Mimvey

Name: Mimvey

What should I avoid while using Mimvey (estradiol and norethindrone)?

Grapefruit and grapefruit juice may interact with estradiol and lead to unwanted side effects. Discuss the use of grapefruit products with your doctor.

Mimvey (estradiol and norethindrone) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • chest pain or heavy feeling, pain spreading to the jaw or shoulder, sweating, feeling short of breath, fainting;

  • sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance;

  • sudden cough, wheezing, rapid breathing, coughing up blood;

  • pain, swelling, warmth, or redness in one or both legs;

  • vomiting, jaundice (yellowing of the skin or eyes);

  • unusual vaginal bleeding; or

  • a lump in your breast.

Common side effects may include:

  • nausea, bloating, stomach cramps;

  • headache, depressed mood;

  • breast pain, back pain;

  • sleep problems (insomnia);

  • hair loss, weight changes, acne; or

  • vaginal itching or discharge, breakthrough bleeding.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Proper Use of estradiol and norethindrone

This section provides information on the proper use of a number of products that contain estradiol and norethindrone. It may not be specific to Mimvey. Please read with care.

It is very important that you use this medicine exactly as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. To do so may cause unwanted side effects.

This medicine comes with a patient information leaflet. Read and follow the instructions carefully. Ask your doctor if you have any questions.

This medicine sometimes comes in a special dispenser pack with a calendar reminder dial.

To use:

  • To use this dispenser, first turn the inner disc so the current day of the week is lined up with the plastic tab. Pull the plastic tab up and break if off. Tip out the first tablet.
  • To get the next tablet out (on the next day), turn the outer transparent dial one space clockwise as shown by the arrow.
  • The transparent dial can be turned only after the tablet in the opening has been removed. This will help you to remember to take one tablet every day.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (tablets):
    • For hot flashes and other symptoms caused by menopause:
      • Adults—One tablet once a day. One tablet contains 1 milligram (mg) of estradiol and 0.5 mg of norethindrone, or 0.5 mg of estradiol and 0.1 mg of norethindrone.
      • Children—Use is not recommended.
    • For treatment of changes in and around the vagina (such as vaginal dryness, itching, and burning) caused by low estrogen levels or menopause.
      • Adults—One tablet once a day. One tablet contains 1 milligram (mg) of estradiol and 0.5 mg of norethindrone.
      • Children—Use is not recommended.
    • For prevention of osteoporosis after menopause:
      • Adults—One tablet once a day. One tablet contains 1 milligram (mg) of estradiol and 0.5 mg of norethindrone, or 0.5 mg of estradiol and 0.1 mg of norethindrone.
      • Children—Use is not recommended.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Mimvey Side Effects

Along with its needed effects, a medicine 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:

More common
  • Body aches or pain
  • chills or fever
  • cold or flu-like symptoms
  • difficulty breathing
  • headache
  • itching of the vagina or genital area
  • nonmenstrual vaginal bleeding
  • pain during sexual intercourse
  • thick, white vaginal discharge with no odor or with a mild odor
  • unusual tiredness or weakness
Incidence not known
  • Abdominal or stomach pain
  • blistering, peeling, or loosening of the skin
  • change in vaginal discharge
  • chest pain, discomfort, or tightness in chest
  • clay-colored stools
  • clear or bloody discharge from the nipple
  • confusion
  • dark urine
  • difficulty speaking
  • difficulty swallowing
  • dizziness or lightheadedness
  • double vision
  • fainting
  • fast heartbeat
  • inability to move the arms, legs, or facial muscles
  • inability to speak
  • joint or muscle pain
  • loss of appetite
  • lump in the breast or under the arm
  • nausea and vomiting
  • noisy breathing
  • pain in the ankles or knees
  • pain or discomfort in the arms, jaw, back, or neck
  • pain or feeling of pressure in the pelvis
  • pain, redness, or swelling in the arm or leg
  • painful, red lumps under the skin, mostly on the legs
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • problems with memory or speech
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • red, irritated eyes
  • redness or swelling of the breast
  • skin rash, hives, or itching
  • sores, ulcers, or white spots in the mouth or on the lips
  • sudden shortness of breath or troubled breathing
  • sweating
  • trouble recognizing objects
  • trouble thinking and planning
  • trouble walking

Some side effects 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
  • Back pain
  • breast pain
  • cramps
  • crying
  • euphoria
  • mental depression
  • paranoia
  • quick to react or overreact emotionally
  • rapidly changing moods
  • trouble sleeping
  • weakness
  • weight gain
Incidence not known
  • Changes in appetite
  • changes in sexual ability, desire, drive, or performance
  • excess air or gas in the stomach or intestines
  • increased hair growth, especially on the face
  • patchy brown or dark brown discoloration of the skin
  • trouble wearing contact lenses

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Dosage Forms and Strengths

Mimvey tablets are available in two strengths:

• Each tablet of Mimvey (estradiol and norethindrone acetate tablets USP) 1 mg/0.5 mg contains 1 mg of estradiol and 0.5 mg of norethindrone acetate. The tablets are white, round, biconvex, film-coated, unscored tablets debossed with stylized b on one side and 34 on the other side. • Each tablet of Mimvey Lo (estradiol and norethindrone acetate tablets USP) 0.5 mg/0.1 mg contains 0.5 mg estradiol and 0.1 mg norethindrone acetate. The tablets are white to off-white, round, biconvex, unscored tablets debossed with stylized b on one side and 53 on the other side.

Contraindications

Mimvey and Mimvey Lo are contraindicated in women with any of the following conditions:

• Undiagnosed abnormal genital bleeding • Known, suspected, or history of breast cancer • Known, past or suspected estrogen-dependent neoplasia • Active DVT, PE, or history of these conditions • Active arterial thromboembolic disease (for example stroke and MI), or a history of these conditions • Known anaphylactic reaction or angioedema or hypersensitivity to Mimvey or Mimvey Lo • Known liver impairment or disease • Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders • Known or suspected pregnancy

Warnings and Precautions

Cardiovascular Disorders

An increased risk of PE, DVT, stroke and MI has been reported with estrogen plus progestin therapy. An increased risk of stroke and DVT has been reported with estrogen-alone therapy. Should any of these occur or be suspected, estrogen with or without progestin therapy should be discontinued immediately.

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) should be managed appropriately.

Stroke

In the WHI estrogen plus progestin substudy, a statistically significant increased risk of stroke was reported 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 per 10,000 women-years) [see Clinical Studies (14.5)]. The increase in risk was demonstrated after the first year and persisted. 1 Should a stroke occur or be suspected, estrogen plus progestin therapy should be discontinued immediately.

In the WHI estrogen-alone substudy, a statistically significant increased risk of stroke was reported 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 per 10,000 women-years). The increase in risk was demonstrated in year 1 and persisted [see Clinical Studies (14.5)]. Should a stroke occur or be suspected, estrogen-alone therapy should be discontinued immediately.

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

In the WHI estrogen plus progestin substudy, there was a statistically non-significant increase risk of coronary heart disease (CHD) events (defined as nonfatal MI, silent MI, or CHD death) reported in 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)].

In the WHI estrogen-alone substudy, no overall effect on CHD events was reported in women receiving estrogen-alone compared to placebo 2[see Clinical Studies (14.5)].

Subgroup analyses of women 50 to 59 years of age suggest a statistically non-significant reduction in CHD events (CE [0.625 mg]-alone compared to placebo) in women with less than 10 years since menopause (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 and 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

In the WHI estrogen plus progestin substudy, a statistically significant 2-fold greater rate of VTE (DVT and PE), was reported 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)]. Should a VTE occur or be suspected, estrogen plus progestin therapy should be discontinued immediately.

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)]. Should a VTE occur or be suspected, estrogen-alone therapy should be discontinued immediately.

If feasible, estrogens should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.

Malignant Neoplasms

Breast Cancer

The most important randomized clinical trial providing information about breast cancer in estrogen plus progestin users is the WHI substudy of daily CE (0.625 mg) plus MPA (2.5 mg). After a mean follow-up of 5.6 years, the estrogen plus progestin substudy reported an increased risk of invasive breast cancer in women who took daily CE plus MPA. 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 [see Clinical Studies (14.5)]. 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 most important randomized clinical trial providing information about breast cancer in estrogen-alone users is the WHI substudy of daily CE (0.625 mg)-alone. 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 6[see Clinical Studies (14.5)].

Consistent with the WHI clinical trials, observational studies have also reported an increased risk of breast cancer for estrogen plus progestin therapy, and a smaller increased risk for estrogen-alone therapy, after several years of use. The risk increased with duration of use, and appeared to return to baseline over about 5 years after stopping treatment (only the observational studies have substantial data on risk after stopping). 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. However, these studies have not 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 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 Mimvey 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

Endometrial hyperplasia (a possible precursor of endometrial cancer) has been reported to occur at a rate of approximately 1 percent or less with Mimvey and Mimvey Lo.

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 times 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 progestin therapy is important. 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.

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 progestin to estrogen therapy in postmenopausal women has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer.

Ovarian Cancer

The WHI estrogen plus progestin substudy reported a statistically non-significant increased 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 CI, 0.77 to 3.24]. The absolute risk for CE plus MPA versus placebo was 4 versus 3 cases per 10,000 women-years.7 In some epidemiologic studies, the use of estrogen plus progestin and estrogen-only products, in particular for 5 or more years, has been associated with an increased risk of ovarian cancer. However, the duration of exposure associated with increased risk is not consistent across all epidemiologic studies, and some report no association.

Probable Dementia

In the WHIMS estrogen plus progestin ancillary study of WHI, 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 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 to 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 of WHI, 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 to 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 to 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)].

Gallbladder Disease

A 2- to 4 fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.

Hypercalcemia

Estrogen administration may lead to severe hypercalcemia in patients with breast cancer and bone metastases. If hypercalcemia occurs, use of the drug should be stopped and appropriate measures taken to reduce the serum calcium level.

Vision Abnormalities

Retinal vascular thrombosis has been reported in patients receiving estrogens. Discontinue medication pending examination if there is a sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, estrogens should be permanently discontinued.

Addition of a Progestin When a Woman Has Not Had a Hysterectomy

Studies of the addition of a progestin 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 progestins with estrogens compared to estrogen-alone regimens. These include an increased risk of breast cancer.

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.

Hypertriglyceridemia

In women with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis. Consider discontinuation of treatment if pancreatitis occurs.

Hepatic Impairment and/or Past History of Cholestatic Jaundice

Estrogens may be poorly metabolized in women with impaired liver function. For women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, caution should be exercised, and in the case of recurrence, medication should be discontinued.

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. These women should have their thyroid function monitored to maintain their free thyroid hormone levels in an acceptable range.

Fluid Retention

Estrogens plus progestins may cause some degree of fluid retention. Women with conditions that might be influenced by this factor, such as a cardiac or renal impairment, warrant careful observation when estrogens plus progestins are prescribed.

Hypocalcemia

Estrogen therapy should be used with caution in women with hypoparathyroidism as estrogen-induced hypocalcemia may occur.

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. For women known to have residual endometriosis post- hysterectomy, the addition of progestin should be considered.

Hereditary Angioedema

Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema.

Exacerbation of Other Conditions

Estrogen therapy may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions.

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.

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 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 HDL2 cholesterol subfraction concentration, reduced low-density lipoprotein (LDL) cholesterol concentration, increased triglyceride levels.

Impaired glucose tolerance.

Mimvey Description

Mimvey® (estradiol and norethindrone acetate tablets USP) 1 mg/0.5 mg is a single tablet for oral administration containing 1 mg of estradiol, USP and 0.5 mg of norethindrone acetate, USP and the following inactive ingredients: colloidal silicon dioxide, copovidone, corn starch, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, polysorbate 80, and titanium dioxide.

Mimvey® Lo (estradiol and norethindrone acetate tablets USP) 0.5 mg/0.1 mg is a single tablet for oral administration containing 0.5 mg of estradiol, USP and 0.1 mg of norethindrone acetate, USP and the following inactive ingredients: colloidal silicon dioxide, copovidone, corn starch, lactose monohydrate, and magnesium stearate.

Estradiol (E2) is a white or almost white crystalline powder. Its chemical name is estra-1, 3, 5 (10)-triene-3, 17β-diol hemihydrate. The structural formula of E2 is as follows:

Estradiol, USP

  C18H24O2, ½ H2O M.W. 281.4

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. The structural formula of NETA is as follows:

Norethindrone Acetate, USP

  C22H28O3 M.W. 340.5

How Supplied/Storage and Handling

How Supplied

Mimvey® (estradiol and norethindrone acetate tablets USP) 1 mg/0.5 mg is available as white, round, biconvex, film-coated, unscored tablet, debossed with stylized b on one side and 34 on the other side.

Available in blister cards of 28 tablets:

  1 blister card per carton (NDC 0093-5455-28)   5 blister cards per carton (NDC 0093-5455-42)

Mimvey® Lo (estradiol and norethindrone acetate tablets USP) 0.5 mg/0.1 mg is available as white to off-white, round, biconvex, unscored tablets, debossed with stylized b on one side and 53 on the other side.

Available in blister cards of 28 tablets:

  3 blister cards per carton (NDC 0093-5454-62)

Storage and Handling

Store in a dry place protected from light.

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

For the Consumer

Applies to estradiol / norethindrone: oral tablet

Other dosage forms:

  • transdermal patch extended release

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
  • Body aches or pain
  • chills or fever
  • cold or flu-like symptoms
  • difficulty breathing
  • headache
  • itching of the vagina or genital area
  • nonmenstrual vaginal bleeding
  • pain during sexual intercourse
  • thick, white vaginal discharge with no odor or with a mild odor
  • unusual tiredness or weakness
Incidence not known
  • Abdominal or stomach pain
  • blistering, peeling, or loosening of the skin
  • change in vaginal discharge
  • chest pain, discomfort, or tightness in chest
  • clay-colored stools
  • clear or bloody discharge from the nipple
  • confusion
  • dark urine
  • difficulty speaking
  • difficulty swallowing
  • dizziness or lightheadedness
  • double vision
  • fainting
  • fast heartbeat
  • inability to move the arms, legs, or facial muscles
  • inability to speak
  • joint or muscle pain
  • loss of appetite
  • lump in the breast or under the arm
  • nausea and vomiting
  • noisy breathing
  • pain in the ankles or knees
  • pain or discomfort in the arms, jaw, back, or neck
  • pain or feeling of pressure in the pelvis
  • pain, redness, or swelling in the arm or leg
  • painful, red lumps under the skin, mostly on the legs
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • problems with memory or speech
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • red, irritated eyes
  • redness or swelling of the breast
  • skin rash, hives, or itching
  • sores, ulcers, or white spots in the mouth or on the lips
  • sudden shortness of breath or troubled breathing
  • sweating
  • trouble recognizing objects
  • trouble thinking and planning
  • trouble walking

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
  • Back pain
  • breast pain
  • cramps
  • crying
  • euphoria
  • mental depression
  • paranoia
  • quick to react or overreact emotionally
  • rapidly changing moods
  • trouble sleeping
  • weakness
  • weight gain
Incidence not known
  • Changes in appetite
  • changes in sexual ability, desire, drive, or performance
  • excess air or gas in the stomach or intestines
  • increased hair growth, especially on the face
  • patchy brown or dark brown discoloration of the skin
  • trouble wearing contact lenses

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