Estradiol/norethindrone acetate

What is Estradiol/norethindrone acetate?

• Estradiol/norethindrone acetate (Activella; CombiPatch) is an estrogen and progestin combination used used in the treatment of vasomotor symptoms, vulvar and vaginal atrophy, and osteoporosis associated with menopause.

Estradiol

Estradiol 3D ball

Norethisterone acetate

What are the uses of this medicine?

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

• Reduce moderate to severe hot flushes
• Treat moderate to severe menopausal changes in and around the vagina
• Help reduce your chances of getting osteoporosis (thin weak bones)

How does this medicine work?

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.

• Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH), and FSH through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.
• Progestin compounds enhance cellular differentiation and generally oppose the actions of estrogens by decreasing estrogen receptor levels, increasing local metabolism of estrogens to less active metabolites, or inducing gene products that blunt cellular responses to estrogen.
• Progestins exert their effects in target cells by binding to specific progesterone receptors that interact with progesterone response elements in target genes. Progesterone receptors have been identified in the female reproductive tract, breast, pituitary, hypothalamus, and central nervous system.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• have unusual vaginal bleeding
• have been diagnosed with a bleeding disorder
• currently have or have had certain cancers
• 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
• have any other medical conditions that may become worse while you are using Estradiol/Norethindrone Acetate Tablets
• are going to have surgery or will be on bed rest
• are pregnant or think you may be pregnant
• are breast feeding

What drug interactions can this medicine cause?

Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following:

• St. John's wort (Hypericum perforatum) preparations
• phenobarbital
• carbamazepine
• rifampin
• erythromycin
• clarithromycin
• ketoconazole
• itraconazole
• ritonavir
• grapefruit juice

Is this medicine FDA approved?

• Initial U.S. Approval: 1998

How should this medicine be used?

Recommended dosage: Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause:

• Take a single Estradiol/Norethindrone Acetate tablet orally once daily for the treatment of moderate to severe vasomotor symptoms due to menopause.
• Estradiol/Norethindrone Acetate Tablets 1 mg/0.5 mg
• Estradiol/Norethindrone Acetate Tablets 0.5 mg/0.1 mg

Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause:

• Take a single Estradiol/Norethindrone Acetate tablet orally once daily for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause.
• Estradiol/Norethindrone Acetate Tablets 1 mg/0.5 mg

Prevention of Postmenopausal Osteoporosis:

• Take a single Estradiol/Norethindrone Acetate tablet orally once daily for the prevention of postmenopausal osteoporosis.
• Estradiol/Norethindrone Acetate Tablets 1 mg/0.5 mg
• Estradiol/Norethindrone Acetate Tablets 0.5 mg/0.1 mg

Administration:

• 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.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Estradiol/Norethindrone Acetate 1 mg/0.5 mg tablet
• Estradiol/Norethindrone Acetate 0.5 mg/0.1 mg tablet

This medicine is available in fallowing brand namesː

• Activella, CombiPatch, Mimvey, Mimvey Lo, Lopreeza, and Amabelz

What side effects can this medication cause?

The most common side effects of this medicine include:

• irregular vaginal bleeding or spotting
• nausea
• stomach or abdominal cramps, bloating
• headache
• vomiting
• back pain
• breast pain
• diarrhea
• fluid retention
• vaginal yeast infection

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

What special precautions should I follow?

• 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. Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia.
• Estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer. 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.
• There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. 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.
• Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia.
• Increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.
• Estrogen administration may lead to severe hypercalcemia in women with breast cancer and bone metastases. Discontinue estrogens, including Estradiol/Norethindrone Acetate Tablets if hypercalcemia occurs, and take appropriate measures to reduce the serum calcium level.
• Retinal vascular thrombosis has been reported in women receiving estrogens. Permanently discontinue estrogens, including Estradiol/Norethindrone Acetate Tablets, if examination reveals papilledema or retinal vascular lesions.
• 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.
• In a small number of case reports, substantial increases in blood pressure.
• In women with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis. Discontinue Estradiol/Norethindrone Acetate Tablets if pancreatitis occurs.
• Estrogens may be poorly metabolized in women with hepatic impairment. In the case of recurrence of cholestatic jaundice, discontinue Estradiol/Norethindrone Acetate Tablets.
• Estrogen administration leads to increased thyroid-binding globulin (TBG) levels. Monitor thyroid function in these women during treatment with Estradiol/Norethindrone Acetate Tablets to maintain their free thyroid hormone levels in an acceptable range.
• Estrogens plus progestogens may cause some degree of fluid retention. Discontinue estrogen plus progestogen therapy, including Estradiol/Norethindrone Acetate Tablets, with evidence of medically concerning fluid retention.
• Estrogen-induced hypocalcemia may occur in women with hypoparathyroidism. Consider whether the benefits of estrogen therapy, including Estradiol/Norethindrone Acetate Tablets, outweigh the risks in such women.
• A few cases of malignant transformation of residual endometrial implants have been reported in women treated post-hysterectomy with estrogen-alone therapy.
• Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema. Consider whether the benefits of estrogen therapy, including Estradiol/Norethindrone Acetate Tablets, outweigh the risks in such women.
• Estrogen therapy, including Estradiol/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.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• nausea
• vomiting
• breast tenderness
• abdominal pain
• drowsiness and fatigue
• withdrawal bleeding

Management of overdosage:

• Treatment of overdose consists of discontinuation of Estradiol/Norethindrone Acetate Tablets therapy with institution of appropriate symptomatic care.

Can this medicine be used in pregnancy?

• Estradiol/Norethindrone Acetate Tablets are not indicated for use in pregnancy.
• There are no data with the use of Estradiol/Norethindrone Acetate Tablets in pregnant women.

Can this medicine be used in children?

• Estradiol/Norethindrone Acetate Tablets are not indicated for use in pediatric patients.
• Clinical studies have not been conducted in the pediatric population.

What are the active and inactive ingredients in this medicine?

• Active ingredients: estradiol and norethindrone acetate
• Inactive Ingredients: lactose monohydrate, starch (corn), copovidone, talc, magnesium stearate, hypromellose, and triacetin.

Who manufactures and distributes this medicine?

Distributed by:

• Breckenridge Pharmaceutical, Inc.
• Berlin, CT

Manufactured by:

• Pharmaceutics International, Inc.
• Hunt Valley, MD

What should I know about storage and disposal of this medication?

• 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.

• Dailymed label info on Estradiol/norethindrone acetate
• FDA Estradiol/norethindrone acetate

Estradiol/norethindrone acetate Resources
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