Dosing & Uses
Dosage Forms & Strengths
copackaged capsules
- Contains elagolix, estradiol, and norethindrone acetate as a fixed-dose capsule copackaged with a single elagolix capsule
-
elagolix/estradiol/norethindrone acetate fixed-dose capsule
- 300mg/1mg/0.5mg
-
elagolix capsule
- 300mg
Uterine Leiomyomas
Indicated for management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women
Take one combination capsule (ie, elagolix 300 mg/estradiol 1 mg/norethindrone acetate 0.5 mg) PO in AM, THEN
Take one elagolix 300 mg capsule PO in PM
Duration of treatment: Not to exceed 24 months
Dosage Modifications
Renal impairment
- No dose adjustment is required for any degree of renal impairment or end-stage renal disease (including women on dialysis)
Hepatic impairment
- Contraindicated
Dosing Considerations
Exclude pregnancy before initiating, or initiate within 7 days from the onset of menses
Limitation of use: Do not exceed duration of use of 24 months owing to risk of continued bone loss, which may not be reversible
Not indicated
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Adverse Effects
>10%
Decreased bone mineral density (BMD) >3% (27%)
Hot flush (22%)
Increased diastolic blood pressure (BP) ≥100 mmHg (11.3%)
1-10%
Headache (9%)
Increased systolic BP ≥160 mmHg (7.1%)
Fatigue (6%)
Metrorrhagia (5%)
Alopecia (3.5%)
Depression (3%)
Decreased BMD ≥8% (1.7%)
Increased ALT/AST (1.1-1.3%)
≥3 to <5%
- Decreased libido
- Arthralgia
- Mood swings
- Influenza
- Abdominal distension
- Upper respiratory tract infection
- Vomiting
- Increased weight
Warnings
Black Box Warnings
Estrogen and progestin combinations increase risk of thrombotic or thromboembolic disorders including pulmonary embolism (PE), deep vein thrombosis (DVT), stroke, or myocardial infarction (MI), especially in women at increased risk for these events
Contraindicated in women with current or history of thrombotic or thromboembolic disorders and in women at increased risk for these events, including women aged ≥35 yr who smoke and women with uncontrolled hypertension
Contraindications
Pregnancy
Osteoporosis
Current or history of breast cancer or other hormonally sensitive malignancies, and with increased risk for hormonally sensitive malignancies
Hepatic impairment or disease
Undiagnosed abnormal uterine bleeding
Anaphylactic reaction, angioedema, or hypersensitivity any of the drug components
OATP1B1 inhibitors
High risk of arterial, venous thrombotic, or thromboembolic disorders
- Women aged ≥35 yr who smoke
- Current or history of DVT or pulmonary embolism
- Vascular disease (eg,, cerebrovascular disease, coronary artery disease, peripheral vascular disease)
- Thrombogenic valvular or thrombogenic rhythm diseases of the heart (eg, subacute bacterial endocarditis with valvular disease, atrial fibrillation)
- Inherited or acquired hypercoagulopathies
- Uncontrolled hypertension
- Headaches with focal neurological symptoms or migraine with aura if aged ≥35 yr
Cautions
Estrogens and progestins increase risk of thromboembolism; discontinue if thrombotic event occurs or suspected; discontinue immediately if there is sudden unexplained partial or complete vision loss, proptosis, diplopia, papilledema, or retinal vascular lesions, and evaluate for retinal vein thrombosis; contraindicated with known thrombotic conditions or individuals at high risk
May decrease BMD in some patients; BMD loss is greater with increasing duration of use; contraindicated with known osteoporosis
Use of estrogen alone and estrogen plus progestin associated with increased risk for abnormal mammograms requiring further evaluation; surveillance measures, such as breast examinations and regular mammography, are recommended; discontinue drug if hormonally sensitive malignancy is diagnosed; contraindicated with current or history of breast cancer or other hormonally sensitive cancer
Suicidal ideation and behavior, including a completed suicide, occurred in women treated with lower doses of elagolix in clinical trials conducted for a different indication; promptly evaluate patients with depressive symptoms to determine whether the risks of continued therapy outweigh the benefits
Monitor transaminases; instruct patients to seek medical attention for signs of liver injury (eg, jaundice); contraindicated with hepatic impairment or disease
Monitor BP; for women with well-controlled hypertension, continue to monitor BP and stop drug if BP increases significantly; contraindicated with uncontrolled hypertension
Small increased risk of developing gallbladder disease; assess risk with history of cholestatic jaundice; discontinue if jaundice occurs
Alopecia reported; unknown if hair loss is reversible
Contains FD&C yellow no. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in susceptible persons; although incidence is low, it is frequently seen in patients who also have aspirin hypersensitivity
Menstrual bleeding pattern and reduced ability to recognize pregnancy
- May delay ability to recognize pregnancy because it may reduce intensity, duration, and amount of menstrual bleeding
- Perform pregnancy testing if pregnancy is suspected, and discontinue drug if pregnancy confirmed
- Effect of hormonal contraceptives on the efficacy of Oriahnn is unknown
- Advise women to use nonhormonal contraception during treatment and for 1 week after discontinuing
Effects on carbohydrate and lipid metabolism
- May decrease glucose tolerance and result in increased glucose levels; more frequent monitoring with prediabetes and diabetes may be needed
- Estrogen therapy may be associated with increased plasma triglycerides leading to pancreatitis; elagolix is associated with increased total cholesterol, LDL-C, HDL-C, and serum triglycerides
Laboratory results
- Estrogens and progestins may raise serum concentrations of binding proteins (eg, thyroid-binding globulin, corticosteroid-binding globulin), which may reduce free thyroid or corticosteroid hormone levels
- Patients with hypothyroidism or hypoadrenalism may require higher doses of thyroid hormone or cortisol replacement therapy, respectively
- May also affect levels of sex hormone-binding globulin, coagulation factors, lipids, and glucose
Drug interaction overview
-
CYP3A substrates
- Elagolix is a weak-to-moderate inducer of CYP3A
- Coadministration may decrease plasma concentrations of drugs that are CYP3A substrates
-
CYP2C19 substrates
- Elagolix is a weak inhibitor of CYP2C19
- Coadministration may increase plasma concentrations of drugs that are CYP2C19 substrates
-
P-gp substrates
- Elagolix inhibits efflux transporter P-glycoprotein (P-gp)
- Coadministration may increase plasma concentrations of drugs that are P-gp substrates
-
Effect of other drugs on Oriahnn
- Elagolix is a substrate of CYP3A, P-gp, and OATP1B1
- Estradiol and norethindrone acetate are metabolized partially by CYP3A
- Strong CYP3A inducers may decrease elagolix, estradiol, and norethindrone plasma concentrations and may result in decreased therapeutic effects
- Strong CYP3A inhibitors are not recommended; coadministration may increase elagolix, estradiol, and norethindrone plasma concentrations and risk of adverse effects
- OATP1B1 inhibitors (eg, rifampin) that are known or expected to significantly increase elagolix plasma concentrations and are contraindicated
Pregnancy & Lactation
Pregnancy
Contraindicated in pregnant women
Exposure early in pregnancy may increase risk of early pregnancy loss
Discontinue drug if pregnancy occurs during treatment
Pregnancy registry monitoring outcomes in women who become pregnant during treatment: 1-833-782-7241
Animal studies
- When pregnant rats and rabbits were dosed with elagolix during organogenesis, postimplantation loss was observed in pregnant rats at doses 12 times the maximum recommended human dose (MRHD); spontaneous abortion and total litter loss were observed in rabbits at doses 4 and 7 times the MRHD
Contraception
- Advise women to use nonhormonal contraception during treatment and for 1 week after discontinuing
Lactation
Data are not available on the presence of elagolix in human milk, the effects on breastfed infants, or on milk production
When estrogen and progestins are administered to lactating women, these compounds and/or their metabolites are detected in human milk and can reduce milk production in breastfeeding females; this reduction can occur at any time, but is less likely to occur once breastfeeding is well established
Advise nursing females to use nonhormonal contraception until breastfeeding discontinued
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.Pharmacology
Mechanism of Action
Elagolix
- Gonadotropin-releasing hormone antagonists (GnRH); inhibits endogenous GnRH signaling by binding competitively to GnRH receptors in the pituitary gland
- Results in dose-dependent suppression of luteinizing hormone and follicle-stimulating hormone, leading to decreased blood concentrations of the ovarian sex hormones estradiol and progesterone and reduces bleeding associated with uterine fibroids
Estradiol
- Acts by binding to nuclear receptors that are expressed in estrogen-responsive tissues
- Addition of exogenous estradiol may reduce the increase in bone resorption and resultant bone loss that can occur due to a decrease in circulating estrogen from elagolix alone
Norethindrone acetate
- Acts by binding to nuclear receptors that are expressed in progesterone-responsive tissues
- May protect uterus from potential adverse endometrial effects of unopposed estrogen
Absorption
Peak plasma time
- Elagolix: 1.5 hr
- Estradiol: 2 hr
- Norethindrone: 1 hr
Peak plasma concentration
- Elagolix: 1200 ng/mL
- Estradiol: 0.06 ng/mL
- Norethindrone: 6.1 ng/mL
AUC
- Elagolix: 2826 ng⋅hr/mL
- Estradiol: 0.86 ng⋅hr/mL
- Norethindrone: 23.8 ng⋅hr/mL
Distribution
Protein bound
- Elagolix: 80%
- Estradiol: 98%
- Norethindrone: 97%
Metabolism
Elagolix: CYP3A (major); minor pathways include CYP2D6, CYP2C8, and UGTs
Estradiol: CYP3A (partial); other pathways include sulfation and glucuronidation
Norethindrone: CYP3A (partial)
Elimination
Excretion (elagolix): Urine (<3%); feces (90%)
Half-life
- Elagolix: 5.9 hr
- Estradiol: 14.5 hr
- Norethindrone: 9.2 hr
Administration
Oral Administration
Take the morning and evening capsules at approximately the same time each day, with or without food
Missed dose
- Within 4 hr of missed dose: Take missed dose and then the next dose at the usual time
- >4 hr past missed dose: Do not to take missed dose; take next dose at the usual time
- Take only 1 morning capsule and 1 evening capsule per day
Storage
Store at 20-25ºC (68-77ºF), excursions permitted to 15-30ºC (59-86ºF)
Dispose of unused medication via a take-back program (or local pharmacy) if available
Otherwise, do not flush down toilet; follow FDA instructions for disposing medication in household trash
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Patient Handout
Formulary
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