Pronunciation:

KON-joo-gay-ted ES-troe-jenz, me-drox-ee-proe-JES-ter-one AS-e-tate

Brand Names:

• Premphase
• Prempro
• Prempro Low Dose

Dosage Forms:

• Tablet

Warnings:

Estrogen with or without progestin should not be used for the prevention of cardiovascular disease or dementia. Increased risks of stroke and deep vein thrombosis in postmenopausal women (50 to 79 years) using estrogen alone have been reported. Increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and DVT in postmenopausal women (50 to 79 years) using estrogen combined with progestin have been reported. An increased risk of developing probable dementia in postmenopausal women 65 years or older has also been reported in women receiving estrogen alone or estrogen combined with progestin. Unopposed estrogens increase the risk of endometrial cancer. Adding a progestin will reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Diagnostic measures should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding. Risks should be assumed to be similar for other doses, 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 possible .

Classifications:

Therapeutic—

Estrogen/Progestin Combination

Pharmacologic—

Estrogen

Uses of This Medicine:

Conjugated estrogens and medroxyprogesterone acetate combination is used to treat moderate to severe hot flashes, dryness in and around the vagina, and other symptoms of menopause. This medicine is also used to prevent osteoporosis (thinning of the bones) after menopause.

This medicine is available only with your doctor's prescription.

Before Using This Medicine:

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:

Allergies—

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.

Children—

Conjugated estrogens and medroxyprogesterone acetate combination is not recommended for children.

Older adults—

Although appropriate studies on the relationship of age to the effects of conjugated estrogens and medroxyprogesterone combination have not been performed in the geriatric population, no geriatric-specific problems have been documented to date. However, elderly patients are more likely to have certain unwanted effects (eg, breast cancer, stroke, or dementia), which may require caution in patients receiving this medicine.

Breast-feeding—

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.

Other 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.

• Amifampridine
• Apalutamide
• Aprepitant
• Armodafinil
• Artemether
• Belzutifan
• Bexarotene
• Bosentan
• Bupropion
• Carbamazepine
• Cenobamate
• Clobazam
• Cosyntropin
• Dabrafenib
• Darunavir
• Dexamethasone
• Donepezil
• Efavirenz
• Elagolix
• Elvitegravir
• Enasidenib
• Encorafenib
• Enzalutamide
• Eslicarbazepine Acetate
• Etravirine
• Fosaprepitant
• Fosphenytoin
• Griseofulvin
• Isotretinoin
• Ivosidenib
• Lesinurad
• Lorlatinib
• Lumacaftor
• Mavacamten
• Meropenem
• Mitapivat
• Mitotane
• Mobocertinib
• Modafinil
• Mycophenolic Acid
• Nafcillin
• Nevirapine
• Oxcarbazepine
• Phenobarbital
• Phenylbutazone
• Phenytoin
• Pitolisant
• Prednisone
• Primidone
• Red Clover
• Repotrectinib
• Rifabutin
• Rifampin
• Rifapentine
• Ritonavir
• Rufinamide
• Secobarbital
• St John's Wort
• Sugammadex
• Tazemetostat
• Telaprevir
• Theophylline
• Topiramate
• Ulipristal

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.

• Etoricoxib
• Ginseng
• Levothyroxine
• Licorice
• Tipranavir

Other interactions—

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.

• Caffeine

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 vaginal bleeding or
• Antithrombin deficiency (blood clotting disorder) or
• Blood clots, or history of or
• Breast cancer, or history of or
• Deep vein thrombosis (blood clot in the leg), or history of or
• Heart attack, or history of or
• Hysterectomy (removal of the uterus), history of or
• Liver disease or
• Protein C deficiency (blood clotting disorder) or
• Protein S deficiency (blood clotting disorder) or
• Pulmonary embolism (blood clot in the lung), or history of or
• Stroke, or history of or
• Tumor (estrogen-dependent)—Should not be used in patients with these conditions.

• Asthma or
• Congestive heart failure or
• Diabetes or
• Edema (fluid retention or body swelling) or
• Epilepsy (seizures) or
• Gallbladder disease or
• Hereditary angioedema (swelling of the face, mouth, or throat) or
• Hypertension (high blood pressure) or
• Hypertriglyceridemia (high fats in the blood) or
• Hypothyroidism (an underactive thyroid) or
• Migraine headache or
• Porphyria (an enzyme problem) or
• Systemic lupus erythematosus (SLE)—Use with caution. May make these conditions worse.

Proper Use of This Medicine:

It is very important that you use this medicine only 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 in the leaflet carefully. Ask your doctor if you have any questions.

Dosing—

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 treatment of menopause symptoms and prevention of osteoporosis:
    • Adults—
      • Premphase®: One tablet once a day for 28 days, then repeat the cycle. The maroon colored tablet is taken on days 1 to 14, and the light blue tablet is taken on days 15 to 28.
      • Prempro®: One tablet once a day for 28 days, then repeat the cycle.
    • Children—Use is not recommended.

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—

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.

Precautions While Using This Medicine:

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.

It is unlikely that a postmenopausal woman may become pregnant. But you should know that using this medicine while you are pregnant can 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 of heart attack, stroke, blood clots, dementia, breast cancer, or uterine cancer. Talk with your doctor about these risks.

Your risk of heart disease or stroke from this medicine is higher if you smoke. Your risk is also increased if you have diabetes or high cholesterol, or if you are overweight. Talk with your doctor about ways to stop smoking. Keep your diabetes under control. Ask your doctor about diet and exercise to control your weight and blood cholesterol level.

Tell the medical doctor in charge that you are using this medicine before you have any kind of surgery. Your doctor will decide whether you should continue using this medicine.

Check with your doctor right away if a severe headache or a sudden loss of vision or any 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).

Pancreatitis may occur while you are using this medicine. Check with your doctor right away if you have sudden and severe stomach pain, chills, constipation, nausea, vomiting, fever, or lightheadedness.

This medicine may cause serious types of allergic reactions, including anaphylaxis and angioedema. Anaphylaxis and angioedema can be life-threatening and require immediate medical attention. Call your doctor right away if you have a rash; itching; hoarseness; trouble breathing; trouble swallowing; or any swelling of your hands, face, mouth, or throat while you are using this medicine.

Before you have any medical tests, tell the medical doctor in charge that you are taking this medicine. The results of some tests may be affected by this medicine.

Do not eat grapefruit or drink grapefruit juice while you are using this medicine. Grapefruit and grapefruit juice may cause the amount of medicine in the blood to be too high.

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 (e.g., St. John's wort) or vitamin supplements.

Side Effects of This Medicine:

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:

Less common

Bloating or swelling of the face, arms, hands, lower legs, or feet

blood in the urine

blurred vision

chest pain

clear or bloody discharge from the nipple

cough or hoarseness

dimpling of the breast skin

dizziness

fast, irregular, pounding, or racing heartbeat or pulse

feeling faint, dizzy, or lightheaded

feeling of warmth or heat

fever or chills

flushing or redness of the skin, especially on the face and neck

headache

inverted nipple

lower back or side pain

lump in the breast or under the arm

nervousness

pain during sexual intercourse

painful or difficult urination

persistent crusting or scaling of the nipple

pounding in the ears

redness or swelling of the breast

severe cramping of the uterus

sore on the skin of the breast that does not heal

sweating

thick, white vaginal discharge with no odor or with a mild odor

tingling of the hands or feet

unusual weight gain or loss

vaginal bleeding that is unusual and heavy

vaginal or genital itching

vaginal yeast infection

Incidence not known

Absent, missed, or irregular menstrual periods

acid or sour stomach

anxiety

backache

breast pain or tenderness

confusion

constipation

darkened urine

decreased vision or other changes in vision

difficulty with speaking

double vision

fainting

heartburn

inability to move the arms, legs, or facial muscles

inability to speak

indigestion

loss of appetite

nausea

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 or tender cysts in the breasts

pains in the stomach, side, or abdomen, possibly radiating to the back

slow speech

sudden shortness of breath or troubled breathing

unexpected or excess milk flow from the breasts

vomiting

yellow eyes or skin

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:

More common

Back pain

depression

excess gas in the stomach or intestines

lack or loss of strength

Less common

Blemishes on the skin

body aches or pain

congestion

depersonalization

diarrhea

difficulty with moving

dry skin

dryness of the vagina

dysphoria

euphoria

excessive muscle tone

feeling paranoid

flu-like symptoms

fullness or swelling of the breasts

hair loss or thinning of the hair

headache, severe and throbbing

leg cramps

loss of bladder control

menstrual periods that are longer or heavier

muscle pain or stiffness

pain in the joints

pain or tenderness around the eyes and cheekbones

pimples or acne

quick to react or overreact emotionally

rapidly changing moods

rash

sleeplessness

sore mouth or tongue

stuffy or runny nose

tender, swollen glands in the neck

tightness of the chest or wheezing

trouble with sleeping

trouble with swallowing

vaginal discharge that is clear or white

voice changes

white patches in the mouth or on the tongue

Incidence not known

Changes in appetite

hives or welts

inability to have or keep an erection

increased hair growth, especially on the face

increased interest in sexual intercourse

irritability

loss in sexual ability, desire, drive, or performance

loss of scalp hair

pain in the ankles or knees

painful, red lumps under the skin, mostly on the legs

patchy brown or dark brown discoloration of the skin

redness of the skin

weight changes

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.