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Elagolix

Medically reviewed by Drugs.com. Last updated on Apr 7, 2019.

Pronunciation

(EL a GOE lix)

Index Terms

  • ABT-620
  • Elagolix Sodium
  • NBI-56418

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Orilissa: 150 mg [contains carmine]

Orilissa: 200 mg

Brand Names: U.S.

  • Orilissa

Pharmacologic Category

  • Gonadotropin Releasing Hormone Antagonist

Pharmacology

Elagolix is a short-acting, nonpeptide, gonadotropin-releasing hormone antagonist that suppresses pituitary and ovarian hormone function in a dose-dependent manner. Concentrations of LH, FSH, and estradiol are decreased during therapy and rapidly return to previous levels once treatment is discontinued. In patients with endometriosis, these actions reduce dysmenorrhea and nonmenstrual pelvic pain (Ng 2017; Struthers 2009; Taylor 2017).

Absorption

Rapid (Ng 2017)

Metabolism

Hepatic via CYP3A (major pathway) and CYP2D6, CYP2C8, and UGTs

Excretion

Feces 90%; urine <3%

Onset of Action

FSH, LH, and estradiol suppression: Within hours of day 1 (initial) administration (Ng 2017)

Time to Peak

1 hour

Duration of Action

FSH, LH, and estradiol concentrations return to baseline or higher within 24 to 48 hours after discontinuation (Ng 2017)

Half-Life Elimination

4 to 6 hours

Protein Binding

80%; to human plasma proteins

Special Populations: Hepatic Function Impairment

Exposure of elagolix is increased by ~3-fold in patients with moderate hepatic impairment and by ~7-fold in patients with severe hepatic impairment (compared to patients with normal hepatic function).

Use: Labeled Indications

Endometriosis: Management of moderate to severe pain associated with endometriosis.

Contraindications

Pregnancy; known osteoporosis; severe hepatic impairment (Child-Pugh class C); concomitant use of strong organic anion transporting polypeptide (OATP) 1B1 inhibitors (eg, cyclosporine, gemfibrozil)

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to elagolix or any component of the formulation; undiagnosed vaginal bleeding

Dosing: Adult

Note: Treatment should be at the lowest effective dose consistent with treatment goals/severity of symptoms; limit duration of use to avoid potential bone loss.

Endometriosis: Oral: Initial: 150 mg once daily; Maximum treatment duration: 24 months

Endometriosis with dyspareunia: Oral: Initial: Consider an initial dose of 200 mg twice daily; Maximum treatment duration: 6 months

Missed dose: If a dose is missed, the dose should be administered on the same day as soon as remembered and then resume the regular schedule. For patients on 150 mg once daily, administer no more than 1 tablet each day; for patients on 200 mg twice daily, administer no more than 2 tablets each day.

Administration

Oral: Administer at approximately the same time(s) each day, with or without food. Treatment should be initiated within 7 days of menses onset otherwise pregnancy must be excluded prior to therapy.

Dietary Considerations

Consider calcium and vitamin D supplementation.

Storage

Store at 2°C to 30°C (36°F to 86°F).

Drug Interactions

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Betrixaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease the betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-glycoprotein inhibitor. Consider therapy modification

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in patients with moderate to severe renal insufficiency who are receiving p-glycoprotein inhibitors. Consider therapy modification

Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. Monitor therapy

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See full monograph for details. Consider therapy modification

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Elagolix. Monitor therapy

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Elagolix. Management: Use of the elagolix 200 mg twice daily dose with a strong CYP3A4 inhibitor for longer than 1 month is not recommended. Limit combined use of the elagolix 150 mg once daily dose with a strong CYP3A4 inhibitor to a maximum of 6 months. Consider therapy modification

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Consider therapy modification

Digoxin: Elagolix may increase the serum concentration of Digoxin. Monitor therapy

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain P-gp inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Estrogen Derivatives (Contraceptive): May diminish the therapeutic effect of Elagolix. Management: Use an alternative, non-hormonal contraceptive during treatment with elagolix and for at least 1 week following discontinuation of elagolix treatment. Consider therapy modification

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Monitor therapy

Midazolam: Elagolix may decrease the serum concentration of Midazolam. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Monitor therapy

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. Monitor therapy

OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors: May increase the serum concentration of Elagolix. Avoid combination

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Exceptions: Loperamide. Monitor therapy

Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy

Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy

RifAMPin: May increase the serum concentration of Elagolix. Management: Use of the elagolix 200 mg twice daily dose with rifampin is not recommended. Limit combined use of the elagolix 150 mg once daily dose with rifampin to a maximum of 6 months. Consider therapy modification

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy

Rosuvastatin: Elagolix may decrease the serum concentration of Rosuvastatin. Monitor therapy

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Management: These listed exceptions are discussed in detail in separate interaction monographs. Monitor therapy

Tolvaptan: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Consider therapy modification

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination

Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Consider a venetoclax dose reduction by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Consider therapy modification

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination

Adverse Reactions

>10%:

Central nervous system: Headache (17% to 20%)

Dermatologic: Night sweats (≤46%)

Endocrine & metabolic: Amenorrhea (4% to 57%), hot flash (≤46%)

Gastrointestinal: Nausea (16%)

Neuromuscular & skeletal: Decreased bone mineral density (≤21%)

1% to 10%:

Central nervous system: Insomnia (6% to 9%), depressed mood (≤6%), depression (≤6%), emotional lability (≤6%), lacrimation (≤6%; including tearfulness), mood changes (≤6%), anxiety (5%), dizziness (≥3% to <5%), irritability (≥3% to <5%)

Endocrine & metabolic: Decreased libido (≥3% to <5%), weight gain (≥3% to <5%)

Gastrointestinal: Abdominal pain (≥3% to <5%), constipation (≥3% to <5%), diarrhea (≥3% to <5%)

Hepatic: Increased serum alanine aminotransferase (≥3 x ULN: 1%)

Neuromuscular & skeletal: Arthralgia (5%)

Frequency not defined:

Endocrine & metabolic: Increased HDL cholesterol, increased LDL cholesterol, increased serum cholesterol, increased triglycerides

Genitourinary: Menstrual flow (reduction in the amount, intensity, or duration of menstrual bleeding)

<1%, postmarketing, and/or case reports: Appendicitis, back pain, suicidal ideation

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding irregularities: Menstrual bleeding patterns may change, causing a decrease in the amount, intensity, or duration of bleeding. Changes in bleeding patterns may alter the ability to detect pregnancy. Pregnancy testing should be conducted if pregnancy is suspected; discontinue use if pregnancy is confirmed.

• BMD loss: A dose-dependent decrease in BMD is associated with elagolix exposure. The risk of BMD loss is increased with duration of use and may not be completely reversible following discontinuation of elagolix. Evaluate patients for osteoporosis risk factors (including a history of low-trauma fracture) prior to therapy. Consider supplementation with calcium and vitamin D. Duration of treatment should be limited to prevent BMD loss. Do not use in patients with known osteoporosis.

• Depression: Elagolix may increase the risk of depression and mood changes; risk may be increased in patients with a history of suicidality or depression. Suicidal ideation/behavior has been reported. Promptly evaluate new or worsening psychiatric symptoms and refer to a mental health care professional if appropriate. Patients should seek immediate medical attention for suicidal ideation and behavior. Consider risks and benefits of therapy if mood disturbances occur.

• Hepatic impairment: Dose-dependent elevations of ALT ≥3 times the upper limit of normal may occur; the lowest effective dose should be used. Promptly evaluate elevations in transaminases to assess risks versus benefits of continuing therapy. Dose adjustment is required in patients with moderate hepatic impairment; do not use in severe hepatic impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitoring Parameters

Pregnancy status prior to therapy; pregnancy test during therapy (if pregnancy is suspected); liver function tests; monitor mental status (for signs/symptoms of depression, suicidal ideation); consider BMD after 12 months (Surrey 2018)

Pregnancy Considerations

Use is contraindicated during pregnancy.

Information related to inadvertent exposure in pregnancy is limited. Elagolix may increase the risk of early pregnancy loss. Pregnancy should be ruled out prior to treatment and if suspected during elagolix therapy; discontinue elagolix if pregnancy occurs.

Ovulation is not fully suppressed during elagolix therapy (Taylor 2017). Nonhormonal contraceptives should be used during therapy and for 1 week after elagolix treatment is discontinued.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience menstrual changes, hot flash, night sweats, headache, nausea, insomnia, or joint pain. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), mood changes, behavioral changes, or anxiety (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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