Overview
Elagolix is an antagonist of gonadotropin-releasing hormone receptors for treating average to extreme aches connected with endometriosis. In the year 2018, the United States Food and Drug Administration (FDA) authorized Elagolix to manage aches connected with endometriosis. It was the first medicine particularly approved for pain control in endometriosis.
How Does Elagolix Drug Work?
Endometriosis is a familiar syndrome that induces considerable aches, morbidity, and disability. Elagolix is an efficacious medicine in managing the manifestations of endometriosis and is a comparatively safer choice. Elagolix is an antagonist of gonadotropin-releasing hormone receptors that interferes with endogenous gonadotropin-releasing hormone signaling by attaching competitively to gonadotropin-releasing hormone receptors in the pituitary gland. Elagolix will suppress the luteinizing hormone and follicle-stimulating hormone, causing reduced concentrations of the ovarian sex hormones, estradiol, and progesterone in the blood.
Uses of Elagolix
Elagolix is indicated mainly for managing and treating medium to intense endometriosis-related aches.
Limitations
The Elagolix limitation is based on its dose and the presence of co-existing conditions in the patient.
Dosage and Administration
Important Dosing Information
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Elagolix tablets should be taken within seven days after the beginning of periods and exclude pregnancy before the administration of Elagolix.
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The drug should be taken simultaneously daily, with or without the food.
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Based on the treatment objective and manifestations, the dosage is planned. The lowest effective dosage should be taken.
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Confine the period of Elagolix usage due to its bone loss manifestation.
How to Use an Elagolix Tablet?
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Take the medication through the mouth. It can be taken with or without food. It is usually given once or twice per day. The dosage and duration vary depending on the condition and the patient's reaction. It is planned to give for 6 to 24 months to reduce the bone loss side effect.
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Take the Elagolix tablet precisely as per the healthcare provider's instructions. It is always better to do a pregnancy test before the beginning of therapy. The Elagolix tablets are recommended to take within seven days after the beginning of the period.
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If the patient takes too much Elagolix, they must inform their healthcare provider or immediately proceed to the closest hospital emergency room. In case of a missing dose of Elagolix: 150 mg (once daily), ingest it immediately as it is on the exact day. Should not intake more than one tablet each day. Also, a dosage of 200 mg maximum daily dose; intake immediately when recognized, as it is on the exact day. Should not intake more than two tablets daily.
Hepatic Impairment:
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There is no dosage adjustment required for women who have mild hepatic impairment.
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Approximated female patients with standard liver action and in cases with average hepatic defect had an average of 3-fold higher Elagolix vulnerabilities, and those with severe hepatic defect had an average of 7-fold higher Elagolix exposures because of these high exposures and hazards for bone loss.
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Elagolix 150 milligrams once every day is suggested for women with average hepatic impairment, with the period of therapy restricted to six months. Use of Elagolix, a maximum daily dose of 200 milligrams, is not suggested for women with average hepatic impairment.
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Elagolix is contraindicated in cases with extreme impairment of the hepatic system.
Missed Dose:
Guide the patient to take a skipped dose of Elagolix in the same daytime immediately when the patient recognizes it and then continue the routine dosing timetable.
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One hundred fifty milligrams (150 mg) one time daily should not be taken on more than one tablet daily.
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Two hundred milligrams (200 mg) is the maximum daily dose.
Dosage Forms and Strengths:
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The 150-milligram medicines are light pink in color, oblong in shape, tablets coated with a film, and EL 150 debossed on one side. Individually the tablet comprises 155.2 milligrams of Elagolix sodium, equivalent to 150 mg of Elagolix.
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The 200-milligram medicines are light orange in color, oblong in shape, and tablets are coated with a film with "EL 200" debossed on one of its sides. Each tablet comprises 207.0 milligrams of Elagolix Sodium, equal to 200 milligrams of Elagolix.
Contraindications
Elagolix is contraindicated in the following women:
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Who are pregnant or are in the early stages of pregnancy. When exposed to Elagolix, it can lead to loss of pregnancy.
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Elagolix has an adverse effect on bone loss. Thus, it is contraindicated in women at high risk of osteoporosis.
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Women with severe impairment of the hepatic system.
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Accepting inhibitors of organic anion transporting polypeptide 1B1, as it is a hepatic uptake transporter that is called or anticipated to especially advance Elagolix plasma concentrations.
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With understood hypersensitivity response to Elagolix or any of its inactive ingredients. Responses have been incorporated as anaphylaxis and angioedema reactions.
Warnings and Precautions
1) Bone Loss: Elagolix generates a dose-based reduction in bone mineral density. Bone mineral density loss is more prominent with an improving usage period and may not be reversible after discontinuing the therapy. Elagolix is contraindicated in cases with known osteoporosis. Proper assessments should be taken on patients to evaluate bone mineral density in women with a record of a low-trauma fracture or other hazard elements for osteoporosis or loss of bone. Restrict the period of usage to decrease the extent of loss of bone. Supplements with vitamin D or calcium may have a good impact.
2) Change in Menstrual Bleeding Pattern and Reduced Ability to Recognize Pregnancy: Patients on Elagolix have reduced intensity and quantity of menstrual bleeding. Thus pregnancy detection can be altered. Elagolix should be discontinued in pregnant patients.
3) Suicidal Ideation, Suicidal Behavior, and Exacerbation of Mood Disorders: Patients taking Elagolix have a more increased incidence of depression and mood changes corresponding to placebo. Patients with exacerbating depression, anxiety, or other mood transformations should be directed to a mental health professional.
4) Hepatic Transaminase Elevations: Use the minimum required dose and evaluate the patient for liver damage while taking Elagolix.
5) Interactions with Hormonal Contraceptives: Estrogen-containing contraceptives are predicted to decrease the effectiveness of Elagolix. The result of progestin-only contraceptives on the effectiveness of Elagolix is not known.
For Patients:
What Is Endometriosis?
Endometriosis is a gynecological condition. The word endometriosis is emanated from the term 'endometrium,' which is the inner lining of the uterus. Endometriosis is a disorder in the endometrial tissue that grows outside the uterus. It is an extremely painful condition. The pain is similar to menstrual cramps. It occurs in the ovary, fallopian tube, uterus ligaments, pelvic cavity lining, and outer uterus lining.
What Are the Symptoms of Endometriosis?
Symptoms of endometriosis involves,
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Severe pain occurs predominantly, like an exaggerated menstrual cramp in the area of the abdomen or the lower back region.
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Extreme pain at the time of intercourse.
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Heavy menstrual bleeding.
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Painful urination and bowel movement during menstrual periods.
Adverse Reactions:
The adverse reaction of Elagolix involves,
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Loss of bone.
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Transformation in menstrual bleeding practice and smaller capability to identify pregnancy.
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Suicidal imagination, suicidal manners, and worsening of mood disorders.
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Increased hepatic transaminase.
Why Is Elagolix Drug Prescribed for Endometriosis?
It decreases the status of particular hormones like follicular stimulating and luteinizing hormones. This reduces the sex hormone estrogen and thus reduces the symptoms and manifestations of endometriosis.
What Should the Patient Discuss With a Doctor Before Beginning Elagolix Therapy?
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Discuss with a doctor in case of pregnancy or planning to get pregnant, as it causes severe side effects in early pregnancy.
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If the patient has any history of bone loss disorders.
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If the patient has any depression, suicidal tendencies, or mood swings.
Use in Specific Populations
Pregnancy:
Elagolix is contraindicated in pregnancy as it can cause severe effects in pregnancy. It causes early pregnancy loss.
Lactation:
There is no report available on the presence of Elagolix or its metabolites in human milk, the results on the breastfed kid, or the consequences on milk production. The developmental and health advantages of breastfeeding should be assessed, along with the patient's clinical condition for Elagolix and any possible adverse impacts on the breastfed child from Elagolix.
Females and Males of Reproductive Potential:
It depends on the mechanism of action. In early pregnancy, Elagolix may cause pregnancy loss.
Pediatric Use:
The safety and establishment of Elagolix are not well explained.
Renal Impairment:
There is no alteration in dosage done for any stage of renal impairment.
Hepatic Impairment:
In the case of mild hepatic impairment, there is no need for alteration of dosage. The 150 mg Elagolix is given once daily and is suggested for women with average hepatic impairment. The period of therapy is restricted to six months. Elagolix is contraindicated in females with extreme hepatic impairment.
What Is the Pharmacology of Elagolix?
Elagolix is a tablet for oral administration containing Elagolix sodium. Elagolix sodium is a nonpeptide small molecule, Gonadotropin-releasing hormone receptor antagonist. Elagolix sodium is chemically defined as sodium 4-({(1R)-2-[5-(2-fluoro-3 methoxyphenyl)-3-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl}-4-methyl-2,6-dioxo-3,6 dihydropyridine-1(2H)-yl]-1-phenylethyl}amino)butanoate. Elagolix 150 mg tablets are light pink, oblong, film-coated tablets with EL 150 debossed on one of their sides. Each tablet comprises 155.2 mg of Elagolix sodium (comparable to 150 mg of Elagolix) as the functioning component, and the passive ingredients like mannitol, pregelatinized starch, povidone, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and high carmine tint. Elagolix 200 mg tablets are light orange, oblong, film-coated tablets with "EL 200" debossed on one of their sides. Each tablet comprises 207.0 mg of Elagolix sodium (similar to the maximum daily dose of 200 mg of Elagolix) as the active component and the subsequent inactive components like mannitol, sodium carbonate monohydrate, gelatin starch, magnesium stearate, povidone, and titanium dioxide.
Clinical Pharmacology
Mechanism of Action
Elagolix is a gonadotropin-releasing hormone receptor antagonist that hinders endogenous gonadotropin-releasing hormone signaling by attaching competitively to gonadotropin-releasing hormone receptors in the pituitary gland. Intake of Elagolix induces dose-conditional suppression of luteinizing hormone and follicle-stimulating hormone, directing to reduced concentrations of the ovarian sex hormones in the blood, estradiol, and progesterone.
Pharmacodynamics
Effect on Ovulation and Estradiol
A 3-menstrual cycle study done on healthy women with Elagolix tablets 150 mg once every day and a maximum daily dose of 200 mg every day causes an ovulation rate of around 50 percent and 32 percent, respectively. In Phase three trials in cases with endometriosis, Elagolix induced a dose-based decrease in median estradiol concentrations to around 42 pg/mL (picograms per milliliter) for the 150 milligrams once daily regimen and 12 pg/mL for the maximum daily dosage of 200 milligrams daily regimen.
Cardiac Electrophysiology
The Elagolix in QTc interval was assessed in a randomized, placebo- and positive-based, open-label, single-dose, crossover thorough QTc study in forty-eight healthy adult premenopausal women. Elagolix concentrations in subjects provided a single dose of 1200 milligrams were 17 times more elevated than the attention in subjects given Elagolix 200 milligrams maximum daily dose. There was no clinically appropriate prolongation of the QTc interval.
Pharmacokinetics
In Specific Populations
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Women With Renal Impairment- Elagolix actions are not changed by the renal impairments. It suggests vulnerabilities are equivalent for women with medium to extreme or final stage renal disease, which implicates women on dialysis as approximated to women with the average renal process.
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Women With Hepatic Impairment- Elagolix vulnerabilities (peak concentration and area under the plasma concentration) are comparable between women with normal hepatic process and women with minimum hepatic impairment. Elagolix vulnerabilities in cases with average and extreme hepatic impairment are about 3-fold and 7-fold, respectively, more elevated than disclosures from cases with the normal hepatic process.
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Racial or Ethnic Groups- No clinically significant distinction in the pharmacokinetics of Elagolix between White and Black subjects was further followed.
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Body Weight or Body Mass Index- This does not affect the pharmacokinetics of Elagolix.
Drug Interactions
Potential for Elagolix to Affect Other Drugs
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Elagolix is a weak to medium inducer of cytochrome P450 (CYP) 3A. If taken along with Elagolix may reduce plasma concentrations of medicines that are CYP3A substrates.
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Elagolix is a weak inhibitor of CYP2C19. Taking it with Elagolix may improve the drug plasma concentrations that are CYP2C19 substrates.
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Elagolix is an efflux transporter P-glycoprotein inhibitor. If taken with may, Elagolix improves plasma concentrations of medications P-gp substrates.
Drug Interactions: Effects of Elagolix on Other Drugs
Potential for Additional Medications to Impact Elagolix
Drug Interactions
Elagolix-CYP3A, P-gp, and OATP1B1 substrate.
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Simultaneous use of Elagolix, a maximum daily dose of 200 mg daily, and potent CYP3A inhibitors for more than one month is not recommended. Restrict simultaneous usage of Elagolix 150 mg one time daily and potent CYP3A inhibitors for six months.
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Simultaneous usage of Elagolix with strong CYP3A inducers may reduce Elagolix plasma concentrations and may lead to a reduction of the medicinal results of Elagolix.
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Simultaneous usage of Elagolix, a maximum daily dose of 200 mg daily with Rifampin is not suggested, and reduce it to 150 mg once daily for six months.
OATP1B1 inhibitors understood or predicted to significantly increase Elagolix plasma concentrations are contraindicated due to the increased risk of Elagolix-associated adverse reactions.
Pharmacogenomics
Hepatic uptake of Elagolix includes the OATP1B1 transporter protein. More increased plasma concentrations of Elagolix have been seen in cases of two decreased function alleles of the gene that encodes OATP1B1. The side effects of Elagolix are not completely assessed in cases of two decreased function alleles of the gene that encodes OATP1B1.
Nonclinical Toxicology:
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Based on the carcinogenicity studies conducted, Elagolix was not genotoxic or mutagenic in a battery of examinations involving the in vitro bacterial reverse mutation assay, the in vitro mammalian cell ahead mutation at the thymidine kinase loci in L5178Y lymphoma style cell types, and the in vivo mouse micronucleus assay.
How Is Elagolix Supplied, or Stored, and Handled?
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Elagolix tablets are available in two doses: 150 mg and 200 mg (maximum daily dose), identical to 155.2 mg and 207.0 mg of Elagolix sodium.
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Elagolix 150-milligram tablets are light pink, oval in shape, and film-coated pills with “ EL 150” debossed on one of their sides. They are packaged in weekly blister packs. Individual blister packages include seven tablets providing the drug for one week. Four blister packs of around 28 tablets are covered into a carton that delivers the drug product for four weeks.
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Elagolix 200-milligram tablets are light orange, oblong-shaped, film-coated tablets with “ EL 200” debossed on one side. The 200 mg tablets are covered in weekly blister packages. Each blister pack includes 14 tablets providing the medication for one week. Four blister packs are cowered in a carton that delivers the drug product for four weeks.
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Elagolix 200 mg tablets are light orange in color, oblong-shaped, film-coated tablets with EL 200 debossed on one side. The 200 mg tablets are covered in weekly blister packs. Each blister packet comprises 14 tablets delivering the drug product for one week. Four blister packs are packaged in a carton that provides the drug product for four weeks.
Do not flush down the tablets in the toilet.
Elagolix Missed Dose Instructions
Train a patient who misses a dose of Elagolix to have the skipped dose on the exact day immediately as soon as they recognize it and then continue the standard dosing program:
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One hundred fifty milligrams one time daily and not more than one tablet every day should be taken.
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Two hundred milligrams maximum daily dose.
Elagolix disposal instructions advise patients to dispose of new prescriptions through a take-back choice if unrestricted or observe FDA education for disposing of prescriptions in the home garbage.
