Oriahnn

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 8/13/2021
Oriahnn Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Oriahnn?

Oriahnn (elagolix, estradiol, and norethindrone acetate capsules; elagolix capsules) is a combination of a gonadotropin-releasing hormone (GnRH) receptor antagonist, an estrogen, and a progestin used to manage heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women. Use of Oriahnn should be limited to 24 months due to the risk of continued bone loss, which may not be reversible.

What Are Side Effects of Oriahnn?

Side effects of Oriahnn include:

  • hot flushes,
  • headache,
  • fatigue, and
  • bleeding between periods

Dosage for Oriahnn

The dose of Oriahnn is one capsule (elagolix 300 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) in the morning and one capsule (elagolix 300 mg) in the evening for up to 24 months.

Oriahnn In Children

Safety and effectiveness of Oriahnn in pediatric patients have not been established.

What Drugs, Substances, or Supplements Interact with Oriahnn?

Oriahnn may interact with other medicines such as:

  • substrates of CYP3A,
  • strong CYP3A inducers and inhibitors,
  • substrates of CYP2C19,
  • substrates of P-gp,
  • OATP1B1 inhibitors,
  • digoxin,
  • midazolam,
  • rosuvastatin,
  • rifampin, and
  • omeprazole

Tell your doctor all medications and supplements you use.

Oriahnn During Pregnancy and Breastfeeding

Oriahnn is not recommended for use during pregnancy; it may increase the risk of pregnancy loss. There is a pregnancy registry that monitors outcomes in women who become pregnant while treated with Oriahnn. Pregnant patients are encouraged to enroll by calling 1-833-782-7241. Women are advised to use non-hormonal contraception during treatment and for one week after discontinuing Oriahnn. It is unknown if Oriahnn passes into breast milk. Nursing women are advised to use non-hormonal contraception until breastfeeding is discontinued. Consult your doctor before breastfeeding.

Additional Information

Our Oriahnn (elagolix, estradiol, and norethindrone acetate capsules; elagolix capsules), Co-Packaged for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

What is pelvic inflammatory disease (PID)? See Answer
Oriahnn Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Oriahnn may increase your risk of heart attack, stroke, or blood clot. Stop using this medicine and seek medical attention right away if you have:

  • chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;
  • swelling, pain, warmth, or redness in an arm or leg;
  • sudden shortness of breath;
  • sudden numbness, weakness, or severe headache;
  • vision problems, bulging eyes; or
  • trouble speaking.

Call your doctor at once if you have:

  • high blood sugar--increased thirst, increased urination, dry mouth, fruity breath odor;
  • any new or worsening mood symptoms--mood or behavior changes, depression, anxiety, thoughts about suicide or hurting yourself; or
  • liver or gallbladder problems--loss of appetite, nausea, vomiting, stomach pain (upper right side), tiredness, bruising, swelling, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

This medicine may cause hair loss that may be permanent.

Common side effects may include:

  • hot flashes;
  • feeling tired;
  • hair loss (may be permanent);
  • headache; or
  • irregular menstrual periods.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Oriahnn (Elagolix, Estradiol, and norethindrone acetate capsules; elagolix capsules)

SLIDESHOW

Pelvic Pain: What's Causing Your Pelvic Pain? See Slideshow
Oriahnn Professional Information

SIDE EFFECTS

The following serious adverse reactions are discussed elsewhere in labeling:

  • Thromboembolic Disorders and Vascular Events [see WARNINGS AND PRECAUTIONS]
  • Bone Loss [see WARNINGS AND PRECAUTIONS]
  • Suicidal Ideation, Suicidal Behavior, and Exacerbation of Mood Disorders [see WARNINGS AND PRECAUTIONS]
  • Hepatic Transaminase Elevations [see WARNINGS AND PRECAUTIONS]
  • Elevated Blood Pressure [see WARNINGS AND PRECAUTIONS]
  • Effects on Carbohydrate and Lipid Metabolism [see WARNINGS AND PRECAUTIONS]
  • Alopecia [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

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, placebocontrolled 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]. 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].

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.

Table 1. Adverse Reactions that Occurred in at Least 5% of Women with Uterine Fibroids Who Received ORIAHNN in Studies UF-1 and UF-2 and at a Greater Incidence Than Placebo

Adverse ReactionORIAHNN
N=395
Placebo
N=196
Hot flush22%9%
Headache9%7%
Fatigue6%4%
Metrorrhagia5%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 <5% in the ORIAHNN group and greater incidence than the placebo group included: libido decreased, arthralgia, hypertension, alopecia, mood swings, influenza, abdominal distension, upper respiratory tract infection, menorrhagia, vomiting, and weight increased.

Thromboembolic And Vascular Events

In the Studies UF-1, UF-2, and UF-3, two (0.4%) thrombotic events occurred in 453 ORIAHNNtreated patients (thrombosis in the calf and pulmonary embolism) [see WARNINGS AND PRECAUTIONS]. One obese woman developed thrombosis in the left calf after 30 days of treatment with ORIAHNN. Another woman developed a pulmonary embolism after taking ORIAHNN for approximately 8 months.

Bone Loss

The effect of ORIAHNN on BMD was assessed by dual-energy X-ray absorptiometry (DXA).

In Studies UF-1 and UF-2, there was a greater decrease in BMD in women treated with ORIAHNN for 6 months compared to women treated with placebo. In Study UF-3, continued bone loss was observed in some women who received ORIAHNN for 12 consecutive months. The mean percent change from baseline in lumbar spine BMD at Month 6 (Studies UF-1 and UF-2) and Month 12 (Study UF-3) is presented in Table 2.

Table 2. Mean Percent Change (On-Treatment) from Baseline in Lumbar Spine BMD in Women with Fibroids at Month 6 in Studies UF-1 and UF-2 and Month 12 in Study UF-3

Studies UF-1 and UF-2
Treatment Month 6
Study UF-3
Treatment Month 12
PlaceboORIAHNNORIAHNN
Number of Subjects150305175
Percent Change from Baseline-0.1-0.7-1.5
Treatment Difference, %
(95% CI)
-0.6
(-1.0, -0.1)
CI: Confidence interval

Following 12 months of ORIAHNN treatment in Study UF-3, a decline in lumbar spine BMD of >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)

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) - Illustration

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.

  • ALT elevations to at least 3 times the upper limit of normal (ULN) occurred in 1.1% (4/379) of ORIAHNN-treated women and no placebo-treated women. Peak elevation of ALT almost 8 times the ULN was reported in 1 ORIAHNN-treated woman.
  • AST elevations to at least 3 times the ULN occurred in 5/379 (1.3%) in ORIAHNNtreated women and no placebo-treated women. Peak elevation of AST 6 times the ULN was reported in 1 ORIAHNN-treated woman.
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 antihypertensives 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 (<130 mg/dL) at baseline, 1/313 (0.3%) ORIAHNN-treated woman shifted to Grade 3 (≥ 190 mg/dL) compared to no placebo-treated woman. Of those with Grade 1 LDL-C (130 to <160 mg/dL) at baseline, 9/54 (16.7%) ORIAHNN-treated women shifted to Grade 3 compared to no placebo-treated woman. Of those with Grade 2 LDL-C (160 to <190 mg/dL) at baseline, 7/10 (70%) ORIAHNN-treated women shifted to Grade 3 compared to 1/5 (20%) placebo-treated woman.

Alopecia

In Phase 3 placebo-controlled clinical trials (Studies UF-1 and UF-2), 3.5% (14/395) of ORIAHNN-treated women experienced alopecia, hair loss, or hair thinning compared to 1.0% (2/196) of placebo-treated women. No specific pattern in hair loss was observed. In almost onethird (4/14) of affected ORIAHNN-treated women, alopecia was a reason for study drug discontinuation; no placebo-treated women discontinued because of alopecia. In ORIAHNNtreated women, 79% of the cases were mild and 21% were moderate in severity. Hair loss was ongoing at the end of the study for 4 out of 14 women (29%). Of these 4 women, one discontinued treatment due to hair loss, two had ongoing hair loss 12 months after discontinuing ORIAHNN, and one was lost to follow-up. In the remaining 10 women (71%), hair loss either resolved while on treatment or resolved within 24 days to approximately 9 months after discontinuing ORIAHNN.

Resumption Of Menses After Discontinuation

After six months of ORIAHNN treatment, resumption of menses was reported by 39%, 68%, and 73% of women within 1, 2, and 6 months, respectively, in Study UF-1 and 39%, 85%, and 92% within 1, 2, and 6 months, respectively, in Study UF-2.

After 12 months of therapy with ORIAHNN (Study UF-1 or Study UF-2 then Study UF-3), resumption of menses was reported by 43%, 82%, and 90% of women within 1, 2, and 6 months after stopping treatment, respectively.

Whether those who did not resume having menses transitioned to a peri-postmenopausal status is unknown.

Read the entire FDA prescribing information for Oriahnn (Elagolix, Estradiol, and norethindrone acetate capsules; elagolix capsules)

© Oriahnn Patient Information is supplied by Cerner Multum, Inc. and Oriahnn Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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