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Activella Side Effects

Generic name: estradiol / norethindrone

Medically reviewed by Drugs.com. Last updated on Jul 25, 2023.

Note: This document contains side effect information about estradiol / norethindrone. Some dosage forms listed on this page may not apply to the brand name Activella.

Applies to estradiol / norethindrone: oral tablet. Other dosage forms:

Warning

Oral route (Tablet)

Estrogen Plus Progestin TherapyCardiovascular Disorders and Probable DementiaThe Women’s Health Initiative (WHI) estrogen plus progestin substudy reported increased risks of deep vein thrombosis (DVT), pulmonary embolism (PE), stroke and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogen (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg), relative to placebo.The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily conjugated estrogen (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia.Breast CancerThe WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer.Only daily oral 0.625 mg CE and 2.5 mg MPA were studied in the estrogen plus progestin substudy of the WHI. Therefore the relevance of the WHI findings regarding adverse cardiovascular events, dementia and breast cancer to lower CE plus other MPA doses, other routes of administration, or other estrogen plus progestogen products is not know. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen plus progestogen therapy, taking into account her individual risk profile.Prescribe estrogens with or without progestogens at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.Estrogen-Alone TherapyEndometrial CancerThere is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens.Adding a progestogen to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer.Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding. Cardiovascular Disorders and Probable DementiaThe WHI estrogen-alone substudy reported increased risks of stroke and DVT in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogen (0.625 mg)-alone, relative to placebo.The WHIMS estrogen-alone ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily conjugated estrogen (0.625 mg)-alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia.Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy of the WHI. Therefore, the relevance of the WHI findings adverse cardiovascular events and dementia to lower CE doses, other routes of administration, or other estrogen-alone products is not known. With out such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen-alone therapy, taking into account her individual risk profile.Prescribe estrogens with or without progestogens at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

Serious side effects of Activella

Along with its needed effects, estradiol/norethindrone 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:

More common

Incidence not known

Other side effects of Activella

Some side effects of estradiol / norethindrone 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

Incidence not known

For Healthcare Professionals

Applies to estradiol / norethindrone: oral tablet, transdermal film extended release.

General

The most common adverse events were vaginal bleeding and breast pain/tenderness. Vaginal bleeding usually occurred in the first months of treatment. Breast pain usually disappeared after a few months of therapy.[Ref]

Genitourinary

Very common (10% or more): Vaginal hemorrhage (26%), breast pain (24%), post-menopausal bleeding (11%), endometrial thickening (10%), breast tenderness, menstruation irregular

Common (1% to 10%): Ovarian cyst, uterine fibroid, breast edema, breast enlargement, uterine fibroids aggravated, uterine fibroids recurrence, uterine fibroids

Uncommon (0.1% to 1%): Endometrial hyperplasia, dysmenorrhea

Rare (less than 0.1%): Fallopian tube cysts, endocervical polyps

Postmarketing reports: Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow, breakthrough bleeding, spotting, increase in size of uterine leiomyomata, change in amount of cervical secretion, changes in cervical ectropion, pre-menstrual-like syndrome, cystitis-like syndrome, nipple discharge, galactorrhea, fibrocystic breast changes, vulvovaginal pruritus[Ref]

Nervous system

Very common (10% or more): Headache (22%)

Common (1% to 10%): Migraine or migraine aggravated, dizziness

Rare (less than 0.1%): Paresthesia

Postmarketing reports: Dizziness, exacerbation of epilepsy, dementia, chorea, stroke[Ref]

Cardiovascular

Common (1% to 10%): Blood pressure increase

Uncommon (0.1% to 1%): Thrombophlebitis superficial, venous thromboembolism

Rare (less than 0.1%): Thrombophlebitis deep, deep venous thromboembolism

Postmarketing reports: Deep and superficial vein thrombosis, thrombophlebitis, myocardial infarction, stroke, hypertension aggravated[Ref]

Gastrointestinal

Very common (10% or more): Nausea (11%)

Common (1% to 10%): Gastroenteritis, diarrhea, abdominal pain, abdominal distention, abdominal discomfort

Uncommon (0.1% to 1%): Flatulence, bloating

Postmarketing reports: Vomiting, abdominal cramps, pancreatitis, dyspepsia[Ref]

Psychiatric

Common (1% to 10%): Insomnia, emotional lability, depression or depression aggravated

Uncommon (0.1% to 1%): Nervousness, changes in libido

Postmarketing reports: Mental depression, mood disturbances, irritability, anxiety[Ref]

Other

Very common (10% or more): Accidental injury (17%)

Common (1% to 10%): Weight increase, weight decreased, edema peripheral, pain, asthenia

Uncommon (0.1% to 1%): Drug ineffective

Postmarketing reports: Fatigue, edema[Ref]

Musculoskeletal

Very common (10% or more): Back pain (10%)

Common (1% to 10%): Pain in extremity, leg cramps[Ref]

Immunologic

Very common (10% or more): Nasopharyngitis (21%), upper respiratory tract infection (18%), sinusitis (15%)

Common (1% to 10%): Infection viral, moniliasis genital, genital candidiasis or vaginitis[Ref]

Dermatologic

Common (1% to 10%): Acne, rash, pruritus, dry skin

Uncommon (0.1% to 1%): Alopecia, hirsutism, urticaria, skin reactions, skin discoloration

Postmarketing reports: Chloasma or melasma that may persist when drug is discontinued, erythema multiforme, erythema nodosum, hemorrhagic eruption, loss of scalp hair, seborrhea, skin rash, seborrhea, angioneurotic edema[Ref]

Oncologic

Uncommon (0.1% to 1%): Breast cancer

Rare (less than 0.1%): Uterine leiomyoma

Postmarketing reports: Ovarian cancer, endometrial cancer[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Hypersensitivity

Rare (less than 0.1%): Allergic reaction

Postmarketing reports: Anaphylactoid/anaphylactic reactions[Ref]

Respiratory

Rare (less than 0.1%): Pulmonary embolism, asthma

Postmarketing reports: Exacerbation of asthma[Ref]

Hepatic

Uncommon (0.1% to 1%): Gallbladder disease, gallstones, transaminases increased

Rare (less than 0.1%): Cholelithiasis

Postmarketing reports: Cholestatic jaundice, gallbladder disease, cholelithiasis aggravated, cholelithiasis recurrence[Ref]

Metabolic

Common (1% to 10%): Fluid retention

Postmarketing reports: Changes in appetite, increased triglycerides[Ref]

Ocular

Postmarketing reports: Retinal vascular thrombosis, intolerance to contact lenses, visual disturbances[Ref]

References

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

2. Cerner Multum, Inc. Australian Product Information.

3. Product Information. Activella (estradiol-norethindrone). Gemini Laboratories. 2017.

4. Product Information. Lopreeza (estradiol-norethindrone). Amneal Pharmaceuticals. 2017.

5. Product Information. Mimvey (estradiol-norethindrone). Teva Pharmaceuticals USA. 2017.

6. Product Information. Amabelz (estradiol-norethindrone). Lupin Pharmaceuticals Inc. 2017.

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.

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