elagolix (Rx)

Brand and Other Names:Orilissa
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 150mg
  • 200mg

Endometriosis

Indicated for management of moderate-to-severe pain associated with endometriosis

Initiate with 150 mg PO qDay for up to 24 months

Coexisting conditions

  • Dyspareunia: Consider initiating with 200 mg BID for up to 6 months
  • Moderate hepatic impairment (Child-Pugh B): Initiate with 150 mg qDay for up to 6 months; 200 mg BID is not recommended

Dosage Modifications

Renal impairment

  • No dosage adjustment required with any degree of renal impairment or end-stage renal disease (including dialysis)

Hepatic impairment

  • Mild (Child-Pugh A): No dosage adjustment required
  • Moderate (Child-Pugh B): Only the 150-mg qDay regimen is recommended for women with moderate hepatic impairment, and the duration of treatment should be limited to 6 months
  • Severe (Child-Pugh C): Contraindicated

Dosing Considerations

Exclude pregnancy before initiating, or start elagolix within 7 days from the onset of menses

Use the lowest effective dose, taking into account the severity of symptoms and treatment objectives

Limit the duration of use because of bone loss

<18 years: Safety and efficacy not established

Next:

Interactions

Interaction Checker

and elagolix

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10%

            Hot flush or night sweats (24-36%)

            Headache (17-20%)

            Nausea (11-16%)

            1-10%

            Insomnia (6-9%)

            Mood altered, mood swings (5-6%)

            Amenorrhea (4-7%)

            Depressed mood, depression, depressive symptoms and/or tearfulness (3-6%)

            Hypersensitivity reactions (5.8%)

            Anxiety (3-5%)

            Arthralgia (3-5%)

            ≥3% to <5%

            • Decreased libido
            • Diarrhea
            • Abdominal pain
            • Weight gain
            • Dizziness
            • Constipation Irritability
            Previous
            Next:

            Warnings

            Contraindications

            Pregnancy

            Known osteoporosis

            Severe hepatic impairment

            Coadministration of strong organic anion transporting polypeptide (OATP) 1B1 inhibitors (eg, cyclosporine and gemfibrozil)

            Cautions

            May reduce the amount, intensity, or duration of menstrual bleeding, which may decrease the ability to recognize the occurrence of a pregnancy in a timely manner; perform pregnancy testing if pregnancy is suspected, and discontinue drug if pregnancy confirmed

            Dose-dependent elevations of ALT ≥3x ULN occurred with elagolix; use the lowest effective dose and instruct patients to promptly seek medical attention in case of symptoms or signs that may reflect liver injury

            Suicidal behavior and mood disorders

            • Suicidal ideation and behavior, including 1 completed suicide, occurred in subjects treated with elagolix in the endometriosis clinical trials
            • Patients taking elagolix had a higher incidence of depression and mood changes compared with placebo
            • Patients with a history of suicidality or depression had a higher incidence of depression compared with subjects without such a history
            • Promptly evaluate patients with depressive symptoms to determine whether the risks of continued therapy outweigh the benefits
            • Patients with new or worsening depression, anxiety, or other mood changes should be referred to a mental health professional, as appropriate
            • Advise patients to seek immediate medical attention for suicidal ideation and behavior
            • Reevaluate the benefits and risks of continuing elagolix if such events occur

            Bone mineral density

            • Dose-dependent decrease in bone mineral density (BMD) reported
            • BMD loss is greater with increasing duration of use and may not be completely reversible after stopping treatment
            • The impact of these BMD decreases on long-term bone health and future fracture risk are unknown
            • Consider assessing BMD with a history of a low-trauma fracture or other risk factors for osteoporosis or bone loss, and do not use in women with known osteoporosis
            • Limit the duration of use to reduce the extent of bone loss

            Drug interaction overview

            • Also see Contraindications
            • OATP1B1 inhibitors
              • Coadministration with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations
              • Concomitant use with strong OATP1B1 inhibitors (eg, cyclosporine, gemfibrozil) is contraindicated
            • CYP3A inhibitors and inducers
              • Elagolix is a CYP3A substrate
              • Coadministration of elagolix 200 mg BID with strong CYP3A inhibitors for >1 month is not recommended; limit coadministration of elagolix 150 mg qDay and strong CYP3A inhibitors to 6 months
              • Coadministration with drugs that induce CYP3A may decrease elagolix plasma concentrations
            • P-gp inhibitors and inducers
              • The effect of concomitant use of P-gp inhibitors or inducers on the pharmacokinetics of elagolix is unknown
            • Estrogen-containing contraceptive
              • Based on elagolix’s mechanism of action, estrogen-containing contraceptives are expected to reduce elagolix efficacy
              • The effect of progestin-only contraceptives on elagolix efficacy is unknown
              • Advise women to use nonhormonal contraceptives during treatment and for 1 week after discontinuing elagolix
            • Effect of elagolix on other drugs
              • Elagolix is a weak-to-moderate CYP3A inducer; coadministration may decrease plasma concentration of CYP3A substrates
              • Elagolix inhibits efflux transporter P-glycoprotein (P-gp); coadministration may increase plasma concentration of P-gp substrates
            Previous
            Next:

            Pregnancy

            Pregnancy

            Contraindicated in pregnant women

            Drug exposure early in pregnancy may increase the risk of early pregnancy loss

            Discontinue elagolix if pregnancy occurs during treatment

            The limited human data with use in pregnant women are insufficient in determining whether there is a risk for major birth defects or miscarriage; although 2 cases of congenital malformations were reported in clinical trials with elagolix, no pattern was identified and miscarriages were reported at a similar incidence across treatment groups

            Animal data

            • When pregnant rats and rabbits were orally dosed with elagolix during the period of organogenesis, postimplantation loss was observed in pregnant rats at doses 20 times the maximum recommended human dose (MRHD)
            • Spontaneous abortion and total litter loss was observed in rabbits at doses 7 and 12 times the MRHD
            • There were no structural abnormalities in the fetuses at exposures up to 40 and 12 times the MRHD for the rat and rabbit, respectively

            Pregnancy testing

            • Exclude pregnancy before initiating treatment with elagolix
            • Perform pregnancy testing if pregnancy is suspected during treatment with elagolix

            Contraception

            • Advise women to use effective nonhormonal contraception during treatment with elagolix and for 1 week after discontinuing elagolix

            Lactation

            There is no information on the presence of elagolix or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production

            There are no adequate animal data on the excretion of elagolix in milk

            The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for elagolix and any potential adverse effects on the breastfed child from elagolix

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

            more...
            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Oral gonadotropin-releasing hormone (GnRH) receptor antagonist; inhibits endogenous GnRH signaling by binding competitively to GnRH receptors in the pituitary gland

            Administration of elagolix results in dose-dependent suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to decreased blood concentrations of the ovarian sex hormones, estradiol and progesterone

            Absorption

            Peak plasma time: 1 hr

            Peak plasma concentration: 574 ng/mL (150-mg dose); 774 ng/mL (200-mg dose)

            AUC: 1292 ng·hr/mL (150-mg dose); 1725 ng·hr/mL (200-mg dose)

            Effect of high-fat meal (relative to fasting): AUC decreases by 24%; peak plasma concentration decreases by 36%

            Distribution

            Vd (steady-state): 1674 L (150-mg dose); 881 L (200-mg dose)

            Protein binding: 80%

            Blood-to-plasma ratio: 0.6

            Metabolism

            Hepatically metabolized by CYP3A4 (major)

            Minor pathways include: CYP2D6, CYP2C8, and uridine glucuronosyl transferases (UGTs)

            Elimination

            Half-life: 4-6 hr

            Oral clearance: 123 L/hr (150-mg dose); 144 L/hr (200-mg dose)

            Excretion: Urine (<3%); feces (90%)

            Pharmacogenomics

            Disposition of elagolix involves the OATP1B1 transporter protein

            Higher plasma concentrations of elagolix observed in individuals who have 2 reduced function alleles of the gene that encodes OATP1B1 (SLCO1B1 521T>C)

            The frequency of this SLCO1B1 521 C/C genotype is generally <5% in most racial/ethnic groups

            Individuals with this genotype are expected to have a 78% mean increase in elagolix concentrations compared with individuals with normal transporter function (ie, SLCO1B1 521T/T genotype)

            Previous
            Next:

            Administration

            Oral Administration

            Take at approximately the same time each day, with or without food

            Missed dose

            • Administer missed dose on the same day as soon as possible and then resume the regular dosing schedule
            • 150 mg qDay: Take no more than 1 tablet each day
            • 200 mg BID: Take no more than 2 tablets each day

            Storage

            Store at 2-30°C (36-86°F)

            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.