ≥3 times the ULN occurred in patients receiving elagolix.1
Use lowest effective dosage.1 Instruct patients to seek medical attention promptly if they experience signs or symptoms suggestive of hepatic injury (e.g., jaundice, dark amber-colored urine, fatigue or exhaustion, nausea and vomiting, generalized swelling, right upper abdominal pain, easy bruising).1 Evaluate patients with elevations in liver function tests promptly to determine whether benefits of continued therapy outweigh risks.1
Interactions with Estrogen-containing Contraceptives
Efficacy of elagolix may be decreased with concomitant use of estrogen-containing contraceptives; effect of progestin-only contraceptives (e.g., injections, implants) on efficacy unknown.1 (See Specific Drugs under Interactions.)
Advise patients to use effective nonhormonal contraceptive methods (e.g., condoms, spermicide) during treatment and for 1 week following discontinuance of the drug.1
Fetal/Neonatal Morbidity and Mortality
Based on mechanism of action, risk of early pregnancy loss exists if elagolix is administered to a pregnant woman.1 Exclude pregnancy prior to initiation of therapy.1 Discontinue drug if pregnancy occurs during treatment.1 (See Contraindications and also see Pregnancy under Cautions.)
Pharmacogenomics
Disposition of elagolix depends on OATP1B1.1 Variations in the gene encoding OATP1B1 (SLCO1B1 521T>C) can affect elagolix exposure and clearance.1 8 (See Special Populations under Pharmacokinetics.) No specific dosage recommendations at this time for patients with OATP1B1 genotypic variants.1
Sensitivity Reactions
Nonserious hypersensitivity reactions (e.g., rash) occurred in about 6% of patients receiving elagolix or placebo; such reactions led to discontinuance of study drug in 0.4 or 0.5% of patients, respectively.1
Specific Populations
Pregnancy
Elagolix exposure in pregnancy may increase risk of early pregnancy loss.1 Use contraindicated in pregnant women.
To monitor fetal outcomes of pregnant women exposed to elagolix, the manufacturer maintains a pregnancy registry.1 Encourage patients who become pregnant while receiving the drug to enroll in the registry by calling 833-782-7241
Insufficient data in humans to inform risk of major birth defects and miscarriage associated with use of elagolix.1 Two major congenital malformations and 5 miscarriages occurred among 49 reported pregnancies in >3500 women receiving elagolix in clinical trials.1 Evidence of early pregnancy loss observed in animal studies.
Advise patients to use effective nonhormonal contraceptive methods (e.g., condoms, spermicide) during treatment with elagolix and for 1 week following drug discontinuance.1 Discontinue elagolix if pregnancy occurs during treatment.1
Lactation
Not known whether elagolix or its metabolites are distributed into milk; effects of drug or its metabolites on breast-fed child or milk production also unknown.
Consider benefits of breast-feeding along with woman’s clinical need for the drug; also consider potential adverse effects on breast-fed child from the drug.
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. Elagolix has been assessed in clinical studies at a dose as high as a single administration of 1,200 mg, which resulted in concentrations of the medication that were 17 times higher than with the typical high clinical dosage of 200 mg twice per day. No adverse effects were mentioned. Chronic overdosage of elagolix may result in greater suppression of estradiol levels and a consequent increased risk of bone loss with long-term therapy.
Each Tablet Contains Elagolix Sodium INN 200mg