Activella

Activella is a prescription medication used after menopause to reduce moderate to severe hot flashes, treat moderate to severe menopausal changes in and around the vagina, and help reduce your chances of getting osteoporosis (thin weak bones).

Activella contains two hormones, estradiol and norethindrone, and belongs to a group of drugs called estrogen and progestin combinations. Activella works as a hormone replacement to relieve issues caused by hormonal changes. 

Activella comes in tablet form and is usually taken once daily, with or without food. 

Common side effects of Activella include headache, breast pain, and irregular vaginal bleeding or spotting.

Activella is a prescription medication used after menopause to reduce moderate to severe hot flashes, treat moderate to severe menopausal changes in and around the vagina, and help reduce your chances of getting osteoporosis (thin weak bones). 

Activella is an estrogen and progestin combination indicated in a woman with a uterus.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

• Amneal Pharmaceuticals, LLC

Serious side effects have been reported with Activella. See the “Activella Precautions” section.

Common side effects of Activella include:

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

This is not a complete list of Activella side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

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

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Drugs that may affect Activella include:

• medications that block a protein in the body (CYP3A4) such as some macrolide antibiotics (clarithromycin, telithromycin), some HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir), some HCV protease inhibitors (boceprevir, telaprevir), some azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole), conivaptan (Vaprisol), delavirdine (Rescriptor), and nefazodone

• medications that increase the activity of the enzyme CYP3A4 such as carbamazepine (Tegretol, Equetro, Carbatrol), phenobarbital, phenytoin (Dilantin), rifampin (Rifadin), St John's wort, and nimodipine (Nimotop)

This is not a complete list of Activella drug interactions. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with Activella including the following:

• heart attack
• stroke
• blood clots
• dementia
• breast cancer
• cancer of the lining of the uterus (womb)
• cancer of the ovary
• high blood pressure
• high blood sugar
• gallbladder disease
• liver problems
• changes in your thyroid hormone levels
• enlargement of benign tumors (“fibroids”)

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

What can I do to lower my chances of a serious side effect with Activella?

• Talk with your healthcare provider regularly about whether you should continue taking Activella.
• If you have a uterus, talk with your healthcare provider about whether the addition of a progestin is right for you.
• The addition of a progestin 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 taking Activella.
• 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.

Do not take Activella if you:

• are allergic to Activella or any of its components
• have had your uterus (womb) removed (hysterectomy)
• have unusual vaginal bleeding
• 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
• have been diagnosed with a bleeding disorder
• think you may be pregnant

Grapefruit and grapefruit juice may interact with Activella and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Before taking Activella, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to Activella or to any of its ingredients
• have any unusual vaginal bleeding
• have any other medical 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
• are breastfeeding or plan to breastfeed

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your doctor if you are pregnant or plan to become pregnant.

Activella should not be used during pregnancy. If you think you may be pregnant, you should have a pregnancy test and know the results. Do not take Activella if the test is positive and talk to your healthcare provider.

Tell your doctor if you are breastfeeding or plan to breastfeed.

Activella should not be used while nursing. Estrogen administration to nursing women has been shown to decrease the quantity and quality of the breast milk. Detectable amounts of estrogen and progestin have been identified in the breast milk of women receiving estrogen plus progestin therapy. Caution should be exercised when Activella is administered to a nursing woman.

Take Activella exactly as your healthcare provider tells you to take it.

Take 1 Activella at the same time each day.

You and your healthcare provider should talk regularly (every 3 to 6 months) about the dose you are taking and whether you still need treatment with Activella.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of Activella at the same time.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• how you respond to this medication

The recommended doses of Activella are as follows:

• to reduce moderate to severe hot flashes or to help reduce your chances of getting osteoporosis (thin weak bones): Activella 1 mg/0.5 mg or Activella 0.5 mg/0.1 mg tablet taken once daily
• to treat moderate to severe menopausal changes in and around the vagina: Activella 1 mg/0.5 mg tablet taken once daily

If you take too much Activella, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

• Store Activella at room temperature between 68°F to 77°F (20°C to 25°C).
• Store Activella in a dry place protected from light.
• Keep this and all medications out of the reach of children. 

Warning: Cardiovascular disorders, breast cancer, endometrial cancer, and probable dementia

Estrogen Plus Progestin Therapy

Cardiovascular Disorders and Probable Dementia

Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia.

The Women’s Health Initiative (WHI) estrogen plus progestin substudy reported increased risks of deep vein thrombosis (DVT), pulmonary embolism (PE), stroke and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogen (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo.

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

Breast Cancer

The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer.

In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA and other combinations and dosage forms of estrogens and progestins.

Estrogens with or without progestins should be prescribed 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 progestin 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.

Cardiovascular Disorders and Probable Dementia

Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or 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.

The WHIMS estrogen-alone ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or 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.

In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other dosage forms of estrogens.

Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment