This information summarizes the major risks and benefits of treatment with PREMPRO or PREMPHASE. Read this PATIENT INFORMATION before using the product and each time you get medicine because there may be new information. Talk with your healthcare provider if you have any questions about this medicine.

What is PREMPRO or PREMPHASE? PREMPRO or PREMPHASE is a combination of two hormones, an estrogen and a progestin.What is PREMPRO or PREMPHASE used for?The use of PREMPRO or PREMPHASE may increase your risk of getting breast cancer,blood clots, heart attacks, and strokes. PREMPRO and PREMPHASE should be used onlyas long as needed. Periodically, you and your healthcare provider should discuss whetheryou still need treatment.PREMPRO and PREMPHASE should not be used to prevent heart disease.PREMPRO and PREMPHASE are used• To reduce moderate to severe menopausal symptoms.Estrogens are hormones produced by a woman’s ovaries. Between the ages of 45 and 55, theovaries normally stop making estrogens. This drop in body estrogen level causes the “changeof life” or menopause (the end of monthly menstrual periods). Sometimes both ovaries areremoved during an operation before natural menopause takes place. The sudden drop inestrogen levels causes “surgical menopause.”When the estrogen levels begin dropping, some women develop very uncomfortablesymptoms, such as feelings of warmth in the face, neck, and chest, or sudden intenseepisodes of heat and sweating (“hot flashes” or “hot flushes”). In some women the symptomsare mild; in others they can be severe. Taking PREMPRO or PREMPHASE can help reducethese symptoms.Every 3 to 6 months you and your healthcare provider should discuss whether you still needPREMPRO or PREMPHASE to control your hot flushes.• To treat itching, burning, and dryness in and around the vagina due to menopause.Every 3 to 6 months you and your healthcare provider should discuss whether you still needPREMPRO or PREMPHASE to control your vaginal symptoms.• To help reduce your chance of getting osteoporosis (thin weak bones).Osteoporosis is a thinning of the bones that makes them weaker and allows them to breakmore easily.If you use PREMPRO or PREMPHASE only to prevent osteoporosis, discuss with yourhealthcare provider whether a different treatment might be more appropriate for you.

24Women who have menopause at an early age, are thin, smoke and/or have a family history ofosteoporosis are more likely to develop osteoporosis.PREMPRO or PREMPHASE may be used as part of a program which includes weight-bearing exercise, like walking or running, and taking calcium and vitamin D supplements toreduce your chances of getting osteoporosis. Before you change your exercise habits orcalcium or vitamin D intake, it is important to discuss these lifestyle changes with yourhealthcare provider to find out if they are safe for you. Before you make any change in youruse of PREMPRO or PREMPHASE, talk with your healthcare provider.During menopause, some women develop nervous symptoms or depression. Estrogens do notrelieve these symptoms. You may have heard that taking estrogens for years after menopausewill keep your skin soft and supple and keep you feeling young. There is no evidence for this.Who should not take PREMPRO or PREMPHASE?Do not take PREMPRO or PREMPHASE• If you think you may be pregnant.Taking PREMPRO or PREMPHASE while you are pregnant may harm your unborn child.Do not take PREMPRO or PREMPHASE to prevent miscarriage.• If you have unusual vaginal bleeding.Unusual vaginal bleeding can be a warning sign of a serious condition, including cancer ofthe uterus, especially if it happens after menopause. If you develop vaginal bleeding whiletaking PREMPRO or PREMPHASE, you may need further evaluation. Your healthcareprovider needs to find out the cause of the bleeding so you can receive proper treatment. Ifyou develop vaginal bleeding while taking PREMPRO or PREMPHASE talk with yourhealthcare provider about proper treatment.• If you have or had certain cancers.Estrogens may increase the risk of certain types of cancer, including cancer of the breast oruterus. If you have or have had cancer, talk with your healthcare provider about whether youshould take PREMPRO or PREMPHASE.• If you have or had blood clots, a heart attack, or a stroke.Talk with your healthcare provider if you have or had these conditions, or if you haveabnormal blood clotting conditions.• If you have recently had a baby.PREMPRO and PREMPHASE can be passed to the nursing baby in the breastmilk. Theeffect of this on the baby is not known. Do not take PREMPRO or PREMPHASE to stopyour breasts from filling with milk after a baby is born.• If you had your uterus removed.PREMPRO or PREMPHASE contain a progestin to decrease the risk of developingendometrial hyperplasia (an overgrowth of the lining of the uterus that may lead to cancer).

25In general, if you do not have a uterus, you do not need a progestin, and you should not takePREMPRO or PREMPHASE.• If you have liver problems.Talk with your healthcare provider about your condition.• If you are allergic to PREMPRO or PREMPHASE or any of their ingredients.How should I take PREMPRO or PREMPHASE?• Take 1 PREMPRO or PREMPHASE tablet each day at the same time.• If you miss a dose, take it as soon as possible. However, if it is almost time for your nextdose, skip the missed dose and go back to your normal schedule. Do not take 2 doses at thesame time.PREMPRO comes in two strengths. Check with your healthcare provider periodically to makesure you are using the appropriate dose.PREMPRO or PREMPHASE use may increase your risk of getting breast cancer, blood clots,heart attacks, and strokes. PREMPRO and PREMPHASE should be used only as long as needed.Periodically, you and your healthcare provider should discuss whether you still need treatment.What are the possible risks and side effects of PREMPRO or PREMPHASE?1. Heart disease, stroke and blood clotsThe use of PREMPRO or PREMPHASE may increase your chance of having a heart attack,a stroke, blood clots, a pulmonary embolus (a blood clot formed in the legs or pelvis thatbreaks off and travels to the lungs), retinal thrombosis (a clot in a blood vessel of the eye), orother blood clotting problems. Any of these conditions may cause death or serious long-termdisability. These conditions have been seen in healthy, postmenopausal women, as well as inwomen with a history of heart disease.2. Cancer of the breastLong-term use of PREMPRO or PREMPHASE may increase your chance of having breastcancer. Regular breast exams by a health professional and monthly self-exams arerecommended for all women. Mammography should be scheduled depending on your ageand risk factors.3. Cancer of the uterusEstrogens increase the risk of getting a condition (endometrial hyperplasia) that may lead tocancer of the lining of the uterus. The risk of cancer of the uterus increases when estrogensare used alone, the longer they are used, and when larger doses are taken. Taking progestinswith estrogens lowers the risk of getting this condition. PREMPRO and PREMPHASEcontain estrogen and progestin.

Ovarian cancer - Some studies suggest that there is a greater risk of ovarian cancer in women who have usedestrogen alone for a long period of time, especially 10 years or more. Other studies have notshown this risk. The risk with PREMPRO or PREMPHASE treatment is unclear.5. Vaginal bleedingIf you develop vaginal bleeding while taking PREMPRO or PREMPHASE, discuss yourbleeding pattern with your healthcare provider. This is because vaginal bleeding aftermenopause may be a warning sign of a serious condition, including cancer of the uterus.6. Gallbladder diseaseWomen who use PREMPRO or PREMPHASE after menopause are more likely to developgallbladder disease needing surgery than women who do not use estrogens.7. Blood pressureSome women who are taking PREMPRO or PREMPHASE may have increases in bloodpressure.8. Liver problemsIf you had yellowing of your skin or eyes associated with pregnancy, or with taking estrogens(eg, oral contraceptives), this condition may occur again with PREMPRO or PREMPHASEtreatment.9. HypothyroidismWomen who are taking PREMPRO or PREMPHASE, and who use thyroid replacementtherapy may require increased doses of their thyroid medication.10. Effects on blood sugarTaking PREMPRO or PREMPHASE may affect blood sugar levels, which might make adiabetic condition worse.11. Other conditionsFluid retention due to PREMPRO or PREMPHASE treatment may make some conditionsworse, such as heart disease or kidney disease. Estrogen treatment may also worsen asthma,epilepsy, migraine, porphyria and endometriosis.In addition to the risks listed above, the following common side effects have been reportedwith estrogen and/or progestin use:• Nausea, vomiting, pain, cramps, swelling, or tenderness in the abdomen.• Breast tenderness or enlargement, pain or discharge.• Enlargement of benign tumors ("fibroids") of the uterus.• Change in amount of cervical secretion.• Vaginal yeast infections.

27• A spotty darkening of the skin, particularly on the face; reddening of the skin; skin rashes.• Retention of fluid (edema).• Headache, migraines, dizziness, or changes in vision (including intolerance to contactlenses).• Mental depression.• Involuntary muscle spasms.• Hair loss or abnormal hairiness.• Increase or decrease in weight.• Changes in sex drive.What can I do to lower my chances of getting a serious side effect with PREMPRO orPREMPHASE?If you take PREMPRO or PREMPHASE you can reduce your risks by doing these things:• See your healthcare provider regularly.Check with your healthcare provider to make sure you do not stay on treatment longer thanneeded. While you are taking PREMPRO or PREMPHASE, it is important to visit yourhealthcare provider at least once a year for a checkup. If you develop vaginal bleeding whiletaking PREMPRO or PREMPHASE, you may need further evaluation. Every 3 to 6 months youand your healthcare provider should discuss whether or not you still need PREMPRO orPREMPHASE to control your hot flushes and vaginal symptoms.You should talk with your healthcare provider about stopping PREMPRO or PREMPHASE 4 to6 weeks before surgery or during prolonged bedrest.If members of your family have had breast cancer or if you have ever had breast lumps or anabnormal mammogram (breast X-ray), you may need to have more frequent breast examinations.Examine your breasts for changes every month.• Be alert to signs of trouble.If any of the following warning signals (or any other unusual symptoms) happen while you areusing PREMPRO or PREMPHASE, call your healthcare provider immediately:• Abnormal bleeding from the vagina (possible uterine abnormality/cancer).• Pains in the calves or chest, a sudden shortness of breath or coughing blood(indicating possible clots in the legs, heart, or lungs).

28• Severe headache or vomiting, dizziness, faintness, or changes in vision or speech,weakness or numbness of an arm or leg (indicating possible clots in the brain [stroke]or eye).• Breast lumps (possible breast cancer). Ask your healthcare provider to show you howto examine your breasts.• Yellowing of the skin and/or whites of the eyes (possible liver problems).• Pain, swelling, or tenderness in the abdomen (possible gallbladder problem).Other information1. Your healthcare provider prescribed this drug for you and you alone. Do not give this drug toanyone else.2. Keep this and all drugs out of reach of children. In case of overdose, call your doctor orhealthcare provider, hospital, or poison control center right away.HOW SUPPLIEDPREMPRO™therapy consists of a single tablet to be taken once daily.PREMPRO 0.625 mg/2.5 mgEach carton includes 3 EZ DIAL™dispensers containing 28 tablets. One EZ DIAL dispensercontains 28 oval, peach tablets containing 0.625 mg of the conjugated estrogens found inPremarin®tablets and 2.5 mg of medroxyprogesterone acetate for oral administration.PREMPRO 0.625 mg/5mgEach carton includes 3 EZ DIAL dispensers containing 28 tablets. One EZ DIAL dispensercontains 28 oval, light-blue tablets containing 0.625 mg of the conjugated estrogens found inPremarin tablets and 5 mg of medroxyprogesterone acetate for oral administration.PREMPHASE®therapy consists of two separate tablets; one maroon Premarin tablet taken dailyon days 1 through 14 and one light-blue tablet taken on days 15 through 28.Each carton includes 3 EZ DIAL dispensers containing 28 tablets. One EZ DIAL dispensercontains 14 oval, maroon Premarin tablets containing 0.625 mg of conjugated estrogens and14 oval, light-blue tablets that contain 0.625 mg of the conjugated estrogens found in Premarintablets and 5 mg of medroxyprogesterone acetate for oral administration.The appearance of PREMPRO tablets is a trademark of Wyeth-Ayerst Laboratories.The appearance of Premarin tablets is a trademark of Wyeth-Ayerst Laboratories. Theappearance of the conjugated estrogens/medroxyprogesterone acetate combination tablets is aregistered trademark.Keep out of reach of children.

29. Store at controlled room temperature 20°C - 25°C (68°F - 77°F).U.S. Patent Nos. 5,547,948; 5,210,081; Re. 36,247®Ayerst LaboratoriesA Wyeth-Ayerst CompanyPhiladelphia, PA 19101CI 7754-1Revised August 20, 2002

Information above came from www.fda.gov