Estradiol and Norethindrone: Uses, Side Effects and Dosage

What is the most important information I should know about Estradiol/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/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/Norethindrone Acetate Tablets.

What is Estradiol/Norethindrone Acetate Tablets?

Estradiol/Norethindrone Acetate Tablets are a prescription medicine that contains two kinds of hormones, an estrogen and a progestogen.

What is Estradiol/Norethindrone Acetate Tablets used for?

Estradiol/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/Norethindrone Acetate Tablets 1.0 mg/0.5 mg to treat these problems. If you use Estradiol/Norethindrone Acetate Tablets 1.0 mg/0.5 mg only to treat your menopausal changes in and around your vagina, talk with your healthcare provider about whether a topical vaginal product would be better for you.

• 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/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/Norethindrone Acetate Tablets.

Who should not use Estradiol/Norethindrone Acetate Tablets?

Do not use Estradiol/Norethindrone Acetate Tablets if you have had your uterus (womb) removed (hysterectomy).

Estradiol/Norethindrone Acetate Tablets contains 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/Norethindrone Acetate Tablets.

Do not start using Estradiol/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/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/Norethindrone Acetate Tablets or any of the ingredients in it.

See the list of ingredients in Estradiol/Norethindrone Acetate Tablets at the end of this leaflet.

Before you use Estradiol/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/Norethindrone Acetate Tablets

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

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

Your healthcare provider will let you know if you need to stop using Estradiol/Norethindrone Acetate Tablets.

• are pregnant or think you may be pregnant

Estradiol/Norethindrone Acetate Tablets is not for pregnant women.

• are breast feeding

The hormones in Estradiol/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/Norethindrone Acetate Tablets works. Estradiol/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/Norethindrone Acetate Tablets?

• Use Estradiol/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/Norethindrone Acetate Tablets.

Follow the instructions below to use your Estradiol/Norethindrone Acetate Tablets Dispenser.

What are the possible side effects of Estradiol/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/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/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 Breckenridge Pharmaceutical, Inc. at 1-800-367-3395 or to FDA at 1-800-FDA-1088.

What can I do to lower my chances of a serious side effect with Estradiol/Norethindrone Acetate Tablets?

• Talk with your healthcare provider regularly about whether you should continue using Estradiol/Norethindrone Acetate Tablets.
• If you have a uterus, talk with your healthcare provider about whether Estradiol/Norethindrone Acetate Tablets is right for you.
• In general, the addition of a progestogen is generally recommended for a woman with a uterus to reduce the chance of getting cancer of the uterus (womb).
• See your healthcare provider right away if you get vaginal bleeding while using Estradiol/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/Norethindrone Acetate Tablets?

• Store Estradiol/Norethindrone Acetate Tablets at room temperature between 68°F to 77°F (20°C to 25°C).
• Store Estradiol/Norethindrone Acetate Tablets in a dry place protected from light.

KEEP Estradiol/Norethindrone Acetate Tablets and all medicines out of the reach of children.

General information about the safe and effective use of Estradiol/Norethindrone Acetate Tablets.

Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use Estradiol/Norethindrone Acetate Tablets for conditions for which it was not prescribed. Do not give Estradiol/Norethindrone Acetate Tablets to other people, even if they have the same symptoms you have. It may harm them.

You can ask your healthcare provider or pharmacist for information about Estradiol/Norethindrone Acetate Tablets that is written for health professionals.

For more information go to www.bpirx.com or call 1-800-367-3395.

What are the ingredients in Estradiol/Norethindrone Acetate Tablets?

Active ingredients: estradiol and norethindrone acetate

Inactive Ingredients: lactose monohydrate, starch (corn), copovidone, talc, magnesium stearate, hypromellose, and triacetin.

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

Distributed by:

Breckenridge Pharmaceutical, Inc.

Berkeley Heights, NJ 07922

Manufactured by:

Pharmaceutics International, Inc.

Hunt Valley, MD 21031

Revised: 01/2024