estradiol valerate 40 mg/ml vl generic delestrogen

Uses

Estradiol

Oral, transdermal, or topical estradiol is used for the management of moderate to severe vasomotor symptoms associated with menopause and for the management of vulvar and vaginal atrophy (atrophic vaginitis, kraurosis vulvae). Oral or transdermal estradiol is used for the treatment of female hypoestrogenism due to hypogonadism, castration, or primary ovarian failure. If estrogens are used solely for the management of vulvar and vaginal atrophy, use of topical vaginal preparations should be considered. Estradiol also may be administered intravaginally as a cream or tablet for the management of vulvar and vaginal atrophy. Estradiol vaginal ring is used for the management of urogenital symptoms associated with postmenopausal atrophy of the vagina (i.e., dryness, burning, pruritus, dyspareunia) and/or lower urinary tract (i.e., urinary urgency, dysuria).

Oral or transdermal estradiol (Alora, Climara, Climara Pro, Estraderm, Menostar, Vivelle, Vivelle-Dot) is used adjunctively with other therapeutic measures (e.g., diet, calcium, weight-bearing exercise [including walking, running], physical therapy) to retard further bone loss and the progression of osteoporosis associated with estrogen deficiency in postmenopausal women. While estrogen replacement therapy is effective for the prevention of osteoporosis in women and has been shown to reduce bone resorption and retard or halt bone loss in postmenopausal women, such therapy is associated with a number of adverse effects. If prevention of postmenopausal osteoporosis is the sole indication for estrogen therapy, alternative therapy (e.g., alendronate, raloxifene, risedronate) also should be considered.

While results from earlier observational studies indicated that estrogen replacement therapy (ERT) or combined estrogen/progestin therapy (HRT) was associated with cardiovascular benefit in postmenopausal women, results from recent controlled studies indicate that hormone therapy does not decrease the incidence of cardiovascular disease. The American Heart Association (AHA), American College of Obstetricians and Gynecologists (ACOG), US Food and Drug Administration (FDA) and manufacturers recommend that hormone therapy not be used to prevent heart disease in healthy women (primary prevention) or to protect women with preexisting heart disease (secondary prevention).

Oral estradiol is used for the palliative treatment of advanced, inoperable, metastatic carcinoma of the breast in postmenopausal women and in men. Estrogens are one of several second-line agents that can be used in certain postmenopausal women with metastatic breast cancer.

Oral estradiol is used for the palliative treatment of advanced carcinoma of the prostate in men; however, the risk of adverse cardiovascular effects of estrogens must be considered.

Estradiol Acetate

Oral estradiol acetate and estradiol acetate vaginal ring are used for management of moderate to severe vasomotor symptoms associated with menopause. Estradiol acetate vaginal ring also is used for the management of moderate to severe symptoms of vulvar and vaginal atrophy associated with menopause. If estradiol acetate vaginal ring is used solely for the management of vulvar and vaginal atrophy, use of an alternative topical vaginal preparation should be considered.

Estradiol Cypionate

Estradiol cypionate is used for the management of moderate to severe vasomotor symptoms associated with menopause. Estradiol cypionate also is used for the management of female hypogonadism.

Estradiol cypionate in fixed combination with testosterone cypionate is used for the management of moderate to severe vasomotor symptoms associated with menopause. While estrogen/androgen combinations were found to be effective for this indication under a determination made by the US Food and Drug Administration (FDA) in 1976, formal administrative proceedings were initiated by the FDA in April 2003 to examine the effectiveness of estrogen/androgen combinations for the management of vasomotor symptoms associated with menopause. FDA is undertaking this action because the agency does not believe there is substantial evidence available to establish the contribution of androgens to the effectiveness of estrogen/androgen combinations for the management of vasomotor symptoms in menopausal women who do not respond adequately to estrogen alone. The FDA will allow continued marketing of combination estrogen/androgen products while the matter is under study.

Estradiol cypionate in fixed combination with medroxyprogesterone acetate is used parenterally as a long-active contraceptive in women. For additional information on contraceptive use of estradiol cypionate in fixed combination with medroxyprogesterone acetate,

Estradiol Valerate

In women, estradiol valerate is used for the management of moderate to severe vasomotor symptoms associated with menopause. Estradiol valerate also is used for the management of vulvar and vaginal atrophy, female hypogonadism and castration, and primary ovarian failure. If estrogens are used solely for the management of vulvar and vaginal atrophy, use of topical vaginal preparations should be considered.

Estradiol valerate is used for the palliative treatment of advanced carcinoma of the prostate in men; however, the risk of adverse cardiovascular effects of estrogens must be considered.

Although in the past estradiol valerate was used for the prevention of postpartum breast engorgement, the FDA has withdrawn approval of estrogen-containing drugs for this indication since estrogens have not been shown to be safe for use in women with postpartum breast engorgement. Data from controlled studies indicate that the incidence of substantial painful engorgement is low in untreated women, and the condition usually responds to appropriate analgesic or other supportive therapy.

Ethinyl Estradiol

Ethinyl estradiol in fixed combination with norethindrone acetate is used for the management of moderate to severe vasomotor symptoms associated with menopause. Ethinyl estradiol in fixed combination with norethindrone acetate also is used adjunctively with other therapeutic measures (e.g., diet, calcium, weight-bearing exercise [including walking, running], physical therapy) to retard further bone loss and the progression of osteoporosis associated with estrogen deficiency in postmenopausal women. While estrogen replacement therapy is effective for the prevention of osteoporosis in women and has been shown to reduce bone resorption and retard or halt bone loss in postmenopausal women, such therapy is associated with a number of adverse effects. If prevention of postmenopausal osteoporosis is the sole indication for estrogen therapy, alternative therapy (e.g., alendronate, raloxifene, risedronate) also should be considered.

Dosage and Administration

Reconstitution and Administration

Estradiol is administered orally, intravaginally, percutaneously by topical application of a transdermal system, and by topical application of a gel, emulsion, or transdermal spray to the skin. Estradiol acetate is administered orally and intravaginally. Ethinyl estradiol is administered orally. Estradiol cypionate and estradiol valerate are administered IM.

Patients receiving a transdermal estradiol system should be carefully instructed in the use of the transdermal system. To obtain optimum results, patients should also be given a copy of the patient instructions provided by the manufacturer. To expose the adhesive surface of the system, the protective strip should be peeled and discarded prior to administration. The transdermal system is applied topically to a clean, dry, and not excessively hairy area of intact skin on the trunk of the body, preferably the abdomen or buttocks, by firmly pressing the system with the adhesive side touching the skin. The system should be applied immediately after removal from its protective pouch and removal of the protective liner. The system should be pressed firmly in place with the palm of the hand for about 10 seconds, ensuring good contact, particularly around the edges. The application site should not be oily, damaged, or irritated. The transdermal system should not be applied to the breasts, and application at the waistline should be avoided, since tight clothing may cause the system to be rubbed off. If the system should inadvertently come off during the period of use, it may be reapplied or, if necessary, a new system may be applied; in either case, the application schedule employed should be continued. To minimize and/or prevent potential skin irritation, each transdermal system should be applied at a different site, with an interval of at least 1 week allowed between applications to a particular site. Estradiol transdermal systems are applied once (Climara, Climara Pro, Estradiol Transdermal System [Mylan], Menostar) or twice (Alora, Combipatch, Estraderm, Vivelle, Vivelle-Dot) weekly; the system in use is removed and discarded and a new system is applied. The transdermal systems for application twice weekly are commercially available in a dispensing package that is designed to aid the user in complying with the prescribed dosage regimen (the same 2 days each week). If a system is not changed on a designated day, it should be replaced as soon as possible.

Patients receiving estradiol topical gel (Elestrin, EstroGel) should be instructed in use of the gel and given a copy of the patient instructions provided by the manufacturer. Estradiol topical gel should be applied topically once daily at the same time each day to clean, dry, intact skin. To apply a dose of Elestrin, the pump should be held with the tip facing the arm and the pump should be firmly and fully depressed. Elestrin gel is applied to the upper arm and shoulder using 2 fingers.To apply a dose of EstroGel, the gel should be collected in the palm of the hand by pressing the pump firmly and fully. EstroGel gel is applied to one arm from shoulder to wrist using the hand. The topical gel should not be applied to the breasts or in or around the vagina. The application site should be allowed to dry for up for 5 minutes before dressing. Hands should be washed with soap and water after application of the gel. It is not known how long bathing and swimming should be delayed after application of the gel. Therefore, estradiol topical gel should be applied after bathing; the time allowed between application of the gel and swimming should be as long as possible (at least 2 hours). Application of sunscreen 10 minutes prior to application of Elestrin increases exposure to estradiol by 55%, and application of sunscreen 25 minutes after application of Elestrin does not alter exposure to estradiol. Application of sunscreen for 7 days to the site of application of Elestrin increased estradiol exposure twofold; this effect was noted when sunscreen was applied before and after application of Elestrin. Concomitant application of EstroGel and sunscreen preparations has not been evaluated.

Patients receiving estradiol topical emulsion (Estrasorb) should be instructed in use of the emulsion and given a copy of the patient instructions provided by the manufacturer. Estradiol topical emulsion should be applied topically once daily every morning to clean, dry, intact skin. To apply a dose, the contents of one pouch should be placed on the left thigh. The emulsion should be rubbed into the entire left thigh and calf for 3 minutes using one or both hands. Any excess emulsion remaining on the hands can be rubbed onto the buttocks. The contents of another pouch should be placed on the right thigh. The emulsion should be rubbed into the entire right thigh and calf for 3 minutes using one or both hands. Any excess emulsion remaining on the hands can be rubbed onto the buttocks. The emulsion should be applied immediately after opening the pouch. The application site should be allowed to dry before dressing. Hands should be washed with soap and water after application of the emulsion. Estradiol topical emulsion should not be applied in close proximity to application of sunscreen. Application of sunscreen 10 minutes prior to application of estradiol topical emulsion increases exposure to estradiol by 35%, and application of sunscreen 25 minutes after application of estradiol topical emulsion increases exposure to estradiol by 15%.

Patients receiving estradiol transdermal spray (Evamist) should be instructed in use of the spray and given a copy of the patient instructions provided by the manufacturer. Estradiol transdermal spray should be applied topically once daily at the same time each day to clean, dry, intact skin on the inside of the forearm between the elbow and the wrist. Prior to initial use, estradiol transdermal spray pump must be primed; it is not necessary to prime the pump before each daily dose. To prime the pump, the applicator is held upright with the cover on and the pump depressed three times. To apply a dose of estradiol transdermal spray, the cover should be removed, the applicator held upright and the cone section of the applicator placed flat against the skin; the pump should then be depressed. One, two, or three sprays may be applied to non-overlapping areas of the inner forearm, starting near the elbow. Estradiol transdermal spray should not be applied to any area other than the inner forearm; the spray should not be applied to the breasts or around the vagina. The application site should be allowed to dry for up for 2 minutes before dressing and 30 minutes before washing the area. The application site should not be massaged or rubbed. Other individuals should not be allowed to have direct contact with the skin at the site of spray application for at least 30 minutes following administration. Patients receiving estradiol transdermal spray should ensure that children and pets avoid contact with the skin at the application site to prevent inadvertent exposure to the drug. (See Cautions.) If a child comes in direct contact with the patient's forearm where Evamist was applied, the general area of contact should be washed with soap and water as soon as possible. Patients who cannot avoid such contact with children should wear clothing with long sleeves to cover the application site. Application of sunscreen 1 hour after application of estradiol transdermal spray decreases exposure to estradiol by 11%; application of sunscreen 1 hour prior to application of estradiol transdermal spray does not alter exposure to estradiol.

Dosage

Dosage of estradiol, estradiol acetate, estradiol cypionate, estradiol valerate, and ethinyl estradiol must be individualized according to the condition being treated and the tolerance and therapeutic response of the patient. To minimize the risk of adverse effects, the lowest possible effective dosage should be used. When short-term estrogen therapy is indicated (e.g., for the management of vasomotor symptoms associated with menopause; vulvar and vaginal atrophy), therapy should be discontinued as soon as possible; attempts to reduce dosage or discontinue the drug should be made at 3- to 6-month intervals. Because of the potential increased risk of cardiovascular events, breast cancer, and venous thromboembolic events, estrogen and estrogen/progestin therapy should be limited to the lowest effective doses and shortest duration of therapy consistent with treatment goals and risks for the individual woman. Estrogen and estrogen/progestin therapy should be periodically reevaluated.

Estrogen therapy is administered continuously or cyclically. While estrogen therapy alone may be appropriate in women who have undergone a hysterectomy, many clinicians currently recommend that a progestin be added to estrogen therapy in women with an intact uterus. Addition of progestin therapy for 10 or more days of a cycle of estrogen administration or daily with estrogen in a continuous regimen reduces the incidence of endometrial hyperplasia and the attendant risk of endometrial carcinoma in women with an intact uterus. Morphologic and biochemical studies of the endometrium suggest that 10-13 days of progestin are needed to provide maximum maturation of the endometrium and to eliminate any hyperplastic changes. The manufacturer of Menostar recommends that women with an intact uterus receive a progestin for 14 days every 6-12 months. When a progestin is used in conjunction with an estrogen, the usual precautions associated with progestin therapy should be observed. Clinicians prescribing progestins should be aware of the risks associated with these drugs and the manufacturers' labeling should be consulted. The choice and dosage of a progestin may be important factors in minimizing adverse effects.

When long-acting parenteral preparations are used in the management of conditions associated with estrogen deficiency, the drugs are usually administered once every 3-4 weeks.

Estradiol

Oral Dosage

For the management of moderate to severe vasomotor symptoms associated with menopause or for the management of vulvar and vaginal atrophy, the usual initial oral dosage of estradiol is 1 or 2 mg daily in a cyclic regimen. For replacement therapy in female hypogonadism, female castration, or primary ovarian failure, the usual initial oral dosage of estradiol is 1 or 2 mg daily. Subsequent dosage should be adjusted according to the patient's therapeutic response, using the lowest possible effective maintenance dosage.

For the prevention of osteoporosis, an oral dosage of estradiol 0.5 mg daily in a cyclic regimen has been used. The lowest effective dosage of estradiol for this indication has not been determined.

When estradiol is used in fixed combination with norethindrone acetate (Activella) for the management of moderate to severe vasomotor symptoms associated with menopause, the management of vulvar and vaginal atrophy associated with menopause, or prevention of postmenopausal osteoporosis, the usual dosage is 1 mg of estradiol combined with 0.5 mg of norethindrone acetate daily.

When estradiol is used in fixed combination with drospirenone (Angeliq) for the management of moderate to severe vasomotor symptoms associated with menopause or for the management of vulvar and vaginal atrophy associated with menopause, the usual dosage is 1 mg of estradiol combined with 0.5 mg of drospirenone daily.

When estradiol is used with norgestimate (Prefest) for the management of moderate to severe vasomotor symptoms associated with menopause, the management of vulvar and vaginal atrophy associated with menopause, or prevention of postmenopausal osteoporosis, the usual dosage is 1 mg of estradiol daily for 3 days followed by 1 mg of estradiol with 0.09 mg of norgestimate daily for 3 days; the regimen is continued without interruption.

For the palliative treatment of advanced, metastatic carcinoma of the breast in appropriately selected men and postmenopausal women, the usual oral dosage of estradiol is 10 mg 3 times daily. Estrogen therapy is usually continued in these patients for at least 3 months.

For the palliative treatment of advanced carcinoma of the prostate, the usual oral dosage of estradiol is 1-2 mg 3 times daily.

Transdermal System Dosage

Transdermal estradiol is commercially available as systems that are applied once or twice weekly. Estradiol transdermal systems that are applied twice weekly include Alora (available as a system delivering 0.025 mg/24 hours, 0.05 mg/24 hours, 0.075 mg/24 hours, or 0.1 mg/24 hours), Estraderm (available as a system delivering 0.05 mg/24 hours or 0.1 mg/24 hours), and Vivelle and Vivelle-Dot (available as a system delivering 0.025 mg/24 hours, 0.0375 mg/24 hours, 0.05 mg/24 hours, 0.075 mg/24 hours, or 0.1 mg/24 hours). Estradiol transdermal systems that are applied once weekly include Climara (available as a system delivering 0.025 mg/24 hours, 0.0375 mg/24 hours, 0.05 mg/24 hours, 0.06 mg/24 hours, 0.075 mg/24 hours, or 0.1 mg/24 hours) and Menostar (available as a system delivering 0.014 mg/24 hours). In addition, transdermal estradiol/norethindrone (CombiPatch) is commercially available as a system delivering 0.05 mg/24 hours of estradiol and 0.14 mg/24 hours of norethindrone acetate and as a system delivering 0.05 mg/24 hours of estradiol and 0.25 mg/24 hours of norethindrone acetate. Transdermal estradiol/levonorgestrel (Climara Pro) is commercially available as a system delivering 0.045 mg/24 hours of estradiol and 0.015 mg/24 hours of levonorgestrel.

When Alora or Estraderm is used for the management of moderate to severe vasomotor symptoms associated with menopause or for the management of vulvar and vaginal atrophy, the usual initial dosage of transdermal estradiol is one system delivering 0.05 mg/24 hours applied twice weekly in a continuous regimen in women who have undergone a hysterectomy or a cyclic regimen (3 weeks on drug followed by 1 week without the drug, and then the regimen is repeated as necessary) in women with an intact uterus.

When Climara is used for the management of moderate to severe vasomotor symptoms associated with menopause, the usual initial dosage of transdermal estradiol is one system delivering 0.025 mg/24 hours applied once weekly in a continuous regimen. Subsequent dosage should be adjusted according to the severity of the symptoms and the patient's therapeutic response, using the lowest possible effective maintenance dosage.

When Vivelle or Vivelle-Dot is used for the management of moderate to severe vasomotor symptoms associated with menopause or for the management of vulvar and vaginal atrophy, the usual initial dosage of transdermal estradiol is one system delivering 0.0375 mg/24 hours applied twice weekly in a cyclic or continuous regimen. Subsequent dosage should be adjusted according to the patient's therapeutic response, using the lowest possible effective maintenance dosage. In women who have undergone hysterectomy, transdermal estradiol Vivelle-Dot may be applied twice a week in a continuous regimen.

When estradiol/levonorgestrel (Climara Pro) is used for the management of moderate to severe vasomotor symptoms associated with menopause in women with an intact uterus, one system delivering 0.045 mg/24 hours of estradiol and 0.015 mg/24 hours of levonorgestrel is applied once weekly in a continuous regimen.

When estradiol/norethindrone acetate (CombiPatch) is used for the management of moderate to severe vasomotor systems associated with menopause, for the management of vulvar and vaginal atrophy, or for the treatment of hypoestrogenism secondary to hypogonadism, castration, or primary ovarian failure, CombiPatch may be administered as a continuous combined regimen or as a continuous sequential regimen. In the continuous combined regimen, one CombiPatch system delivering 0.05 mg/24 hours of estradiol and 0.14 mg/24 hours of norethindrone acetate is applied twice weekly in a continuous regimen. If necessary, the dosage of norethindrone acetate may be increased by using the dosage system that delivers 0.25 mg/24 hours of norethindrone acetate. In the continuous sequential regimen, one system of transdermal estradiol delivering 0.05 mg/24 hours (i.e., Vivelle) is applied twice weekly for the first 14 days of a 28-day cycle then one estradiol/norethindrone acetate (CombiPatch) system delivering 0.05 mg/24 hours of estradiol and 0.14 mg/24 hours of norethindrone acetate is applied twice weekly for the remaining 14 days of the cycle. If necessary, the dosage of norethindrone acetate may be increased by using the dosage system that delivers 0.25 mg/24 hours of norethindrone acetate.

When Alora is used for the prevention of postmenopausal osteoporosis, the minimum dose that has been shown to be effective is one system delivering 0.025 mg/24 hours applied twice weekly in a continuous regimen.

When Climara is used for the prevention of postmenopausal osteoporosis, the minimum dose that has been shown to be effective is one system delivering 0.025 mg/24 hours applied once weekly in a continuous regimen.

For the prevention of osteoporosis, the usual initial dosage of transdermal estradiol (Estraderm) is one system delivering 0.05 mg/24 hours applied twice weekly in a cyclic regimen in women with an intact uterus. In women who have undergone hysterectomy, one Estraderm system is applied twice weekly in a continuous regimen. Subsequent dosage can be adjusted according to the patient's response.

For the prevention of osteoporosis, the usual dosage of transdermal estradiol (Menostar) is one system delivering 0.014 mg/24 hours applied once weekly in a continuous regimen.

When Vivelle or Vivelle-Dot is used for the prevention of postmenopausal osteoporosis, the usual dosage is one system delivering 0.025 mg/24 hours applied twice weekly.

When estradiol/levonorgestrel (Climara Pro) is used for the prevention of postmenopausal osteoporosis in women with an intact uterus, one system delivering 0.045 mg/24 hours of estradiol and 0.015 mg/24 hours of levonorgestrel is applied once weekly in a continuous regimen.

In women who are currently not receiving an oral estrogen, transdermal estradiol therapy can be initiated immediately. In women who are currently receiving an oral estrogen, transdermal estradiol therapy can be initiated 1 week after discontinuance of oral therapy or sooner if symptoms reappear before the week has passed.

Topical Gel Dosage

Commercially available estradiol 0.06% topical gel (Elestrin) is supplied in a non-aerosol metered-dose pump. Each depression of the pump delivers 0.87 g of gel containing 0.52 mg of estradiol. When estradiol gel (Elestrin) is used for the management of moderate to severe vasomotor symptoms associated with menopause, the usual initial dosage is 0.87 g of gel (0.52 mg of estradiol) applied topically once daily. Prior to using the pump for the first time, the pump must be primed by fully depressing the pump 10 times; this gel should be discarded in a manner that avoids accidental exposure or ingestion by household members or pets.

Commercially available estradiol 0.06% topical gel (EstroGel) is supplied in a non-aerosol metered-dose pump. Each depression of the pump delivers 1.25 g of gel containing 0.75 mg of estradiol. When estradiol gel (EstroGel) is used for the management of moderate to severe vasomotor symptoms associated with menopause or the treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with menopause, 1.25 g of gel (0.75 mg of estradiol) is applied topically once daily. Prior to using the pump for the first time, the pump must be primed by fully depressing the 93-g pump twice or depressing the 25-g pump 3 times; this gel should be discarded in a manner that avoids accidental exposure or ingestion by household members or pets.

Topical Emulsion Dosage

Commercially available estradiol hemihydrate 0.25% topical emulsion (Estrasorb) is supplied in foil-laminated pouches. Each pouch contains 1.74 g of emulsion. When estradiol topical emulsion (Estrasorb) is used for the management of moderate to severe vasomotor symptoms associated with menopause, the contents of 2 pouches (delivering a total of 0.05 mg of estradiol/24 hours) are applied topically once daily.

Transdermal Spray Dosage

Commercially available estradiol transdermal spray (Evamist) is supplied in a metered-dose pump. The metered pump delivers a metered 90-mcL spray that contains 1.53 mg of estradiol per actuation. When estradiol transdermal spray is used for the management of moderate to severe vasomotor symptoms associated with menopause, the recommended initial dose is one spray to the inner forearm once daily. Subsequent dosage is based on clinical response. One, two, or three sprays may be administered each morning to adjacent, non-overlapping areas of the inner forearm.

Vaginal Dosage

For the management of symptoms of vulvar and vaginal atrophy associated with menopause, 2-4 g of estradiol vaginal cream may be administered intravaginally once daily for 1-2 weeks, then gradually reduced to one-half the initial dosage for a similar period. Maintenance dosages of 1 g of estradiol vaginal cream administered intravaginally 1-3 times weekly may be used after restoration of the vaginal mucosa has occurred.

When estradiol vaginal ring (Estring) is used for the management of postmenopausal urogenital symptoms, one ring (delivering estradiol 0.0075 mg/24 hours) is inserted into the upper third of the vaginal vault; the ring is to remain in place for 3 months. After 3 months, the ring should be removed and, if appropriate, replaced with a new ring. If the ring is expelled, the ring should be rinsed in lukewarm water and reinserted.

For the management of atrophic vaginitis, one vaginal tablet containing 25 mcg of estradiol (Vagifem) is inserted intravaginally once daily (preferably at the same time each day) for 2 weeks (initial dosage). For maintenance therapy for this condition, one vaginal tablet containing 25 mcg of the drug is inserted intravaginally twice weekly.

Estradiol Acetate

Estradiol acetate (Femtrace) is commercially available for oral administration as tablets containing 0.45, 0.9, or 1.8 mg of estradiol acetate; the tablets are administered once daily. When estradiol acetate tablets are used for the management of moderate to severe vasomotor symptoms associated with menopause, therapy should be initiated with the lowest dose.

Estradiol acetate vaginal ring (Femring) is commercially available as a ring delivering estradiol 0.05 mg/24 hours or 0.1 mg/24 hours. When estradiol acetate vaginal ring (Femring) is used for the management of moderate to severe vasomotor symptoms or symptoms of vulvar and vaginal atrophy associated with menopause, therapy should be initiated with the lowest dose. To initiate therapy, one ring delivering estradiol 0.05 mg/24 hours is inserted into the vaginal vault; the ring remains in place for 3 months. After 3 months, the ring should be removed and, if appropriate, replaced with a new ring.

Estradiol Cypionate

For the management of moderate to severe vasomotor symptoms associated with menopause, the usual dosage of estradiol cypionate is 1-5 mg administered IM once every 3-4 weeks.

For replacement therapy in female hypogonadism, the usual dosage of estradiol cypionate is 1.5-2 mg once every month.

When estradiol cypionate in fixed combination with testosterone cypionate is used for the management of moderate to severe vasomotor symptoms associated with menopause, the usual dosage of estradiol cypionate is 2 mg in combination with testosterone 50 mg administered IM every 4 weeks.

Estradiol Valerate

For the management of moderate to severe vasomotor symptoms or for the management of vulvar and vaginal atrophy associated with menopause, and for replacement therapy in female hypogonadism, female castration, or primary ovarian failure, the usual dosage of estradiol valerate is 10-20 mg once every 4 weeks as necessary.

For the palliative treatment of advanced carcinoma of the prostate, the usual dosage of estradiol valerate is 30 mg or more once every 1 or 2 weeks.

Ethinyl Estradiol

Estrogen-Progestin Combination Therapy

Ethinyl estradiol in fixed combination with norethindrone acetate (Femhrt) is commercially available for oral administration as tablets containing 2.5 mcg of ethinyl estradiol with 0.5 mg of norethindrone acetate and as tablets containing 5 mcg of ethinyl estradiol with 1 mg of norethindrone acetate; the tablets are administered once daily. When ethinyl estradiol is used in combination with norethindrone acetate for the management of moderate to severe vasomotor symptoms associated with menopause or the prevention of postmenopausal osteoporosis, therapy should be initiated with the lowest dose.

Cautions

Estradiol, estradiol acetate, estradiol cypionate, estradiol valerate, and ethinyl estradiol share the toxic potentials of other estrogens, and the usual cautions, precautions, and contraindications associated with estrogen therapy should be observed. In addition, when estradiol or ethinyl estradiol is used in conjunction with progestins, the cautions, precautions, and contraindications associated with progestins must be considered in addition to those associated with estrogens. For additional information,

In clinical studies, the most common adverse effect reported with transdermal estradiol therapy was erythema and irritation at the application site. Dermatologic reactions have been reported in up to 97% of patients using transdermal systems. The irritation generally resolves completely within a day or so. Rash has been reported rarely in patients receiving transdermal estradiol therapy. Rotation of application sites minimizes and/or prevents potential skin irritation. If erythema persists or severe irritation or rash occurs, patients should contact their physician.

Estrace 2-mg tablets contain the dye tartrazine (FD&C yellow No. 5), which may cause allergic reactions including bronchial asthma in susceptible individuals. Although the incidence of tartrazine sensitivity is low, it frequently occurs in patients who are sensitive to aspirin.

The US Food and Drug Administration (FDA) is reviewing reports of adverse effects associated with estradiol transdermal spray (Evamist) in children and pets who may have been inadvertently exposed to the drug through skin contact with women receiving the drug. Children exposed to the drug may experience signs of premature puberty including nipple swelling and breast development in females and breast enlargement in males. If such a child shows signs of premature puberty (e.g., nipple or breast swelling, breast tenderness or enlargement), the parents should be advised to contact the child's clinician and to inform the clinician of the child's possible exposure to the drug.

Some estradiol topical preparations (e.g., gel, solution) contain alcohol. Preparations containing alcohol are flammable; exposure to open flame or lighted cigarettes should be avoided until the applied product has dried.