Medicine guide

Estradiol and Norethindrone Acetate

.5 mg + 1 mg · Tablet

Prescription only
Estrogen

Active substance: Estradiol and Norethindrone Acetate
Used in: Urinary and reproductive system, hormones
Made by: Naari Pte. Limited
Source: Official label

Quoted from the official source. Not yet reviewed by Mediclarum — the leaflet in your pack is authoritative.

At a glance

Quoted from the official label · 2024-06-11

What it is

Estrogen

Used for

Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause (1.1)

The label’s usual adult dose

Estradiol and Norethindrone acetate tablets 1 mg/0.5 mg

Full directions ↓

Serious warning

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

All warnings ↓

Good to know

Prescription only
FDA enforcement reports list no ongoing recall, and none from the last two years, for this product code · checked 2026-10-02

11other products contain Estradiol and Norethindrone Acetate — compare makers, forms and strengths

Every line above is selected, not written, from the official label. Nothing is reworded. DailyMed

What it is for

Estradiol and Norethindrone acetate tablets is indicated for:

Estradiol and Norethindrone acetate tablet is an estrogen and progestin combination indicated in a woman with a uterus for:
Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause (1.1)
Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause (1.2) Limitations of Use:
When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, first consider the use of topical vaginal products.
Prevention of Postmenopausal Osteoporosis (1.3) Limitations of Use:
When prescribing solely for the prevention of postmenopausal osteoporosis, first consider the use of non-estrogen medications. Consider estrogen therapy only for women at significant risk of osteoporosis. 1.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause 1.2 Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause Limitation of Use When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, topical vaginal products should be considered. 1.3 Prevention of Postmenopausal Osteoporosis Limitation of Use When prescribing solely for the prevention of postmenopausal osteoporosis, first consider the use of non-estrogen medications. Consider estrogen therapy only for women at significant risk of osteoporosis.

From the official label · 2024-06-11 · DailyMed

How it works

From this product’s own US prescribing label.

Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics.
Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level.

Peak level after0.5–1.5 h

Half-life12–14 h

Mostly cleared after≈ 3 daysfive half-lives — our arithmetic

The shape is a standard model drawn from the two times above, not a measurement. How fast a medicine acts and wears off also depends on the dose, the form and the person.

How the body breaks it down

Estradiol Exogenous estrogens are metabolized in the same manner as endogenous estrogens.

How it leaves the body

Norethindrone Acetate The most important metabolites of norethindrone are isomers of 5α-dihydro-norethindrone and tetrahydro-norethindrone, which are excreted mainly in the urine as sulfate or glucuronide conjugates.

With food

Administration of estradiol and norethindrone acetate tablets 1 mg/0.5 mg with food did not modify the bioavailability of estradiol.

Quoted from the prescribing label, sections “Mechanism of Action” and “Pharmacokinetics”. DailyMed · 2024-06-11

Serious warning

The strongest warning the FDA requires. It is printed in a box at the top of the label.

CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, BREAST CANCER, and ENDOMETRIAL CANCER WARNING:
CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, BREAST CANCER, and ENDOMETRIAL CANCER See 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) ( 5.1 ) The WHI estrogen plus progestin substudy reported increased risks of invasive breast cancer ( 5.2 ) 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 ( 5.3 )
Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia ( 5.1 , 5.3 ) Estrogen-Alone Therapy There is an increased risk of endometrial cancer in a woman with a uterus who use unopposed estrogens ( 5.2 ) The WHI estrogen-alone substudy reported increased risks of stroke and DVT ( 5.1 ) The WHIMS estrogen-alone ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older ( 5.3 )
Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia ( 5.2 , 5.3 ) 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 [see Warnings and Precautions ( 5.1 ), and Clinical Studies ( 14.5 )] .
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 [see Warnings and Precautions ( 5.3 ), Use in Specific Populations ( 8.5 ), and Clinical Studies ( 14.6 )] .
Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia [see Warnings and Precautions ( 5.1 , 5.3 ), and Clinical Studies ( 14.5 , 14.6 )] .
Breast Cancer The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer [see Warnings and Precautions ( 5.2 ), and Clinical Studies ( 14.5 )] .
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.
Estrogen-Alone Therapy Endometrial Cancer There 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 [see Warnings and Precautions ( 5.2 )] .
Cardiovascular Disorders and Probable Dementia 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 [see Warnings and Precautions ( 5.1 ), and Clinical Studies ( 14.5 )].
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 [see Warnings and Precautions ( 5.3 ), Use in Specific Populations ( 8.5 ), and Clinical Studies ( 14.6 )].
Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia [see Warnings and Precautions ( 5.1 , 5.3 ), and Clinical Studies ( 14.5 , 14.6 )] .
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.
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.
What is the most important information I should know about estradiol and norethindrone acetate tablets (a combination of estrogen and progestogen)?
Do not use estrogens with or without progestogens to prevent heart disease, heart attacks, strokes, or dementia (decline of brain function).
Using estrogens with progestogens may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots.
Using estrogens with progestogens may increase your chance of getting dementia, based on a study of women 65 years of age and older.
Using estrogen-alone may increase your chance of getting cancer of the uterus (womb).
Do not use estrogen-alone to prevent heart disease, heart attacks, strokes, or dementia (decline in brain function).
Using estrogen-alone may increase your chances of getting strokes or blood clots.
Using estrogen-alone may increase your chance of getting dementia, based on a study of women 65 years of age and older.
Only one estrogen with progestogen product and dose have been shown to increase your chances of getting heart attacks, strokes, breast cancer, blood clots, and dementia.
Only one estrogen-alone product and dose have been shown to increase your chances of getting strokes, blood clots, and dementia.
Because other products and doses have not been studied in the same way, it is not known how the use of estradiol and norethindrone acetate tablets will affect your chances of these conditions.
You and your healthcare provider should talk regularly about whether you still need treatment with estradiol and norethindrone acetate tablets.

Quoted from the official label, section “Boxed Warning”.

Do not take it if

Undiagnosed abnormal genital bleeding (4)
Breast cancer or a history of breast cancer (4, 5.2)
Estrogen-dependent neoplasia (4, 5.2)
Active DVT, PE, or history of these conditions (4, 5.1)
Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions (4, 5.1)
Known anaphylactic reaction, angioedema, or hypersensitivity to Estradiol and Norethindrone acetate tablets (4)
Hepatic impairment or disease (4, 5.10)
Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders (4) Estradiol and Norethindrone acetate tablets is contraindicated in women with any of the following conditions:
Undiagnosed abnormal genital bleeding [see Warnings and Precautions (5.2)]
Breast cancer or history of breast cancer [see Warnings and Precautions (5.2)]
Estrogen-dependent neoplasia [see Warnings and Precautions (5.2)]
Active DVT, PE, or history of these conditions [see Warnings and Precautions (5.1)]
Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions [see Warnings and Precautions (5.1)]
Known anaphylactic reaction, angioedema, or hypersensitivity to Estradiol and Norethindrone acetate tablets
Hepatic impairment or disease
Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders

Quoted from the official label, section “Contraindications”.

How to take it

These directions are for this exact strength and form. Another one is different.

Take a single Estradiol and Norethindrone acetate tablets orally once daily for the Treatment of Moderate to severe Vasomotor Symptoms due to Menopause and for the Prevention of Postmenopausal Osteoporosis (2.1, 2.3)
Estradiol and norethindrone acetate tablets are taken orally once daily for the Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause (2.2) Use estrogen-alone, or in combination with a progestogen, at the lowest effective dose and the shortest duration consistent with treatment goals and risks for the individual woman. Reevaluate postmenopausal women periodically as clinically appropriate to determine whether treatment is still necessary. 2.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause Take a single Estradiol and Norethindrone acetate tablet orally once daily for the treatment of moderate to severe vasomotor symptoms due to menopause.
Estradiol and Norethindrone acetate tablets 1 mg/0.5 mg 2.2 Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause Take a single Estradiol and Norethindrone acetate tablet orally once daily for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause.
Estradiol and Norethindrone acetate tablets 1 mg/0.5 mg 2.3 Prevention of Postmenopausal Osteoporosis Take a single Estradiol and Norethindrone acetate tablet orally once daily for the prevention of postmenopausal osteoporosis.
Estradiol and Norethindrone acetate tablets 1 mg/0.5 mg

Quoted from the official label, section “Dosage & Administration”.

Other warnings

Estrogens increase the risk of gall bladder disease ( 5.4 ) Discontinue estrogen if severe hypercalcemia, loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs ( 5.5 , 5.6 , 5.9 , 5.10 ) Monitor thyroid function in women on thyroid replacement therapy ( 5.11 , 5.18 )
5.1 Cardiovascular Disorders Increased risks of PE, DVT, stroke and MI are reported with estrogen plus progestin therapy.
Increased risks of stroke and DVT are reported with estrogen-alone therapy.
Immediately discontinue estrogen with or without progestogen therapy if any of these occur or is suspected.
Manage appropriately any risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus).
Stroke The WHI estrogen plus progestin substudy reported a statistically significant increased risk of stroke in women 50 to 79 years of age receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women in the same age group receiving placebo (33 versus 25 strokes per 10,000 women-years) [see Clinical Studies ( 14.5 )] .
The increase in risk was demonstrated after the first year and persisted.1 Immediately discontinue estrogen with or without progestogen therapy if a stroke occurs or is suspected.
The WHI estrogen-alone substudy reported a statistically significant increased risk of stroke in women 50 to 79 years of age receiving daily CE (0.625 mg)-alone compared to women in the same age group receiving placebo (45 versus 33 strokes per 10,000 women-years, respectively).
The increase in risk was demonstrated in year 1 and persisted [see Clinical Studies ( 14.5 )] .
Immediately discontinue estrogen-alone therapy if a stroke occurs or is suspected.
Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving CE (0.625 mg)-alone versus those receiving placebo (18 versus 21 per 10,000 women-years). 1 Coronary Heart Disease The WHI estrogen plus progestin substudy reported an increased risk (not statistically significant) of coronary heart disease (CHD) events (defined as nonfatal MI, silent MI, or CHD death) in those women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000 women-years). 1 An increase in relative risk was demonstrated in year 1, and a trend toward decreasing relative risk was reported in years 2 through 5 [see Clinical Studies ( 14.5 )].
The WHI estrogen-alone substudy reported no overall effect on CHD events in women receiving estrogen-alone compared to placebo 2 [see Clinical Studies ( 14.5 )].
Subgroup analyses of women 50 to 59 years of age, who were less than 10 years since menopause, suggest a reduction (not statistically significant) in CHD events in those women receiving daily CE (0.625 mg)-alone compared to placebo (8 versus 16 per 10,000 women-years). 1 In postmenopausal women with documented heart disease (n=2,763), average 66.7 years of age, in a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study;
HERS), treatment with daily CE (0.625 mg plus MPA (2.5 mg) demonstrated no cardiovascular benefit.
During an average follow-up of 4.1 years, treatment with CE plus MPA did not reduce the overall rate of CHD events in postmenopausal women with established CHD.
There were more CHD events in the CE plus MPA-treated group than in the placebo group in year 1, but not during the subsequent years.
Two thousand three hundred twenty-one (2,321) women from the original HERS trial agreed to participate in an open label extension of HERS, HERS II.
Average follow-up in HERS II was an additional 2.7 years, for a total of 6.8 years overall.
Rates of CHD events were comparable among women in the CE plus MPA group and the placebo group in HERS, HERS II, and overall.
Venous Thromboembolism The WHI estrogen plus progestin substudy reported a statistically significant 2-fold greater rate of VTE (DVT and PE) in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (35 versus 17 per 10,000 women-years).
Statistically significant increases in risk for both DVT (26 versus 13 per 10,000 women-years) and PE (18 versus 8 per 10,000 women-years) were also demonstrated.
The increase in VTE risk was demonstrated during the first year and persisted 3 [see Clinical Studies ( 14.5 )] .
Immediately discontinue estrogen plus progestogen therapy if a VTE occurs or is suspected.
In the WHI estrogen-alone substudy, the risk of VTE was increased for women receiving daily CE (0.625 mg)-alone compared to placebo (30 versus 22 per 10,000 women-years), although only the increased risk of DVT reached statistical significance (23 versus 15 per 10,000 women-years).
The increase in VTE risk was demonstrated during the first 2 years 4 [see Clinical Studies ( 14.5 )] .
Immediately discontinue estrogen-alone therapy if a VTE occurs or is suspected.
If feasible, discontinue estrogens at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.
5.2 Malignant Neoplasms Breast Cancer After a mean follow-up of 5.6 years, the WHI substudy of daily CE (0.625 mg) plus MPA (2.5 mg) reported an increased risk of invasive breast cancer in women who took daily CE plus MPA compared to placebo.
In this substudy, prior use of estrogen-alone or estrogen plus progestin therapy was reported by 26 percent of the women.
The relative risk of invasive breast cancer was 1.24, and the absolute risk was 41 versus 33 cases per 10,000 women-years, for CE plus MPA compared with placebo.
Among women who reported prior use of hormone therapy, the relative risk of invasive breast cancer was 1.86, and the absolute risk was 46 versus 25 cases per 10,000 women-years, for CE plus MPA compared with placebo.
Among women who reported no prior use of hormone therapy, the relative risk of invasive breast cancer was 1.09, and the absolute risk was 40 versus 36 cases per 10,000 women-years, for CE plus MPA compared with placebo.
In the same substudy, invasive breast cancers were larger, were more likely to be node positive, and were diagnosed at a more advanced stage in the CE (0.625 mg) plus MPA (2.5 mg) group compared with the placebo group.
Metastatic disease was rare, with no apparent difference between the two groups.
Other prognostic factors, such as histologic subtype, grade and hormone receptor status did not differ between the groups 5 [see Clinical Studies ( 14.5 )] .
The WHI substudy of daily CE (0.625 mg)-alone provided information about breast cancer in estrogen-alone users.
In the WHI estrogen-alone substudy, after an average follow-up of 7.1 years, daily CE-alone was not associated with an increased risk of invasive breast cancer [relative risk (RR) 0.80] compared to placebo 6 [see Clinical Studies ( 14.5 )] .
Consistent with the WHI clinical trials, observational studies have also reported an increased risk of breast cancer with estrogen plus progestin therapy, and a smaller increase in the risk for breast cancer with estrogen-alone therapy, after several years of use.
One large meta-analysis of prospective cohort studies reported increased risks that were dependent upon duration of use and could last up to >10 years after discontinuation of estrogen plus progestin therapy and estrogen-alone therapy.
Extension of the WHI Trials also demonstrated increased breast cancer risk associated with estrogen plus progestin therapy.
Observational studies also suggest that the risk of breast cancer was greater, and became apparent earlier, with estrogen plus progestin therapy as compared to estrogen-alone therapy.
These studies have not generally found significant variation in the risk of breast cancer among different estrogen plus progestin combinations, doses, or routes of administration.
The use of estrogen-alone and estrogen plus progestin therapy has been reported to result in an increase in abnormal mammograms requiring further evaluation.
In a one-year trial among 1,176 women who received either unopposed 1 mg estradiol or a combination of 1 mg estradiol plus one of three different doses of NETA (0.1, 0.25, 0.5 mg), seven new cases of breast cancer were diagnosed, two of which occurred among the group of 295 women treated with Estradiol and Norethindrone acetate tablets 1 mg/0.5 mg and two of which occurred among the group of 294 women treated with 1 mg estradiol/0.1 mg NETA.
All women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations.
In addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results.
Endometrial Cancer An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in a woman with a uterus.
The reported endometrial cancer risk among unopposed estrogen users is about 2-to 12-fold greater than in nonusers, and appears dependent on duration of treatment and on estrogen dose.
Most studies show no significant increased risk associated with use of estrogens for less than 1 year.
The greatest risk appears to be associated with prolonged use, with increased risks of 15-to 24-fold for 5 to 10 years or more.
This risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued.
Clinical surveillance of all women using estrogen-alone or estrogen plus progestogen therapy is important.
Perform adequate diagnostic measures, including directed or random endometrial sampling when indicated, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding with unknown etiology.
There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose.
Adding a progestogen to estrogen therapy in postmenopausal women has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer.
Endometrial hyperplasia occured at a rate of approximately 1 percent or less with Estradiol and Norethindrone acetate tablets in a clinical trial.
Ovarian Cancer The CE plus MPA substudy of WHI reported that estrogen plus progestin increased the risk of ovarian cancer.
After an average follow-up of 5.6 years, the relative risk for ovarian cancer for CE plus MPA versus placebo was 1.58 (95 percent confidence interval [CI], 0.77-3.24), but it was not statistically significant.
The absolute risk for CE plus MPA versus placebo was 4 versus 3 cases per 10,000 women-years 7 A meta-analysis of 17 prospective and 35 retrospective epidemiology studies found that women who used hormonal therapy for menopausal symptoms had an increased risk for ovarian cancer.
The primary analysis, using case-control comparisons, included 12,110 cancer cases from the 17 prospective studies.
The relative risks associated with current use of hormonal therapy was 1.41 (95% CI 1.32 to 1.50); there was no difference in the risk estimates by duration of the exposure (less than 5 years [median of 3 years] vs. greater than 5 years [median of 10 years] of use before the cancer diagnosis).
The relative risk associated with combined current and recent use (discontinued use within 5 years before cancer diagnosis) was 1.37 (95% CI 1.27-1.48), and the elevated risk was significant for both estrogen-alone and estrogen plus progestin products.
The exact duration of hormone therapy use associated with an increased risk of ovarian cancer, however, is unknown.
5.3 Probable Dementia In the WHI Memory Study (WHIMS) estrogen plus progestin ancillary study, a population of 4,532 postmenopausal women 65 to 79 years of age was randomized to daily CE (0.625 mg) plus MPA (2.5 mg) or placebo.
After an average follow-up of 4 years, 40 women in the CE plus MPA group and 21 women in the placebo group were diagnosed with probable dementia.
The relative risk of probable dementia for the CE plus MPA versus placebo was 2.05 (95 percent CI, 1.21-3.48).
The absolute risk of probable dementia for CE plus MPA versus placebo was 45 versus 22 cases per 10,000 women-years 8 [see Use in Specific Populations ( 8.5 ), and Clinical Studies ( 14.6 )] .
In the WHIMS estrogen-alone ancillary study, a population of 2,947 hysterectomized women 65 to 79 years of age was randomized to daily CE (0.625 mg)-alone or placebo.
After an average follow-up of 5.2 years, 28 women in the estrogen-alone group and 19 women in the placebo group were diagnosed with probable dementia.
The relative risk of probable dementia for CE-alone versus placebo was 1.49 (95 percent CI, 0.83-2.66).
The absolute risk of probable dementia for CE-alone versus placebo was 37 versus 25 cases per 10,000 women-years 8 [see Use in Specific Populations ( 8.5 ), and Clinical Studies ( 14.6 )].
When data from the two populations in the WHIMS estrogen-alone and estrogen plus progestin ancillary studies were pooled as planned in the WHIMS protocol, the reported overall relative risk of probable dementia was 1.76 (95 percent CI, 1.19-2.60).
Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women 8 [see Use in Specific Populations ( 8.5 ), and Clinical Studies ( 14.6 )] .
5.4 Gallbladder Disease A 2-to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.
5.5 Hypercalcemia Estrogen administration may lead to severe hypercalcemia in women with breast cancer and bone metastases.
Discontinue estrogens, including Estradiol and Norethindrone acetate tablets if hypercalcemia occurs, and take appropriate measures to reduce the serum calcium level.
5.6 Vision Abnormalities Retinal vascular thrombosis has been reported in women receiving estrogens.
Discontinue Estradiol and Norethindrone acetate tablet pending examination if there is a sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine.
Permanently discontinue estrogens, including Estradiol and Norethindrone acetate tablet, if examination reveals papilledema or retinal vascular lesions
5.7 Addition of a Progestogen When a Woman Has Not Had a Hysterectomy Studies of the addition of a progestogen for 10 or more days of a cycle of estrogen administration, or daily with estrogen in a continuous regimen, have reported a lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone.
Endometrial hyperplasia may be a precursor to endometrial cancer.
There are, however, possible risks that may be associated with the use of progestogens with estrogens compared to estrogen-alone regimens.
These include an increased risk of breast cancer.
5.8 Elevated Blood Pressure In a small number of case reports, substantial increases in blood pressure have been attributed to idiosyncratic reactions to estrogens.
In a large, randomized, placebo-controlled clinical trial, a generalized effect of estrogen therapy on blood pressure was not seen.
5.9 Exacerbation of Hypertriglyceridemia In women with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis.
Discontinue Estradiol and Norethindrone acetate tablet if pancreatitis occurs.
5.10 Hepatic Impairment and/or Past History of Cholestatic Jaundice Estrogens may be poorly metabolized in women with hepatic impairment.
Exercise caution in any woman with a history of cholestatic jaundice associated with past estrogen use or with pregnancy.
In the case of recurrence of cholestatic jaundice, discontinue Estradiol and Norethindrone acetate tablet.
5.11 Exacerbation of Hypothyroidism Estrogen administration leads to increased thyroid-binding globulin (TBG) levels.
Women with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range.
Women dependent on thyroid hormone replacement therapy who are also receiving estrogen may require increased doses of their thyroid replacement therapy.
Monitor thyroid function in these women during treatment with Estradiol and Norethindrone acetate tablet to maintain their free thyroid hormone levels in an acceptable range.
5.12 Fluid Retention Estrogens plus progestogens may cause some degree of fluid retention.
Monitor any woman with a condition(s) that might predispose her to fluid retention, such as a cardiac or renal impairment.
Discontinue estrogen plus progestogen therapy, including Estradiol and Norethindrone acetate tablets, with evidence of medically concerning fluid retention.
5.13 Hypocalcemia Estrogen-induced hypocalcemia may occur in women with hypoparathyroidism.
Consider whether the benefits of estrogen therapy, including Estradiol and Norethindrone acetate tablets, outweigh the risks in such women.
5.14 Exacerbation of Endometriosis A few cases of malignant transformation of residual endometrial implants have been reported in women treated post-hysterectomy with estrogen-alone therapy.
5.15 Hereditary Angioedema Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema.
Consider whether the benefits of estrogen therapy, including estradiol and norethindrone acetate tablets, outweigh the risks in such women.
5.16 Exacerbation of Other Conditions Estrogen therapy, including estradiol and norethindrone acetate tablets, may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas.
Consider whether the benefits of estrogen therapy outweigh the risks in such women.
5.17 Laboratory Tests Serum follicle stimulating hormone (FSH) and estradiol levels have not been shown to be useful in the management of moderate to severe vasomotor symptoms and moderate to severe symptoms of vulvar and vaginal atrophy.
5.18 Drug-Laboratory Test Interactions Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, and beta-thromboglobulin; decreased levels of anti-factor Xa and antithrombin III, decreased antithrombin III activity, increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity.
Increased thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels as measured by protein-bound iodine (PBI), T4 levels (by column or by radioimmunoassay), or T3 levels by radioimmunoassay.
T3 resin uptake is decreased, reflecting the elevated TBG.
Free T4 and free T3 concentrations are unaltered.
Women on thyroid replacement therapy may require higher doses of thyroid hormone.
Other binding proteins may be elevated in serum, for example, corticosteroid binding globulin (CBG), sex hormone-binding globulin (SHBG), leading to increased total circulating corticosteroids and sex steroids, respectively.
Free hormone concentrations, such as testosterone and estradiol, may be decreased.
Other plasma proteins may be increased (angiotensinogen/rennin substrate, alpha-1 antitrypsin, ceruloplasmin).
Increased plasma high-density lipoprotein (HDL) and HDL 2 cholesterol subfraction concentration, reduced low-density lipoprotein (LDL) cholesterol concentration, increased triglyceride levels.
Impaired glucose tolerance.

Quoted from the official label, section “Warnings”.

Pregnancy and breastfeeding

Risk Summary Estradiol and norethindrone acetate tablets are not indicated for use in pregnancy.
There are no data with the use of estradiol and norethindrone acetate tablets in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalities and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogen and progestins) before conception or during early pregnancy.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
IN SPECIFIC POPULATIONS
8.1 Pregnancy Risk Summary Estradiol and norethindrone acetate tablets are not indicated for use in pregnancy.
There are no data with the use of estradiol and norethindrone acetate tablets in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalities and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogen and progestins) before conception or during early pregnancy.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
8.2 Lactation Risk Summary Estrogens plus progestogens are present in human milk and can reduce milk production in breast-feeding women.
This reduction can occur at any time but is less likely to occur once breast-feeding is well established.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for estradiol and norethindrone acetate tablets and any potential adverse effects on the breastfed child from estradiol and norethindrone acetate tablets or from the underlying maternal condition.
8.4 Pediatric Use Estradiol and norethindrone acetate tablets are not indicated for use in pediatric patients.
Clinical studies have not been conducted in the pediatric population.
8.5 Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing estradiol and norethindrone acetate tablets to determine whether those over 65 years of age differ from younger subjects in their response to estradiol and norethindrone acetate tablets.
The Women’s Health Initiative Studies In the WHI estrogen plus progestin substudy (daily CE [0.625 mg] plus MPA [2.5 mg] versus placebo), there was a higher relative risk of nonfatal stroke and invasive breast cancer in women greater than 65 years of age [see Clinical Studies ( 14.5 )] .
In the WHI estrogen-alone substudy (daily CE [0.625 mg]-alone versus placebo), there was a higher relative risk of stroke in women greater than 65 years of age [see Clinical Studies ( 14.5 )] .
The Women’s Health Initiative Memory Study In the WHIMS ancillary studies of postmenopausal women 65 to 79 years of age, there was an increased risk of developing probable dementia in women receiving estrogen plus progestin or estrogen-alone when compared to placebo.
It is unknown whether this finding applies to younger postmenopausal women [see Warnings and Precautions ( 5.3 ), and Clinical Studies ( 14.6 )] .
Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women 8 [see Warnings and Precautions ( 5.3 ), and Clinical Studies ( 14.6 )] .
Risk Summary Estrogens plus progestogens are present in human milk and can reduce milk production in breast-feeding women.
This reduction can occur at any time but is less likely to occur once breast-feeding is well established.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for estradiol and norethindrone acetate tablets and any potential adverse effects on the breastfed child from estradiol and norethindrone acetate tablets or from the underlying maternal condition.

Quoted from the official label, section “OTC — Pregnancy or Breast Feeding”.

Other medicines

Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration.
(7) Co-administration of estradiol with norethindrone acetate did not elicit any apparent influence on the pharmacokinetics of norethindrone acetate.
Similarly, no relevant interaction of norethindrone acetate on the pharmacokinetics of estradiol was found within the NETA dose range investigated in a single dose study.
Estradiol In-vitro and in-vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4).
Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism.
Inducers of CYP3A4 such as St.
John’s wort ( Hypericum perforatum ) preparations, phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile.
Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and result in adverse reactions.
Norethindrone Acetate Drugs or herbal products that induce or inhibit cytochrome P-450 enzymes, including CYP3A4, may decrease or increase the serum concentrations of norethindrone.

Quoted from the official label, section “Drug Interactions”.

If you take too much

In an emergency, call your local emergency number or a poison control centre.

Overdosage of estrogen plus progestogen may cause nausea, vomiting, breast tenderness, abdominal pain, drowsiness and fatigue, and withdrawal bleeding may occur in women.
Treatment of overdose consists of discontinuation of estradiol and norethindrone acetate tablets therapy with institution of appropriate symptomatic care.

Quoted from the official label, section “Overdosage”.

Use in children

Estradiol and norethindrone acetate tablets are not indicated for use in pediatric patients. Clinical studies have not been conducted in the pediatric population.

Quoted from the official label, section “Pediatric Use”.

Use in older people

There have not been sufficient numbers of geriatric women involved in clinical studies utilizing estradiol and norethindrone acetate tablets to determine whether those over 65 years of age differ from younger subjects in their response to estradiol and norethindrone acetate tablets.
The Women’s Health Initiative Studies In the WHI estrogen plus progestin substudy (daily CE [0.625 mg] plus MPA [2.5 mg] versus placebo), there was a higher relative risk of nonfatal stroke and invasive breast cancer in women greater than 65 years of age [see Clinical Studies ( 14.5 )] .
In the WHI estrogen-alone substudy (daily CE [0.625 mg]-alone versus placebo), there was a higher relative risk of stroke in women greater than 65 years of age [see Clinical Studies ( 14.5 )] .
The Women’s Health Initiative Memory Study In the WHIMS ancillary studies of postmenopausal women 65 to 79 years of age, there was an increased risk of developing probable dementia in women receiving estrogen plus progestin or estrogen-alone when compared to placebo.
It is unknown whether this finding applies to younger postmenopausal women [see Warnings and Precautions ( 5.3 ), and Clinical Studies ( 14.6 )] .
Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women 8 [see Warnings and Precautions ( 5.3 ), and Clinical Studies ( 14.6 )] .

Quoted from the official label, section “Geriatric Use”.

Side effects

The most common adverse reactions (incidence ≥ 5 percent) with Estradiol and Norethindrone acetate tablets are:
back pain, headache, pain in the extremity, nausea, diarrhea, gastroenteritis, insomnia, emotional lability, upper respiratory tract infection, sinusitis, nasopharyngitis, weight increase, breast pain, post-menopausal bleeding, uterine fibroid vaginal hemorrhage, ovarian cyst, endometrial thickening, viral infection, moniliasis genital, and accidental injury. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The following serious adverse reactions are discussed elsewhere in the labeling:
Cardiovascular Disorders [see Boxed Warning, Warnings and Precautions ( 5.1 )]
Malignant Neoplasms [see Boxed Warning, Warnings and Precautions ( 5.2 )] 6.1 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 practice. Adverse reactions reported with estradiol and norethindrone acetate tablets 1 mg/0.5 mg by investigators during clinical trials regardless of causality assessment are shown in Table 1. Table 1:
All Treatment-Emergent Adverse Reactions Regardless of Relationship Reported at a Frequency of ≥ 5 Percent with Estradiol and Norethindrone Acetate Tablets 1 mg/0.5 mg Endometrial Hyperplasia Study (12-Months) Vasomotor Symptoms Study (3-Months) Osteoporosis Study (2-Years) Estradiol and Norethindrone Acetate Tablets 1 mg/0.5 mg (n=295) 1 mg E 2 (n=296) Estradiol and Norethindrone Acetate Tablets 1 mg/0.5 mg (n=29) Placebo (n=34) Estradiol and Norethindrone Acetate Tablets 1 mg/0.5 mg (n=47) Placebo (n=48) Body as a Whole Back Pain 6% 5% 3% 3% 6% 4% Headache 16% 16% 17% 18% 11% 6% Digestive System Nausea 3% 5% 10% 0% 11% 0% Gastroenteritis 2% 2% 0% 0% 6% 4% Nervous System Insomnia 6% 4% 3% 3% 0% 8% Emotional Lability 1% 1% 0% 0% 6% 0% Respiratory System Upper Respiratory Tract Infection 18% 15% 10% 6% 15% 19% Sinusitis 7% 11% 7% 0% 15% 10% Metabolic and Nutritional Weight Increase 0% 0% 0% 0% 9% 6% Urogenital System Breast Pain 24% 10% 21% 0% 17% 8% Post-Menopausal Bleeding 5% 15% 10% 3% 11% 0% Uterine Fibroid 5% 4% 0% 0% 4% 8% Ovarian Cyst 3% 2% 7% 0% 0% 8% Resistance Mechanism Infection Viral 4% 6% 0% 3% 6% 6% Moniliasis Genital 4% 7% 0% 0% 6% 0% Secondary Terms Injury Accidental 4% 3% 3% 0% 17% including one upper extremity fracture in each group 4% Other Events 2% 3% 3% 0% 6% 4% Adverse reactions reported with estradiol and norethindrone acetate tablets 0.5 mg/0.1 mg by investigators during clinical trials regardless of causality assessment are shown in Table 2. Table 2:
All Treatment-Emergent Adverse Reactions Regardless of Relationship Reported at a Frequency of ≥ 5 Percent with Estradiol and Norethindrone Acetate Tablets 0.5 mg/0.1 mg Estradiol and Norethindrone Acetate Tablets 0.5 mg/0.1 mg (n=194) Placebo (n=200) Body as a Whole Back Pain 10% 4% Headache 22% 19% Pain in extremity 5% 4% Digestive System Nausea 5% 4% Diarrhea 6% 6% Respiratory System Nasopharyngitis 21% 18% Urogenital System Endometrial thickening 10% 4% Vaginal hemorrhage 26% 12% 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of estradiol and norethindrone acetate tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Genitourinary System Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; dysmenorrhea, increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; pre-menstrual-like syndrome; cystitis-like syndrome; ovarian cancer; endometrial hyperplasia; endometrial cancer. Breast Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer. Cardiovascular Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction, stroke; increase in blood pressure. Gastrointestinal Nausea, vomiting; changes in appetite; cholestatic jaundice; abdominal pain/cramps, flatulence, bloating; increased incidence of gallbladder disease and pancreatitis. Skin Chloasma or melasma that may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; seborrhea; hirsutism; itching; skin rash; pruritus. Eyes Retinal vascular thrombosis, intolerance to contact lenses. Central Nervous System Headache; migraine; dizziness; mental depression; chorea; insomnia; nervousness; mood disturbances; irritability; exacerbation of epilepsy; dementia. Miscellaneous Increase or decrease in weight; edema; leg cramps; changes in libido; fatigue; exacerbation of asthma; increased triglycerides; hypersensitivity; anaphylactoid/anaphylactic reactions.

Quoted from the official label, section “Adverse Reactions”.

What to discuss with your doctor

Advise women to read the FDA-approved patient labeling (Patient Information Vaginal Bleeding Inform postmenopausal women to report any vaginal bleeding to their healthcare provider as soon as possible [see Warnings and Precautions (5.2)] . Possible Serious Adverse Reactions with Estrogen Plus Progestogen Therapy Inform postmenopausal women of possible serious adverse reactions of estrogen plus progestogen therapy including Cardiovascular Disorders, Malignant Neoplasms, and Probable Dementia [see Warnings and Precautions (5.1, 5.2, 5.3)] . Possible Common Adverse Reactions with Estrogen Plus Progestogen Therapy Inform postmenopausal women of possible less serious but common adverse reactions of estrogen plus progestogen therapy such as headache, breast pain and tenderness, nausea and vomiting. Rx Only Manufactured For:
Naari Pte Limited 36 Robinson Road, #13-06 City House, Singapore 068877 Issued March 2024 Patient Information Estradiol and Norethindrone Acetate Tablets (es-truh-dahy-awl and nawr-eth-in-deohnl) 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 is the most important information I should know about estradiol and norethindrone acetate tablets (a combination of estrogen and progestogen)?
Do not use estrogens with or without progestogens to prevent heart disease, heart attacks, strokes, or dementia (decline of brain function). Using estrogens with progestogens may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots. Using estrogens with progestogens may increase your chance of getting dementia, based on a study of women 65 years of age and older. Using estrogen-alone may increase your chance of getting cancer of the uterus (womb).
Do not use estrogen-alone to prevent heart disease, heart attacks, strokes, or dementia (decline in brain function). Using estrogen-alone may increase your chances of getting strokes or blood clots. Using estrogen-alone may increase your chance of getting dementia, based on a study of women 65 years of age and older. Only one estrogen with progestogen product and dose have been shown to increase your chances of getting heart attacks, strokes, breast cancer, blood clots, and dementia. Only one estrogen-alone product and dose have been shown to increase your chances of getting strokes, blood clots, and dementia. Because other products and doses have not been studied in the same way, it is not known how the use of estradiol and norethindrone acetate tablets will affect your chances of these conditions. You and your healthcare provider should talk regularly about whether you still need treatment with estradiol and norethindrone acetate tablets. What is Estradiol and Norethindrone acetate tablets? Estradiol and Norethindrone acetate tablet is a prescription medicine that contains two kinds of hormones, an estrogen and a progestin. What are Estradiol and Norethindrone acetate tablets used for? Estradiol and Norethindrone acetate tablets are used after menopause to:
Reduce 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.
Treat 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 mg/0.5 mg to treat these problems.
If you use Estradiol and Norethindrone acetate tablets 1 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.
Help 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 the 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), or 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 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. 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
breast cancer
cancer of the lining of the uterus (womb)
cancer of the ovary
dementia
high or low blood calcium levels
gallbladder disease
visual abnormalities
high blood pressure
high levels of fat (triglycerides) in your blood
liver problems
changes in your thyroid hormone levels
fluid retention
cancer changes of endometriosis
enlargement of benign tumors of the uterus (“fibroids”)
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 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 are 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 they were not prescribed. Do not give estradiol and norethindrone acetate tablets to other people, even if they have the same symptoms
you have. They 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, call x-xxx-xxx-xxxx. What are the ingredients in Estradiol and Norethindrone acetate tablets? Active ingredients:
E stradiol and Norethindrone acetate Inactive Ingredients:
lactose monohydrate, starch (corn), copovidone, polysorbate 80, magnesium stearate, hypromellose, talc and triacetin. This Patient Information has been approved by the U.S. Food and Drug Administration. Manufactured for:
Naari Pte Limited 36 Robinson Road, #13-06 City House, Singapore 068877 Issued March 2024 image description

Quoted from the official label, section “Patient Counseling Information”.

Strengths and forms

FORMS AND STRENGTHS
Estradiol and norethindrone acetate 1 mg/0.5 mg tablet (3) Estradiol and Norethindrone acetate tablets, USP 1 mg/0.5 mg are available as follows:
Each Estradiol and Norethindrone acetate tablet, USP contains 1 mg of estradiol and 0.5 mg of norethindrone acetate. The tablets are white to off-white, round, biconvex, film coated tablets, debossed with "EX1" on one side and plain on other side.

Quoted from the official label, section “Dosage Forms & Strengths”.

What it looks like and how it is packed

16.1 How Supplied Estradiol and norethindrone acetate tablets, USP 1 mg/0.5 mg are white to off-white, round, biconvex, film coated tablets, debossed with "EX1" on one side and plain on other side.
The blister packs are available in box (NDC 79929-012-07) containing 3 pouch and each pouch contain 1 blister pack of 28 tablets
16.2 Storage and Handling Store in dry place protected from light.
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Quoted from the official label, section “How Supplied”.

What is in it

Estradiol and norethindrone acetate tablets USP, 1 mg/0.5 mg are a single tablet for oral administration containing 1 mg of estradiol and 0.5 mg of norethindrone acetate and the following excipients:
lactose monohydrate, starch (corn), copovidone, polysorbate 80, magnesium stearate, hypromellose, talc and triacetin.
Estradiol (E 2 ), is a white or almost white crystalline powder.
Its chemical name is estra-1, 3, 5 (10)-triene-3, 17β-diol hemihydrate with the empirical formula of C 18 H 24 O 2 , ½ H 2 O and a molecular weight of 281.4.
The structural formula of E 2 is as follows:
Estradiol Norethindrone acetate (NETA), is a white or yellowish-white crystalline powder.
Its chemical name is 17β -acetoxy-19-nor-17α -pregn-4-en-20-yn-3-one with the empirical formula of C 22 H 28 O 3 and molecular weight of 340.5.
The structural formula of NETA is as follows:
Norethindrone Acetate image description image description

Quoted from the official label, section “Description”.

Ingredients people check for

Lactose, gluten, dyes, sugars and other ingredients that matter with an allergy, intolerance or diet — as this product’s FDA label lists them.

The stored label for this product has no list of inactive ingredients. The list on the pack is the one to check.

Quoted from the FDA label. A label that does not name an ingredient is not a guarantee that the product is free of it, and formulations change. With an allergy, check the pack and ask a pharmacist.

Same active substance, strength and form in other countries

Matched on active substance, strength and kind of form only. This is not a statement that the products are equivalent or interchangeable: other ingredients, release and approved uses can differ — ask a pharmacist before swapping.

Medicine passport: one printable page to show a pharmacist abroad

CanadaNo exact match for this strength and form

Every strength and form (6)

Details

Made by	Naari Pte. Limited
Active substance	Estradiol and Norethindrone Acetate
Used in	Urinary and reproductive system, hormones
Strength	.5 mg + 1 mg
Form	Tablet
Route	Oral
Packs	84 BLISTER PACK in 1 POUCH / 28 TABLET in 1 BLISTER PACK
NDC	79929-012

Source: NDC Directory · 2026-09-13 · not reviewed by a clinician

Source: US Food and Drug Administration, NDC Directory. Reuse terms: US government work (FDA).

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Other strengths and forms

4 products are sold under this name. Grouped by form; a number on a strength means several companies make it.

Tablet4 products
- .5 mg + 1 mg
- .5 mg + .1 mg2
  .5 mg + .1 mg · 2 companies
  - A-S Medication Solutions
  - Ingenus Pharmaceuticals, LLC
- 1 mg + .5 mg

Same active substance

These contain the same substance. That does not mean one can replace another — ask a pharmacist.

Abigale1 mg + .5 mgPrescription onlyTablet Xiromed LLC · Estradiol and Norethindrone Acetate Abigale Lo.5 mg + .1 mgPrescription onlyTablet Xiromed LLC · Estradiol and Norethindrone Acetate Estradiol / Norethindrone Acetate1 mg + .5 mgPrescription onlyTablet, Film Coated A-S Medication Solutions · Estradiol and Norethindrone Acetate Estradiol / Norethindrone Acetate1 mg + .5 mgPrescription onlyTablet, Film Coated Breckenridge Pharmaceutical, Inc. · Estradiol and Norethindrone Acetate Estradiol / Norethindrone Acetate.5 mg + .1 mgPrescription onlyTablet, Film Coated Breckenridge Pharmaceutical, Inc. · Estradiol and Norethindrone Acetate Estradiol and Norethindrone Acetate.5 mg + .1 mgPrescription onlyTablet A-S Medication Solutions · Estradiol and Norethindrone Acetate

See every product with Estradiol and Norethindrone Acetate