Myfembree Vs. Orilissa: Drug Comparison

Myfembree^® is a combination medication containing relugolix, estradiol, and norethindrone acetate, used to manage heavy menstrual bleeding associated with uterine fibroids. It works by reducing estrogen and progesterone production, which helps shrink fibroids and decrease bleeding by modulating the hormonal balance. Its FDA-approved indication is for the treatment of heavy menstrual bleeding due to endometriosis in premenopausal women. Myfembree is available as an oral tablet, typically taken once daily. Common side effects include hot flashes, headaches, and mood changes, and it carries a boxed warning for the risk of bone loss with prolonged use, as well as an increased risk of clotting events like pulmonary embolism (PE), deep vein thrombosis (DVT), stroke, and heart attack.

Orilissa^® (elagolix) is a medication used to manage moderate to severe pain associated with endometriosis by reducing estrogen levels through its action as a gonadotropin-releasing hormone (GnRH) antagonist. It works by suppressing ovarian hormone production, which helps alleviate the symptoms of endometriosis-related pain. Orilissa is FDA approved for the treatment of endometriosis-related pain and is available in tablet form, typically taken once or twice daily depending on the dosage. Common side effects include hot flashes, headaches, and insomnia, while long-term use can lead to bone loss, so treatment is generally limited. Caution is advised for patients with a history of osteoporosis or liver disease, and Orilissa may interact with medications that affect liver enzymes, such as rifampin.

Relugolix: gonadotropin-releasing hormone (GnRH) receptor antagonist

Estradiol: estrogen

Norethindrone acetate: progestin

Gonadotropin-releasing hormone (GnRH) receptor antagonist

Myfembree (relugolix, estradiol, and norethindrone acetate) is indicated in premenopausal women for the:

• Management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids)

• Management of moderate to severe pain associated with endometriosis

Orilissa (elagolix) is indicated:

• For the management of moderate to severe pain associated with endometriosis

• Typically taken orally once daily

• Comes in 40 mg/1 mg/ 0.5 mg tablets

• Typically taken orally once or twice daily

• Comes in 150 mg and 200 mg tablets

In women with heavy menstrual bleeding associated with uterine fibroids, most common adverse reactions (incidence ≥3%) are:

• Hot flashes and night sweats

• Uterine bleeding

• Hair loss

• Decreased libido

In women with moderate to severe pain associated with endometriosis, most common adverse reactions (incidence ≥3%) are:

• Headache

• Hot flashes and night sweats

• Mood disorders

• Abnormal uterine bleeding

• Nausea

• Toothache

• Back pain

• Decreased sexual desire and arousal

• Joint pain

• Fatigue

• Dizziness

Most common adverse reactions (>5%) in clinical trials included:

• Hot flushes and night sweats

• Headache

• Nausea

• Insomnia

• Lack of menstruation

• Anxiety

• Joint pain

• Depression-related adverse reactions and mood changes

• High risk of arterial, venous thrombotic, or thromboembolic disorder

• Pregnancy

• Known osteoporosis

• Current or history of breast cancer or other hormone-sensitive malignancies

• Known hepatic impairment or disease

• Undiagnosed abnormal uterine bleeding

• Known hypersensitivity to components of Myfembree

• Drug interactions: oral P-gp inhibitors, combined P-gp and strong CYP3A inducers

• Pregnancy

• Known osteoporosis

• Severe liver impairment

• Organic anion transporting polypeptide (OATP) 1B1 inhibitors that significantly increase elagolix plasma concentrations

• Hypersensitivity reactions

• Drug interactions: see the full prescribing information for a list of clinically important drug interactions

• Thromboembolic disorders and vascular events

• Bone loss

• Suicidal ideation and mood disorders (including depression)

• Liver impairment and transaminase elevations

• Elevated blood pressure

• Change in menstrual bleeding pattern and reduced ability to recognize pregnancy:

• Risk of early pregnancy loss

• Uterine fibroid prolapse or expulsion

• Hypersensitivity reactions

• Bone loss

• Reduced ability to recognize pregnancy

• Suicidal ideation and mood disorders

• Liver transaminase elevations

• Interactions with hormonal contraceptives

WARNING: THROMBOEMBOLIC DISORDERS AND VASCULAR EVENTS

Estrogen and progestin combinations, including Myfembree, increase the risk of thrombotic or thromboembolic disorders, especially in women at increased risk for these events.

Myfembree is contraindicated in women with current or a history of thrombotic or thromboembolic disorders and in women at increased risk for these events, including women over 35 years of age who smoke or women with uncontrolled hypertension.

*This information is from the label for brand name Myfembree^®. See the Full Prescribing Information for more complete information. Relugolix, estradiol, and norethindrone, the active ingredients in Myfembree, may also be the active ingredients in other medications, and this information may not be accurate for all medications that include the active ingredients relugolix, estradiol, and norethindrone.

*This information is from the label for brand name Orilissa^®. See the Full Prescribing Information for more complete information.