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Estradiol

Pronunciation

Pronunciation: ES-tra-DYE-ol
Class: Estrogens

Trade Names

Alora
- Transdermal system 0.77 mg
- Transdermal system 1.5 mg
- Transdermal system 2.3 mg
- Transdermal system 3.1 mg

Climara
- Transdermal system 2 mg
- Transdermal system 2.85 mg
- Transdermal system 3.8 mg
- Transdermal system 4.55 mg
- Transdermal system 5.7 mg
- Transdermal system 7.6 mg

Divigel
- Topical gel 0.25 g
- Topical gel 0.5 g
- Topical gel 1 g

Elestrin
- Topical gel 0.87 g/actuation

Estrace
- Tablets micronized estradiol 0.5 mg
- Tablets micronized estradiol 1 mg
- Tablets micronized estradiol 2 mg
- Vaginal cream 0.1 mg/g

Estraderm
- Transdermal system 4 mg
- Transdermal system 8 mg

Estrasorb
- Topical emulsion estradiol hemihydrate 2.5 mg/g

Estring
- Ring 2 mg

Estrogel
- Topical gel 0.75 mg per 1.25 g unit dose

Evamist
- Topical solution 1.53 mg

Femring
- Ring estradiol acetate 0.05 mg/day
- Ring estradiol acetate 0.1 mg/day

Femtrace
- Tablets estradiol acetate 0.45 mg
- Tablets estradiol acetate 0.9 mg
- Tablets estradiol acetate 1.8 mg

Gynodiol
- Tablets micronized estradiol 0.5 mg
- Tablets micronized estradiol 1 mg
- Tablets micronized estradiol 1.5 mg
- Tablets micronized estradiol 2 mg

Menostar
- Transdermal system 0.14 mg

Vagifem
- Tablets estradiol hemihydrate 25.8 mcg

Vivelle
- Transdermal system 3.28 mg
- Transdermal system 4.33 mg
- Transdermal system 6.57 mg
- Transdermal system 8.66 mg

Vivelle
- Transdermal system 0.0375 mg
- Transdermal system 0.05 mg
- Transdermal system 0.075 mg
- Transdermal system 0.1 mg

Vivelle-Dot
- Transdermal system 0.39 mg
- Transdermal system 0.585 mg
- Transdermal system 0.78 mg
- Transdermal system 1.17 mg
- Transdermal system 1.56 mg

Estradiol Valerate

Delestrogen
- Injection 10 mg/mL
- Injection 20 mg/mL
- Injection 40 mg/mL

Estradiol Cypionate

Depo-Estradiol
- Injection 5 mg/mL

Estradot (Canada)
Estrogel (Canada)
Sandoz Estradiol derm (Canada)

Pharmacology

Promotes growth and development of female reproductive system and secondary sex characteristics; affects release of pituitary gonadotropins; inhibits ovulation and prevents postpartum breast engorgement; conserves calcium and phosphorous and encourages bone formation; overrides stimulatory effects of testosterone.

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Pharmacokinetics

Absorption

Well absorbed through the skin, mucous membranes, and GI tract.

Distribution

Approximately 80% is bound to sex hormone–binding globulin; most of the rest is loosely bound to albumin, and approximately 20% is unbound. Crosses the placenta.

Metabolism

Orally administered estradiol undergoes first-pass effect. Metabolic conversion occurs primarily in the liver but also at local target tissue sites. Also undergoes enterohepatic recirculation.

Elimination

A certain portion is excreted in the bile and then reabsorbed from the intestine. Excreted in the urine as conjugates.

Indications and Usage

Alora, Climara, Delestrogen, Depo-Estradiol, Divigel, Elestrin, Estrace tablets, Estraderm, Estrasorb, Estring, EstroGel, Evamist, Femring, Femtrace, Gynodiol, Vivelle, Vivelle-Dot

Treatment of moderate to severe vasomotor symptoms associated with menopause.

Alora, Climara, Delestrogen, Depo-Estradiol, Estraderm, Estrace tablets, Femtrace, Gynodiol, Vivelle, Vivelle-Dot

Treatment of hypoestrogenism due to hypogonadism.

Alora, Climara, Delestrogen, Estraderm, Estrace tablets, Gynodiol, Vivelle, Vivelle-Dot

Treatment of castration or primary ovarian failure.

Alora, Climara, Delestrogen, Depo-Estradiol, Estrace cream and tablets, Estraderm, Estring, EstroGel, Femring, Gynodiol, Vagifem, Vivelle, Vivelle-Dot

Treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with menopause.

Alora, Climara, Estraderm, Gynodiol, Vivelle, Vivelle-Dot

Prevention of postmenopausal osteoporosis.

Delestrogen, Estrace tablets, Gynodiol

Treatment of advanced androgen-dependent carcinoma of the prostate (palliation only).

Estrace tablets, Gynodiol

Treatment of breast cancer in appropriately selected women and men with metastatic disease.

Contraindications

Undiagnosed abnormal genital bleeding; known, suspected, or history of breast cancer; known or suspected estrogen-dependent neoplasia; active deep vein thrombosis, pulmonary embolism, or history of theses conditions; active or recent (within past year) arterial thromboembolic disease (eg, stoke, MI); liver dysfunction or disease; known or suspected pregnancy; hypersensitivity to any component of the product.

Dosage and Administration

Treatment of Hypoestrogenism Due to Hypogonadism
Adults Alora , Vivelle , Vivelle-Dot

Transdermal Apply 1 patch twice a week.

Climara

Transdermal Start with 0.025 mg/day system applied to skin once/wk; adjust dose as needed to control symptoms.

Delestrogen

IM 10 to 20 mg every 4 wk.

Depo-Estradiol

IM 1.5 to 2 mg at monthly intervals.

Estraderm

Transdermal Start with 0.05 mg/day system applied to skin twice/wk; adjust dose as needed to control symptoms.

Estrace tablets

PO 1 to 2 mg/day; adjust dose as needed to control symptoms.

Femtrace

PO Take 1 tablet by mouth daily.

Gynodiol

PO 1 to 2 mg by mouth daily.

Prevention of Postmenopausal Osteoporosis
Adults Alora , Vivelle , Vivelle-Dot

Transdermal Apply 1 patch twice a week.

Climara

Transdermal Start with 0.025 mg/day system applied to skin once/wk; adjust dose as needed to control symptoms.

Estrace

PO Start with 1 to 2 mg daily; adjust dose as needed to control symptoms.

Estraderm

Transdermal Start with 0.05 mg/day system applied to skin twice/wk; adjust dose as needed to control symptoms.

Gynodiol

PO Administer 0.5 mg/day cyclically (eg, 23 days on and 5 days off) as soon as possible after menopause. Adjust dosage if necessary to control concurrent menopausal symptoms. Discontinuation may re-establish natural rate of bone loss. The mainstays of prevention and management of osteoporosis are estrogen and calcium; exercise and nutrition may be important adjuncts.

Menostar

Transdermal Apply one 14 mcg/day system once/wk.

Vasomotor Symptoms
Adults Alora , Vivelle , Vivelle-Dot

Transdermal Apply 1 patch twice a week.

Climara

Transdermal Start with 0.025 mg/day system applied to skin once/wk; adjust dose as needed to control symptoms.

Delestrogen

IM 10 to 20 mg every 4 wk.

Depo-Estradiol

IM 1 to 5 mg every 3 to 4 wk.

Divigel

Topical Start with 0.25 g (entire contents of unit dose packet) applied once daily to the right or left upper thigh. Adjust dose as needed to control symptoms.

Elestrin

Topical 1 pump per day (0.87 g/day) on upper arm.

Estrace

PO Start with 1 to 2 mg daily; adjust dose as needed to control symptoms. Administer cyclically (eg, 3 wk on and 1 wk off).

Estraderm

Transdermal Start with 0.05 mg/day system applied to skin twice/wk; adjust dose as needed to control symptoms.

Estrasorb emulsion

Topical Apply 3.48 g daily to clean, dry skin on both legs each morning.

Estring

Ring Insert 1 ring vaginally for 3 months.

EstroGel

Topical Apply 1.25 g (1 complete pump depression) to clean, dry, unbroken skin of 1 arm.

Evamist

Transdermal Start with 1 spray (1.53 mg) daily; adjust dose as needed to control symptoms.

Femring

Ring Start with lowest dose. Insert into vagina. Exact position is not critical to function. When ring is in place, patient should not feel anything. If patient feels discomfort, Femring should be pushed gently further into the vagina. The ring should remain in place for 3 mo and then be replaced by a new Femring .

Femtrace

PO Start with 0.45 mg/day; adjust dose as needed to control symptoms.

Gynodiol

PO Take one 0.5 mg tablet by mouth daily.

Vagifem

Vaginal Tablet Insert 1 tablet vaginally for 3 months.

Castration or Primary Ovarian Failure
Adults Alora , Vivelle , Vivelle-Dot

Transdermal Apply 1 patch twice a week.

Climara

Transdermal Start with 0.025 mg/day system applied to skin once/wk; adjust dose as needed to control symptoms.

Estrace

PO Start with 1 mg/day; adjust dose as needed to control symptoms.

Estraderm

Transdermal Start with 0.05 mg/day system applied to skin twice/wk; adjust dose as needed to control symptoms.

Gynodiol

PO 1 to 2 mg by mouth daily.

Vulva/Vaginal Atrophy Associated With Menopause
Adults Alora , Vivelle , Vivelle-Dot

Transdermal Apply 1 patch twice a week.

Climara

Transdermal Start with 0.025 mg/day system applied to skin once/wk; adjust dose as needed to control symptoms.

Delestrogen

IM 10 to 20 mg every 4 wk.

Depo-Estradiol

IM 1 to 5 mg injected every 3 to 4 weeks.

Estrace

PO Start with 1 to 2 mg/day; adjust dose as needed to control symptoms. Administer cyclically (eg, 3 wk on and 1 wk off).

Estrace cream

Topical 2 to 4 g (marked on applicator) daily for 1 or 2 wk, then gradually reduce to 50% of initial dose for 1 to 2 wk. Maintenance dose: 1 g 1 to 3 times/wk after restoration of vaginal mucosa achieved.

Estraderm

Transdermal Start with 0.05 mg/day system applied to skin twice/wk; adjust dose as needed to control symptoms.

Estring

Ring Start with lowest dose. Insert as deeply as possible into the upper one-third of vaginal vault. The ring is to remain in place continuously for 3 mo, then removed and, if appropriate, replaced by a new ring.

EstroGel

Topical Apply 1.25 g (1 complete pump depression) to clean, dry, unbroken skin of 1 arm.

Femring

Ring Start with lowest dose. Insert into vagina. Exact position is not critical to function. When ring is in place, patient should not feel anything. If patient feels discomfort, Femring should be pushed gently further into the vagina. The ring should remain in place for 3 mo and then be replaced by a new Femring .

Gynodiol

PO 1 to 2 mg by mouth daily.

Vagifem

Vaginal tablet Start with 1 tablet vaginally once/day for 2 wk. Maintenance dose: 1 tablet vaginally twice/wk.

Breast Cancer
Adults Estrace

PO Suggested dosage is 10 mg 3 times daily for at least 3 mo.

Gynodiol

PO For palliation only. The usual dosage is 10 mg 3 times daily for at least 3 months.

Treatment of Advanced Androgen-Dependent Carcinoma of the Prostate (Palliative Only)
Adults Delestrogen

IM 30 mg or more every 1 to 2 wk.

Estrace

PO Start with 1 to 2 mg 3 times daily; adjust dose as needed.

Gynodiol

PO For palliation only. Administer 1 to 2 mg 3 times daily. Judge the efficacy of therapy by phosphatase determinations and symptomatic improvement of the patient.

General Advice

Tablets
  • Administer prescribed dose without regard to meals. Administer with food if GI upset occurs.
Transdermal system
  • Open pouch; remove protective liner from patch and immediately apply patch to clean, dry skin on lower abdomen or upper quadrant of buttock. Do not apply patch to breasts or skin areas that are oily, damaged, irritated, have had powder, lotion, or moisturizer applied, or where clothing or sitting could dislodge patch.
  • Press firmly with palm of hand for approximately 10 sec. Be sure good contact is made, especially at edges. If patch falls off, attempt to reapply. Apply new patch to different site if necessary.
  • Rotate application sites so that no site is used more than once per week.
Estradiol ring
  • Remove vaginal ring from protective pouch; press opposite sides of ring together and have patient insert into the vagina. If patient has difficulty inserting ring, health care provider can insert ring. If patient feels discomfort, gently push ring further into the vagina.
Topical emulsion ( Estrasorb )
  • Emulsion is applied once daily in the morning, while in a comfortable seated position, to skin on both legs that is clean, dry, and not irritated.
  • Cut or tear first pouch at notches indicated near the top of the pouch; push the entire contents from the bottom of the pouch through the neck of the pouch to the left thigh. Have patient use 1 or both hands to rub the emulsion into the entire left thigh and calf for 3 min until thoroughly absorbed; have patient rub any excess emulsion remaining on hands on the buttocks. Repeat this process using the second pouch and the right thigh and calf, including rubbing any remaining emulsion on the hands on the buttocks. Have patient wash hands with soap and water to remove any residual medication.
  • Instruct patient to allow application areas to dry thoroughly before covering with clothing to avoid transfer to other individuals.
Vaginal tablet
  • Gently insert into vagina as far as it can comfortably go without force, using supplied applicator.
Injection
  • For IM administration only. Not for intradermal, subcutaneous, or IV administration.
  • Inspect solution visually before administration. Do not administer if solution is cloudy, discolored, or contains particulate matter. Crystals may form if solution is stored at low temperature but will dissolve readily when solution is warmed.
  • Administer prescribed dose by deep IM injection into upper outer quadrant of gluteal muscle.

Storage/Stability

Depo-Estradiol

Store at 68° to 77°F.

Divigel, Femtrace

Store at 59° to 86°F.

Estrace

Store at 68° to 77°F. Protect from light.

Estrace cream

Store at room temperature. Protect from temperatures above 104°F.

Estraderm, Menostar transdermal patch

Store below 87°F. Apply immediately upon removal from protective pouch.

Estrasorb, Estring and Femring vaginal ring, EstroGel, Vagifem vaginal tablet

Store at 59° to 86°F.

Evamist transdermal spray

Store at 59° to 86°F. Do not freeze.

Drug Interactions

Corticosteroids (eg, prednisone)

Increased pharmacologic and toxicologic effects of corticosteroids may occur.

Hydantoins (eg, phenytoin)

Loss of seizure control or decreased estrogenic effects may occur.

Inducers of CYP3A4 (eg, barbiturates [eg, phenobarbital], bosentan, carbamazepine, modafinil, rifampin, St. John's wort, topiramate)

May reduce plasma estrogens, resulting in a decrease in therapeutic effects and changes in uterine bleeding profile.

Inhibitors of CYP3A4 (eg, azole antifungal agents [eg, itraconazole, ketoconazole], grapefruit juice, macrolide antibiotics [eg, clarithromycin, erythromycin], ritonavir)

May elevate estrogen plasma levels, resulting in increased adverse reactions.

Thyroid hormones (eg, levothyroxine)

Serum free thyroxine concentrations may be decreased, increasing serum thyrotropin concentrations and the need for thyroid hormone.

Laboratory Test Interactions

Increased thyroid-binding globulin levels, T4 levels, or T3 levels; T3 resin uptake is decreased; patients on thyroid replacement therapy may require higher doses of thyroid hormone; accelerated PT, partial thromboplastin, 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-thromboglubulin; decreased levels of antifactor Xa and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity; other serum-binding proteins may be elevated (eg, corticosteroid-binding globulin, sex hormone–binding globulin); free hormone concentrations may be increased; other plasma proteins may be increased (eg, ceruloplasmin); reduced response to metyrapone test; increased plasma HDL and HDL 2 cholesterol subfraction concentrations; reduced LDL cholesterol concentrations; increased triglyceride levels; reduced response to metyrapone test.

Adverse Reactions

Cardiovascular

Syncope (1% to 3%); thrombophlebitis.

CNS

Headache (20%); asthenia, dizziness (5%); insomnia (3% to 5%); depression (3%); anxiety, nervousness (2%); migraine (1% to 3%).

Dermatologic

Rash (7%); pruritus (5%); dermatitis, skin hypertrophy (1% to 3%).

EENT

Nasopharyngitis (6%); otitis media (1% to 3%); pharyngitis (1%).

GI

Abdominal distension, abdominal pain, flatulence (7%); nausea (6%); constipation, dyspepsia (5%); diarrhea (4%); gastritis, hemorrhoids, toothache, tooth disorder (1% to 3%).

Genitourinary

Endometrial disorder (15%); breast pain (13%); breast tenderness, leucorrhea, vaginal candidiasis (11%); intermenstrual bleeding, metrorrhagia (10%); vaginitis (9%); cervical polyps, nipple pain, vaginal bleeding (7%); genital moniliasis, genital pruritus (6%); breast pain, suspicious pap smear including atypical squamous cell, uterine pain, vaginal discharge (5%); hematuria, vaginal discomfort (3% to 5%); asymptomatic genital bacterial growth; UTI, vaginal hemorrhage (4%); UTI (2%); dysuria, genital eruption, urinary incontinence, urogenital pruritus (1% to 3%); breast pain (1%).

Local

Redness and irritation (transdermal, 17%).

Metabolic-Nutritional

Weight gain (2%).

Musculoskeletal

Arthralgia (12%); back pain (7%); myalgia (5%); arthritis (4%); arthralgia (3%); skeletal pain (2%).

Respiratory

Upper respiratory tract infection (11%); bronchitis, sinusitis (6%).

Miscellaneous

Infection (17%); accidental injury (14%); pain (13%); flu-like symptoms (5%); allergy, hematuria (3% to 5%); fungal infection (3%); hot flashes (2%); chest pain, cystitis, leg edema (1% to 3%); allergy (1%); toxic shock syndrome.

Precautions

Warnings

Endometrial cancer

Close clinical surveillance of all women taking estrogens is important. The use of unopposed estrogen in women with intact uteri has been associated with an increased risk of endometrial cancer. 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.

CV and other risks

Estrogens with or without progestins should not be used for prevention of CV disease. The Women's Health Initiative (WHI) study reported increased risk of MI, stoke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women 50 to 79 yr of age during 5.6 yr of treatment with oral conjugated estrogens 0.625 mg combined with medroxyprogesterone acetate 2.5 mg compared with placebo.

Dementia

A subsidiary of WHI, the WHI Memory Study, reported increased risk of developing probable dementia in postmenopausal women 65 yr of age or older during 4 yr of treatment with oral conjugated estrogens plus medroxyprogesterone acetate compared with placebo. It is unknown if this finding applies to younger postmenopausal women or women taking estrogen alone.


Monitor

Monitor BP at beginning of therapy and at regular intervals during treatment. Periodically monitor thyroid function.


Pregnancy

Contraindicated in pregnancy.

Estrace, Vagifem

Category X .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

Estrace, Femtrace, Vagifem

Use with caution, usually starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Special Risk Patients

Since asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas may be exacerbated by estrogens, use with caution.

Breast cancer

Estrogen and estrogen/progestin therapy in postmenopausal women has been associated with an increased risk of breast cancer. The increased risk is apparent after 4 yr of treatment.

Elevated BP

Substantial increases in BP have been attributed to idiosyncratic reactions to estrogens.

Endometriosis

May be exacerbated by estrogens.

Fluid retention

Because estrogens may cause fluid retention, carefully monitor patients with conditions influenced by fluid retention (eg, cardiac dysfunction or renal function impairment).

Gallbladder disease

The risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogen is increases 2- to 4-fold.

Glucose intolerance

Impaired glucose tolerance may occur.

Hypercalcemia

Severe hypercalcemia in patients with breast cancer and bone metastases may occur.

Hypertriglyceridemia

In patients with preexisting hypertriglyceridemia, estrogen therapy may be associated with elevations in plasma triglycerides, leading to pancreatitis and other complications.

Hypocalcemia

Use with caution.

Hypothyroidism

Estrogen administration leads to increased thyroid-binding globulin levels. Ensure that thyroid function is periodically monitored in patients with hypothyroidism and that thyroid replacement dose is adjusted, if necessary, to maintain free thyroid levels in an acceptable range.

Impaired liver function

Estrogens may be poorly metabolized in patients with impaired liver function.

Ovarian cancer

Estrogen plus progestin has been reported to increase the risk of cancer.

Surgery/Immobilization

Consider discontinuing therapy during periods of prolonged immobilization and, if possible, 4 to 6 wk before surgery associated with an increased risk of thromboembolic disease.

Tapering/Withdrawal

Attempts should be made every 3 to 6 mo to discontinue therapy or reduce the dose of medication.

Toxic shock syndrome

Has been reported with use of estradiol vaginal ring.

Vaginal irritation

Estradiol vaginal ring may not be suitable for women with narrow, short, or stenosed vaginas. Conditions that make the vagina more susceptible to vaginal ring irritation or ulceration include narrow vagina, vaginal stenosis, prolapse, and vaginal infections.

Vaginal ring movement

Moving or gliding of estradiol vaginal ring as well as expulsion in connection with bowel movement, strain, or constipation have been reported.

Visual abnormalities

Retinal vascular thrombosis may occur, leading to loss of vision, sudden onset of proptosis, diplopia, or migraine.

Overdosage

Symptoms

Nausea, withdrawal bleeding in women.

Patient Information

  • Advise patient to review patient information leaflet before starting therapy and with each refill.
  • Instruct patient to take (or use) as prescribed and not to change the dose or stop taking unless advised by health care provider.
  • Advise patient taking tablets that medication can be taken without regard to meals, but to take with food if GI upset occurs.
  • Instruct diabetic patient to monitor blood glucose more frequently when drug is started or dose is changed and to inform health care provider of significant changes in readings.
  • Review the following nonhormonal modalities that help prevent osteoporosis: 1,500 mg/day of calcium, vitamin D supplementation, exercise.
  • Instruct patient to report the following symptoms to health care provider: abnormal vaginal bleeding, breast lumps, dizziness or fainting, pain in groin or calves, severe abdominal pain or swelling, severe depression, sharp chest pain or sudden shortness of breath, sudden severe headache, vision or speech problems, weakness or numbness of arms or legs, yellowing of skin or eyes.
  • Teach patient proper method of breast self-examination.
  • Advise patient that follow-up visits and examinations, including Pap smear, at least once a year will be required to monitor therapy and to keep appointments.
  • Transdermal system
  • Advise patient not to apply patch to breasts or to skin areas that are oily, damaged, or irritated, have had powder, moisturizer, or lotion applied, or where clothing or sitting could dislodge patch.
  • Teach patient proper procedure for applying patch as follows: open pouch, remove protective liner from patch, and immediately apply patch to clean, dry skin on lower abdomen or upper quadrant of buttock. Press firmly with palm of hand for approximately 10 sec. Be sure good contact is made, especially at edges.
  • Advise patient that if patch falls off, it should be reapplied to a different site. If patch cannot be reapplied, instruct patient to apply a new patch at a different site but to continue to follow the original dosing scheduled.
  • Teach patient proper procedure for changing patch as follows: Slowly peel off used patch, fold in half, and discard in trash. Apply new patch at different site. Instruct patient to rotate application sites so that no site is used more than once a week.
  • Advise patient that if scheduled patch change is missed to remove the old patch and apply a new patch to a different site but to continue to follow the original application schedule.
  • Advise patient to notify health care provider if skin irritation or persistent redness or itching occur at the application site.
  • Estradiol ring
  • Teach patient proper procedure for inserting or replacing ring as follows: Wash hands before and after insertion; remove vaginal ring from protective pouch, press opposite sides of ring together, and insert into the vagina. If patient has difficulty inserting ring, health care provider can insert it. If ring causes discomfort, gently push it further into the vagina.
  • Advise patient that the ring should not be felt when in place, nor should it interfere with sexual intercourse; repositioning the ring should result in resolution of any abnormal sensation. Advise patient to notify health care provider if repositioning ring does not resolve abnormal sensations.
  • Advise patient that if ring is totally expelled from vagina, to clean it in warm water and reinsert.
  • Remind patient that ring should be removed and replaced by a new ring every 3 mo in order to maintain beneficial effects.
  • Topical emulsion
  • Advise patient to apply emulsion every day in the morning to skin on both legs that is clean and dry.
  • Caution patient not to apply emulsion to any skin area that appears to be red or irritated.
  • Teach patient proper procedure for applying emulsion as follows: cut or tear first pouch at notches indicated near the top of the pouch; while in a comfortable seated position, push the entire contents from the bottom of the pouch through the neck of the pouch onto the left thigh; using 1 or both hands, rub the emulsion into the entire left thigh and calf for 3 min until thoroughly absorbed; rub any excess emulsion remaining on hands on the buttocks; repeat this process using the second pouch and the right thigh and calf including rubbing any remaining emulsion on the hands on the buttocks; wash hands with soap and water to remove any residual medication.
  • Instruct patient to allow application areas to dry thoroughly before covering with clothing to avoid transfer to other individuals.
  • Advise patient that if application of the emulsion in the morning is missed, to apply it as soon as remembered and to never apply the emulsion more than once each day.
  • Injection
  • Advise patient that medication will be prepared and administered by health care provider in a medical setting on a scheduled basis.
  • Evamist transdermal spray
  • Instruct patient that prior to first application, the applicator must be primed by fully depressing the applicator 3 times.
  • Instruct patient that the applicator should be primed only once and not to prime the applicator before each day's dose.
  • Instruct patient to apply to clean, dry, unbroken skin on the inside of the forearm between the elbow and wrist and not to other areas of the skin.
  • Inform patient that if health care provider increases the dose to 2 or 3 sprays, the cone should be moved before the second or third spray to an area of skin next to but not touching the area of the previous spray.
  • Instruct patient not to massage or rub the product into the skin but to allow the spray to dry for at least 2 min before dressing and at least 30 min before washing.
  • Instruct patient that product contains alcohol and not to apply while standing near a flame and to avoid fire, flame, or smoking when using product.
  • Instruct patient that if a dose is missed, not to double the dose on the next day; however, if the next dose is less than 12 h away, wait and apply the normal dose the next day. If it is more than 12 h until the next dose, the missed dose should be applied and the normal dosing schedule should be resumed on the next day.
  • EstroGel topical gel
  • Instruct patient that prior to first application, the applicator must be primed by fully depressing the pump 2 times. Discard the unused gel.
  • After priming, 1 complete pump depression will dispense the same amount of product each time.
  • Advise patient to apply daily dose at the same time each day. If bathing, showering, or using the sauna, apply after bath, shower, or use of sauna. If swimming, leave as much time as possible between product application and swimming.
  • Instruct patient to apply dose by collecting the gel into the palm of the hand and applying the gel to one arm. Spread the gel as thinly as possible over the entire area on the inside and outside of the arm, from wrist to shoulder.
  • Instruct patient to allow gel of dry for up to 5 min before dressing.
  • Instruct patient that product contains alcohol and to avoid fire, flame, or smoking until gel has dried.
  • Instruct patient to wash hands with soap and water after application.
  • Instruct patient that if a dose is missed, not to double the dose on the next day; however, if the next dose is less than 12 h away, wait and apply the normal dose the next day. If it is more than 12 h until the next dose, the missed dose should be applied and the normal dosing schedule should be resumed on the next day.
  • Divigel topical gel
  • Advise patient to apply daily dose, entire contents of 1 unit dose packet, at the same time each day.
  • Instruct patient to apply dose to right or left upper thigh.
  • Instruct patient to allow gel to dry before dressing.
  • Instruct patient that product contains alcohol and to avoid fire, flame, or smoking until gel has dried.
  • Instruct patient to wash hands with soap and water after application.
  • Instruct patient that if a dose is missed, not to double the dose the next day; however, if the next dose is less than 12 h away, wait and apply the normal dose the next day. If it is more than 12 h until the next dose, the missed dose should be applied and the normal dosing schedule should be resumed the next day.

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