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Estradiol / norethindrone / relugolix Side Effects

Medically reviewed by Drugs.com. Last updated on Aug 2, 2023.

Applies to estradiol / norethindrone / relugolix: oral tablet.

Warning

Oral route (Tablet)

Estrogen and progestin combination products, including relugolix/estradiol/norethindrone acetate, increase the risk of thrombotic or thromboembolic disorders including pulmonary embolism (PE), deep vein thrombosis (DVT), stroke and myocardial infarction (MI), especially in women at increased risk for these events. Relugolix/estradiol/norethindrone acetate 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.

Serious side effects

Along with its needed effects, estradiol / norethindrone / relugolix may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking estradiol / norethindrone / relugolix:

More common

Less common

Rare

Incidence not known

Other side effects

Some side effects of estradiol / norethindrone / relugolix may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Less common

For Healthcare Professionals

Applies to estradiol / norethindrone / relugolix: oral tablet.

General

In women with heavy menstrual bleeding associated with uterine fibroids, the most common adverse reactions occurring in 3% of patients or greater included vasomotor symptoms, uterine bleeding, alopecia, and decreased libido. Serious adverse reactions occurring in up to 3% of patients included uterine myoma expulsion and menorrhagia, uterine leiomyoma (prolapse), cholecystitis, and pelvic pain.

In women with moderate to severe pain associated with endometriosis, the most common adverse reactions occurring in 3% of patients or greater included headache, vasomotor symptoms, mood disorders, abnormal uterine bleeding, nausea, toothache, back pain, decreased sexual desire and arousal, arthralgia, fatigue, and dizziness. Serious adverse reactions occurring in up to 3% of patients included uterine hemorrhage, suicidal ideation, cholelithiasis, and cholecystitis.[Ref]

Cardiovascular

Common (1% to 10%): Hot flush, new/worsening hypertension

Rare (0.01% to 0.1%): Thromboembolic events (deep vein thrombosis [DVT], pulmonary embolism [PE])

Postmarketing reports for relugolix monotherapy: Thromboembolic events[Ref]

Dermatologic

Common (1% to 10%): Alopecia/hair loss/hair thinning, hyperhidrosis, night sweats

Uncommon (0.1% to 1%): Angioedema, urticaria

Postmarketing reports, including relugolix monotherapy: Drug eruption[Ref]

Gastrointestinal

Common (1% to 10%): Dyspepsia, nausea, toothache, diarrhea[Ref]

Genitourinary

Very common (10% or more): Resumption of menstruation after drug discontinuation (up to 100%), amenorrhea (up to 71%), irregular bleeding pattern (32%), cyclic bleeding (15%)

Common (1% to 10%): Abnormal uterine bleeding (menorrhagia, metrorrhagia, vaginal hemorrhage, uterine hemorrhage, polymenorrhea, and menstruation irregular), vulvovaginal dryness

Uncommon (0.1% to 1%): Uterine myoma expulsion, uterine leiomyoma (prolapse), pelvic pain

Postmarketing reports, including relugolix monotherapy: Uterine leiomyoma degeneration[Ref]

Hepatic

Uncommon (less than 1%): Elevated AST and/or ALT greater than 3 times the upper limit of normal

Frequency not reported: Gallbladder disease, cholelithiasis and cholecystitis[Ref]

Hypersensitivity

Postmarketing reports: Anaphylactoid reaction[Ref]

Musculoskeletal

Very common (10% or more): Decline in lumbar spine bone mineral density (up to 23%)

Common (1% to 10%): Back pain, arthralgia, bone loss

Uncommon (0.1% to 1%): Low trauma fractures[Ref]

In some women who had normal bone mineral density (BMD) at start of treatment with this drug, a bone loss varying from greater than 3 to 8% was reported.[Ref]

Nervous system

Very common (10% or more): Headache (33%)

Other

Very common (10% or more): Decreased high-density lipoprotein (HDL) cholesterol (up to 22.2%), vasomotor symptoms including hot flush, hyperhidrosis, night sweats, and flushing (up to 13%), increased total cholesterol (up to 13.7%)

Common (1% to 10%): Increased low-density lipoprotein (LDL) cholesterol, breast cyst, fatigue, peripheral edema[Ref]

Psychiatric

Common (1% to 10%): Decreased sexual desire and arousal (libido decreased, libido disorder, loss of libido, female sexual arousal disorder), mood disorders (affect lability, affective disorder, anxiety, depressed mood, mood swings, depression, emotional distress, generalized anxiety disorder, irritability, mixed anxiety and depressive disorder, mood altered, mood swings, suicidal ideation)[Ref]

Respiratory

Frequency not reported: Pulmonary embolism[Ref]

References

1. Cerner Multum, Inc. UK Summary of Product Characteristics.

2. Product Information. Myfembree (estradiol / norethindrone / relugolix). Myovant Sciences, Inc. 2023.

3. Product Information. Ryeqo 40/1/0.5 (estradiol/norethisterone/relugolix). Gedeon Richter Australia Pty Ltd. 2023;RYEQO PI 0012 07 Feb.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.