Oriahnn is indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women.
Limitation of Use:
Use of Oriahnn should be limited to 24 months due to the risk of continued bone loss, which may not be reversible [see Dosage and Administration (2.1) and Warnings and Precautions (5.2)].
Oriahnn Dosage and Administration Important Dosing InformationInstruct the patient to take the missed dose of Oriahnn within 4 hours of the time that it was supposed to be taken and then the next dose at the usual time. If more than 4 hours have passed since a capsule is usually taken, instruct the patient not to takethe missed dose and take the next dose at the usual time. Take only one morning capsule and one evening capsule per day.
Dosage Forms and StrengthsOriahnn consists of two capsules:
Oriahnn is contraindicated in women:
Oriahnn is contraindicated in women with current or history of thrombotic or thromboembolic disorders and in women at increased risk for these events [see Contraindications (4)]. In the Phase 3 clinical trials (Studies UF-1, UF-2, and UF-3), two thrombotic events occurred in 453 Oriahnn-treated women (thrombosis in the calf and pulmonary embolism) [see Adverse Reactions (6.1) and Clinical Studies (14)]. Estrogen and progestin combinations, including the estradiol/norethindrone acetate component of Oriahnn, increase the risk of thrombotic or thromboembolic disorders, including pulmonary embolism, deep vein thrombosis, stroke, and myocardial infarction, especially in women at high risk for these events. In general, the risk is greatest among women over 35 years of age who smoke, and women with uncontrolled hypertension, dyslipidemia, vascular disease, or obesity.
Discontinue Oriahnn if an arterial or venous thrombotic, cardiovascular, or cerebrovascular event occurs or is suspected. If feasible, discontinue Oriahnn at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.
Stop Oriahnn immediately if there is sudden unexplained partial or complete loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis as these have been reported in patients receiving estrogens and progestins.
Bone LossOriahnn is contraindicated in women with known osteoporosis [see Contraindications (4)]. Oriahnn may cause a decrease in bone mineral density (BMD) in some patients. BMD loss is greater with increasing duration of use and may not be completely reversible after stopping treatment [see Adverse Reactions (6.1)].
In the Phase 3 clinical trials (Studies UF-1, UF-2, and UF-3) [see Clinical Studies (14)], seven out of 453 (1.5%) Oriahnn-treated women experienced fractures, including one (0.2%) with a fragility fracture, compared to one out of 196 (0.5%) placebo-treated women (patient had a non-fragility fracture). Five of the seven Oriahnn-treated women reported these fractures in the post-treatment follow-up period. The impact of BMD decreases on long-term bone health and future fracture risk in premenopausal women is unknown.
Consider the benefits and risks of Oriahnn treatment in patients with a history of a low-trauma fracture or other risk factors for osteoporosis or bone loss, including taking medications that may decrease BMD (e.g., systemic or chronic inhaled corticosteroids, anticonvulsants, or proton pump inhibitors).
Assessment of BMD by dual-energy X-ray absorptiometry (DXA) is recommended at baseline and periodically thereafter. Consider discontinuing Oriahnn if the risk associated with bone loss exceeds the potential benefit of treatment. Limit the duration of use to 24 months to reduce the extent of bone loss [see Indications and Usage (1) and Dosage and Administration (2.1)].
Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation for patients with inadequate dietary intake may be beneficial.
Hormonally-Sensitive MalignanciesOriahnn is contraindicated in women with current or history of breast cancer and in women at increased risk for hormonally-sensitive malignancies, such as those with mutations in BRCA genes [see Contraindications (4)].
In the Phase 3 clinical trials (Studies UF-1, UF-2, and UF-3), two (0.4%) cases of breast cancer in 453 Oriahnn-treated women were observed. No breast cancer cases were seen in placebo-treated women [see Adverse Reactions (6.1)].
The use of estrogen alone and estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation. Surveillance measures, such as breast examinations and regular mammography, are recommended. Discontinue Oriahnn if a hormonally-sensitive malignancy is diagnosed.
Suicidal Ideation, Suicidal Behavior, and Exacerbation of Mood DisordersIn Phase 3 placebo-controlled clinical trials (Studies UF-1 and UF-2), Oriahnn-treated women had a higher incidence (3%) of depression, depressed mood, and/or tearfulness compared to placebo-treated women (1%) [see Adverse Reactions (6.1)]. 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. 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 Oriahnn if such events occur.
Hepatic Impairment and Transaminase ElevationsContraindication in Patients with Hepatic Impairment
Oriahnn is contraindicated in women with known hepatic impairment or disease [see Contraindications (4), Use in Specific Populations (8.7), and Clinical Pharmacology (12.3)].
Transaminase Elevations
In Phase 3 placebo-controlled clinical trials (Studies UF-1 and UF-2), elevations (> 3 times the upper limit of the reference range) in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) occurred in 1.1% (4/379) and 1.3% (5/379) of Oriahnn-treated patients, respectively, compared to no elevations in placebo. Transaminases peaked at 8 times the upper limit for ALT and 6 times the upper limit for AST. No pattern in time to onset of these liver transaminase elevations was identified. Transaminase levels returned to baseline within 4 months after peak values in these patients.
Instruct patients to promptly seek medical attention in case of symptoms or signs that may reflect liver injury, such as jaundice [see Adverse Reactions (6.1)].
Elevated Blood PressureOriahnn is contraindicated in women with uncontrolled hypertension [see Contraindications (4)]. In Studies UF-1 and UF-2, a maximum mean increase in systolic blood pressure of 5.1 mmHg [95% confidence interval (CI) 2.68, 7.59] occurred at Month 5, and a maximum mean increase in diastolic blood pressure of 2.1 mmHg (95% CI 0.43, 3.84) occurred at Month 4 in Oriahnn-treated women, as compared to placebo-treated women [see Adverse Reactions (6.1)].
For women with well-controlled hypertension, continue to monitor blood pressure and stop Oriahnn if blood pressure rises significantly. Monitor blood pressure in normotensive women treated with Oriahnn.
Gallbladder Disease or History of Cholestatic JaundiceStudies among estrogen users suggest a small increased relative risk of developing gallbladder disease. For women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, assess the risk-benefit of continuing therapy. Discontinue Oriahnn if jaundice occurs.
Change in Menstrual Bleeding Pattern and Reduced Ability to Recognize PregnancyOriahnn may delay the ability to recognize the occurrence of a pregnancy because it may reduce the intensity, duration, and amount of menstrual bleeding [see Adverse Reactions (6.1)]. Perform pregnancy testing if pregnancy is suspected, and discontinue Oriahnn if pregnancy is confirmed [see Use in Specific Populations (8.1, 8.3)].
The effect of hormonal contraceptives on the efficacy of Oriahnn is unknown. Advise women to use non-hormonal contraception during treatment and for one week after discontinuing Oriahnn [see Use in Specific Populations (8.1, 8.3)].
Effects on Carbohydrate and Lipid MetabolismOriahnn may decrease glucose tolerance and result in increased glucose levels. More frequent monitoring in Oriahnn-treated women with prediabetes and diabetes may be needed.
In women with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis. Use of elagolix is associated with increases in total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and serum triglycerides. Monitor lipid levels and consider discontinuing Oriahnn if hypercholesterolemia or hypertriglyceridemia worsens [see Adverse Reactions (6.1)].
AlopeciaIn Phase 3 clinical trials (Studies UF-1 and UF-2), more women experienced alopecia, hair loss, and hair thinning with Oriahnn (3.5%) compared to placebo (1.0%). In almost one-third (4/14) of affected Oriahnn-treated women, alopecia was a reason for discontinuing treatment. No specific pattern was described. In the majority of affected women, hair loss was continuing when Oriahnn was stopped. Whether the hair loss is reversible is unknown. Consider discontinuing Oriahnn if hair loss becomes a concern [see Adverse Reactions (6.1)].
Effect on Other Laboratory ResultsThe use of estrogen and progestin combinations may raise serum concentrations of binding proteins (e.g., thyroid-binding globulin, corticosteroid-binding globulin), which may reduce the free thyroid or corticosteroid hormone levels. Patients with hypothyroidism and hypoadrenalism may require higher doses of thyroid hormone or cortisol replacement therapy, respectively.
The use of estrogen and progestin may also affect the levels of sex hormone-binding globulin, coagulation factors, lipids, and glucose [see Pharmacodynamics (12.2)].
Risk of Allergic Reactions Due to the Inactive Ingredient (FD&C Yellow No. 5)Oriahnn contains FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.
Adverse ReactionsThe following serious adverse reactions are discussed elsewhere in labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety of Oriahnn was evaluated in two 6-month, randomized, double-blind, placebo-controlled trials (Studies UF-1 and UF-2), in which 790 premenopausal women received at least 1 dose of Oriahnn (n=395), elagolix 300 mg twice daily (n=199), or placebo (n=196) [see Clinical Studies (14)]. Women who completed 6-month treatment in either Study UF-1 or Study UF-2 and met eligibility criteria (n=433) entered a 6-month extension study (Study UF-3), receiving either Oriahnn (n=276) or elagolix 300 mg twice daily (n=157). Elagolix 300 mg twice daily is not an approved dosage but was included as a reference arm. A total of 341women received Oriahnn for 6 months and 182 women received Oriahnn for 12 months.
Serious Adverse Events
Serious adverse events were reported in three (0.8%) Oriahnn-treated women in Studies UF-1 and UF-2. Two women had heavy menstrual bleeding and required blood transfusion due to anemia (0.5%) and one woman with history of bariatric surgery had a laparoscopic cholecystectomy due to cholelithiasis.
In Study UF-3, two women were diagnosed with breast cancer. One woman had completed 6 months of treatment with Oriahnn in Study UF-1 and received 34 additional days of Oriahnn in Study UF-3 when diagnosed. The second woman had received placebo in Study UF-2 and completed 6 months of Oriahnn in Study UF-3 when diagnosed [see Warnings and Precautions (5.3)].
Adverse Reactions Leading to Study Discontinuation
In Studies UF-1 and UF-2, the discontinuation rate due to adverse reactions was 10% among Oriahnn-treated women and 7% among placebo-treated women. The most common adverse reactions leading to study drug discontinuation in the Oriahnn group were nausea (1%), headache (1%), alopecia (1%), metrorrhagia (1%), menorrhagia (1%), and hot flush (1%). One event each of the following adverse reactions led to study drug discontinuation: affect lability, angina pectoris, depression, hepatic enzyme increased, homicidal ideation, hypertension, irritability, thrombosis.
In women who received Oriahnn in Studies UF-1 or UF-2 and then in Study UF-3, 4% discontinued treatment due to adverse reactions. Three women discontinued due to serious adverse events (one each for breast cancer, menorrhagia with pelvic pain, and hysterectomy).
Common Adverse Reactions
Adverse reactions reported in ≥5% of Oriahnn-treated women in Studies UF-1 and UF-2 and at a greater frequency than placebo-treated women are presented in Table 1.
| Adverse Reaction | Oriahnn N=395 | Placebo N=196 |
| Hot flush | 22% | 9% |
| Headache | 9% | 7% |
| Fatigue | 6% | 4% |
| Metrorrhagia | 5% | 1% |
The most commonly reported adverse reactions in the blinded extension trial (Study UF-3) were consistent with those in the placebo-controlled trials.
Less Common Adverse Reactions
In Studies UF-1 and UF-2, adverse reactions reported in ≥3% and 3% was seen in 27% (48/175) of women and a decline of ≥8% was seen in 1.7% (3/175) of women.
To assess for recovery, the change in BMD over time was analyzed for women who received continuous Oriahnn treatment for up to 12 months and were then followed after cessation of therapy for an additional 12 months in Study UF-3 (Figure 1). The LS mean percent change from baseline in BMD 12 months after cessation of therapy was -0.72 (95% CI -1.2, -0.2), -0.59 (-1.0, -0.2), and -0.95 (-1.6, -0.3) at the lumbar spine, total hip, and femoral neck, respectively. Twelve months after cessation of Oriahnn, continued bone loss was observed at the lumbar spine, total hip, and femoral neck in 24%, 32%, and 40% of women, respectively. Partial recovery was observed in 46%, 33%, and 38% and full recovery was observed in 30%, 35%, and 22% of women at these same sites. The time to maximum recovery in women who partially recovered is unknown.
Figure 1. Mean Percent Change From Baseline in Lumbar Spine BMD in Women Who Received 12 Months of Oriahnn (On-Treatment) and 12 Months of Follow Up (Off Treatment)
Suicidal Ideation, Suicidal Behavior, and Exacerbation of Mood Disorders
In the placebo-controlled trials (Studies UF-1 and UF-2), Oriahnn was associated with adverse mood changes. Depression, depressed mood, and/or tearfulness were reported in 3% of Oriahnn-treated women compared to 1% of placebo-treated women. One woman treated with lower dose elagolix alone for another disease completed suicide 2 days after elagolix discontinuation.
Hepatic Transaminase Elevations
In Studies UF-1 and UF-2, elevations of serum ALT and AST with no concurrent elevations of bilirubin were reported.
Blood Pressure Elevations
There were more Oriahnn-treated women with systolic blood pressure ≥ 160 mmHg (7.1%) and diastolic blood pressure ≥ 100 mmHg (11.3%) compared to placebo-treated women (3.7% and 6.3%, respectively). The incidence of hypertensive adverse reactions was 3.8% in Oriahnn-treated women and 3.1% placebo-treated women. One Oriahnn-treated woman in Study UF-1, with no prior history but with elevated cholesterol levels, had severe hypertension (BP 204/112) and chest pain. ECG was negative. Her hypertension was controlled with anti-hypertensives and she completed Study UF-3.
Changes in Lipid Parameters
Increases in total cholesterol, low-density lipoprotein cholesterol (LDL-C), serum triglycerides, and apolipoprotein B were noted during Oriahnn treatment in Studies UF-1 and UF-2.
Of the women with Grade 0 LDL-C ( 2 g/dL in Hgb at Month 6
Oriahnn consists of two capsules: one to be taken in the morning (AM) and one to be taken in the evening (PM).
Oriahnn is packaged in weekly blister packs. Each blister pack contains seven AM capsules and seven PM capsules. Four blisters are packaged into a carton (NDC 0074-1017-56).
Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15˚C to 30˚C (59˚F to 86˚F). [See USP Controlled Room Temperature].
Dispose unused medication via a take-back option if available. Otherwise, follow FDA instructions for disposing medication in the household trash, www.fda.gov/drugdisposal. Do NOT flush down the toilet.
Patient Counseling InformationAdvise the patient to read the FDA-approved patient labeling (Medication Guide).
Thromboembolic Disorders and Vascular Events
Advise patients that use of estrogen and progestin combinations may increase the risk of thromboembolic disorders and vascular events, especially in women at high risk for these events [see Boxed Warning, Contraindications (4), Warnings and Precautions (5.1), and Adverse Reactions (6.1)].
Bone Loss
Advise patients about the risk of bone loss. Advise patients that supplementary calcium and vitamin D may be beneficial if dietary intake of calcium and vitamin D is not adequate. Advise patients that oral iron supplement should not be taken at the same time as calcium and vitamin D [see Warnings and Precautions (5.2) and Adverse Reactions (6.1)].
Suicidal Ideation and Exacerbation of Mood Disorders
Advise patients that suicidal ideation and exacerbation of mood disorders may occur with Oriahnn use. Instruct patients with new onset or worsening depression, anxiety, or other mood changes to promptly seek medical attention [see Warnings and Precautions (5.3) and Adverse Reactions (6.1)].
Liver Injury
Advise patients to promptly seek medical attention in case of signs or symptoms that may reflect liver injury, such as jaundice [see Warnings and Precautions (5.5) and Adverse Reactions (6.1)].
Change in Menstrual Bleeding Pattern
Advise patients that Oriahnn may delay the recognition of pregnancy because it may reduce the duration and amount of menstrual bleeding. Advise patients to use effective non-hormonal contraception while taking Oriahnn and to discontinue Oriahnn if pregnancy is diagnosed. Advise pregnant patients that there is a pregnancy registry that monitors pregnancy outcomes in women exposed to Oriahnn during pregnancy [see Warnings and Precautions (5.8) and Use in Specific Populations (8.1, 8.3)].
Alopecia
Advise patients that alopecia, hair loss, and hair thinning in no specific pattern, may occur with Oriahnn use. Advise patients that hair loss and hair thinning may not resolve completely after stopping Oriahnn. Advise patients to contact their healthcare provider if they have concerns about changes to their hair [see Warnings and Precautions (5.10) and Adverse Reactions (6.1)].
Drug Interactions
Advise patients to inform their healthcare providers of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products. Advise patients to avoid grapefruit juice while taking Oriahnn [see Drug Interactions (7)].
Oriahnn Missed Dose Instructions
Instruct patients about what to do in the event a dose is missed. See “If you miss a dose of Oriahnn” section in FDA-approved Medication Guide.
Oriahnn Disposal Instructions
Instruct patients to dispose of unused medication via a take-back option if available or to otherwise follow FDA instructions for disposing of medication in the household trash, www.fda.gov/drugdisposal, and not to flush down the toilet.
Manufactured by AbbVie Inc. North Chicago, IL 60064
Oriahnn is a trademark of AbbVie Inc.
© 2020 AbbVie Inc. All rights reserved.
03-B969
| MEDICATION GUIDE Oriahnn (or-ee-ahn) (elagolix, estradiol, and norethindrone acetate capsules; elagolix capsules) co-packaged for oral use | |
| What is the most important information I should know about Oriahnn? Oriahnn may cause serious side effects, including:
| |
| What is Oriahnn? Oriahnn is a prescription medicine used to control heavy menstrual bleeding in premenopausal women (before “change of life” or menopause) with uterine fibroids. It is not known if Oriahnn is safe and effective in children under 18 years of age. | |
Do not take Oriahnn if you:
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Before you take Oriahnn, tell your healthcare provider about all of your medical conditions, including if you:
Women on thyroid or cortisol replacement therapy may need increased doses of the hormone. Know the medicines you take. Keep a list of your medicines with you to show to your healthcare provider and pharmacist when you get a new medicine. | |
How should I take Oriahnn?
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What should I avoid while taking Oriahnn?
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| What are the possible side effects of Oriahnn? Oriahnn may cause serious side effects including:
These are not all the possible side effects of Oriahnn. For more information, ask your healthcare provider or pharmacist. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. | |
How should I store Oriahnn?
| |
| General information about the safe and effective use of Oriahnn. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Oriahnn for a condition for which it was not prescribed. Do not give Oriahnn to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Oriahnn that is written for health professionals. | |
| What are the ingredients in Oriahnn? Yellow/White AM Capsule: Active ingredient: elagolix, estradiol, norethindrone acetate. Inactive ingredients: anhydrous sodium carbonate, polyethylene glycol 3350, crospovidone, colloidal silicon dioxide, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, purified water, lactose monohydrate, starch (corn), copovidone, talc, hypromellose, triacetin, and a gelatin capsule shell. The capsule shell contains the following ingredients: FD&C Red #40, FD&C Yellow #5, FD&C Yellow #6, titanium dioxide, gelatin, and printing ink (shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, strong ammonia solution, black iron oxide, potassium hydroxide, and purified water). Light Blue/White PM Capsule: Active ingredient: elagolix. Inactive ingredients: anhydrous sodium carbonate, polyethylene glycol 3350, crospovidone, colloidal silicon dioxide, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talc, purified water, and a gelatin capsule shell. The capsule shell contains the following ingredients: FD&C Blue #2, FDA/E172 yellow iron oxide, titanium dioxide, gelatin, and printing ink (shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, strong ammonia solution, black iron oxide, potassium hydroxide, and purified water). | |
| Manufactured by AbbVie Inc. North Chicago, IL 60064 Oriahnn is a trademark of AbbVie Inc. For more information, go to www.Oriahnn.com or call 1-844-674-2466. |
This Medication Guide has been approved by the Issued: May, 2020
U.S. Food and Drug Administration.
03-B969
NDC 0074-1017-56
Rx only
56 CAPSULES
FOR 28 DAYS IN 4 WEEKLY BLISTER PACKS
Oriahnn™
elagolix, estadiol and norethindrone acetate capsules and elagolix capsules 300 mg/1 mg/0.5 mg and 300 mg
Co-Packaged for Oral Use
300 mg / 1 mg / 0.5 mg 300mg
*Elagolix 300 mg (equivalent to 310 mg of elagolix sodium)
Contains FD&C Yellow No. 5 (Tartrazine) as a color additive
Each weekly blister pack contains 7 capsules to be taken in the morning
Each capsule contains elagolix* (300 mg), estradiol (1 mg) and norethindrone acetate (0.5 mg)
Each weekly blister pack contains 7 capsules to be taken in the evening
Each capsule contains elagolix* (300 mg)
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| Labeler - AbbVie Inc. (078458370) |
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