Estring

Grapefruit and grapefruit juice may interact with Estring and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Before using Estring, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to Estring or to any of its ingredients
• have or have ever had asthma
• have seizures
• have migraine headaches
• have a history of strokes
• have a history of heart attack
• have a known or suspected history of breast cancer
• have a known or suspected estrogen-dependent cancer
• have a history of blood clots
• have endometriosis (a condition in which the type of tissue that lines the uterus [womb] grows in other areas of the body)
• have uterine fibroids (growths in the uterus that are not cancer)
• have or have had yellowing of the skin or eyes, especially during pregnancy or while you were using an estrogen product
• have very high or very low levels of calcium in your blood
• have porphyria (condition in which abnormal substances build up in the blood and cause problems with the skin or nervous system) or gallbladder, thyroid, pancreas, liver or kidney disease
• are pregnant or breastfeeding

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

Store Estring at 15° to 30° C (59° to 86° F).

Keep this and all medicines out of the reach of children.

This section provides information on the proper use of a number of products that contain estrogen. It may not be specific to Estring. Please read with care.

Vaginal estrogen products usually come with patient directions. Read them carefully before using this medicine.

Wash your hands before and after using the medicine. Also, keep the medicine out of your eyes. If this medicine does get into your eyes, wash them out immediately, but carefully, with large amounts of tap water. If your eyes still burn or are painful, check with your doctor.

Use this medicine only as directed. Do not use more of it and do not use it for a longer time than your doctor ordered. It can take up to 4 months to see the full effect of the estrogens. Your doctor may reconsider continuing your estrogen treatment or may lower your dose several times within the first one or two months, and every 3 to 6 months after that. Sometimes a switch to oral estrogens may be required for added benefits or for higher doses. When using the estradiol vaginal insert or ring, you will need to replace it every 3 months or remove it after 3 months.

For vaginal creams or suppositories:

• Vaginal creams and some vaginal suppositories are inserted with a plastic applicator. Directions for using the applicator are supplied with your medicine. If you do not see your dose marked on the applicator, ask your health care professional for more information.
• To fill the applicator for cream dosage forms:
  • Screw the applicator onto the tube.
  • Squeeze the medicine into the applicator slowly until it is measured properly.
  • Remove the applicator from the tube. Replace the cap on the tube.
• To fill the applicator for suppository dosage form:
  • Place the suppository into the applicator.
• To place the dose using the applicator for cream and suppository dosage forms:
  • Relax while lying on your back with your knees bent or stand with one foot on a chair.
  • Hold the full applicator in one hand. Slide the applicator slowly into the vagina. Stop before it becomes uncomfortable.
  • Slowly press the plunger until it stops.
  • Withdraw the applicator. The medicine will be left behind in the vagina.
• To care for the applicator for cream and suppository dosage forms:
  • Clean the applicator after use by pulling the plunger out of the applicator and washing both parts completely in warm, soapy water. Do not use hot or boiling water.
  • Rinse well.
  • After drying the applicator, replace the plunger.

For vaginal insert or ring dosage form:

• To place the vaginal insert:
  • Relax while lying on your back with your knees bent or stand with one foot on a chair.
  • Pinch or press the sides of the vaginal insert together, between your forefinger and middle finger.
  • With one hand, part the folds of skin around your vagina.
  • Slide the vaginal insert slowly into the upper third of your vagina. Stop before it becomes uncomfortable. The exact location is not too important but it should be comfortable.
  • If it seems uncomfortable, then carefully push the vaginal insert higher into the vagina.
• To remove the vaginal insert:
  • Stand with one foot on a chair.
  • Slide one finger into the vagina and hook it around the closest part of the vaginal insert.
  • Slowly pull the vaginal insert out.
  • Dispose of the vaginal insert by wrapping it up and throwing it into the trash. Do not flush it down the toilet.

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 conjugated estrogens
• For vaginal dosage form (cream):
  • For treating inflammation of the vagina (atrophic vaginitis):
    • Adults—At first, 0.5 gram (g) of conjugated estrogens inserted into the vagina once a day or as directed by your doctor to achieve the lowest dose possible. Usually your doctor will want you to use this medicine for only three weeks of each month (three weeks on and one week off). Your doctor may increase your dose as needed. However, the dose is usually not more than 2 grams per day.
  • For treating a genital skin condition (vulvar atrophy):
  • Adults—0.5 gram (g) of conjugated estrogens inserted into the vagina two times per week. Usually your doctor will want you to use this medicine for only three weeks of each month (three weeks on and one week off).

For estradiol
• For vaginal dosage form (cream):
  • For treating a genital skin condition (vulvar atrophy) and inflammation of the vagina (atrophic vaginitis):
    • Adults—200 to 400 micrograms (mcg) of estradiol (two to four grams of cream) inserted into the vagina once a day for one to two weeks, decreasing the dose by one half over two and four weeks. After four weeks, your doctor will probably ask you to use the medicine less often, such as 100 mcg (one gram of cream) one to three times a week and for only three weeks of each month (three weeks on and one week off).
• For vaginal dosage form (insert or ring):
  • For treating a genital skin condition (vulvar atrophy), inflammation of the vagina (atrophic vaginitis) in postmenopausal women, and inflammation of the urethra (urethritis) in postmenopausal women:
    • Adults—One insert containing 2 to 24.8 milligrams (mg) of estradiol inserted into the vagina every three months. The insert will slowly release estradiol at a rate of 7.5 to 100 micrograms (mcg) every twenty-four hours with continuous use.

For estrone
• For vaginal dosage form (cream):
  • For treating a genital skin condition (vulvar atrophy) and inflammation of the vagina (atrophic vaginitis) in postmenopausal women:
    • Adults—2 to 4 milligrams (mg) of estrone (two to four grams of cream) inserted into the vagina once a day or as directed by your doctor.
• For vaginal dosage form (suppository):
  • For treating a genital skin condition (vulvar atrophy) and inflammation of the vagina (atrophic vaginitis) in postmenopausal women:
    • Adults—250 to 500 micrograms (mcg) inserted into the vagina once a day or as directed by your doctor.

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.

When using the suppository or cream several times a week: If you miss a dose of this medicine and remember it within 1 or 2 days of the missed dose, use the missed dose 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.

When using the cream or suppositories more than several times a week: If you miss a dose of this medicine, use it as soon as possible if remembered within 12 hours of the missed dose. 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.

The risk of any serious adverse effect is unlikely for most women using low doses of estrogens vaginally. Even women with special risks have used vaginal estrogens without problems.

Check with your doctor immediately if any of the following side effects occur:

• Breast pain
• enlarged breasts
• itching of the vagina or genitals
• headache
• nausea
• stinging or redness of the genital area
• thick, white vaginal discharge without odor or with a mild odor

• Feeling of vaginal pressure (with estradiol vaginal insert or ring)
• unusual or unexpected uterine bleeding or spotting
• vaginal burning or pain (with estradiol vaginal insert or ring)

• Diarrhea
• dizziness
• fast heartbeat
• feeling faint
• fever
• hives
• hoarseness
• itching
• joint pain, stiffness, or swelling
• muscle pain
• rash
• shortness of breath
• skin redness
• swelling of eyelids, face, lips, hands, or feet
• tightness in the chest
• trouble with breathing or swallowing
• vomiting
• wheezing

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:

• Abdominal or back pain
• clear vaginal discharge (usually means the medicine is working)

• Acne
• enlargement of penis or testes
• growth of pubic hair
• rapid increase in height
• swelling of the breasts or breast soreness in males

Also, many women who are using estrogens with a progestin (another female hormone) will start having monthly vaginal bleeding that is similar to menstrual periods. This effect will continue for as long as the medicine is taken. However, monthly bleeding will not occur in women who have had the uterus removed by surgery (hysterectomy).

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.

• Tell all of your health care providers that you take Estring. This includes your doctors, nurses, pharmacists, and dentists.
• If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
• Be sure to have regular breast exams and gynecology check-ups. Your doctor will tell you how often to have these. You will also need to do breast self-exams as your doctor has told you. Talk with your doctor.
• High blood pressure has happened with drugs like this one. Have your blood pressure checked as you have been told by your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
• Do not smoke. Smoking raises the chance of heart disease. Talk with your doctor.
• Limit your drinking of alcohol.
• If you drink grapefruit juice or eat grapefruit often, talk with your doctor.
• This medicine may raise the chance of blood clots, a stroke, or a heart attack. Talk with the doctor.
• Talk with your doctor if you will need to be still for long periods of time like long trips, bedrest after surgery, or illness. Not moving for long periods may raise your chance of blood clots.
• If you are 65 or older, use Estring with care. You could have more side effects.
• This medicine is not approved for use in children. Talk with the doctor.
• Tell your doctor if you have trouble getting the ring out.
• Toxic shock syndrome (TSS) has happened in a few patients using vaginal rings. TSS is rare, but can be very bad and sometimes deadly. Tell your doctor right away if you have loose stools (diarrhea), dizziness or light-headedness, passing out, fever, muscle pain, upset stomach, throwing up, or a sunburn-like rash.

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

• Follow how to use as you have been told by the doctor or read the package insert.
• Wash your hands before use.
• Put into the vagina and leave in place for 90 days.
• To use, wash your hands and take ring from the pouch.
• Be sure your hands are dry before you touch Estring.
• Press sides of ring at the same time between thumb and index finger and put folded ring into the vagina.
• Perfect placement is not needed for the ring to work. The ring will not hurt.
• If the ring comes out, rinse with lukewarm water and put back in.
• To take out, hook your index finger around the rim or hold rim between index finger and middle finger and pull out.
• Do not throw the vaginal ring in the toilet.
• Wash your hands after use.

What do I do if I miss a dose?

• Use 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 use 2 doses at the same time or extra doses.

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.

Estrogen-Alone Therapy

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 and random endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal genital bleeding. (See WARNINGS, Malignant Neoplasms, Endometrial Cancer.)

Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia. (See CLINICAL STUDIES and WARNINGS, Cardiovascular Disorders, and Probable Dementia.)

The Women's Health Initiative (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 conjugated estrogens (CE) [0.625 mg]-alone, relative to placebo. (See CLINICAL STUDIES and WARNINGS, Cardiovascular Disorders.)

The WHI Memory Study (WHIMS)estrogen-alone ancillary study of the 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. (See CLINICAL STUDIES and WARNINGS, Probable Dementia and PRECAUTIONS, Geriatric Use.)

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.

Estrogen Plus Progestin Therapy

Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia. (See CLINICAL STUDIES and WARNINGS, Cardiovascular Disorders and Probable Dementia.)

The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism (PE), stroke and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral CE (0.625 mg) combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo. (See CLINICAL STUDIES and WARNINGS, Cardiovascular Disorders.)

The 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. (See CLINICAL STUDIES and WARNINGS, Probable Dementia and PRECAUTIONS, Geriatric Use.)

The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer. (See CLINICAL STUDIES and WARNINGS, Malignant Neoplasms, Breast Cancer.)

In the absence of comparable data, these risks should be assumed to be similar for other doses of CE plus MPA, and other combinations and dosage forms of estrogens and progestins.

Estrogens with or without progestins should be prescribed at the lowest doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

Estring® (estradiol vaginal ring) is a slightly opaque ring with a whitish core containing a drug reservoir of 2 mg estradiol. Estradiol, silicone polymers and barium sulfate are combined to form the ring. When placed in the vagina, Estring releases estradiol, approximately 7.5 mcg per 24 hours, in a consistent stable manner over 90 days. Estring has the following dimensions: outer diameter 55 mm; cross-sectional diameter 9 mm; core diameter 2 mm. One Estring should be inserted into the upper third of the vaginal vault, to be worn continuously for three months.

Estradiol is chemically described as estra-1, 3, 5(10)-triene-3, 17β-diol. The molecular formula of estradiol is C18H24O2 and the structural formula is:

The molecular weight of estradiol is 272.39.

Overdosage of estrogen may cause nausea, vomiting, breast tenderness, abdominal pain, drowsiness and fatigue, and withdrawal bleeding may occur in women. Treatment of overdose consists of discontinuation of Estring together with institution of appropriate symptomatic care.

NDC 0013-2150-36

Rx only

Estring®
(estradiol vaginal ring)
2 mg

Store at controlled room temperature
15 °C to 25 °C (59 °F to 77 °F).

DOSAGE AND USE
See accompanying prescribing information.

Package Not Child-Resistant.
Keep out of reach of children.

One ring, 7.5 mcg/24 hrs of estradiol is released over 90 days.

612796

Pfizer

Pharmacia & Upjohn Co
Division of Pfizer Inc, NY, NY 10017

LOT
EXP