Usual Adult Dose for Atrophic Vaginitis

Vaginal cream:
Initial dose: 2 to 4 grams intravaginally once a day for 1 or 2 weeks

• Gradually reduce to one-half the initial dose over 1 or 2 weeks

Maintenance dose: 1 gram intravaginally 1 to 3 times a week

Vaginal ring:
Insert 1 vaginal ring (2 mg) as deeply as possible into the upper one-third of the vaginal vault; the ring should remain in place continuously for 3 months, after which it should be removed and replaced by a new ring if indicated

Vaginal insert:
Initial dose: 10 mcg inserted into the vagina once a day for 2 weeks, then, 1 insert into vagina twice a week

• Dose adjustment should be guided by clinical response

Maintenance dose: 10 or 25 mcg inserted into the vagina twice a week

Comments:

• For women with a uterus, a progestin should be considered to reduce the risk of endometrial cancer.
• Treatment should be with the lowest effective dose for the shortest duration consistent with treatment goals and risks; periodically reevaluate to determine if treatment is still needed.
• Vaginal cream: Maintenance dose is to be used once restoration of the vaginal mucosa has been achieved.
• Vaginal ring: Should the ring be removed or fall out during the 90-day treatment period, the ring should be rinsed and reinserted.

Uses:

• Treatment of atrophic vaginitis due to menopause (vaginal insert).
• Treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause (vaginal cream, vaginal ring).

Usual Adult Dose for Dyspareunia

Initial dose: 4 mcg into the vagina once a day for 2 weeks; then, 1 insert into vagina every 3 to 4 days

• Dose adjustment should be guided by clinical response

Maintenance dose: 4 or 10 mcg into vagina every 3 to 4 days

Comments:

• For women with a uterus, a progestin should be considered to reduce the risk of endometrial cancer.
• Treatment should be with the lowest effective dose for the shortest duration consistent with treatment goals and risks; periodically reevaluate to determine if treatment is still needed.

Use: Treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy due to menopause (vaginal inserts)

Renal Dose Adjustments

Use with caution

Liver Dose Adjustments

Liver impairment or disease: Contraindicated

Precautions

US BOXED WARNINGS: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER and PROBABLE DEMENTIA:
ESTROGEN-ALONE THERAPY:

• Endometrial Cancer: 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 postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.
• Cardiovascular Disorders and Probable Dementia: Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or 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 oral conjugated estrogens 0.625 mg/day relative to placebo. The WHI Memory Study (WHIMS) reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment conjugated estrogens 0.625 mg/day relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.
• In the absence of comparable data, these risks should be assumed to be similar for other doses of conjugate estrogens 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:

• Cardiovascular Disorders and Probable Dementia: Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or 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 conjugated estrogen 0.625 mg/day combined with medroxyprogesterone acetate 2.5 mg/day relative to placebo.
• The WHIMS study reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment conjugated estrogen 0.625 mg/day combined with medroxyprogesterone acetate 2.5 mg/day relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.

Breast Cancer: The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer.

• In the absence of comparable data, these risks should be assumed to be similar for other doses of conjugated estrogen plus medroxyprogesterone, 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.

CONTRAINDICATIONS:

• Known anaphylactic reaction or angioedema
• Undiagnosed abnormal genital bleeding
• Known, suspected, or history of breast cancer
• Known or suspected estrogen-dependent neoplasia (e.g., endometrial cancer)
• Previous or current venous thromboembolism (e.g., deep venous thrombosis, pulmonary embolism)
• Active or history of arterial thromboembolic disease (e.g., angina, myocardial infarction, stroke)
• Known liver impairment or disease
• Known protein C, protein S, antithrombin deficiency, or other known thrombophilic disorders

Safety and efficacy have not been established in premenopausal women.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:
Vaginal Cream:

• Place cream in vagina using applicator that is provided
• Once applicator is secured to tube; squeeze tube from bottom until the prescribed amount is in the applicator
• Remove applicator from tube
• Lie on back with knees drawn up and gently insert applicator deeply into vagina, press plunger to release cream into vagina
• Clean applicator with mild soap and warm water; do not boil or use hot water

Vaginal Inserts:
Imvexxy(R):

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

Vagifem(R):

• Administer intravaginally using the supplied applicator

Vaginal Ring:

• Insert as deeply as possible into the upper one-third of the vaginal vault; once in place, it should not be felt; if there is discomfort, gently push further into the vagina
• The ring should remain in place continuously for 3 months, remove and replace with a new ring at 90 days, if appropriate
• If the ring is removed or falls out during the 90-day period, rinse in lukewarm water and reinsert; straining at defecation may make the ring move down, if so, push back up with a finger
• To remove ring, hook a finger through the ring and pull it out
• Keeping the ring in for longer than 90 days will result in progressive loss of efficacy and an increased risk of vaginal infections and/or erosions

Storage requirements: Protect from temperatures exceeding 40C (104F)

General:

• Use of estrogen-alone, or in combination with a progestin, should be done with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual patient.
• Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary.

Monitoring:

• Monitor thyroid function in women on thyroid hormone replacement therapy

Patient advice:
Read the US FDA-approved patient labeling (Patient Information and Instructions for Use).

• Women should be instructed to report abnormal vaginal bleeding to their healthcare provider as soon as possible.
• Women should understand the serious risks of therapy including cardiovascular disorders, malignant neoplasms, and dementia.