estradiol vaginal (Rx)

Brand and Other Names:Femring, Vagifem, more...Estrace Vaginal, Estring, estradiol intravaginal, Yuvafem, Imvexxy
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

vaginal cream

  • 0.1mg/g (0.01%) (Estrace Vaginal)

vaginal insert

  • 4mcg (Imvexxy)
  • 10mcg (Imvexxy, Vagifem, Yuvafem)

vaginal ring

  • 2mg/ring (releases ~7.5mcg/24hr) (Estring)
  • 12.4mg/ring (releases 0.05mg/24hr for 3 months) (Femring)
  • 24.8mg/ring (releases 0.1mg/24hr for 3 months) (Femring)

Menopausal Vasomotor Symptoms

Femring

  • Indicated for treatment of moderate-to-severe vasomotor symptoms caused by menopause
  • 1 ring intravaginally for 90 days; replace with new ring at 90 days if continuing therapy
  • Initiate with lowest effective dose and the shortest duration consistent with treatment goals
  • Initial: 0.05 mg/day; dosage adjustment should be guided by the clinical response
  • Attempts to taper or discontinue the medication should be made at 3-6 month intervals

Menopausal Vulvar and Vaginal Atrophy

Estrace Vaginal

  • Indicated for treatment of vulvar and vaginal atrophy
  • Initial: 2-4 g (marked on the applicator) intravaginally qDay x1-2 weeks, then gradually reduced to 50% of initial dosage for a similar period
  • Maintenance: 1 g intravaginally 1-3 times/week may be used after restoration of the vaginal mucosa has been achieved

Estring

  • Indicated for treatment of moderate-to-severe vulvar and vaginal atrophy caused by menopause
  • 1 ring inserted intravaginally for 90 days; replace with new ring at 90 days if continuing therapy
  • Attempts to taper or discontinue the medication should be made at 3-6 month intervals

Femring

  • Indicated for treatment of moderate-to-severe vulvar and vaginal atrophy caused by menopause
  • 1 ring intravaginally for 90 days; replace with new ring at 90 days if continuing therapy
  • Initiate with lowest effective dose and the shortest duration consistent with treatment goals
  • Initial: 0.05 mg/day; dosage adjustment should be guided by the clinical response
  • Attempts to taper or discontinue the medication should be made at 3-6 month intervals

Vagifem, Yuvafem

  • Indicated for treatment of atrophic vaginitis caused by menopause
  • Administer intravaginally using the supplied applicator
  • Insert one 10 mg-insert vaginally qDay x2 weeks; followed by one 10 mg-insert twice weekly (eg, Tuesday and Friday)
  • Generally, women should be started with 10 mg/day

Dyspareunia

Imvexxy

  • Indicated for moderate-to-severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause
  • Administer 1 insert intravaginally qDay at ~same time for 2 weeks, followed by 1 insert twice weekly, every 3-4 days (eg, Monday and Thursday)
  • Generally, women should start at 4 mcg; dosage adjustment based on clinical response
  • Use of estrogen-alone, or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman
  • Re-evaluate postmenopausal women periodically as clinically appropriate to determine if treatment is still necessary
  • Also see Administration

Not indicated

Next:

Interactions

Interaction Checker

and estradiol vaginal

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10%

            Headache (5-16%)

            1-10%

            Vulvovaginal mycotic infection (5-8%)

            Vulvovaginal pruritus (8%)

            Back pain (7%)

            Abdominal pain (7%)

            Diarrhea (5%)

            Postmarketing Reports

            Causality not confirmed

            Genitourinary system: Endometrial cancer, endometrial hyperplasia, vaginal irritation, vaginal pain, vaginismus, vaginal ulceration

            Malignancies: Breast cancer

            Cardiovascular: DVT

            Gastrointestinal: Diarrhea

            Skin: Urticaria, erythematous or pruritic rash, genital pruritus

            Central nervous system: Aggravated migraine, depression, insomnia

            Miscellaneous: Fluid retention, weight increase, drug ineffectiveness, hypersensitivity, blood estrogen increase

            Previous
            Next:

            Warnings

            Black Box Warnings

            Increased risk of endometrial cancer

            • Close clinical surveillance of all women taking estrogens is important
            • Risk of endometrial cancer in women with a uterus increases with use of unopposed estrogens; adding progestin to estrogen therapy may reduce risk of endometrial hyperplasia, a precursor to endometrial cancer
            • Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding

            Cardiovascular risks

            • Estrogens with and without progestins should not be used to prevent cardiovascular disease
            • Estrogens plus progestins: Women’s Health Initiative (WHI) Estrogen Plus Progestin substudy reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary embolism (PE), and deep vein thrombosis (DVT) in postmenopausal women (50-79 years) during 5.6 years of treatment with daily PO conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) in comparison with placebo
            • Estrogens alone: Substudy of WHI study reported increased risk of stroke and DVT in postmenopausal women (50-79 years) during 6.8 years of treatment with PO conjugated estrogens (0.625 mg/day) alone in comparison with placebo

            Dementia risks

            • Estrogens with and without progestins should not be used to prevent dementia
            • Women's Health Initiative Memory Study (WHIMS), substudy of WHI study, reported increased risk of developing probable dementia in postmenopausal women ≥65 years during 4 years of treatment with daily PO conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) in comparison with placebo
            • Estrogens alone: Substudy of WHIMS reported increased risk of developing probable dementia in postmenopausal women ≥65 years during 5.2 years of treatment with conjugated estrogens (0.625 mg/day) alone in comparison with placebo
            • Unknown whether these findings apply to younger postmenopausal women

            Breast cancer

            • The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer; prescribe estrogens with or without progestins at the lowest doses and for the shortest duration

            Dose & duration

            • In the absence of comparable data, these risks should be assumed to be similar for other doses of conjugated estrogens and medroxyprogesterone acetate, as well as for other combinations and dosage forms of estrogens and progestins
            • Because of these risks, estrogens with or without progestins should be prescribed at lowest effective dose and for shortest duration consistent with treatment goals and individual risks

            Contraindications

            Undiagnosed abnormal genital bleeding

            Known, suspected, or history of breast cancer

            Known or suspected estrogen-dependent neoplasia

            Active DVT, PE, or history of these conditions

            Active arterial thromboembolic disease (eg, stroke, MI), or a history of these conditions

            Known anaphylactic reaction or angioedema to estrogen

            Known liver impairment or disease

            Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders

            Known or suspected pregnancy

            Cautions

            System absorption occurs with intravaginal administration; consider warnings, precautions, and adverse effects associated with systemic estrogen-alone therapy

            Increased risk of stroke and DVT reported with estrogen-alone therapy; increased risk of PE, DVT, stroke, and MI reported with estrogen plus progestin therapy; discontinue drug immediately if these conditions occur or are suspected (see Black Box Warnings)

            Increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in a woman with a uterus (see Black Box Warnings)

            The WHI estrogen plus progestin substudy reported a statistically nonsignificant increased risk of ovarian cancer (4 vs 3 cases per 10,000 women-years)

            Estrogen with or without progesterone may increase risk of dementia (see Black Box Warnings)

            Increased risk of gallbladder disease (2- to 4-fold) requiring surgery in postmenopausal women receiving estrogen has been reported

            Severe hypercalcemia in women with breast cancer and bone metastases reported with estrogen use; if hypercalcemia occurs, discontinue estrogen and initiate appropriate treatment to reduce serum calcium level

            Retinal vascular thrombosis reported; discontinue estrogen pending examination if there is a sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine; if papilledema or retinal vascular lesions diagnosed, permanently discontinue estrogens

            Rare occurrences reported of substantial blood pressure increases that were attributed to idiosyncratic reactions to estrogens

            May cause elevated triglycerides that lead to pancreatitis in women with preexisting hypertriglyceridemia; discontinue estrogens if pancreatitis occurs

            Estrogens may be poorly metabolized with hepatic impairment; if cholestatic jaundice occurs, discontinued estrogens

            Estrogen administration leads to increased thyroid-binding globulin (TBG) levels; women with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range, however, women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy

            Estrogens may cause some degree of fluid retention; women with conditions that might be influenced by this factor (eg, cardiac or renal impairment) warrant careful observation

            Malignant transformation of residual endometrial implants have been reported in women treated posthysterectomy with estrogen-alone therapy; if residual endometriosis posthysterectomy exists, the addition of progestin should be considered

            Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema

            Estrogen therapy may exacerbate asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas

            Local abrasion induced by vaginal tablet applicator reported

            Serum follicle stimulating hormone (FSH) and estradiol levels not shown for the management of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause

            Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of antifactor and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity

            Breast cancer

            • The most important randomized clinical trial providing information about breast cancer in estrogen-alone users is the Women’s Health Initiative (WHI) substudy of daily PO conjugated estrogens (CE) (0.625 mg)-alone
            • In the WHI estrogen-alone substudy, after an average follow-up of 7.1 years, daily CE-alone was not associated with an increased risk of invasive breast cancer (see Black Box Warnings)

            Drug interactions overview

            • CYP3A4 inducers or inhibitors may affect estrogen drug metabolism
            • CYP3A4 inducers (eg, St. John's wort [Hypericum perforatum] preparations, phenobarbital, carbamazepine, and rifampin) may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile
            • CYP3A4 inhibitors (eg, erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, grapefruit juice) may increase plasma concentrations of estrogens and may result in side effects
            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

            Estrogens should not be used during pregnancy (see Contraindications)

            There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins as an oral contraceptive inadvertently during early pregnancy

            Lactation

            Should not be used during lactation; estrogen administration to nursing women has been shown to decrease the quantity and quality of the breast milk

            Detectable amounts of estrogens have been identified in the breast milk of women receiving estrogen therapy

            Caution should be exercised when estrogen is administered to a nursing woman

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

            more...
            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics

            Absorption

            Estrogen drug products are well absorbed through the skin, mucous membranes, and the GI tract

            Vaginal delivery of estrogens circumvents first-pass metabolism

            Peak plasma concentration (Imvexxy): 4.8-7.3 pg/mL

            Distribution

            Distribution of exogenous estrogens is similar to that of endogenous estrogens

            Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs

            Estrogens circulate in the blood largely bound to sex hormone-binding globulin (SHBG) and albumin

            Metabolism

            Exogenous estrogens are metabolized in the same manner as endogenous estrogens

            Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions that take place mainly in the liver

            Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite

            Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption

            In postmenopausal women, a significant portion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens

            Elimination

            Excretion: Estradiol, estrone, and estriol are excreted in the urine along with glucuronide and sulfate conjugates

            Previous
            Next:

            Administration

            Intravaginal Administration

            Intravaginal ring

            • Insert in upper third of vaginal vault; the ring is to remain in place continuously for 3 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, rinse the ring in lukewarm water and reinsert (by the patient, or, if necessary, by a physician or nurse)

            Vaginal tablet or cream

            • Use applicator provided with drug to insert vaginal tablet or measure dose of vaginal cream
            • Lay on back with pelvis slightly tilted upward, or stand with one knee bent (ie, foot on seat of chair or toilet), insert the prescribed dose with applicator
            • The applicator should be inserted (without forcing) as far as comfortably possible, or until half of the applicator is inside vagina
            • Note: The vaginal tablet dissolves gradually over several hours, so bedtime application may be desired

            Vaginal insert

            • Administer intravaginally
            • Insert with the smaller end up for a depth of about 2 inches into the vaginal canal

            Storage

            Estrace Vaginal: Room temperature; protect from temperatures exceeding 40°C (104°F)

            Estring: Controlled room temperature 15-25°C (59-77°F)

            Vagifem: Controlled room temperature 25°C (77°F), excursions permitted to 15-30°C (59-86°F); do not refrigerate

            Femring: Controlled room temperature 25°C (77°F), excursions permitted to 15-30°C (59-86°F); do not store out of the protective pouch; insert immediately upon remove from the protective pouch

            Imvexxy: Store at 20-25°C (68-77°F), excursions permitted to 15-30°C (59-86°F)

            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.