Estring

Clinical summary

Indications and usage INDICATIONS AND USAGE ESTRING is indicated for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause. Dosage and administration DOSAGE AND ADMINISTRATION One ESTRING (estradiol vaginal system) is to be inserted as deeply as possible into the upper one-third of the vaginal vault. The ring is to remain in place continuously for three months, after which it is to be removed and, if appropriate, replaced by a new ring. Should the ring be removed or fall out at any time during the 90-day treatment period, the ring should be rinsed in lukewarm water and re-inserted by the patient, or, if necessary, by a physician or nurse. Retention of the ring for greater than 90 days does not represent overdosage but will result in progressively greater underdosage with the attendant risk of loss of efficacy and increasing risk of vaginal infections and/or erosions. Instructions for Use ESTRING (estradiol vaginal system) insertion The ring should be pressed into an oval and inserted into the upper third of the vaginal vault. The exact position is not critical. When ESTRING is in place, the patient should not feel anything. If the patient feels discomfort, ESTRING is probably not far enough inside. Gently push ESTRING further into the vagina. ESTRING use ESTRING should be left in place continuously for 90 days and then, if continuation of therapy is deemed appropriate, replaced by a new ESTRING. The patient should not feel ESTRING when it is in place and it should not interfere with sexual intercourse. Straining at defecation may make ESTRING move down in the lower part of the vagina. If so, it may be pushed up again with a finger. If ESTRING is expelled totally from the vagina, it should be rinsed in lukewarm water and reinserted by the patient (or doctor/nurse if necessary). ESTRING removal ESTRING may be removed by hooking a finger through the ring and pulling it out. For patient instructions, see Patient Information . Warnings and cautions WARNINGS 1. Endometrial Cancer with Unopposed Estrogen in Women with a Uterus In ESTRING-treated menopausal women with a uterus with persistent or recurring abnormal genital bleeding of unknown etiology, perform adequate diagnostic measures, including directed or random endometrial sampling when indicated, to assess for endometrial cancer. There is an increased risk of endometrial cancer with the use of systemic estrogens alone in women with a uterus. The reported endometrial cancer risk among unopposed systemic estrogen users is about 2 to 12 times greater than in non-users and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with the use of systemically administered estrogens for less than one year. The greatest risk appears to be associated with prolonged use, with increased risks of 15- to 24-fold for 5 to 10 years or more. This risk has been shown to persist for at least 8 to 15 years after systemic estrogen therapy is discontinued. There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose. Adding a progestogen to estrogen-alone therapy has been shown to reduce the risk of endometrial hyperplasia (possible precursor to endometrial cancer). There is, however, a different risk profile associated with the use of progestogens plus estrogens compared to estrogen-alone regimens. 2. Risks Associated with Concomitant Use of Estrogen Plus Progestogen If ESTRING is administered with a progestogen, there are possible risks associated with the concomitant use of estrogen with progestogen that differ from those of estrogen-alone regimens. Refer to the prescribing information for progestogens indicated for the prevention of endometrial hyperplasia in nonhysterectomized women receiving estrogens for a discussion of the risks of estrogen and progestogen concomitant therapy. 3. Risks with Systemic Estrogen-Alone Therapy Systemic absorption occurs with the use of ESTRING, although the exposure is generally lower than that of systemic estrogens indicated for vasomotor symptoms. As such, the relevance or extent of the following risks of systemic estrogens to ESTRING is not known. The following adverse reactions have been reported with systemic estrogen therapy: Cardiovascular diseases: The Women’s Health Initiative (WHI) estrogen-alone trial reported increased risks of pulmonary embolism (PE), deep vein thrombosis (DVT), and stroke, in postmenopausal women (50 to 79 years of age, average age 63.4 years) during 7.2 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg] relative to placebo. (See CLINICAL STUDIES .) Breast cancer: In the WHI estrogen-alone trial, after an average follow-up of 7.1 years, daily oral CE-alone was not associated with an increased risk of invasive breast cancer. (See CLINICAL STUDIES .) However, a large meta-analysis including 24 p