VIVELLE-DOT

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VIVELLE-DOT (VIVELLE-DOT).

How it works

Estradiol replacement therapy; binds to estrogen receptors (ERα and ERβ) to regulate gene transcription, exerting effects on tissues including breast, endometrium, bone, and cardiovascular system.

What the body does with it

Metabolism	Metabolized primarily in the liver via CYP3A4; undergoes enterohepatic recirculation. Major metabolites include estrone and estriol, which are conjugated (glucuronide and sulfate) and excreted in urine.
Excretion	Primarily renal (estrogen metabolites, as glucuronide and sulfate conjugates), 90-95% of absorbed dose excreted in urine; <5% in feces via biliary elimination.
Half-life	Terminal half-life of estradiol is approximately 2-4 hours due to rapid metabolism, but after transdermal administration, the apparent half-life is longer (around 5-10 hours) due to continuous absorption from the depot; clinical dosing every 3.5 days maintains steady-state.
Protein binding	Estradiol is bound 97-99% to plasma proteins, primarily to sex hormone-binding globulin (SHBG) and albumin.
Volume of Distribution	Approximately 1.2 L/kg; indicates extensive distribution into tissues, consistent with lipophilic nature of estradiol.
Bioavailability	Transdermal: 5-10% of the delivered dose is absorbed systemically (actual bioavailability depends on patch formulation and site); oral estradiol bioavailability is ~5% due to extensive first-pass metabolism, but transdermal route avoids first-pass effect.
Onset of Action	Transdermal: Estradiol levels reach therapeutic range within 2-4 hours of application; clinical effect (e.g., vasomotor symptom relief) begins within 1-2 weeks.
Duration of Action	Each patch provides sustained release of estradiol for approximately 3.5 days (84 hours); recommended twice-weekly application; clinical effects persist with continuous use.

Classification & Brands

Dosing & administration

Transdermal: 0.025 mg/day, 0.0375 mg/day, 0.05 mg/day, 0.075 mg/day, or 0.1 mg/day applied twice weekly (every 3-4 days).

Dosage form	SYSTEM
Renal impairment	No specific dose adjustment required for renal impairment; use with caution in severe renal disease due to potential accumulation of excipients.
Liver impairment	Contraindicated in patients with impaired liver function or active liver disease; no dose recommendations for Child-Pugh classes.
Pediatric use	Not indicated for pediatric use; safety and efficacy not established in children.
Geriatric use	Initiate at lowest effective dose (0.025 mg/day) and titrate cautiously; increased risk of cardiovascular and thromboembolic events.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VIVELLE-DOT (VIVELLE-DOT).

Breastfeeding	Estradiol is excreted in human milk; M/P ratio not established. Use during lactation may suppress milk production and decrease infant serum estradiol levels. Breastfeeding is generally not recommended while using VIVELLE-DOT.
Teratogenic Risk	Estrogens are contraindicated in pregnancy. First trimester exposure may cause congenital anomalies including cardiovascular and limb defects (based on diethylstilbestrol data). Second and third trimester exposure increases risk of fetal harm, including urogenital abnormalities and potential long-term neurodevelopmental effects.

Warnings & precautions

■ FDA Black Box Warning

Estrogens increase the risk of endometrial cancer in women with an intact uterus; concomitant progestin therapy is required. Cardiovascular disorders (e.g., stroke, DVT, pulmonary embolism) and probable dementia risk increased in women aged 65 years or older. Estrogens should not be used for prevention of cardiovascular disease or dementia.

Side Effect Profile

Serious Effects

Absolute Contraindications

Undiagnosed abnormal genital bleeding, known or suspected pregnancy, known or suspected breast cancer (except in selected cases), known or suspected estrogen-dependent neoplasia, active DVT or PE, history of DVT or PE (unless on anticoagulants), active arterial thromboembolic disease, known protein C, protein S, or antithrombin deficiency, liver dysfunction or disease, hypersensitivity to estrogens or components of the patch.

Clinical Precautions

Precautions

Risk of endometrial cancer, cardiovascular disorders (stroke, DVT, PE), probable dementia, breast cancer, gallstones, hypercalcemia, fluid retention, and exacerbation of endometriosis. Discontinue if jaundice or visual disturbances occur. Monitor thyroid function in patients on thyroid replacement therapy.

Clinical Tips & Counseling

Drug interactions

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VIVELLE-DOT

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VIVELLE-DOT (VIVELLE-DOT).

How it works

Estradiol replacement therapy; binds to estrogen receptors (ERα and ERβ) to regulate gene transcription, exerting effects on tissues including breast, endometrium, bone, and cardiovascular system.

What the body does with it

Metabolism	Metabolized primarily in the liver via CYP3A4; undergoes enterohepatic recirculation. Major metabolites include estrone and estriol, which are conjugated (glucuronide and sulfate) and excreted in urine.
Excretion	Primarily renal (estrogen metabolites, as glucuronide and sulfate conjugates), 90-95% of absorbed dose excreted in urine; <5% in feces via biliary elimination.
Half-life	Terminal half-life of estradiol is approximately 2-4 hours due to rapid metabolism, but after transdermal administration, the apparent half-life is longer (around 5-10 hours) due to continuous absorption from the depot; clinical dosing every 3.5 days maintains steady-state.
Protein binding	Estradiol is bound 97-99% to plasma proteins, primarily to sex hormone-binding globulin (SHBG) and albumin.
Volume of Distribution	Approximately 1.2 L/kg; indicates extensive distribution into tissues, consistent with lipophilic nature of estradiol.
Bioavailability	Transdermal: 5-10% of the delivered dose is absorbed systemically (actual bioavailability depends on patch formulation and site); oral estradiol bioavailability is ~5% due to extensive first-pass metabolism, but transdermal route avoids first-pass effect.
Onset of Action	Transdermal: Estradiol levels reach therapeutic range within 2-4 hours of application; clinical effect (e.g., vasomotor symptom relief) begins within 1-2 weeks.
Duration of Action	Each patch provides sustained release of estradiol for approximately 3.5 days (84 hours); recommended twice-weekly application; clinical effects persist with continuous use.

Classification & Brands

Dosing & administration

Transdermal: 0.025 mg/day, 0.0375 mg/day, 0.05 mg/day, 0.075 mg/day, or 0.1 mg/day applied twice weekly (every 3-4 days).

Dosage form	SYSTEM
Renal impairment	No specific dose adjustment required for renal impairment; use with caution in severe renal disease due to potential accumulation of excipients.
Liver impairment	Contraindicated in patients with impaired liver function or active liver disease; no dose recommendations for Child-Pugh classes.
Pediatric use	Not indicated for pediatric use; safety and efficacy not established in children.
Geriatric use	Initiate at lowest effective dose (0.025 mg/day) and titrate cautiously; increased risk of cardiovascular and thromboembolic events.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VIVELLE-DOT (VIVELLE-DOT).

Breastfeeding	Estradiol is excreted in human milk; M/P ratio not established. Use during lactation may suppress milk production and decrease infant serum estradiol levels. Breastfeeding is generally not recommended while using VIVELLE-DOT.
Teratogenic Risk	Estrogens are contraindicated in pregnancy. First trimester exposure may cause congenital anomalies including cardiovascular and limb defects (based on diethylstilbestrol data). Second and third trimester exposure increases risk of fetal harm, including urogenital abnormalities and potential long-term neurodevelopmental effects.