恶拉戈利钠(elagolix)适应症,功效与作用,用法用量,副作用,疗效？

Elagolix sodium (elagolix) indications

On July 23, 2018, elagolix sodium (elagolix) was approved for the treatment of endometriosis, becoming the first new drug approved by the US Food and Drug Administration for the treatment of endometriosis.

Effects and functions

1. Relieve pain: It can be used to relieve pain caused by dysmenorrhea. It reduces the occurrence and severity of dysmenorrhea by inhibiting the production and action of estrogen in the ovaries and reducing endometrial hyperplasia and shedding.

2. Control endometriosis: Elagolix can also be used to treat endometriosis. The disease is a condition in which endometrial tissue grows in areas outside the uterus, often accompanied by pain and other symptoms. Elagolix inhibits the production and action of ovarian hormones, reducing the growth and lesions of ectopic endometrium, thereby controlling the progression of the disease and the appearance of symptoms.

Usage and Dosage

1. Instructions for use

Exclude pregnancy before starting elagolix treatment or start elagolix treatment within 7 days after the start of menstruation. Take elagolix at approximately the same time each day, with or without food.

2. Dosage schedule

1. Start treatment with elagolix sodium (elagolix) 150 mg once a day, with a maximum course of 24 months.

2. Start using elagolix sodium (elagolix), 200 mg twice a day, each time, and the longest course of treatment is 6 months.

3. Start elagolix sodium (elagolix), 150 mg once a day. It is not recommended to use 200 mg twice a day. The maximum treatment duration is 6 months.

3. Missed doses

Instruct patients to take the missed dose of elagolix as soon as they remember, and then resume the regular dosing schedule.

1. 150mg once a day: You can only take one pill at most a day.

2. 200mg twice daily: No more than 2 tablets should be taken a day.

IV. Dose adjustment for patients with liver damage

1. Mild liver damage: For women with mild liver damage, there is no need to adjust the dose of the drug.

2. Moderate liver damage: For women with moderate liver damage, it is recommended to use elagolix sodium (elagolix) 150 mg each time, and the treatment course is limited to 6 months. For women with moderate liver damage, it is not recommended to take elagolix sodium (elagolix) 200 mg twice a day

3. Severe liver damage: Elagolix sodium (elagolix) is contraindicated in female patients with severe liver damage.

Dosage forms and specifications

1. The 150 mg tablets are light pink, oval, film-coated tablets, with "EL 150" engraved on one side. Each tablet contains 155.2 mg elagolix sodium, equivalent to 150 mg elagolix sodium.

2. The 200 mg tablets are light orange, oval, film-coated tablets with “EL 200” debossed on one side. Each tablet contains 207.0 mg elagolix sodium, equivalent to 200 mg elagolix sodium.

Contraindications

1. Pregnant women should not take elagolix to avoid affecting the health of the fetus.

2. Women suffering from osteoporosis should not use it, otherwise it will further aggravate the condition.

3. It is prohibited for women with severe liver damage.

4. It is contraindicated in patients using organic anion transporting polypeptide (OATP) 1B1 (hepatic uptake transporter) inhibitors that are known or expected to significantly increase the plasma concentration of elagolix.

5. It is prohibited for patients who are known to have a hypersensitivity reaction to elagolix sodium (elagolix) or any of its inactive ingredients to avoid allergic symptoms such as immediate allergic reactions and angioedema.

Side effects

The most common adverse reactions reported in clinical trials include insomnia, headache, hot flashes and night sweats, nausea, joint pain, amenorrhea, anxiety, depression-related adverse reactions, and mood changes.

Measures for dealing with side effects

1. Adjust dosage: If side effects such as headache and insomnia are severe or persistent, patients can reduce the dosage of the drug under the evaluation of a doctor to avoid side effects that continue to harm their health.

2. Adjust diet: It is recommended that patients eat a light diet while taking elagolix and avoid eating spicy and greasy foods, such as fried dough sticks, peppers, etc., which can help relieve gastrointestinal discomfort.

3. Improve your lifestyle: You can soak your feet while sleeping, avoid drinking irritating drinks such as alcohol and coffee, and create a comfortable and quiet sleeping environment.

4. Pay attention to rest: Mood changes and insomnia are one of the common side effects of elagolix. Patients are advised to avoid overexertion, ensure adequate rest time, and find ways to relax, such as meditation, massage, or warm water soaks.

5. Drug treatment: Patients can receive symptomatic treatment under the guidance of a doctor. For example, diarrhea can be treated with antidiarrheal drugs, headaches can be treated with analgesics, and insomnia can be treated with sedatives and sleeping pills.

6. Change drugs: If the side effects still do not improve after the above methods, the drug can be stopped under the evaluation of the doctor and replaced with other drugs.

Clinical efficacy analysis

Endometriosis-related pain is a considerable burden for women, permeating all aspects of life, from the ability to perform daily activities to quality of life. Although there are many options for the treatment of endometriosis-related pain, they are often limited by insufficient efficacy, inconvenient routes of administration, and/or intolerable side effects.

Elagolix, a non-peptide small molecule gonadotropin-releasing hormone (GnRH) receptor antagonist, is the first new oral therapy approved in the United States for the treatment of endometriosis-related pain in more than a decade. Modulation of estradiol by elagolix is ​​dose-dependent and ranges from partial to complete inhibition.

Clinical evidence shows that both approved doses of elagolix (150 mg once daily and 200 mg twice daily) are effective in reducing pelvic pain symptoms (dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia), improving quality of life, and reducing the use of rescue analgesics (NSAIDs and/or opioids). The availability of two dosage options allows for individualized treatment based on baseline clinical factors and treatment response.

Compared with GnRH agonists, elagolix is ​​well tolerated and has no obvious estrogen-reducing effect.

Drug interactions

1. The potential of elagolix to affect other drugs

1. CYP3A substrate: Elagolix is ​​a weak to moderate inducer of cytochrome P450 (CYP) 3A. Coadministration with elagolix may decrease plasma concentrations of CYP3A substrates.

2. Weak inhibitor of CYP2C19: Co-administration with CYP3A substrates can increase the plasma concentration of CYP 2C19 substrate drugs.

3. Inhibitors of the efflux transporter P-glycoprotein (P-gp): Coadministration with CYP3A substrates can increase the plasma concentration of P-gp substrate drugs.

2. The potential of other drugs to affect elagolix

1. Strong CYP3A inhibitor: Elagolix is ​​a substrate of CYP3A, P-gp and OATP1B1. Concomitant use of elagolix 200 mg twice daily with strong CYP3A inhibitors for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily with a strong CYP3A inhibitor for up to 6 months.

2. CYP3A inducers: Co-administration of elagolix sodium (elagolix) and strong CYP3A inducers can reduce the plasma concentration of elagolix sodium (elagolix) and may lead to a reduction in the therapeutic effect of elagolix sodium (elagolix).

3. Rifampicin: It is not recommended to use elagolix sodium (elagolix) 200 mg twice a day together with rifampicin. Limit concomitant use of elagolix 150 mg once daily and rifampicin for up to 6 months.

Notes

1. Loss: Bone mineral density (BMD) decreases in a dose- and time-dependent manner and may not be completely reversible. Assessing BMD in women with additional risk factors for bone loss.

2. Reduced ability to confirm pregnancy: Elagolix can change menstrual bleeding, which may reduce the ability to confirm pregnancy. If pregnancy is suspected, take a pregnancy test. If pregnancy is confirmed, discontinue medication.

3. Suicidal ideation and mood disorders: It is recommended that patients seek medical treatment when they experience suicidal ideation, suicidal behavior, new or worsening depression, anxiety or other mood changes.

4. Elevated liver transaminases: Serum alanine aminotransferase (ALT) increased in a dose-dependent manner. Inform patients of the signs and symptoms of liver injury.

5. Interaction with hormonal contraceptives: Use non-hormonal contraceptives during treatment and within 28 days after stopping elagolix. Coadministration of elagolix 200 mg twice daily with estrogen-containing contraceptives is not recommended due to the potential for increased estrogen-related risks.

Coadministration of elagolix with estrogen-containing contraceptives may reduce the efficacy of elagolix. Concomitant administration of progestin-containing oral contraceptives may decrease the effectiveness of the contraceptives.

Special medication groups

1. Pregnancy: Pregnant women should not use this drug.

2. Breastfeeding women: There is no information on the presence of elagolix or its metabolites in human milk, its effects on breastfed infants, or its effects on milk production. The developmental and health benefits of breastfeeding, as well as the mother's clinical need for elagolix, should be considered before using elagolix.

3. Pediatric use: The safety and effectiveness of elagolix in pediatric patients has not been determined, so its use by children is not recommended.

Drug Storage

The storage temperature of elagolix sodium is 36℉-86℉ (2℃-30℃). Do not store medicines that are expired or no longer needed.

Drug Price

1. The reference price of 150mg*28 tablets is about 13,340$.
2. The reference price of 200mg*56 tablets is approximately $13,340.

References

Leyland N, Estes SJ, Lessey BA, Advincula AP,

Taylor HS. A Clinician's Guide to the Treatment of Endometriosis with

Elagolix. J Womens Health (Larchmt). 2021 Apr;30(4):569-578. doi:

10.1089/jwh.2019.8096. Epub 2020 Sep 22. PMID: 32975461; PMCID:

PMC8064963.

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