Note: Treatment should be at the lowest effective dose consistent with treatment goals/severity of symptoms; limit duration of use based on dose and coexisting conditions 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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild, moderate, or severe impairment: No dosage adjustment necessary.
ESRD: No dosage adjustment necessary.
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): Initial dose: 150 mg once daily for a maximum treatment duration of 6 months. The 200 mg twice daily dose is not recommended.
Severe impairment (Child-Pugh class C): Use is contraindicated.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Orilissa: 150 mg [contains carmine]
Orilissa: 200 mg
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Orilissa: 150 mg [contains carmine]
Orilissa: 200 mg
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/210450s004s005s006lbl.pdf#page=27, must be dispensed with this medication.
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.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Elagolix may cause reproductive toxicity and has a structural or toxicity profile similar to existing hazardous agents. Assess risk to determine appropriate containment strategy (USP-NF 2017).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends single gloving for administration of intact tablets or capsules (NIOSH 2016).
Endometriosis: Management of moderate to severe pain associated with endometriosis.
Limitation of use: Use should be limited based on dose and coexisting conditions.
Elagolix may be confused with cetrorelix, degarelix, ganirelix
Orilissa may be confused with orlistat
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Endocrine & metabolic: Amenorrhea (4% to 57%; dose-dependent), hot flash (24% to 46%)
Gastrointestinal: Nausea (16%)
Nervous system: Headache (17% to 20%)
Neuromuscular & skeletal: Decreased bone mineral density (≤21%; dose-dependent)
1% to 10%:
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%; dose-dependent)
Nervous system: Anxiety (5%), depressed mood (≤6%), depression (≤6%), dizziness (3% to <5%), emotional lability (≤6%; including tearfulness), insomnia (6% to 9%), irritability (3% to <5%), mood changes (≤6%)
Neuromuscular & skeletal: Arthralgia (5%)
<1%:
Gastrointestinal: Appendicitis
Nervous system: Suicidal ideation, suicidal tendencies
Neuromuscular & skeletal: Back pain
Frequency not defined:
Dermatologic: Night sweats
Endocrine & metabolic: Increased HDL cholesterol (dose-dependent), increased LDL cholesterol (dose-dependent), increased serum cholesterol (dose-dependent), increased triglycerides (dose-dependent)
Genitourinary: Menstruation (dose-dependent; reduction in the amount, intensity, or duration of menstrual bleeding)
Postmarketing: Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction
Hypersensitivity to elagolix or any component of the formulation; pregnancy; known osteoporosis; severe hepatic impairment (Child-Pugh class C); concomitant use of organic anion transporting polypeptide (OATP) 1B1 that are known or expected to significantly increase elagolix plasma concentrations.
Canadian labeling: Additional contraindications (not in US labeling): Undiagnosed vaginal bleeding
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.
• 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.
Substrate of CYP3A4 (major), OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C19 (weak), P-glycoprotein/ABCB1; Induces CYP3A4 (weak)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider therapy modification
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: Monitor therapy
Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination
CarBAMazepine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: Monitor therapy
CloBAZam: CYP2C19 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of CloBAZam. CYP2C19 Inhibitors (Weak) may increase the serum concentration of CloBAZam. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. Risk C: 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-gp inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See interaction monograph for details. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May decrease the serum concentration of Elagolix. Risk C: 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. Risk D: Consider therapy modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy
Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider therapy modification
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Risk C: Monitor therapy
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fosphenytoin-Phenytoin: May decrease the serum concentration of Elagolix. Elagolix may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Hormonal Contraceptives: May diminish the therapeutic effect of Elagolix. Specifically, estrogen-containing hormonal contraceptives may diminish the therapeutic effects of elagolix. Elagolix may increase the serum concentration of Hormonal Contraceptives. Specifically, concentrations of ethinyl estradiol may be increased with elagolix therapy. Elagolix may decrease the serum concentration of Hormonal Contraceptives. Specifically, concentrations of progestins may be decreased with elagolix therapy. Management: Use an alternative, nonhormonal contraceptive during treatment with elagolix and for at least 28 days following discontinuation of elagolix treatment. Use of elagolix 200 mg twice daily with an estrogen-containing hormonal contraceptive is not recommended Risk D: Consider therapy modification
Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Risk C: Monitor therapy
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy
Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Risk D: Consider therapy modification
Mavacamten: CYP2C19 Inhibitors (Weak) may increase the serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a weak CYP2C19 inhibitor. For those stable on mavacamten who are initiating a weak CYP2C19 inhibitor, reduce mavacamten dose by one dose level. Risk D: Consider therapy modification
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Risk C: Monitor therapy
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. Risk C: Monitor therapy
OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors: May increase the serum concentration of Elagolix. Risk X: Avoid combination
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Risk C: Monitor therapy
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider therapy modification
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy
Rosuvastatin: Elagolix may decrease the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Selpercatinib: CYP3A4 Inducers (Weak) may decrease the serum concentration of Selpercatinib. Risk C: Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk C: Monitor therapy
Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider therapy modification
Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
Tacrolimus (Systemic): CYP3A4 Inducers (Weak) may decrease the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Tegaserod: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod. Risk C: Monitor therapy
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Ubrogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Risk D: Consider therapy modification
Ubrogepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a P-gp inhibitor. Risk D: Consider therapy modification
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Risk D: Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
Voclosporin: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Evaluate pregnancy status prior to use. Exclude pregnancy prior to treatment or start elagolix within 7 days from the onset of menses. Treatment with elagolix may reduce the amount, intensity, or duration of menstrual bleeding, which may make it more difficult to recognize pregnancy. Perform pregnancy testing if pregnancy is suspected during elagolix therapy.
Ovulation is not fully suppressed during elagolix therapy (Taylor 2017). Use of hormonal contraception may be associated with increased adverse events, decreased contraceptive efficacy, or decreased efficacy of elagolix; consult drug interactions database for more detailed information related to elagolix and specific contraceptives. Nonhormonal contraceptives should be used during therapy and for 28 days after elagolix treatment is discontinued.
Use is contraindicated during pregnancy.
Information related to inadvertent exposure in pregnancy is limited. Elagolix may increase the risk of early pregnancy loss.
Data collection to monitor pregnancy and infant outcomes following exposure to elagolix is ongoing. Health care providers are encouraged to enroll females exposed to elagolix during pregnancy in the pregnancy registry (833-782-7241).
It is not known if elagolix is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Consider calcium and vitamin D supplementation.
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)
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).
Note: The pharmacokinetics of elagolix are not influenced by BMI.
Onset: FSH, LH, and estradiol suppression: Within hours of day 1 (initial) administration (Ng 2017)
Duration: FSH, LH, and estradiol concentrations return to baseline or higher within 24 to 48 hours after discontinuation (Ng 2017)
Absorption: Rapid (Ng 2017)
Protein binding: 80%; to human plasma proteins
Metabolism: Hepatic via CYP3A (major pathway) and CYP2D6, CYP2C8, and UGTs
Half-life elimination: Terminal: 4 to 6 hours
Time to peak: 1 hour
Excretion: Feces 90%; urine <3%
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).
Tablets (Orilissa Oral)
150 mg (per each): $44.86
200 mg (per each): $22.43
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