Premphase

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

• St. John's Wort (Hypericum perforatum)
• phenobarbital
• carbamazepine
• rifampin
• erythromycin
• clarithromycin
• ketoconazole
• itraconazole
• ritonavir

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

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 an increased risk of deep vein thrombosis (DVT), pulmonary embolism, stroke and myocardial infarction 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 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 deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral CE (0.625 mg), relative to placebo.

The WHIMS estrogen-alone ancillary study of 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 goals and risks for the individual woman.

Do not use this medication if you have:

• a history of heart attack, stroke, or blood clot (especially in your lung or your lower body);

• abnormal vaginal bleeding that a doctor has not checked;

• a bleeding or blood-clotting disorder;

• liver disease; or

• any type of breast, uterine, or hormone-dependent cancer.

To make sure you can safely take conjugated estrogens and medroxyprogesterone, tell your doctor if you have any of these other conditions:

• high blood pressure, heart disease, or circulation problems;

• a personal or family history of stroke;

• endometriosis;

• liver or kidney disease;

• asthma;

• epilepsy or other seizure disorder;

• migraines;

• diabetes;

• underactive thyroid;

• high cholesterol or triglycerides;

• high or low levels of calcium in your blood;

• porphyria;

• systemic lupus erythematosus (SLE); or

• gallbladder disease.

Conjugated estrogens increase your risk of developing endometrial hyperplasia, a condition that may lead to cancer of the uterus. The medroxyprogesterone contained in this medication may lower this risk. If your uterus has not been removed, talk with your doctor about your specific risk of developing uterine cancer while taking conjugated estrogens and medroxyprogesterone.

Long-term use of conjugated estrogens and medroxyprogesterone may increase your risk of breast cancer, heart attack, stroke, or blood clot. Talk with your doctor about your individual risks before using this medication long term, especially if you smoke or are overweight. Your doctor should check your progress on a regular basis (every 3 to 6 months) to determine whether you should continue this treatment.

FDA pregnancy category X. This medication can harm an unborn baby or cause birth defects. Do not use conjugated estrogens and medroxyprogesterone if you are pregnant. Tell your doctor right away if you become pregnant during treatment. Use effective birth control while you are using this medication.

Conjugated estrogens and medroxyprogesterone can pass into breast milk and may harm a nursing baby. This medication may also slow breast milk production. Do not use if you are breast-feeding a baby.

Do not give this medication to anyone under 18 years old without the advice of a doctor.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop taking this medication and call your doctor at once if you have any of these serious side effects:

• chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;

• sudden numbness or weakness, especially on one side of the body;

• sudden severe headache, confusion, problems with vision, speech, or balance;

• pain, swelling, warmth, or redness in one or both legs;

• abnormal vaginal bleeding;

• migraine headache;

• pain, swelling, or tenderness in your stomach;

• confusion, problems with memory or concentration;

• jaundice (yellowing of the skin or eyes);

• swelling in your hands, ankles, or feet; or

• a breast lump.

Less serious side effects may include:

• mild nausea, vomiting, bloating, stomach pain;

• breast pain, tenderness, or swelling;

• freckles or darkening of facial skin;

• acne, increased hair growth, loss of scalp hair;

• changes in weight or appetite;

• problems with contact lenses;

• vaginal itching or discharge;

• changes in your menstrual periods, decreased sex drive; or

• headache, nervousness, dizziness, tired feeling.

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

Estrogens and progestins are female hormones. They are produced by the body and are necessary for the normal sexual development of the female and for the regulation of the menstrual cycle during the childbearing years.

The ovaries begin to produce less estrogen after menopause (the change of life). This medicine is prescribed to make up for the lower amount of estrogen. Estrogens help relieve signs of menopause, such as hot flashes and unusual sweating, chills, faintness, or dizziness. Progestins help to regulate the effects of estrogens.

Estrogens are prescribed for several reasons:

• to provide additional hormone when the body does not produce enough of its own, such as during menopause. They can also help to relieve a genital skin condition called vaginal or vulvar atrophy.
• to help prevent weakening of bones (osteoporosis) in women past menopause.

Estrogens may also be used for other conditions as determined by your doctor.

There is no medical evidence to support the belief that the use of estrogens will keep the patient feeling young, keep the skin soft, or delay the appearance of wrinkles. Nor has it been proven that the use of estrogens during menopause will relieve emotional and nervous symptoms, unless these symptoms are caused by other menopausal symptoms, such as hot flashes or hot flushes.

Estrogens and progestins are available only with your doctor's prescription.

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group 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.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of estrogens and progestins in the elderly with use in other age groups.

Pregnancy

Estrogens and progestins are not recommended for use during pregnancy or right after giving birth. Becoming pregnant or maintaining a pregnancy is not likely to occur around the time of menopause.

Breast Feeding

Estrogens and progestins pass into the breast milk and can change the content or lower the amount of breast milk. Use of this medicine is not recommended in nursing mothers.

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 any of these medicines, 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 medicines in this class with any of the following medicines is not recommended. Your doctor may decide not to treat you with a medication in this class or change some of the other medicines you take.

• Boceprevir
• Dasabuvir
• Ombitasvir
• Paritaprevir
• Ritonavir
• Tranexamic Acid

Using medicines in this class 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.

• Anagrelide
• Aprepitant
• Boceprevir
• Bosentan
• Bupropion
• Carbamazepine
• Ceritinib
• Conivaptan
• Dabrafenib
• Darunavir
• Dasabuvir
• Dexamethasone
• Donepezil
• Efavirenz
• Eliglustat
• Enzalutamide
• Fosphenytoin
• Griseofulvin
• Idelalisib
• Isotretinoin
• Lesinurad
• Lixisenatide
• Lumacaftor
• Mitotane
• Modafinil
• Netupitant
• Oxcarbazepine
• Paclitaxel
• Paclitaxel Protein-Bound
• Phenytoin
• Piperaquine
• Pitolisant
• Pixantrone
• Prednisone
• Rifabutin
• Rifampin
• St John's Wort
• Sugammadex
• Theophylline
• Tizanidine
• Topiramate
• Ulipristal
• Valproic Acid

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. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of medicines in this class. Make sure you tell your doctor if you have any other medical problems, especially:

• Asthma or
• Calcium, too much or too little in blood or
• Diabetes mellitus (sugar diabetes)
• Epilepsy (seizures) or
• Heart problems or
• Kidney problems or
• Liver tumors, benign or
• Lupus erythematosus, systemic or
• Migraine headaches or
• Porphyria—Estrogens may worsen these conditions.

• Blood clotting problems (or history of during previous estrogen therapy)—Estrogens usually are not used until blood clotting problems stop; using estrogens is not a problem for most patients without a history of blood clotting problems due to estrogen use.

• Breast cancer or
• Bone cancer or
• Cancer of the uterus or
• Fibroid tumors of the uterus—Estrogens may interfere with the treatment of breast or bone cancer or worsen cancer of the uterus when these conditions are present.

• Changes in genital or vaginal bleeding of unknown causes—Use of estrogens may delay diagnosis or worsen condition. The reason for the bleeding should be determined before estrogens are used.

• Endometriosis or
• Gallbladder disease or gallstones (or history of) or
• High cholesterol or triglycerides (or history of) or
• Liver disease or
• Pancreatitis (inflammation of pancreas)—Estrogens may worsen these conditions; while estrogens can improve blood cholesterol, they may worsen blood triglycerides for some people.

• Hypothyroid (too little thyroid hormone)—Dose of thyroid medicine may need to be increased.

• Vision changes, sudden onset including
• Bulging eyes or
• Double vision or
• Migraine headache or
• Vision loss, partial or complete—Estrogens may cause these problems. Tell your doctor if you have had any of these problems, especially while taking estrogen or oral contraceptives (“birth control pills”).

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 Premphase. 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.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take Premphase at the same time of day.
• Take with or without food. Take with food if it causes an upset stomach.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• 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.

This information should not be used to decide whether or not to take Premphase or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Premphase. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017