Elagolix-Estradiol-Norethindrone Acetate

Elagolix-Estradiol-Norethindrone Acetate is a combination medication indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women.

• Elagolix-Estradiol-Norethindrone Acetate is available under the following different brand names: Oriahnn.

Common side effects of Elagolix-Estradiol-Norethindrone Acetate include:

• hot flushes
• headache
• fatigue
• bleeding between periods

Serious side effects of Elagolix-Estradiol-Norethindrone Acetate include:

• suicidal thoughts, suicidal behavior, and worsening of mood
• lumps in the breast
• mental/mood changes (such as new or worsening depression, anxiety, unusual changes in behavior) 
• signs of liver damage (such as nausea/vomiting that doesn't stop, loss of appetite, stomach/abdominal pain, yellowing eyes/skin, dark urine)
• unusual changes in vaginal bleeding (such as continuous spotting, sudden heavy bleeding)
• symptoms of high blood sugar (such as increased thirst/urination)

Rare side effects of Elagolix-Estradiol-Norethindrone Acetate include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

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

• 300 mg/1 mg/0.5 mg

Elagolix capsule

• 300 mg

Uterine leiomyomas

Adult dosage

• Take one combination capsule (ie, elagolix 300 mg/estradiol 1 mg/norethindrone acetate 0.5 mg) orally in the morning, then
• Take one elagolix 300 mg capsule orally in the evening
• Duration of treatment: Not to exceed 24 months

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Elagolix-Estradiol-Norethindrone Acetate has severe interactions with the following drugs:
  • clotrimazole
  • cyclosporine
  • encorafenib
  • erythromycin base
  • erythromycin ethylsuccinate
  • erythromycin lactobionate
  • erythromycin stearate
  • fezolinetant
  • gemfibrozil
  • glecaprevir/pibrentasvir
  • lenvatinib
  • lonafarnib
  • mavacamten
  • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
  • ospemifene
  • pazopanib
• Elagolix-Estradiol-Norethindrone Acetate has serious interactions with at least 84 other drugs
• Elagolix-Estradiol-Norethindrone Acetate has moderate interactions with at least 545 other drugs
• Elagolix-Estradiol-Norethindrone Acetate has minor interactions with at least 23 other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

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 of any of the drug components
• OATP1B1 inhibitors
• High risk of arterial, venous thrombotic, or thromboembolic disorders
• Women aged 35 years and older who smoke
• Current or history of deep vein thrombosis 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 years and older

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Elagolix-Estradiol-Norethindrone Acetate?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Elagolix-Estradiol-Norethindrone Acetate?”

Cautions

• Estrogens and progestins increase the risk of thromboembolism; discontinue if a thrombotic event occurs or is 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 bone mineral density (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 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 (1eg, jaundice); contraindicated with hepatic impairment or disease
• Monitor BP; for women with well-controlled hypertension, continue to monitor BP and stop the drug if BP increases significantly; contraindicated with uncontrolled hypertension
• Small increased risk of developing gallbladder disease; assess risk with a 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 the ability to recognize pregnancy because it may reduce the intensity, duration, and amount of menstrual bleeding
• Perform pregnancy testing if pregnancy is suspected, and discontinue the drug if pregnancy confirmed
• The 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 of 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 and Lactation

• Contraindicated in pregnant women
• Exposure early in pregnancy may increase the risk of early pregnancy loss
• Discontinue drug if pregnancy occurs during treatment
• There is a pregnancy registry that monitors pregnancy outcomes in women exposed to therapy during pregnancy; healthcare providers are encouraged to register patients, or pregnant women may enroll themselves in the registry by calling 1-833-782-7241 or visiting https://www.bloompregnancyregistry.com
• Contraception
  • Advise women to use nonhormonal contraception during treatment and for 1 week after discontinuing
• Lactation
  • There is no information on the presence of this drug or its metabolites in human milk, its effects on breastfed children, or 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 women; this reduction can occur at any time but is less likely to occur once breastfeeding is well established
  • Advise nursing women to use nonhormonal contraception until breastfeeding discontinued
  • The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed child from the drug or the underlying maternal condition