Medication Guide — 28 Estradiol Norethindrone Acetate 1 Mg 0 5 Mg 1

Patient-friendly FDA guidance and safety information.

Last updated · May 16, 2026Source: DailyMed ↗

Boxed Warning

WARNING: CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, BREAST CANCER, and ENDOMETRIAL CANCER

S ee full prescribing information for complete boxed warning

Estrogen Plus Progestin Therapy

The 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)

The WHI estrogen plus progestin substudy reported increased risks of invasive breast cancer

The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older

Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia

Estrogen-Alone Therapy

There is an increased risk of endometrial cancer in a woman with a uterus who use unopposed estrogens

The WHI estrogen-alone substudy reported increased risks of stroke and DVT

The WHIMS estrogen-alone ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older

Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia

Estrogen Plus Progestin Therapy

Cardiovascular Disorders and Probable Dementia

The 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 (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [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 and older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (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 [see Warnings and Precautions, and Clinical Studies].

Breast Cancer

The 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 known. 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.

Endometrial Cancer

There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progest ogen 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 .

The 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 CE (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 and older during 5.2 years of treatment with daily CE (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 regarding adverse cardiovascular events and dementia to lower CE doses, other routes of administration, or other estrogen-alone products is not known. 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-alone therapy, taking into account her individual risk profile.

Poison Help

If you suspect an overdose or accidental ingestion, call Poison Control: 1-800-222-1222 (free, 24/7, U.S.). For life-threatening symptoms, call 911.

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Patient Information

Estradiol and Norethindrone Acetate

(ES-tra-DYE-ol/nor-eth-IN-drone as-i-teyt)

Tablets , USP

Read this Patient Information before you start using estradiol and norethindrone acetate tablets and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your menopausal symptoms or your treatment.

What are estradiol and norethindrone acetate tablets?

Estradiol and norethindrone acetate tablets are prescription medicines that contain two kinds of hormones, an estrogen and a progestogen.

What are estradiol and norethindrone acetate tablets used for?

Estradiol and norethindrone acetate tablets are used after menopause to:

• R educe moderate to severe hot flushes

Estrogens are hormones made by a woman's ovaries. The ovaries normally stop making estrogens when a woman is between 45 and 55 yrs old. This drop in body estrogen levels causes the "change of life" or menopause, the end of monthly menstrual periods. Sometimes both ovaries are removed during an operation before natural menopause takes place. The sudden drop in estrogen levels causes "surgical menopause."

When estrogen levels begin dropping, some women get very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden, intense feelings of heat and sweating ("hot flashes" or "hot flushes"). In some women, the symptoms are mild, and they will not need to use estrogens. In other women, symptoms can be more severe.

• T reat moderate to severe menopausal changes in and around the vagina

You and your healthcare provider should talk regularly about whether you still need treatment with estradiol and norethindrone acetate tablets 1.0 mg/0.5 mg to treat these problems. If you use estradiol and norethindrone acetate tablets 1.0 mg/0.5 mg only to treat your menopausal changes in and around your vagina, talk with your healthcare provider about whether a topical vaginal product would be better for you.

• H elp reduce your chances of getting osteoporosis (thin weak bones)

Osteoporosis from menopause is a thinning of the bones that makes them weaker and easier to break. If you use estradiol and norethindrone acetate tablets to prevent osteoporosis due to menopause, talk with your healthcare provider about whether a different treatment or medicine without estrogens might be better for you.

You and your healthcare provider should talk regularly about whether you still need treatment with estradiol and norethindrone acetate tablets.

Who should not use estradiol and norethindrone acetate tablets ?

Do not use estradiol and norethindrone acetate tablets if you have had your uterus (womb) removed (hysterectomy).

Estradiol and norethindrone acetate tablets contain a progestogen to decrease the chance of getting cancer of the uterus. If you do not have a uterus, you do not need a progestogen and you should not use estradiol and norethindrone acetate tablets.

Do not start using estradiol and norethindrone acetate tablets if you:

• have unusual vaginal bleeding

Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.

• have been diagnosed with a bleeding disorder

• currently have or have had certain cancers

Estrogens may increase the chance of getting certain types of cancers, including cancer of the breast or uterus (womb). If you have or have had cancer, talk with your healthcare provider about whether you should use estradiol and norethindrone acetate tablets.

• had a stroke or heart attack

• currently have or have had blood clots

• currently have or have had liver problems

• are allergic to estradiol and norethindrone acetate tablets or any of its ingredients in it

See the list of ingredients in estradiol and norethindrone acetate tablets at the end of this leaflet.

Before you use estradiol and norethindrone acetate tablets , tell your healthcare provider about all of your medical conditions, including if you:

• have any unusual vaginal bleeding

Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.

• have any other medical conditions that may become worse while you are using estradiol and norethindrone acetate tablets

Your healthcare provider may need to check you more carefully if you have certain conditions, such as asthma (wheezing), epilepsy (seizures), diabetes, migraine, endometriosis, lupus, angioedema (swelling of face and tongue), problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood.

• are going to have surgery or will be on bed rest

Your healthcare provider will let you know if you need to stop using estradiol and norethindrone acetate tablets.

• are pregnant or think you may be pregnant

Estradiol and norethindrone acetate tablets are not for pregnant women.

• are breast feeding

The hormones in estradiol and norethindrone acetate tablets can pass into your breast milk.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines may affect how estradiol and norethindrone acetate tablets work. Estradiol and norethindrone acetate tablets may also affect how your other medicines work. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.

How should I use estradiol and norethindrone acetate tablets ?

• Use estradiol and norethindrone acetate tablets exactly as your healthcare provider tells you to use it.

• Take 1 tablet at the same time each day.

• You and your healthcare provider should talk regularly (every 3 to 6 months) about your dose and whether you still need treatment with estradiol and norethindrone acetate tablets.

Follow the instructions below to use your estradiol and norethindrone acetate tablets compact

Estradiol and norethindrone acetate tablets are available as a blister card placed within a white compact with the days of the week imprinted on the white compact preset for a Sunday start. The estradiol and norethindrone acetate tablets blister card and the imprinted days of the week on the compact is shown in the picture below.

On the above blister card find where on the card to start taking tablets, in what order to take the tablets and the week numbers. Day 1 stickers are also provided.

You will use a Day 1 Start if you take your first tablet not on Sunday. Refer to Day 1 Start instructions below:

1. Pick the day label strip that starts with the first day of you first tablet.

2. Place this day label strip over the area on the plastic compact which already has the days of the week (starting with Sunday) imprinted and press firmly. See the picture below as an example.

To remove a tablet, i) ensure the blister is properly placed into the compact with the entire blister locked on the right V notch and placed under the six plastic lips of the compact, ii) press down the tablet with even pressure with your thumb or finger. The tablet will be pushed through the back of the compact tablet dispenser. Do not press with your thumbnail, fingernail, or any other sharp object.

• Take 1 tablet every day in the order on the blister card at the same time each day.

• After taking the last tablet on Day 28 from the blister card, start taking the first tablet from a new pack, on the same day of the week as the first pack.

What are the possible side effects of estradiol and norethindrone acetate tablets?

Side effects are grouped by how serious they are and how often they happen when you are treated.

Serious, but less common side effects include:

• heart attack

• stroke

• blood clots

• dementia

• breast cancer

• cancer of the lining of the uterus (womb)

• cancer of the ovary

• liver problems

• changes in your thyroid hormone levels

• fluid retention

• cancer changes of endometriosis

• enlargement of benign tumors of the uterus ("fibroids")

• high or low blood calcium levels

• gallbladder disease

• visual abnormalities

• high blood pressure

• high levels of fat (triglycerides) in your blood

• worsening swelling of face and tongue (angioedema) in women who have a history of angioedema

• changes in laboratory tests results such as bleeding times and high blood sugar levels

Call your healthcare provider right away if you get any of the following warning signs or any other unusual symptoms that concern you:

• new breast lumps

• unusual vaginal bleeding

• changes in vision or speech

• sudden new severe headaches

• severe pains in your chest or legs with or without shortness of breath, weakness and fatigue

Common side effects of estradiol and norethindrone acetate tablets include:

• irregular vaginal bleeding or spotting

• nausea

• stomach or abdominal cramps, bloating

• headache

• vomiting

• back pain

• breast pain

• diarrhea

• fluid retention

• vaginal yeast infection

These are not all the possible side effects of estradiol and norethindrone acetate tablets. For more information, ask your healthcare provider or pharmacist. Tell your healthcare provider if you have any side effects that bother you or do not go away.

You may report side effects to Ingenus Pharmaceuticals, LLC. at 1-877-748-1970 or to FDA at 1-800-FDA-1088.

What can I do to lower my chances of a serious side effect with estradiol and norethindrone acetate tablets?

• Talk with your healthcare provider regularly about whether you should continue using estradiol and norethindrone acetate tablets.

• If you have a uterus, talk with your healthcare provider about whether estradiol and norethindrone acetate tablets is right for you.

• In general, the addition of a progestogen is generally recommended for a woman with a uterus to reduce the chance of getting cancer of the uterus (womb).

• See your healthcare provider right away if you get vaginal bleeding while using estradiol and norethindrone acetate tablets.

• Have a pelvic exam, breast exam and mammogram (breast X-ray) every year unless your healthcare provider tells you something else.

• If members of your family have had breast cancer or if you have ever had breast lumps or an abnormal mammogram (breast x-ray), you may need to have breast exams more often.

• If you have high blood pressure, high cholesterol (fat in the blood), diabetes, are overweight, or if you use tobacco, you may have higher chances for getting heart disease.

• Ask your healthcare provider for ways to lower your chances for getting heart disease.

How should I store estradiol and norethindrone acetate tablets?

• Store estradiol and norethindrone acetate tablets at room temperature between 68°F to 77°F (20°C to 25°C).

• Store estradiol and norethindrone acetate tablets in a dry place protected from light.

KEEP estradiol and norethindrone acetate tablets and all medicines out of the reach of children.

General information about the safe and effective use of estradiol and norethindrone acetate tablets.

Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use estradiol and norethindrone acetate tablets for conditions for which it was not prescribed. Do not give estradiol and norethindrone acetate tablets to other people, even if they have the same symptoms you have. It may harm them.

You can ask your healthcare provider or pharmacist for information about estradiol and norethindrone acetate tablets that is written for health professionals.

For more information go to www.ingenus.com or call 1-877-748-1970.

What are the ingredients in estradiol and norethindrone acetate tablets?

Active ingredients: estradiol and norethindrone acetate

Inactive Ingredients: lactose monohydrate, starch (corn), polysorbate 80, copovidone, magnesium stearate, polyvinyl alcohol, titanium dioxide, talc, macrogol/polyethylglycol 3350, lecithin (soya), D&C Yellow NO.10 Aluminum lake and FD&C Blue NO.2 Aluminum lake.

The 1 mg/0.5 mg tablet also contains FD&C Red No.40 Aluminum lake.

The 0.5 mg/0.1 mg tablet also contains FD&C Yellow No.6 Aluminum lake.

This Patient Information has been approved by the U.S. Food and Drug Administration.

Rx Only

Iss: 03/2024

Rev.D

Manufactured for:

Ingenus Pharmaceuticals, LLC

Orlando, FL 32839-6408

Product of China

Image Image Image Image

Sources

RxCUI: 1359127

NDC: [{'@sourceNdc9': '51991-0474', 'ndc9': ['54868-4677']}]

Last fetched: May 16, 2026

Source: DailyMed ↗

⚠️ Disclaimer

This information is for educational purposes only and is not medical advice. Always consult your doctor, pharmacist, or other licensed healthcare professional before starting, stopping, or changing any medicine. Read full medical disclaimer.