Activella

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

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.

In the U.S.

• Activella
• Alesse
• Alesse-28
• Angeliq
• Cyclessa
• Estinyl
• Femtrace
• Feostat
• Hemocyte
• Loestrin 1/20
• Loestrin 1.5/30
• Mircette
• Necon
• Ortho-Novum
• Premphase
• Prempro

Available Dosage Forms:

• Tablet
• Tablet, Chewable

This section provides information on the proper use of a number of products that contain estrogen and progestin combination (ovarian hormone therapy). It may not be specific to Activella. Please read with care.

Estrogens and progestins usually come with patient information or directions. Read them carefully before taking this medicine.

Take this medicine only as directed by your doctor. Do not take more of it and do not take or use it for a longer time than your doctor ordered. Try to take the medicine at the same time each day to reduce the possibility of side effects and to allow it to work better.

For patients taking estrogens and progestins by mouth:

• Nausea may occur during the first few weeks after you start taking estrogens. This effect usually disappears with continued use. If the nausea is bothersome, it can usually be prevented or reduced by taking each dose with food or immediately after food.

Dosing

The dose medicines in this class 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 these medicines. 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 17 beta-estradiol and norgestimate
• For oral dosage forms (tablets):
  • For treating a genital skin condition (vaginal or vulvar atrophy), or vasomotor symptoms of menopause:
    • Adults—Oral, 1 mg estradiol for three days followed by 1 mg of estradiol combined with 0.09 mg of norgestimate for three days. The regimen is repeated continuously without interruption.
  • To prevent loss of bone (osteoporosis):
    • Adults—Oral, 1 mg estradiol for three days followed by 1 mg of estradiol combined with 0.09 mg of norgestimate for three days. The regimen is repeated continuously without interruption.

For ethinyl estradiol and norethindrone
• For oral dosage forms (tablets):
  • For treating vasomotor symptoms of menopause:
    • Adults—Oral, 2.5 mcg (0.025 mg) ethinyl estradiol and 0.5 mg norethindrone once daily.
  • To prevent loss of bone (osteoporosis):
    • Adults—Oral, 2.5 mcg (0.025 mg) ethinyl estradiol and 0.5 mg norethindrone once daily.

For estradiol and norethindrone
• For oral dosage forms (tablets):
  • For treating vasomotor symptoms of menopause or treatment of vaginal or vulvar atrophy:
    • Adults—Oral, 1 mg estradiol and 0.5 mg norethindrone once daily.
  • To prevent loss of bone (osteoporosis):
    • Adults—Oral, 1 mg estradiol and 0.5 mg norethindrone once daily.

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

Keep out of the reach of children.

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

Do not keep outdated medicine or medicine no longer needed.

• If you have an allergy to estradiol, norethindrone, or any other part of Activella (estradiol and norethindrone tablets).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have had any of these health problems: Bleeding disorder, blood clots, a higher risk of having a blood clot, breast cancer, liver problems or liver tumor, heart attack, stroke, or a tumor where estrogen makes it grow.
• If you have unexplained vaginal bleeding.
• If you are pregnant or may be pregnant. Do not take this medicine if you are pregnant.

This is not a list of all drugs or health problems that interact with Activella.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

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)]

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 Activella 1 mg/0.5 mg by investigators in the Phase 3 studies regardless of causality assessment are shown in Table 1.

Adverse reactions reported with Activella 0.5 mg/0.1 mg by investigators during the Phase 3 study 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 Activella 0.5 MG/0.1 MG

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Activella. 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.

Overdosage of estrogen plus progestin 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 Activella therapy with institution of appropriate symptomatic care.

NDC 60846-201

Activella ®

(estradiol/norethindrone

acetate) tablets

0.5 mg/0.1 mg

28 tablets

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.

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.

Regimen 1 (Cyclic Combined Estrogen-Progestin Therapy): Conjugated estrogens 0.625 mg orally once a day AND Medroxyprogesterone acetate 5 mg orally once a day for 14 days per month.

-or-

Regimen 2 (Continuous Combined Estrogen-Progestin Therapy): Conjugated estrogens 0.45 mg orally once a day AND Medroxyprogesterone acetate 1.5 mg orally once a day or conjugated estrogens 0.625 mg orally once a day AND Medroxyprogesterone acetate 2.5 mg or 5 mg orally once a day.

The hepatic metabolism of conjugated estrogens may be impaired in patients with liver disease and caution is recommended if patients with liver disease must receive conjugated estrogen therapy. The use of medroxyprogesterone is considered to be contraindicated for use in patients with liver disease.

Data not available