How does this medication work? What will it do for me?
This is a combination medication that contains estradiol and norethindrone acetate. Estradiol belongs to the class of medications called estrogens, while norethindrone acetate belongs to the class of medications known as progestins.
This medication is used as an oral hormone replacement therapy to relieve menopausal symptoms and vaginal symptoms associated with menopause.
Estrogens and progestins are female hormones. They are produced by the body and are needed for normal female sexual development and for regulating the menstrual cycle during the childbearing years. During and after menopause, the ovaries start to produce less of these hormones. A deficiency of estrogen can result in symptoms associated with menopause such as hot flashes, unusual sweating, chills, dryness of the vagina, and sleep disturbances.
This medication is designed for women who have not had a hysterectomy (removal of the uterus or womb). These women require progestin while taking estrogen to prevent complications associated with taking estrogen alone, such as the overgrowth of the uterine lining (endometrial hyperplasia).
This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.
Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.
Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.
What form(s) does this medication come in?
Each white, round, biconvex, film-coated tablet engraved with "NOVO 291" on one side and "APIS" on the other side contains 0.5 mg of estradiol (as the hemihydrate) and 0.1 mg of norethindrone acetate. Nonmedicinal ingredients: lactose monohydrate, maize starch, hydroxypropylcellulose, talc, magnesium stearate, hypromellose, and triacetin.
How should I use this medication?
The recommended dose of norethindrone acetate - estradiol is one tablet daily at approximately the same time each day, with or without food.
Many things can affect the dose of a medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.
It is important to take this medication be taken prescribed by your doctor. If you miss a dose, take it as soon as you remember and continue with your regular schedule. If it is within 12 hours of your next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice. Forgetting a dose of this medication may increase the risk of breakthrough bleeding and spotting.
Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children.
Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.
Who should NOT take this medication?
Do not take this medication if you:
- are allergic to estradiol, norethindrone acetate, or any ingredients of this medication
- are breast-feeding
- are or may be pregnant
- have active liver disease
- have classical migraines
- have endometrial hyperplasia (thickening of the inner lining of the uterus)
- have known or suspected estrogen-dependent or progestin-dependent tumours such as breast cancer or endometrial cancer, or a history of any of these cancers
- have or have had a stroke or heart attack or coronary heart disease
- have or have had active blood clotting disorders (e.g., thrombophlebitis, deep vein thrombosis, or pulmonary embolism)
- have partial or complete loss of vision from blood vessel disease of the eyes
- have porphyria
- have unusual vaginal bleeding that has not been checked by a doctor
What side effects are possible with this medication?
Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.
The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.
The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.
Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.
- back/neck pain
- bloating or gas
- breast tenderness
- changes in menstrual flow
- darkened skin (chloasma)
- discomfort wearing contact lenses
- fluid retention
- hot flushes
- increased body hair
- irregular vaginal bleeding (in the first 3 months)
- leg cramps
- menstrual pain
- muscle aches
- vaginal itching with or without discharge
- weight gain or loss
Although most of the side effects listed below don't happen very often, they could lead to serious problems if you do not seek medical attention.
Check with your doctor as soon as possible if any of the following side effects occur:
- abdominal pain
- breast lumps
- breast pain
- change in vaginal discharge
- discoloration of skin and mucous membranes
- discharge from nipple
- easy bruising, many or prolonged, exceptionally heavy periods
- endometrial thickening (e.g., abnormal vaginal bleeding, vaginal discharge)
- increased blood pressure
- migraine headache
- painful reddish skin growths
- rapid weight gain
- signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
- signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
- signs of pancreatitis (e.g., abdominal pain on the upper left side, back pain, nausea, fever, chills, rapid heartbeat, swollen abdomen)
- swelling of the arms, feet, or lower legs
- unexpected vaginal bleeding (after you have been taking this medication for 6 months)
- vaginal infections
Stop taking the medication and seek immediate medical attention if any of the following occur:
- rapid pulse or dizziness
- rash with target-shaped reddening or sores
- signs of a serious allergic reaction (e.g., abdominal cramps, difficulty breathing, nausea and vomiting, or swelling of the face and throat)
- signs of blood clot formation (e.g., coughing blood, pains in chest, groin or leg, especially in calf of leg, weakness or numbness in arm or leg)
- signs of heart attack (e.g., chest pain, tightness, sweating, nausea)
- signs of stroke (e.g., sudden or severe headache, sudden loss of coordination, sudden and unexplained shortness of breath, sudden slurring of speech, sudden vision changes)
- tender or painful inflammation of the veins
Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.
Are there any other precautions or warnings for this medication?
Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.
Note the following important information about estrogen replacement therapy:
The Women's Health Initiative (WHI) study results indicated an increased risk of heart attack, stroke, breast cancer, blood clots in the lungs, and blood clots in the leg veins in postmenopausal women during 5 years of treatment with 0.625 mg conjugated equine estrogens and 2.5 mg medroxyprogesterone compared to women receiving sugar tablets. Other combinations of estrogen and progestins were not studied. However, until additional data are available, the risks should be assumed to be similar for other hormone replacement products. Therefore,
- estrogens with or without progestins should be used at the lowest dose that relieves your menopausal symptoms for the shortest time period possible, as directed by your doctor; and
- estrogens with or without progestins should not be used to prevent heart disease, heart attacks, or strokes.
Blood clotting disorders: Estrogens with or without progestins are associated with an increased risk of blood clots in the lungs and legs. This risk also increases with age, a personal or family history of blood clots, smoking, and obesity. The risk of blood clots is also increased if you are immobilized for prolonged periods and with major surgery. If possible, this medication should be stopped 4 weeks before major surgery. Talk about the risk of blood clots with your doctor.
Blood pressure: Women may experience increased blood pressure when using hormone replacement therapy. Your doctor may want to monitor your blood pressure more frequently while you are using norethindrone acetate - estradiol, especially if high doses of estrogen are used. Ask your doctor how often you should have your blood pressure checked.
Breast and ovarian cancer: Studies indicate an increased risk of breast and ovarian cancers with long-term use of estrogen replacement therapy. If you have a history of breast cancer, do not use estrogens. If you have a family history of breast cancer or if you have had breast lumps, breast biopsies, or abnormal mammograms, your doctor will closely monitor your condition while you are using estrogens.
Have a mammogram before starting hormone replacement therapy, have regular breast examinations while taking it, and become familiar with your breasts so you can let your doctor know if anything has changed.
Dementia: Women over age 65 receiving combined hormone replacement therapy (estrogen and progestin) may be at increased risk of developing dementia (loss of memory and intellectual function). If you are over 65, talk to your doctor about whether you should be tested for dementia.
Diabetes: Hormone changes, including hormone replacement therapy, may cause an increase in blood sugar levels (may cause a loss of blood glucose control) and glucose tolerance may change. People with diabetes may find it necessary to monitor their blood sugar more frequently while using this medication.
If you have diabetes or are at risk for developing diabetes, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.
Endometrial cancer: There is evidence from several studies that estrogen replacement therapy can increase the risk of cancer of the endometrium (lining of the uterus). Taking a progestin at the right time along with an estrogen reduces this risk of endometrial cancer to the same level as that of a woman who does not take estrogen. The norethindrone acetate (progestin) in this medication should counteract the risk of endometrial cancer.
Endometriosis: Estrogen replacement therapy can cause endometriosis to reappear or get worse. If you have or have had endometriosis, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.
Fibroids: This medication may worsen fibroids by causing sudden enlargement, pain, or tenderness. If you notice these effects, contact your doctor.
Fluid retention: Estrogen may cause fluid retention, which can worsen some medical conditions (e.g., heart disease, kidney disease, epilepsy, asthma). Talk to your doctor if you have any concerns.
Follow-up examinations: It is important to have a follow-up examination 3 to 6 months after starting this medication to assess the response to treatment. Examinations should be done at least once a year after the first one.
Gallbladder disease: This medication can aggravate gallbladder disease or increase the risk of developing it. If you have gallbladder disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.
Galactose intolerance: This medication is prepared with lactose. If you have lactose or galactose intolerance you should not take these medications.
Heart disease and stroke: Studies indicate an increased risk of heart disease and stroke with estrogen (with or without progestin) for postmenopausal women. Get immediate medical attention if you experience symptoms of a heart attack (chest pain, tightness or pressure, sweating, nausea, feeling of impending doom) or stroke (sudden dizziness, headache, loss of speech, changes in vision, weakness or numbness in the arms and legs).
High cholesterol or triglycerides: Estrogen may increase triglyceride levels in those who already have high levels. Your doctor will monitor your cholesterol and triglyceride levels while you are taking this medication. If you have a condition known as familial hypertriglyceridemia (a disorder leading to high levels of fats known as triglycerides in the blood), discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.
Hypercalcemia and kidney disease: Prolonged use of estrogens can change the metabolism of calcium and phosphorus. If you have a disorder that changes the levels of calcium and phosphorus in the blood, such as metabolic or malignant bone diseases or kidney disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.
Liver disease: People with active liver disease or liver tumours should not use norethindrone acetate - estradiol. If you have or have had liver problems, you may require special monitoring by your doctor while you use this medication. Make sure to tell your doctor if you have ever had liver problems. Your doctor may do blood work to monitor your liver function while you are using norethindrone acetate - estradiol.
If you experience symptoms of liver problems such as fatigue, feeling unwell, loss of appetite, nausea, yellowing of the skin or whites of the eyes, dark urine, pale stools, abdominal pain or swelling, and itchy skin, contact your doctor immediately.
Migraine headaches: For some people who experience migraine headaches, estrogen can aggravate the condition. Talk to your doctor if you notice any change in your migraine pattern while using estrogen.
Other medical conditions: Discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed, if you have any of the following conditions:
- otosclerosis (an ear condition)
- thyroid disease
Systemic lupus erythematosus (SLE, or lupus): Estrogen has been shown to make the symptoms of SLE worse. If you have SLE, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.
Pregnancy: Estrogen should not be used during pregnancy. If you become pregnant while taking this medication, contact your doctor.
Breast-feeding: This medication passes into breast milk. If you are a breast-feeding mother and are using norethindrone acetate - estradiol, it may affect your baby. This medication is not recommended for use by breast-feeding mothers.
Children: The safety and effectiveness of using this medication have not been established for children. This medication is not intended for use by children.
What other drugs could interact with this medication?
There may be an interaction between norethindrone acetate - estradiol and any of the following medications:
- azole antifungal medications (e.g., itraconazole, ketoconazole voriconazole)
- barbiturates (e.g., butalbital, phenobarbital)
- corticosteroids (e.g., dexamethasone, fluticasone, hydrocortisone, prednisone)
- diabetes medications (e.g., acarbose, canagliflozin, glyburide, insulin, linagliptin, lixisenatide, metformin, rosiglitazone)
- grapefruit juice
- HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., efavirenz, etravirine, nevirapine)
- HIV protease inhibitors (e.g., atazanavir, indinavir, ritonavir, saquinavir)
- low-molecular-weight heparins (e.g., dalteparin, enoxaparin, tinzaparin)
- medications used to treat high blood pressure (e.g., atenolol, ramipril, enalapril, lisinopril, amlodipine)
- St. John's wort
- theophyllines (e.g., aminophylline, oxtriphylline, theophylline)
- thyroid replacements (e.g., desiccated thyroid, levothyroxine)
- tranexamic acid
If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:
- stop taking one of the medications,
- change one of the medications to another,
- change how you are taking one or both of the medications, or
- leave everything as is.
An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.
Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.
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