Generic name: estradiol and norethindrone (oral route) [ es-tra-DYE-ol, nor-ETH-in-drone-AS-e-tate ]
Drug class: Sex hormone combinations
Estrogen Plus Progestin TherapyCardiovascular Disorders and Probable DementiaThe 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 (0.625 mg) combined with medroxyprogesterone acetate (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 conjugated estrogen (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia.Breast CancerThe WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer.Only daily oral 0.625 mg CE and 2.5 mg MPA were studied in the estrogen plus progestin substudy of the WHI. Therefore the relevance of the WHI findings regarding adverse cardiovascular events, dementia and breast cancer to lower CE plus other MPA doses, other routes of administration, or other estrogen plus progestogen products is not know. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen plus progestogen therapy, taking into account her individual risk profile.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.Estrogen-Alone TherapyEndometrial CancerThere is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens.Adding a progestogen 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 DementiaThe 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 conjugated estrogen (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 conjugated estrogen (0.625 mg)-alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia.Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy of the WHI. Therefore, the relevance of the WHI findings adverse cardiovascular events and dementia to lower CE doses, other routes of administration, or other estrogen-alone products is not known. With out such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen-alone therapy, taking into account her individual risk profile.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 .
Commonly used brand name(s)
In the U.S.
Available Dosage Forms:
Therapeutic Class: Estrogen/Progestin Combination
Pharmacologic Class: Estrogen
Uses for Activella
Estradiol and norethindrone combination is used to treat moderate to severe symptoms of menopause (eg, feelings of warmth in the face, neck, and chest, sudden strong feelings of heat and sweating [hot flashes], and vaginal problems). This medicine is also used prevent osteoporosis after menopause.
This medicine is available only with your doctor’s prescription.
Before using Activella
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Appropriate studies have not been performed on the relationship of age to the effects of estradiol and norethindrone combination in the pediatric population. Use of estradiol and norethindrone combination is not indicated for use in children.
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of estradiol and norethindrone combination in the geriatric population. However, elderly patients are more likely to have breast cancer, strokes, or dementia, which may require caution in patients receiving estradiol and norethindrone combination.
There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.
Interactions with medicines
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
- Tranexamic Acid
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Clavulanic Acid
- Eslicarbazepine Acetate
- Guar Gum
- Mycophenolate Mofetil
- Mycophenolic Acid
- Penicillin G
- Penicillin G Procaine
- Penicillin V
- Red Clover
- St John’s Wort
- Valproic Acid
Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Interactions with food/tobacco/alcohol
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.
Other medical problems
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:
- Abnormal or unusual vaginal bleeding or
- Bleeding problems or
- Blood clots (eg, deep vein thrombosis, pulmonary embolism), active or history of or
- Breast cancer, known or suspected, or a history of or
- Dementia or
- Heart attack, history of or
- Heart or blood vessel disease or
- Liver disease or
- Protein C, protein S, or antithrombin deficiency, or other known blood clotting disorders or
- Stroke, history of or
- Tumors (estrogen-dependent, including cancer of the uterus), known or suspected—Should not be used in patients with these conditions.
- Asthma or
- Cancer, history of or
- Diabetes or
- Edema (fluid retention or body swelling) or
- Endometriosis or
- Epilepsy (seizures) or
- Gallbladder disease or
- Hereditary angioedema (swelling of the face, lips, tongue, or throat) or
- Hypercalcemia (high calcium in the blood) or
- Hypocalcemia (low calcium in the blood) or
- Hypercholesterolemia (high cholesterol or fats in the blood) or
- Hypertension (high blood pressure) or
- Hypertriglyceridemia (high triglycerides or fats in the blood) or
- Hypothyroidism (an underactive thyroid) or
- Jaundice during pregnancy or from using hormonal therapy in the past or
- Kidney disease or
- Liver tumors or
- Migraine headache or
- Obesity or
- Porphyria (an enzyme problem) or
- Systemic lupus erythematosus (SLE)—Use with caution. May make these conditions worse.
Proper use of Activella
This section provides information on the proper use of a number of products that contain estradiol and norethindrone. It may not be specific to Activella. 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.
Do not eat grapefruit or drink grapefruit juice while you are using this medicine. Grapefruit and grapefruit juice may change the amount of this medicine that is absorbed in the body.
- 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.
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 moderate to severe hot flashes:
- Adults—One tablet once a day. Each 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 moderate to severe vaginal problems or dryness:
- Adults—One tablet once a day. Each 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. Each 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 moderate to severe hot flashes:
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.
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.
Detailed Activella dosage information
Precautions while using Activella
It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly and does not cause unwanted effects. These visits may be every 3 to 6 months. Blood or urine tests, pelvic exam, breast exam, and mammogram (breast x-ray) may be needed to check for unwanted effects, unless your doctor tells you otherwise. Be sure to keep all appointments.
It is unlikely that a postmenopausal woman may become pregnant. But, you should know that using this medicine while you are pregnant could harm your unborn baby. If you think you have become pregnant while using the medicine, tell your doctor right away.
Using this medicine may increase your risk for having blood clots, strokes, or heart attacks. This risk may continue even after you stop using the medicine. Your risk for these serious problems is even greater if you have high blood pressure, high cholesterol in your blood, diabetes, or if you are overweight or smoke cigarettes. Contact your doctor immediately if you experience chest pain, confusion, difficulty speaking, double vision, headaches, an inability to move arms, legs or facial muscle, or an inability to speak.
Using this medicine for a long period of time may increase your risk of endometrial cancer, breast cancer, or uterine cancer. Talk with your doctor about this risk. Do not use this medicine if you have had your uterus (womb) removed (hysterectomy). Check with your doctor immediately if your experience abnormal vaginal bleeding.
Using this medicine may increase your risk of dementia, especially in women 65 years of age and older.
This medicine may increase your risk of having gallbladder disease. Check with your doctor if you start to have stomach pains, nausea, and vomiting.
Check with your doctor immediately if severe headache or sudden loss of vision or any other change in vision occurs while you are using this medicine. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).
Tell your doctor or dentist who treats you knows that you are using this medicine before any kind of surgery (eg, surgery that will require inactivity for a long time) or emergency treatment. Your doctor will decide whether you should continue using this medicine. This medicine may also affect the results of certain medical tests.
Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John’s wort) or vitamin supplements.
Activella 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:
- Body aches or pain
- chills or fever
- cold or flu-like symptoms
- difficulty breathing
- itching of the vagina or genital area
- non-menstrual 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
- Blistering, peeling, or loosening of the skin
- breast tenderness
- change in vaginal discharge
- change in vision
- chest pain, discomfort, or tightness
- clay-colored stools
- clear or bloody discharge from the nipple
- dark urine
- difficulty speaking
- difficulty swallowing
- dizziness or lightheadedness
- double vision
- 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
- stomach pain
- trouble breathing
- trouble recognizing objects
- trouble thinking and planning
- trouble walking
- unexpected or excess milk flow from the breasts
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:
- Back pain
- mental depression
- quick to react or overreact emotionally
- rapidly changing moods
- trouble sleeping
- 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.