Vagifem vaginal inserts contain estradiol, a form of estrogen. Estrogen is a female sex hormone that regulates many processes in the body.

Vagifem is used after menopause to treat menopause symptoms (such as dryness, burning, and irritation) in and around the vagina.

Vagifem is a small, white, round, film-coated, bi-convex vaginal insert containing 10 mcg of estradiol. Each vaginal insert is 6 mm in diameter and is administered in a disposable applicator.

You should not use Vagifem if you have: undiagnosed vaginal bleeding, liver disease, a bleeding disorder, if you will have major surgery, or if you have ever had a heart attack, a stroke, a blood clot, or cancer of the breast, uterus/cervix, or vagina.

Do not use Vagifem if you are pregnant.

Estradiol may increase your risk of developing a condition that may lead to uterine cancer. Report any unusual vaginal bleeding right away.

Using Vagifem can increase your risk of blood clots, stroke, heart attack, or cancer of the breast, uterus, or ovaries. Vagifem should not be used to prevent heart disease, stroke, or dementia.

Before taking this medicine

You should not use Vagifem if you are allergic to estradiol, or if you have:

• unusual vaginal bleeding that has not been checked by a doctor;

• liver disease;

• a history of heart attack, stroke, or blood clot;

• an increased risk of having blood clots due to a heart problem or a hereditary blood disorder; or

• a history of hormone-related cancer, or cancer of the breast, uterus/cervix, or vagina.

Do not use Vagifem if you are pregnant. Tell your doctor right away if you become pregnant during treatment.

Using Vagifem vaginal inserts can increase your risk of blood clots, stroke, or heart attack. You are even more at risk if you have high blood pressure, diabetes, high cholesterol, if you are overweight, or if you smoke.

Vagifem should not be used to prevent heart disease, stroke, or dementia. This medicine may actually increase your risk of developing these conditions.

To make sure Vagifem is safe for you, tell your doctor if you have:

• heart disease;

• liver problems, or jaundice caused by pregnancy or taking hormones;

• kidney disease;

• gallbladder disease;

• asthma;

• epilepsy or other seizure disorder;

• migraines;

• lupus;

• endometriosis or uterine fibroid tumors;

• hereditary angioedema;

• porphyria (a genetic enzyme disorder that causes symptoms affecting the skin or nervous system);

• a thyroid disorder; or

• high or low levels of calcium in your blood.

Using estradiol may increase your risk of cancer of the breast, uterus, or ovaries. Talk with your doctor about this risk.

Estradiol can slow breast milk production. Tell your doctor if you are breast-feeding.

Use Vagifem exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets.

Estradiol may increase your risk of developing a condition that may lead to uterine cancer. Your doctor may prescribe a progestin to help lower this risk. Call your doctor at once if you have any unusual vaginal bleeding.

Wash your hands before and after inserting Vagifem.

Each Vagifem tablet is supplied in a single-use disposable applicator. Throw the tablet applicator away after one use.

Instructions for use of the applicator:

• Tear off a single applicator.

• Separate the plastic wrap and remove the applicator from the plastic wrap. If after opening the package you see that the insert has come out of the applicator but has not fallen out of the package, carefully put it back into the applicator for insertion. Please keep your hands clean and dry while handling the insert.

• Hold the applicator so that the finger of one hand can press the applicator plunger.

• Next select the best position for vaginal insertion of Vagifem vaginal inserts that is most comfortable for you e.g. reclining or standing.

• Using the other hand, guide the applicator gently and comfortably through the vaginal opening. If prior to insertion the insert falls out of the applicator, throw the insert and applicator away and use a new insert-filled applicator.

• The applicator should be inserted (without forcing) as far as comfortably possible, or until half of the applicator is inside your vagina, whichever is less.

• Once the insert-filled applicator has been inserted, gently press the plunger until the plunger is fully depressed. This will eject the insert inside your vagina where it will dissolve slowly over several hours.

• After depressing the plunger, gently remove the applicator and dispose of it the same way you would a plastic tampon applicator. The applicator is of no further use and should be discarded properly. Insertion may be done at any time of the day. It is advisable to use the same time daily for all applications of Vagifem vaginal inserts. If you have any questions, please consult your healthcare provider or pharmacist.

Your doctor should check your progress on a regular basis to determine whether you should continue this treatment. Self-examine your breasts for lumps on a monthly basis and have a mammogram every year while using Vagifem.

If you need major surgery or will be on long-term bed rest, you may need to stop using Vagifem for a short time. Any doctor or surgeon who treats you should know that you are using Vagifem.

Store Vagifem at room temperature away from moisture and heat.

You should not use Vagifem if you are allergic to estradiol, or if you have:

• unusual vaginal bleeding that has not been checked by a doctor;

• liver disease;

• a history of heart attack, stroke, or blood clot;

• an increased risk of having blood clots due to a heart problem or a hereditary blood disorder; or

• a history of hormone-related cancer, or cancer of the breast, uterus/cervix, or vagina.

Do not use Vagifem if you are pregnant. Tell your doctor right away if you become pregnant during treatment.

Using Vagifem vaginal inserts can increase your risk of blood clots, stroke, or heart attack. You are even more at risk if you have high blood pressure, diabetes, high cholesterol, if you are overweight, or if you smoke.

Vagifem should not be used to prevent heart disease, stroke, or dementia. This medicine may actually increase your risk of developing these conditions.

To make sure Vagifem is safe for you, tell your doctor if you have:

• heart disease;

• liver problems, or jaundice caused by pregnancy or taking hormones;

• kidney disease;

• gallbladder disease;

• asthma;

• epilepsy or other seizure disorder;

• migraines;

• lupus;

• endometriosis or uterine fibroid tumors;

• hereditary angioedema;

• porphyria (a genetic enzyme disorder that causes symptoms affecting the skin or nervous system);

• a thyroid disorder; or

• high or low levels of calcium in your blood.

Using estradiol may increase your risk of cancer of the breast, uterus, or ovaries. Talk with your doctor about this risk.

Estradiol can slow breast milk production. Tell your doctor if you are breast-feeding.

Use the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not use two doses at one time.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Avoid smoking. It can greatly increase your risk of blood clots, stroke, or heart attack while using Vagifem.

Avoid using other vaginal products without your doctor's advice.

Grapefruit may interact with estradiol and lead to unwanted side effects. Avoid the use of grapefruit products.

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

Call your doctor at once if you have:

• heart attack symptoms - chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;

• signs of a stroke - sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance;

• signs of a blood clot - sudden vision loss, stabbing chest pain, feeling short of breath, coughing up blood, pain or warmth in one or both legs;

• swelling or tenderness in your stomach;

• jaundice (yellowing of the skin or eyes);

• memory problems, confusion, unusual behavior;

• unusual vaginal bleeding, pelvic pain;

• a lump in your breast; or

• high levels of calcium in your blood - nausea, vomiting, constipation, increased thirst or urination, muscle weakness, bone pain, lack of energy.

Common Vagifem side effects may include:

• nausea, vomiting, bloating, stomach cramps;

• headache;

• swelling in your hands or feet, weight gain;

• breast pain; or

• vaginal itching or discharge, changes in your menstrual periods, breakthrough bleeding.

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.

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

Many drugs can interact with estradiol. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any medicine you start or stop using.